Trial Outcomes & Findings for Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy (NCT NCT01994889)

NCT ID: NCT01994889

Last Updated: 2019-04-24

Results Overview

All-cause mortality and frequency of cardiovascular hospitalization were analyzed using Finkelstein-Schoenfeld method. The method combines all-cause mortality and frequency of CV-related hospitalizations in a hierarchical fashion using all-cause mortality first. The method compares every participant with every other participant within strata, assigning a +1 to the "better" participant and a -1 to the "worse" participant and 0 if they are "tied". Participants who discontinued for transplantation (heart transplantation and combined heart and liver transplantation) or for implantation of a cardiac mechanical assist device, were handled in the same manner as death. 'Win' represents a participant doing better based on hierarchical comparison. The reported unit is the total "wins" for each treatment group from performing such a hierarchical comparison across all 4 strata in the study.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

441 participants

Primary outcome timeframe

Baseline up to Month 30

Results posted on

2019-04-24

Participant Flow

Pooled analysis of the tafamidis treatment groups \[20 milligrams (mg) and 80 mg\] was performed in comparison to placebo group.

Participant milestones

Participant milestones
Measure	Tafamidis 20 mg Participants with variant transthyretin cardiomyopathy (TTR-CM) genotype or wild-type TTR-CM genotype received one tafamidis 20 milligram (mg) capsule + 3 placebo capsules (matched to tafamidis) orally once daily for 30 months.	Tafamidis 80 mg Participants with variant TTR-CM genotype or wild-type TTR-CM genotype received tafamidis 80 mg (4 capsules of 20 mg each) orally once daily for 30 months.	Placebo Participants with variant TTR-CM genotype or wild-type TTR-CM genotype received 4 placebo capsules matched to tafamidis orally once daily for 30 months.
Overall Study STARTED	88	176	177
Overall Study COMPLETED	60	113	85
Overall Study NOT COMPLETED	28	63	92

Reasons for withdrawal

Reasons for withdrawal
Measure	Tafamidis 20 mg Participants with variant transthyretin cardiomyopathy (TTR-CM) genotype or wild-type TTR-CM genotype received one tafamidis 20 milligram (mg) capsule + 3 placebo capsules (matched to tafamidis) orally once daily for 30 months.	Tafamidis 80 mg Participants with variant TTR-CM genotype or wild-type TTR-CM genotype received tafamidis 80 mg (4 capsules of 20 mg each) orally once daily for 30 months.	Placebo Participants with variant TTR-CM genotype or wild-type TTR-CM genotype received 4 placebo capsules matched to tafamidis orally once daily for 30 months.
Overall Study Adverse Event	5	12	11
Overall Study Cardiac Device Implantation	0	2	0
Overall Study Organ Transplantation	1	5	5
Overall Study No longer willing to participate	8	17	37
Overall Study Lost to Follow-up	0	1	0
Overall Study Protocol Violation	0	1	1
Overall Study Death	14	25	38

Baseline Characteristics

Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tafamidis 20 mg n=88 Participants Participants with variant transthyretin cardiomyopathy (TTR-CM) genotype or wild-type TTR-CM genotype received one tafamidis 20 milligram (mg) capsule + 3 placebo capsules (matched to tafamidis) orally once daily for 30 months.	Tafamidis 80 mg n=176 Participants Participants with variant TTR-CM genotype or wild-type TTR-CM genotype received tafamidis 80 mg (4 capsules of 20 mg each) orally once daily for 30 months.	Placebo n=177 Participants Participants with variant TTR-CM genotype or wild-type TTR-CM genotype received 4 placebo capsules matched to tafamidis orally once daily for 30 months.	Total n=441 Participants Total of all reporting groups
Age, Continuous	73.3 years STANDARD_DEVIATION 7.07 • n=5 Participants	75.2 years STANDARD_DEVIATION 7.24 • n=7 Participants	74.1 years STANDARD_DEVIATION 6.69 • n=5 Participants	74.3 years STANDARD_DEVIATION 7.01 • n=4 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	18 Participants n=7 Participants	20 Participants n=5 Participants	43 Participants n=4 Participants
Sex: Female, Male Male	83 Participants n=5 Participants	158 Participants n=7 Participants	157 Participants n=5 Participants	398 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants	14 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	84 Participants n=5 Participants	171 Participants n=7 Participants	170 Participants n=5 Participants	425 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	11 Participants n=7 Participants	5 Participants n=5 Participants	18 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	11 Participants n=5 Participants	26 Participants n=7 Participants	26 Participants n=5 Participants	63 Participants n=4 Participants
Race (NIH/OMB) White	75 Participants n=5 Participants	136 Participants n=7 Participants	146 Participants n=5 Participants	357 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline up to Month 30

Population: ITT analysis set:participants in safety population(randomized participants who received at least 1 dose of double-blind medication)having at least 1 post baseline efficacy.Pre-specified intent of study was to compare results between tafamidis with placebo,irrespective of tafamidis doses. Analysis based on pooled dose groups,as per study protocol.

Outcome measures

Outcome measures
Measure	Tafamidis n=264 Participants Participants with variant TTR-CM genotype or wild-type TTR-CM genotype received one tafamidis 20 mg + 3 placebo capsules (matched to tafamidis) or 80 mg (4 capsules of 20 mg each) capsule orally once daily for 30 months.	Placebo n=177 Participants Participants with variant TTR-CM genotype or wild-type TTR-CM genotype received 4 placebo capsules matched to tafamidis orally once daily for 30 months.
Hierarchical Combination of All-Cause Mortality and Frequency of Cardiovascular-Related Hospitalizations	8595 wins	5071 wins

SECONDARY outcome

Timeframe: Baseline up to Month 30

Population: ITT analysis set: all participants in the safety population who had at least 1 post baseline efficacy evaluation. The pre-specified intent of this study was to compare the results between tafamidis with placebo, irrespective of the tafamidis doses. Therefore, this analysis was based on the pooled dose groups, as per the study protocol.

Number of deaths due to any cause was analyzed. Participants who discontinued for transplantation (heart transplantation and combined heart and liver transplantation) or for implantation of a cardiac mechanical assist device were handled in the same manner as death.

Outcome measures

Outcome measures
Measure	Tafamidis n=264 Participants Participants with variant TTR-CM genotype or wild-type TTR-CM genotype received one tafamidis 20 mg + 3 placebo capsules (matched to tafamidis) or 80 mg (4 capsules of 20 mg each) capsule orally once daily for 30 months.	Placebo n=177 Participants Participants with variant TTR-CM genotype or wild-type TTR-CM genotype received 4 placebo capsules matched to tafamidis orally once daily for 30 months.
All-Cause Mortality Deaths (all causes)	69 Participants	72 Participants
All-Cause Mortality Heart transplants	7 Participants	4 Participants
All-Cause Mortality Cardiac Mechanical Assist Devices	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline to Month 30

CV related hospitalizations per year is calculated as participant's number of CV related hospitalizations upon duration on study in years.

Outcome measures

Outcome measures
Measure	Tafamidis n=264 Participants Participants with variant TTR-CM genotype or wild-type TTR-CM genotype received one tafamidis 20 mg + 3 placebo capsules (matched to tafamidis) or 80 mg (4 capsules of 20 mg each) capsule orally once daily for 30 months.	Placebo n=177 Participants Participants with variant TTR-CM genotype or wild-type TTR-CM genotype received 4 placebo capsules matched to tafamidis orally once daily for 30 months.
Frequency of Cardiovascular-Related Hospitalizations	0.999 CV hospitalization per year Standard Deviation 2.2777	0.884 CV hospitalization per year Standard Deviation 1.2032

SECONDARY outcome

Timeframe: Baseline, Month 30

Population: Analysis performed on ITT analysis set. The pre-specified intent of this study was to compare the results between tafamidis with placebo, irrespective of the tafamidis doses. This analysis was based on the pooled dose groups, as per the study protocol. Here, 'number analyzed' = participants evaluable for this outcome at specified time points.

6MWT is the total distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed.

Outcome measures

Outcome measures
Measure	Tafamidis n=264 Participants Participants with variant TTR-CM genotype or wild-type TTR-CM genotype received one tafamidis 20 mg + 3 placebo capsules (matched to tafamidis) or 80 mg (4 capsules of 20 mg each) capsule orally once daily for 30 months.	Placebo n=177 Participants Participants with variant TTR-CM genotype or wild-type TTR-CM genotype received 4 placebo capsules matched to tafamidis orally once daily for 30 months.
Change From Baseline in the Total Distance Walked During 6 Minute Walk Test (6MWT) at Month 30 Baseline	350.55 meters Standard Deviation 121.296	353.26 meters Standard Deviation 125.983
Change From Baseline in the Total Distance Walked During 6 Minute Walk Test (6MWT) at Month 30 Change at Month 30	-30.46 meters Standard Deviation 87.886	-89.67 meters Standard Deviation 105.159

SECONDARY outcome

Timeframe: Baseline, Month 30

KCCQ is a 23-item participant-completed questionnaire that assesses health status and health-related quality of life in participants with heart failure. Eight domain scores were calculated for the KCCQ: Physical limitation, Social limitation, Quality of life, Self-efficacy, Symptom stability, Symptom frequency, Symptom burden, and Total symptoms (calculated as the mean of Symptom frequency and Symptom burden scores). Two summary scores were also calculated: Clinical Summary (calculated as mean of Physical limitation and Total symptom scores) and Overall Summary (calculated as mean of Physical limitation, Social limitation, Total symptoms, and Quality of life scores). Domain and summary scores were scaled to range from 0 (minimum) to 100 (maximum); higher scores represent better health status.

Outcome measures

Outcome measures
Measure	Tafamidis n=264 Participants Participants with variant TTR-CM genotype or wild-type TTR-CM genotype received one tafamidis 20 mg + 3 placebo capsules (matched to tafamidis) or 80 mg (4 capsules of 20 mg each) capsule orally once daily for 30 months.	Placebo n=177 Participants Participants with variant TTR-CM genotype or wild-type TTR-CM genotype received 4 placebo capsules matched to tafamidis orally once daily for 30 months.
Change From Baseline in Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS) at Month 30 Baseline	67.274 units on a scale Standard Deviation 21.3561	65.898 units on a scale Standard Deviation 21.7357
Change From Baseline in Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS) at Month 30 Change at Month 30	-3.855 units on a scale Standard Deviation 19.3075	-14.637 units on a scale Standard Deviation 21.4078

SECONDARY outcome

Timeframe: Baseline up to Month 30

Deaths adjudicated as CV-related and indeterminate are reported. Participants who discontinued for transplantation (heart transplantation and combined heart and liver transplantation) or for implantation of a cardiac mechanical assist device, were handled in the same manner as death.

Outcome measures

Outcome measures
Measure	Tafamidis n=264 Participants Participants with variant TTR-CM genotype or wild-type TTR-CM genotype received one tafamidis 20 mg + 3 placebo capsules (matched to tafamidis) or 80 mg (4 capsules of 20 mg each) capsule orally once daily for 30 months.	Placebo n=177 Participants Participants with variant TTR-CM genotype or wild-type TTR-CM genotype received 4 placebo capsules matched to tafamidis orally once daily for 30 months.
Number of Participants With Cardiovascular-Related Mortality	64 Participants	63 Participants

SECONDARY outcome

Timeframe: Month 1

Population: Analysis performed on ITT analysis set. The pre-specified intent of this study was to compare the results between tafamidis with placebo, irrespective of the tafamidis doses. This analysis was based on the pooled dose groups, as per the study protocol. Here, 'number of participants analyzed' = participants evaluable for this outcome.

TTR stabilization is a measure of the degree of stabilization afforded the TTR molecule by tafamidis.

Outcome measures

Outcome measures
Measure	Tafamidis n=245 Participants Participants with variant TTR-CM genotype or wild-type TTR-CM genotype received one tafamidis 20 mg + 3 placebo capsules (matched to tafamidis) or 80 mg (4 capsules of 20 mg each) capsule orally once daily for 30 months.	Placebo n=170 Participants Participants with variant TTR-CM genotype or wild-type TTR-CM genotype received 4 placebo capsules matched to tafamidis orally once daily for 30 months.
Percentage of Participants With Stabilized Transthyretin (TTR) at Month 1	86.1 percentage of participants	3.5 percentage of participants

Adverse Events

Tafamidis 20 mg

Serious events: 66 serious events

Other events: 86 other events

Deaths: 23 deaths

Tafamidis 80 mg

Serious events: 133 serious events

Other events: 170 other events

Deaths: 49 deaths

Placebo

Serious events: 140 serious events

Other events: 171 other events

Deaths: 72 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Tafamidis 20 mg n=88 participants at risk Participants with variant transthyretin cardiomyopathy (TTR-CM) genotype or wild-type TTR-CM genotype received one tafamidis 20 milligram (mg) capsule + 3 placebo capsules (matched to tafamidis) orally once daily for 30 months.	Tafamidis 80 mg n=176 participants at risk Participants with variant TTR-CM genotype or wild-type TTR-CM genotype received tafamidis 80 mg (4 capsules of 20 mg each) orally once daily for 30 months.	Placebo n=177 participants at risk Participants with variant TTR-CM genotype or wild-type TTR-CM genotype received 4 placebo capsules matched to tafamidis orally once daily for 30 months.
Blood and lymphatic system disorders Anaemia	1.1% 1/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Coagulopathy	1.1% 1/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Microcytic anaemia	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.56% 1/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Neutrophilia	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.56% 1/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Acute coronary syndrome	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Acute left ventricular failure	1.1% 1/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.56% 1/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Acute myocardial infarction	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	1.7% 3/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Angina pectoris	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Angina unstable	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Aortic valve stenosis	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Arrhythmia	2.3% 2/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	1.1% 2/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Arrhythmia supraventricular	1.1% 1/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.56% 1/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Atrial fibrillation	8.0% 7/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	6.2% 11/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	4.5% 8/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Atrial flutter	2.3% 2/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.3% 4/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.8% 5/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Atrial tachycardia	1.1% 1/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.56% 1/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Atrial thrombosis	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.56% 1/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Atrioventricular block	1.1% 1/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Atrioventricular block complete	1.1% 1/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.3% 4/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.56% 1/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Atrioventricular block second degree	1.1% 1/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.56% 1/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Bradycardia	1.1% 1/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.8% 5/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.8% 5/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Cardiac amyloidosis	2.3% 2/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	1.7% 3/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.8% 5/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Cardiac arrest	1.1% 1/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	1.1% 2/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	3.4% 6/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Cardiac failure	18.2% 16/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	19.3% 34/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	22.0% 39/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Cardiac failure acute	4.5% 4/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	13.1% 23/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	9.6% 17/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Cardiac failure chronic	1.1% 1/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	1.1% 2/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.56% 1/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Cardiac failure congestive	17.0% 15/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	11.4% 20/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	18.1% 32/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.56% 1/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Cardiogenic shock	3.4% 3/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	1.1% 2/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.3% 4/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Cardiomyopathy	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.56% 1/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Cardiorenal syndrome	1.1% 1/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Chronic left ventricular failure	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.56% 1/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Conduction disorder	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Coronary artery disease	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	1.1% 2/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Left ventricular failure	1.1% 1/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	1.7% 3/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	3.4% 6/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Myocardial depression	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Myocardial infarction	1.1% 1/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.56% 1/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Nodal rhythm	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Pericardial effusion	1.1% 1/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Right ventricular failure	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.

Other adverse events
Measure	Tafamidis 20 mg n=88 participants at risk Participants with variant transthyretin cardiomyopathy (TTR-CM) genotype or wild-type TTR-CM genotype received one tafamidis 20 milligram (mg) capsule + 3 placebo capsules (matched to tafamidis) orally once daily for 30 months.	Tafamidis 80 mg n=176 participants at risk Participants with variant TTR-CM genotype or wild-type TTR-CM genotype received tafamidis 80 mg (4 capsules of 20 mg each) orally once daily for 30 months.	Placebo n=177 participants at risk Participants with variant TTR-CM genotype or wild-type TTR-CM genotype received 4 placebo capsules matched to tafamidis orally once daily for 30 months.
Infections and infestations Labyrinthitis	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	1.1% 2/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Localised infection	2.3% 2/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Lower respiratory tract infection	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	1.7% 3/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Anaemia	5.7% 5/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.7% 10/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.3% 13/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Anaemia macrocytic	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.56% 1/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Coagulopathy	1.1% 1/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.56% 1/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Haemorrhagic disorder	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Heparin-induced thrombocytopenia	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Hypoprothrombinaemia	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.56% 1/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	1.7% 3/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	1.7% 3/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Leukocytosis	1.1% 1/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.56% 1/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Leukopenia	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.56% 1/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Lymphadenopathy	2.3% 2/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.56% 1/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Macrocytosis	1.1% 1/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Microcytic anaemia	1.1% 1/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Neutrophilia	1.1% 1/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Normocytic anaemia	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.56% 1/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Splenic infarction	1.1% 1/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Splenomegaly	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Thrombocytopenia	1.1% 1/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	3.4% 6/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.8% 5/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Accelerated idioventricular rhythm	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.56% 1/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Acute myocardial infarction	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.56% 1/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Angina pectoris	2.3% 2/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	1.7% 3/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.56% 1/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Aortic valve incompetence	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	1.1% 2/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Aortic valve stenosis	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	1.1% 2/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Arrhythmia	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.8% 5/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.56% 1/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Arrhythmia supraventricular	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	1.1% 2/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	1.7% 3/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Arteriosclerosis coronary artery	1.1% 1/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Atrial fibrillation	14.8% 13/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	15.9% 28/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	17.5% 31/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Atrial flutter	5.7% 5/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	4.5% 8/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	6.8% 12/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Atrial tachycardia	3.4% 3/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	3.4% 6/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	4.0% 7/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Atrial thrombosis	1.1% 1/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.3% 4/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Atrioventricular block	1.1% 1/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Atrioventricular block complete	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	1.1% 2/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	1.7% 3/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Atrioventricular block first degree	2.3% 2/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	1.7% 3/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	1.1% 2/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Atrioventricular block second degree	1.1% 1/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	1.1% 2/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Bradyarrhythmia	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Bradycardia	1.1% 1/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	1.1% 2/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	1.7% 3/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Bundle branch block right	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	1.1% 2/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Cardiac amyloidosis	0.00% 0/88 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.57% 1/176 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/177 • Baseline up to 28 days after last dose of study drug (Month 31) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.