Trial Outcomes & Findings for Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention (NCT NCT02270242)

Last Updated: 2021-01-13

Results Overview

Number of participants with first occurrence of clinically relevant bleeding episode, defined as Bleeding Academic Research Consortium (BARC) Types 2, 3 or 5 bleeding. BARC bleeding types range from 0 (no bleeding) to 5 (fatal bleeding).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

9006 participants

Primary outcome timeframe

12 months after randomization

Results posted on

2021-01-13

Participant Flow

From July 2015 through December 2017, 9006 patients were enrolled, and 7119 underwent randomization after 3 months

1887 excluded from randomization (106 lost to follow up, 243 had adverse events between enrollment and randomization: a) myocardial infarction, stroke or death, b) revascularizations, and/or c) BARC type 3b or higher bleedings, 1148 were not adherent to DAPT, 267 withdrew consent or declined to participate, and 123 had other reasons.)

Participant milestones

Participant milestones
Measure	Placebo + Ticagrelor placebo pill daily p.o. for 12 months - match for enteric coated aspirin 81mg-100mg and ticagrelor 90mg tablet bid for 12 months	Aspirin + Ticagrelor enteric coated aspirin 81mg-100mg daily p.o. for 12 months and ticagrelor 90mg tablet bid for 12 months
Overall Study STARTED	3555	3564
Overall Study COMPLETED	3496	3511
Overall Study NOT COMPLETED	59	53

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo + Ticagrelor placebo pill daily p.o. for 12 months - match for enteric coated aspirin 81mg-100mg and ticagrelor 90mg tablet bid for 12 months	Aspirin + Ticagrelor enteric coated aspirin 81mg-100mg daily p.o. for 12 months and ticagrelor 90mg tablet bid for 12 months
Overall Study Withdrawal by Subject	18	25
Overall Study Lost to Follow-up	41	27
Overall Study Physician Decision	0	1

Baseline Characteristics

multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo + Ticagrelor n=3555 Participants placebo pill daily p.o. for 12 months - match for enteric coated aspirin 81mg-100mg and ticagrelor 90mg tablet bid for 12 months	Aspirin + Ticagrelor n=3564 Participants enteric coated aspirin 81mg-100mg daily p.o. for 12 months and ticagrelor 90mg tablet bid for 12 months	Total n=7119 Participants Total of all reporting groups
Age, Continuous	65.2 years STANDARD_DEVIATION 10.3 • n=3555 Participants	65.1 years STANDARD_DEVIATION 10.4 • n=3564 Participants	65.1 years STANDARD_DEVIATION 10.3 • n=7119 Participants
Sex: Female, Male Female	846 Participants n=3555 Participants	852 Participants n=3564 Participants	1698 Participants n=7119 Participants
Sex: Female, Male Male	2709 Participants n=3555 Participants	2712 Participants n=3564 Participants	5421 Participants n=7119 Participants
Race/Ethnicity, Customized Nonwhite race	1110 Participants n=3555 Participants	1086 Participants n=3564 Participants	2196 Participants n=7119 Participants
Race/Ethnicity, Customized Unknown	2445 Participants n=3555 Participants	2478 Participants n=3564 Participants	4923 Participants n=7119 Participants
Region of Enrollment North America	1484 Participants n=3555 Participants	1488 Participants n=3564 Participants	2972 Participants n=7119 Participants
Region of Enrollment Europe	1251 Participants n=3555 Participants	1258 Participants n=3564 Participants	2509 Participants n=7119 Participants
Region of Enrollment China	512 Participants n=3555 Participants	516 Participants n=3564 Participants	1028 Participants n=7119 Participants
Region of Enrollment India	308 Participants n=3555 Participants	302 Participants n=3564 Participants	610 Participants n=7119 Participants
Body Mass Index (BMI)	28.6 kg/m^2 STANDARD_DEVIATION 5.5 • n=3555 Participants	28.5 kg/m^2 STANDARD_DEVIATION 5.6 • n=3564 Participants	28.6 kg/m^2 STANDARD_DEVIATION 5.6 • n=7119 Participants
Diabetes Mellitus	1319 Participants n=3555 Participants	1301 Participants n=3564 Participants	2620 Participants n=7119 Participants
Diabetes treated with Insulin	335 Participants n=3555 Participants	374 Participants n=3564 Participants	709 Participants n=7119 Participants
Chronic Kidney Disease (CKD)	572 Participants n=3410 Participants • multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.	573 Participants n=3425 Participants • multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.	1145 Participants n=6835 Participants • multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.
Anemia	675 Participants n=3405 Participants • multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.	654 Participants n=3423 Participants • multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.	1329 Participants n=6828 Participants • multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.
Current smoker	726 Participants n=3553 Participants • multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.	822 Participants n=3562 Participants • multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.	1548 Participants n=7115 Participants • multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.
Hypercholesterolemia	2157 Participants n=3555 Participants	2146 Participants n=3564 Participants	4303 Participants n=7119 Participants
Hypertension	2580 Participants n=3554 Participants • multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.	2574 Participants n=3563 Participants • multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.	5154 Participants n=7117 Participants • multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.
Peripheral Arterial Disease (PAD)	245 Participants n=3555 Participants	244 Participants n=3564 Participants	489 Participants n=7119 Participants
Previous Myocardial Infarction (MI)	1020 Participants n=3555 Participants	1020 Participants n=3564 Participants	2040 Participants n=7119 Participants
Previous Percutaneous Coronary Intervention (PCI)	1502 Participants n=3555 Participants	1496 Participants n=3564 Participants	2998 Participants n=7119 Participants
Previous Coronary Artery Bypass Graft (CABG)	362 Participants n=3554 Participants • multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.	348 Participants n=3564 Participants • multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.	710 Participants n=7118 Participants • multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.
Multivessel Coronary Artery Disease (CAD)	2272 Participants n=3555 Participants	2194 Participants n=3564 Participants	4466 Participants n=7119 Participants
Previous Major Bleeding Event	31 Participants n=3555 Participants	32 Participants n=3564 Participants	63 Participants n=7119 Participants
Indication for PCI Asymptomatic	234 Participants n=3554 Participants • multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.	223 Participants n=3563 Participants • multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.	457 Participants n=7117 Participants • multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.
Indication for PCI Stable angina	1047 Participants n=3554 Participants • multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.	999 Participants n=3563 Participants • multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.	2046 Participants n=7117 Participants • multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.
Indication for PCI Unstable angina	1249 Participants n=3554 Participants • multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.	1245 Participants n=3563 Participants • multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.	2494 Participants n=7117 Participants • multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.
Indication for PCI NSTEMI (non-ST-segment elevation MI)	1024 Participants n=3554 Participants • multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.	1096 Participants n=3563 Participants • multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.	2120 Participants n=7117 Participants • multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.

PRIMARY outcome

Timeframe: 12 months after randomization

Population: Data for the intention-to-treat population

Outcome measures

Outcome measures
Measure	Placebo + Ticagrelor n=3555 Participants placebo pill daily p.o. for 12 months - match for enteric coated aspirin 81mg-100mg and ticagrelor 90mg tablet bid for 12 months	Aspirin + Ticagrelor n=3564 Participants enteric coated aspirin 81mg-100mg daily p.o. for 12 months and ticagrelor 90mg tablet bid for 12 months
Number of Participants With BARC Type 2, 3, or 5	141 Participants	250 Participants

SECONDARY outcome

Timeframe: 12 months after randomization

Population: data for the per-protocol population , i.e., the participants who underwent randomization and had no major deviations from the protocol.

Number of participants with first occurrence of confirmed all-cause death, non-fatal myocardial infarction or stroke.

Outcome measures

Outcome measures
Measure	Placebo + Ticagrelor n=3524 Participants placebo pill daily p.o. for 12 months - match for enteric coated aspirin 81mg-100mg and ticagrelor 90mg tablet bid for 12 months	Aspirin + Ticagrelor n=3515 Participants enteric coated aspirin 81mg-100mg daily p.o. for 12 months and ticagrelor 90mg tablet bid for 12 months
Number of Participants With Ischemic Episode	135 Participants	137 Participants

Adverse Events

Placebo + Ticagrelor

Serious events: 262 serious events

Other events: 0 other events

Deaths: 34 deaths

Aspirin + Ticagrelor

Serious events: 370 serious events

Other events: 0 other events

Deaths: 45 deaths

Serious adverse events

Serious adverse events
Measure	Placebo + Ticagrelor n=3555 participants at risk placebo pill daily p.o. for 12 months - match for enteric coated aspirin 81mg-100mg and ticagrelor 90mg tablet bid for 12 months	Aspirin + Ticagrelor n=3564 participants at risk enteric coated aspirin 81mg-100mg daily p.o. for 12 months and ticagrelor 90mg tablet bid for 12 months
Cardiac disorders Myocardial Infarction	2.7% 95/3524 • 1 year All bleeding AE were reported in the intention-to-treat (ITT) cohort. - Placebo + Ticagrelor (N=3555) and Aspirin + Ticagrelor (N=3564) All ischemic AE were reported in the per protocol (PP) cohort. - Placebo + Ticagrelor (N=3524) and Aspirin + Ticagrelor (N=3515) All-cause mortality were reported in the per protocol (PP) cohort. - Placebo + Ticagrelor (N=3524) and Aspirin + Ticagrelor (N=3515)	2.8% 97/3515 • 1 year All bleeding AE were reported in the intention-to-treat (ITT) cohort. - Placebo + Ticagrelor (N=3555) and Aspirin + Ticagrelor (N=3564) All ischemic AE were reported in the per protocol (PP) cohort. - Placebo + Ticagrelor (N=3524) and Aspirin + Ticagrelor (N=3515) All-cause mortality were reported in the per protocol (PP) cohort. - Placebo + Ticagrelor (N=3524) and Aspirin + Ticagrelor (N=3515)
Vascular disorders Ischemic Stroke	0.51% 18/3524 • 1 year All bleeding AE were reported in the intention-to-treat (ITT) cohort. - Placebo + Ticagrelor (N=3555) and Aspirin + Ticagrelor (N=3564) All ischemic AE were reported in the per protocol (PP) cohort. - Placebo + Ticagrelor (N=3524) and Aspirin + Ticagrelor (N=3515) All-cause mortality were reported in the per protocol (PP) cohort. - Placebo + Ticagrelor (N=3524) and Aspirin + Ticagrelor (N=3515)	0.28% 10/3515 • 1 year All bleeding AE were reported in the intention-to-treat (ITT) cohort. - Placebo + Ticagrelor (N=3555) and Aspirin + Ticagrelor (N=3564) All ischemic AE were reported in the per protocol (PP) cohort. - Placebo + Ticagrelor (N=3524) and Aspirin + Ticagrelor (N=3515) All-cause mortality were reported in the per protocol (PP) cohort. - Placebo + Ticagrelor (N=3524) and Aspirin + Ticagrelor (N=3515)
Injury, poisoning and procedural complications Stent Thrombosis, definite or probable	0.40% 14/3524 • 1 year All bleeding AE were reported in the intention-to-treat (ITT) cohort. - Placebo + Ticagrelor (N=3555) and Aspirin + Ticagrelor (N=3564) All ischemic AE were reported in the per protocol (PP) cohort. - Placebo + Ticagrelor (N=3524) and Aspirin + Ticagrelor (N=3515) All-cause mortality were reported in the per protocol (PP) cohort. - Placebo + Ticagrelor (N=3524) and Aspirin + Ticagrelor (N=3515)	0.57% 20/3515 • 1 year All bleeding AE were reported in the intention-to-treat (ITT) cohort. - Placebo + Ticagrelor (N=3555) and Aspirin + Ticagrelor (N=3564) All ischemic AE were reported in the per protocol (PP) cohort. - Placebo + Ticagrelor (N=3524) and Aspirin + Ticagrelor (N=3515) All-cause mortality were reported in the per protocol (PP) cohort. - Placebo + Ticagrelor (N=3524) and Aspirin + Ticagrelor (N=3515)
Vascular disorders BARC 235	4.0% 141/3555 • 1 year All bleeding AE were reported in the intention-to-treat (ITT) cohort. - Placebo + Ticagrelor (N=3555) and Aspirin + Ticagrelor (N=3564) All ischemic AE were reported in the per protocol (PP) cohort. - Placebo + Ticagrelor (N=3524) and Aspirin + Ticagrelor (N=3515) All-cause mortality were reported in the per protocol (PP) cohort. - Placebo + Ticagrelor (N=3524) and Aspirin + Ticagrelor (N=3515)	7.0% 250/3564 • 1 year All bleeding AE were reported in the intention-to-treat (ITT) cohort. - Placebo + Ticagrelor (N=3555) and Aspirin + Ticagrelor (N=3564) All ischemic AE were reported in the per protocol (PP) cohort. - Placebo + Ticagrelor (N=3524) and Aspirin + Ticagrelor (N=3515) All-cause mortality were reported in the per protocol (PP) cohort. - Placebo + Ticagrelor (N=3524) and Aspirin + Ticagrelor (N=3515)

Other adverse events

Adverse event data not reported

Additional Information

Dr. Roxana Mehran

Icahn School of Medicine at Mount Sinai

Phone: 212-659-9691

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Investigator remains responsible \& has final approval for any publication and can publish/present results but shall submit manuscript/material proposed for publication/presentation relating to results to AZ for review ≤45 days prior to submission. AZ has 45 days to respond with comments. If requested by AZ, Investigator shall delay submission for further period ≤45 days, for deemed appropriate measures to establish/preserve parties' proprietary rights in intellectual property disclosed.
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