Trial Outcomes & Findings for Management of LDL-cholesterol With Inclisiran + Usual Care Compared to Usual Care Alone in Participants With a Recent Acute Coronary Syndrome (NCT NCT04873934)

NCT ID: NCT04873934

Last Updated: 2025-10-16

Results Overview

Percent change from baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Day 330

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

400 participants

Primary outcome timeframe

Baseline and Day 330

Results posted on

2025-10-16

Participant Flow

This study was conducted at 87 study centers. Of the 201 participants randomized to inclisiran + usual care, 1 participant was randomized erroneously and did not receive inclisiran. Of the 199 participants randomized to usual care, 3 participants received commercially available inclisiran as part of their concomitant medications.

Participant milestones

Participant milestones
Measure	Inclisiran With Usual Care Inclisiran sodium 300 mg / 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care Usual Care Alone
Overall Study STARTED	201	199
Overall Study Full Analysis Set	201	199
Overall Study Safety Set	203	197
Overall Study COMPLETED	183	173
Overall Study NOT COMPLETED	18	26

Reasons for withdrawal

Reasons for withdrawal
Measure	Inclisiran With Usual Care Inclisiran sodium 300 mg / 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care Usual Care Alone
Overall Study Adverse Event	0	1
Overall Study Death	0	2
Overall Study Lost to Follow-up	13	9
Overall Study Physician Decision	1	1
Overall Study Protocol deviation	2	1
Overall Study Subject decision	1	8
Overall Study Withdrew consent	0	4
Overall Study Missing	1	0

Baseline Characteristics

Management of LDL-cholesterol With Inclisiran + Usual Care Compared to Usual Care Alone in Participants With a Recent Acute Coronary Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Inclisiran With Usual Care n=201 Participants Inclisiran sodium 300 mg / 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=199 Participants Usual Care Alone	Total n=400 Participants Total of all reporting groups
Age, Continuous	60.8 years STANDARD_DEVIATION 10.90 • n=5 Participants	60.2 years STANDARD_DEVIATION 11.69 • n=7 Participants	60.5 years STANDARD_DEVIATION 11.29 • n=5 Participants
Sex: Female, Male Female	63 Participants n=5 Participants	53 Participants n=7 Participants	116 Participants n=5 Participants
Sex: Female, Male Male	138 Participants n=5 Participants	146 Participants n=7 Participants	284 Participants n=5 Participants
Race/Ethnicity, Customized White	166 Participants n=5 Participants	167 Participants n=7 Participants	333 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	25 Participants n=5 Participants	24 Participants n=7 Participants	49 Participants n=5 Participants
Race/Ethnicity, Customized Asian	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Multiple	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Day 330

Population: Full Analysis Set (FAS) comprised all randomized participants. The number of participants analyzed corresponds to the number of subjects who had LDL-C values at baseline and Day 330.

Percent change from baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Day 330

Outcome measures

Outcome measures
Measure	Inclisiran With Usual Care n=171 Participants Inclisiran sodium 300 mg / 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=163 Participants Usual Care Alone
Percent Change From Baseline to Day 330 in LDL-C	-45.6 Percent change in LDL-C Interval -51.5 to -39.6	1.4 Percent change in LDL-C Interval -4.7 to 7.5

PRIMARY outcome

Timeframe: Day 330

Population: Full Analysis Set (FAS) comprised all randomized participants.

Percentage of participants achieving Low-Density Lipoprotein Cholesterol (LDL-C) \< 70 mg/dL at Day 330

Outcome measures

Outcome measures
Measure	Inclisiran With Usual Care n=201 Participants Inclisiran sodium 300 mg / 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=199 Participants Usual Care Alone
Achievement of LDL-C < 70 mg/dL at Day 330	66.7 Percentage of participants Interval 59.2 to 74.1	28.1 Percentage of participants Interval 21.0 to 35.3

SECONDARY outcome

Timeframe: Baseline, Day 90, Day 270 and Day 330

Population: Full Analysis Set (FAS) comprised all randomized participants. The number of participants analyzed corresponds to the number of subjects who had LDL-C values at baseline and Day 90, Day 270 and Day 330 respectively.

Absolute change from baseline in low-density lipoprotein cholesterol (LDL-C) by visit

Outcome measures

Outcome measures
Measure	Inclisiran With Usual Care n=188 Participants Inclisiran sodium 300 mg / 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=178 Participants Usual Care Alone
Absolute Change From Baseline in LDL-C Day 90	-44.2 mg/dL Interval -47.9 to -40.5	-2.2 mg/dL Interval -6.0 to 1.6
Absolute Change From Baseline in LDL-C Day 270	-34.6 mg/dL Interval -39.2 to -30.1	-3.8 mg/dL Interval -8.6 to 1.0
Absolute Change From Baseline in LDL-C Day 330	-41.2 mg/dL Interval -45.9 to -36.5	-3.5 mg/dL Interval -8.3 to 1.4

SECONDARY outcome

Timeframe: Baseline, from Day 90 to Day 330

Population: Full Analysis Set (FAS) comprised all randomized participants. The number of participants analyzed corresponds to the number of subjects who had at least one LDL-C change from baseline value available.

Average percent change from baseline in low-density lipoprotein cholesterol (LDL-C) levels to each post-baseline visit

Outcome measures

Outcome measures
Measure	Inclisiran With Usual Care n=194 Participants Inclisiran sodium 300 mg / 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=184 Participants Usual Care Alone
Average Percent Change From Baseline in LDL-C Levels	-44.3 Average percent change in LDL-C Interval -48.5 to -40.1	2.4 Average percent change in LDL-C Interval -1.8 to 6.7

SECONDARY outcome

Timeframe: Baseline, From Day 90 to Day 330

Average absolute change from baseline in low-density lipoprotein cholesterol (LDL-C) levels to each post-baseline visit

Outcome measures

Outcome measures
Measure	Inclisiran With Usual Care n=194 Participants Inclisiran sodium 300 mg / 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=184 Participants Usual Care Alone
Average Absolute Change From Baseline in LDL-C Levels	-40.0 mg/dL Interval -43.6 to -36.4	-2.7 mg/dL Interval -6.4 to 1.0

SECONDARY outcome

Timeframe: Baseline, Day 330

Population: Full Analysis Set (FAS) comprised all randomized participants.

Percentage of participants achieving ≥50% reduction from baseline in low-density lipoprotein cholesterol (LDL-C) at Day 330

Outcome measures

Outcome measures
Measure	Inclisiran With Usual Care n=201 Participants Inclisiran sodium 300 mg / 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=199 Participants Usual Care Alone
Achieving ≥50% Reduction From Baseline in LDL-C	45.3 Percentage of participants Interval 38.4 to 52.2	6.5 Percentage of participants Interval 3.1 to 10.0

SECONDARY outcome

Timeframe: Day 330

Population: Full Analysis Set (FAS) comprised all randomized participants.

Percentage of participants achieving low-density lipoprotein cholesterol (LDL-C) \<100 mg/dL (among the subset of participants with baseline LDL-C \>= 100 mg/dL) and LDL-C \< 55 mg/dL at Day 330

Outcome measures

Outcome measures
Measure	Inclisiran With Usual Care n=201 Participants Inclisiran sodium 300 mg / 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=199 Participants Usual Care Alone
Achieving LDL-C < 100 mg/dL and LDL-C < 55 mg/dL Achieving LDL-C < 100 mg/dL	75.8 Percentage of participants Interval 65.1 to 86.5	40.4 Percentage of participants Interval 27.0 to 53.7
Achieving LDL-C < 100 mg/dL and LDL-C < 55 mg/dL Achieving LDL-C < 55 mg/dL	54.2 Percentage of participants Interval 47.3 to 61.1	13.6 Percentage of participants Interval 8.8 to 18.3

SECONDARY outcome

Timeframe: Baseline and Day 330

Population: Full Analysis Set (FAS) comprised all randomized participants. The number of participants analyzed corresponds to the number of subjects who had values at baseline and Day 330.

Percent change in apolipoprotein B, very-low-density lipoprotein (VLDL), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol, lipoprotein(a) (Lp\[a\]), HDL-C and triglycerides from baseline to Day 330

Outcome measures

Outcome measures
Measure	Inclisiran With Usual Care n=177 Participants Inclisiran sodium 300 mg / 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=166 Participants Usual Care Alone
Percent Change in Lipids and Other Lipoproteins From Baseline to Day 330 apolipoprotein B	-35.5 Percent change Interval -40.6 to -30.5	2.0 Percent change Interval -3.2 to 7.1
Percent Change in Lipids and Other Lipoproteins From Baseline to Day 330 VLDL Cholesterol	5.7 Percent change Interval -1.0 to 12.3	12.1 Percent change Interval 5.2 to 18.9
Percent Change in Lipids and Other Lipoproteins From Baseline to Day 330 non-HDL-Cholesterol	-35.2 Percent change Interval -39.6 to -30.8	2.5 Percent change Interval -2.0 to 7.1
Percent Change in Lipids and Other Lipoproteins From Baseline to Day 330 Total Cholesterol	-21.4 Percent change Interval -24.7 to -18.1	4.1 Percent change Interval 0.6 to 7.5
Percent Change in Lipids and Other Lipoproteins From Baseline to Day 330 Lp[a]	-10.4 Percent change Interval -25.9 to 5.0	5.9 Percent change Interval -9.7 to 21.6
Percent Change in Lipids and Other Lipoproteins From Baseline to Day 330 HDL-Cholesterol	14.0 Percent change Interval 10.8 to 17.3	10.6 Percent change Interval 7.2 to 13.9
Percent Change in Lipids and Other Lipoproteins From Baseline to Day 330 triglycerides	7.3 Percent change Interval 0.1 to 14.4	12.3 Percent change Interval 4.9 to 19.6

SECONDARY outcome

Timeframe: Baseline and Day 330

Population: Full Analysis Set (FAS) comprised all randomized participants. The number of participants analyzed corresponds to the number of subjects who had values at baseline and Day 330.

Absolute change in apolipoprotein B, very-low-density lipoprotein (VLDL), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol, HDL-C and triglycerides from baseline to Day 330

Outcome measures

Outcome measures
Measure	Inclisiran With Usual Care n=177 Participants Inclisiran sodium 300 mg / 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=166 Participants Usual Care Alone
Absolute Change in Lipids and Other Lipoproteins From Baseline to Day 330 apolipoprotein B	-31.0 mg/dL Interval -34.2 to -27.8	-2.6 mg/dL Interval -5.8 to 0.6
Absolute Change in Lipids and Other Lipoproteins From Baseline to Day 330 VLDL Cholesterol	-0.4 mg/dL Interval -2.0 to 1.3	1.8 mg/dL Interval 0.0 to 3.5
Absolute Change in Lipids and Other Lipoproteins From Baseline to Day 330 non-HDL-Cholesterol	-41.4 mg/dL Interval -46.5 to -36.3	-1.3 mg/dL Interval -6.5 to 4.0
Absolute Change in Lipids and Other Lipoproteins From Baseline to Day 330 total Cholesterol	-35.2 mg/dL Interval -40.5 to -30.0	2.5 mg/dL Interval -2.9 to 7.9
Absolute Change in Lipids and Other Lipoproteins From Baseline to Day 330 HDL-Cholesterol	5.7 mg/dL Interval 4.3 to 7.1	3.8 mg/dL Interval 2.4 to 5.3
Absolute Change in Lipids and Other Lipoproteins From Baseline to Day 330 triglycerides	1.1 mg/dL Interval -8.7 to 10.8	9.8 mg/dL Interval -0.3 to 19.9

SECONDARY outcome

Timeframe: Baseline and Day 330

Population: Full Analysis Set (FAS) comprised all randomized participants. The number of participants analyzed corresponds to the number of subjects who had values at baseline and Day 330.

Absolute change in lipoprotein(a) (Lp\[a\]) from baseline to Day 330

Outcome measures

Outcome measures
Measure	Inclisiran With Usual Care n=160 Participants Inclisiran sodium 300 mg / 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=158 Participants Usual Care Alone
Absolute Change in Lp[a] From Baseline to Day 330	-19.3 nmol/L Interval -26.2 to -12.4	-5.3 nmol/L Interval -12.2 to 1.7

SECONDARY outcome

Timeframe: Baseline and Day 330

Population: Full Analysis Set (FAS) comprised all randomized participants. The number of participants analyzed corresponds to the number of subjects who had a record for Day 330 study visit date.

Percentage of participants by intensity of lipid lowering therapy (dose decrease, increase or no change)

Outcome measures

Outcome measures
Measure	Inclisiran With Usual Care n=184 Participants Inclisiran sodium 300 mg / 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=174 Participants Usual Care Alone
Intensity of Lipid Lowering Therapy Decrease in statin intensity	9.8 Percentage of participants Interval 5.9 to 15.0	4.6 Percentage of participants Interval 2.0 to 8.9
Intensity of Lipid Lowering Therapy No change in statin intensity	89.1 Percentage of participants Interval 83.7 to 93.2	92.5 Percentage of participants Interval 87.6 to 96.0
Intensity of Lipid Lowering Therapy Increase in statin intensity	1.1 Percentage of participants Interval 0.1 to 3.9	2.9 Percentage of participants Interval 0.9 to 6.6

SECONDARY outcome

Timeframe: Baseline through last date of participation, up to 330 Days

Population: Full Analysis Set (FAS) comprised all randomized participants.

Total number of days on either statin, ezetimibe, or PCSK9 inhibiting monoclonal antibody therapies divided by total number of study days. If a participant did not take any of the 3 medications, then the total number of days was assumed to be zero.

Outcome measures

Outcome measures
Measure	Inclisiran With Usual Care n=201 Participants Inclisiran sodium 300 mg / 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=199 Participants Usual Care Alone
Proportion of Days Covered	0.926 Proportion of days Interval 0.9 to 0.953	0.965 Proportion of days Interval 0.939 to 0.992

SECONDARY outcome

Timeframe: Baseline and Day 330

Population: Full Analysis Set (FAS) comprised all randomized participants. Participants with Medical History of Statin Intolerance were excluded.

Percentage of participants discontinuing statin therapy. Discontinuation of statin therapy was defined as no statin use ≥ 30 days before the end-of-study visit. Participants for whom it could not be ascertained that they were on statin therapy at the end of study or who discontinued from the study early were assumed to have discontinued statin therapy.

Outcome measures

Outcome measures
Measure	Inclisiran With Usual Care n=173 Participants Inclisiran sodium 300 mg / 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=178 Participants Usual Care Alone
Discontinuation of Statin Therapy	14.5 Percentage of participants Interval 9.2 to 19.7	18.0 Percentage of participants Interval 12.3 to 23.6

Adverse Events

Inclisiran + Usual Care

Serious events: 32 serious events

Other events: 52 other events

Deaths: 0 deaths

Usual Care

Serious events: 34 serious events

Other events: 35 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Inclisiran + Usual Care n=203 participants at risk Inclisiran sodium 300 mg / 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=197 participants at risk Usual Care Alone
Cardiac disorders Angina pectoris	3.4% 7/203 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 330 days. All safety analyses were conducted in the Safety Set.	1.5% 3/197 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 330 days. All safety analyses were conducted in the Safety Set.
General disorders Injection site pain	4.9% 10/203 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 330 days. All safety analyses were conducted in the Safety Set.	0.00% 0/197 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 330 days. All safety analyses were conducted in the Safety Set.
General disorders Non-cardiac chest pain	3.9% 8/203 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 330 days. All safety analyses were conducted in the Safety Set.	5.1% 10/197 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 330 days. All safety analyses were conducted in the Safety Set.
Infections and infestations COVID-19	4.9% 10/203 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 330 days. All safety analyses were conducted in the Safety Set.	4.6% 9/197 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 330 days. All safety analyses were conducted in the Safety Set.
Infections and infestations Upper respiratory tract infection	3.0% 6/203 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 330 days. All safety analyses were conducted in the Safety Set.	3.0% 6/197 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 330 days. All safety analyses were conducted in the Safety Set.
Investigations Blood creatine phosphokinase increased	2.5% 5/203 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 330 days. All safety analyses were conducted in the Safety Set.	3.0% 6/197 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 330 days. All safety analyses were conducted in the Safety Set.
Musculoskeletal and connective tissue disorders Arthralgia	3.9% 8/203 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 330 days. All safety analyses were conducted in the Safety Set.	1.5% 3/197 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 330 days. All safety analyses were conducted in the Safety Set.
Nervous system disorders Dizziness	3.0% 6/203 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 330 days. All safety analyses were conducted in the Safety Set.	3.0% 6/197 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 330 days. All safety analyses were conducted in the Safety Set.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: + 1 862 778 8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER