Trial Outcomes & Findings for A Randomized Study to Evaluate the Effect of an "Inclisiran First" Implementation Strategy Compared to Usual Care in Patients With Atherosclerotic Cardiovascular Disease and Elevated LDL-C Despite Receiving Maximally Tolerated Statin Therapy (VICTORION-INITIATE) (NCT NCT04929249)

Last Updated: 2025-05-16

Results Overview

Percent change from baseline in Low-Density Lipoprotein Cholesterol (LDL-C) of an "inclisiran first" implementation strategy compared to usual care at Day 330.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

450 participants

Primary outcome timeframe

Baseline, Day 330

Results posted on

2025-05-16

Participant Flow

The study was conducted in 43 centers in the United States

Participant milestones

Participant milestones
Measure	Inclisiran First Inclisiran sodium 300 mg 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care Treating physicians were recommended to treat patients in accordance with the 2018 ACC/AHA guidelines
Overall Study STARTED	225	225
Overall Study Full Analysis Set (FAS)	225	225
Overall Study Safety Set	234	216
Overall Study COMPLETED	212	195
Overall Study NOT COMPLETED	13	30

Reasons for withdrawal

Reasons for withdrawal
Measure	Inclisiran First Inclisiran sodium 300 mg 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care Treating physicians were recommended to treat patients in accordance with the 2018 ACC/AHA guidelines
Overall Study Adverse Event	2	1
Overall Study Death	2	1
Overall Study Lost to Follow-up	3	11
Overall Study Technical problems	0	1
Overall Study Subject decision	6	8
Overall Study Withdrew consent	0	8

Baseline Characteristics

A Randomized Study to Evaluate the Effect of an "Inclisiran First" Implementation Strategy Compared to Usual Care in Patients With Atherosclerotic Cardiovascular Disease and Elevated LDL-C Despite Receiving Maximally Tolerated Statin Therapy (VICTORION-INITIATE)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Inclisiran First n=225 Participants Inclisiran sodium 300 mg 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=225 Participants Treating physicians were recommended to treat patients in accordance with the 2018 ACC/AHA guidelines	Total n=450 Participants Total of all reporting groups
Age, Continuous	66.3 years STANDARD_DEVIATION 9.01 • n=5 Participants	66.8 years STANDARD_DEVIATION 9.84 • n=7 Participants	66.5 years STANDARD_DEVIATION 9.43 • n=5 Participants
Sex: Female, Male Female	67 Participants n=5 Participants	72 Participants n=7 Participants	139 Participants n=5 Participants
Sex: Female, Male Male	158 Participants n=5 Participants	153 Participants n=7 Participants	311 Participants n=5 Participants
Race/Ethnicity, Customized White	186 Participants n=5 Participants	187 Participants n=7 Participants	373 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	27 Participants n=5 Participants	29 Participants n=7 Participants	56 Participants n=5 Participants
Race/Ethnicity, Customized Asian	8 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	4 Participants n=5 Participants	4 Participants n=7 Participants	8 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, Day 330

Population: Full Analysis Set (FAS) comprised of all randomized patients. 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) of an "inclisiran first" implementation strategy compared to usual care at Day 330.

Outcome measures

Outcome measures
Measure	Inclisiran First n=205 Participants Inclisiran sodium 300 mg 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=174 Participants Treating physicians were recommended to treat patients in accordance with the 2018 ACC/AHA guidelines
Percent Change From Baseline in LDL-C	-60.0 percent change in LDL-C Interval -64.7 to -55.2	-7.0 percent change in LDL-C Interval -12.0 to -1.9

PRIMARY outcome

Timeframe: Day 330

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

Percentage of patients who discontinued statin therapy ≥ 30 days before the end-of-study visit of an "inclisiran first" implementation strategy compared to usual care, for patients in the FAS excluding those with a medical history of statin intolerance.

Outcome measures

Outcome measures
Measure	Inclisiran First n=166 Participants Inclisiran sodium 300 mg 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=168 Participants Treating physicians were recommended to treat patients in accordance with the 2018 ACC/AHA guidelines
Percentage of Participants Who Discontinued Statin Therapy	6.0 Percentage of participants Interval 1.9 to 10.2	16.7 Percentage of participants Interval 10.2 to 23.1

SECONDARY outcome

Timeframe: Baseline, Day 330

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

Absolute change in Low-Density Lipoprotein Cholesterol (LDL-C) of an "inclisiran first" implementation strategy compared to usual care at Day 330

Outcome measures

Outcome measures
Measure	Inclisiran First n=205 Participants Inclisiran sodium 300 mg 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=174 Participants Treating physicians were recommended to treat patients in accordance with the 2018 ACC/AHA guidelines
Absolute Change From Baseline in LDL-C	-58.0 mg/dL Interval -61.6 to -54.4	-10.5 mg/dL Interval -14.3 to -6.6

SECONDARY outcome

Timeframe: Up to 330 Days

Population: Full Analysis Set (FAS) comprised of all randomized patients. Number of participants analyzed corresponds to the number of subjects who had LDL-C average change from baseline values.

Average percent change in Low-Density Lipoprotein Cholesterol (LDL-C) of an "inclisiran first" implementation strategy compared to usual care across visits. Calculated by averaging the observed post-baseline values (percent change) for each participant across analysis visits.

Outcome measures

Outcome measures
Measure	Inclisiran First n=222 Participants Inclisiran sodium 300 mg 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=209 Participants Treating physicians were recommended to treat patients in accordance with the 2018 ACC/AHA guidelines
Average Percent Change From Baseline in LDL-C Levels Across Visits	-57.2 Average percent change in LDL-C Interval -60.3 to -54.0	-2.8 Average percent change in LDL-C Interval -6.0 to 0.5

SECONDARY outcome

Timeframe: Up to 330 days

Population: Full Analysis Set (FAS) comprised of all randomized patients. Number of participants analyzed corresponds to the number of subjects who had LDL-C average change from baseline values.

Average absolute change in Low-Density Lipoprotein Cholesterol (LDL-C) of an "inclisiran first" implementation strategy compared to usual care across visits. Calculated by averaging the observed post-baseline values (absolute change) for each participant across analysis visits.

Outcome measures

Outcome measures
Measure	Inclisiran First n=222 Participants Inclisiran sodium 300 mg 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=209 Participants Treating physicians were recommended to treat patients in accordance with the 2018 ACC/AHA guidelines
Average Absolute Change From Baseline in LDL-C Levels Across Visits	-55.0 mg/dL Interval -57.8 to -52.2	-6.0 mg/dL Interval -8.9 to -3.2

SECONDARY outcome

Timeframe: Baseline, Day 330

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

Percentage of patients achieving a ≥ 50% reduction from baseline in Low-Density Lipoprotein Cholesterol (LDL-C) levels of an "inclisiran first" implementation strategy compared to usual care at Day 330. Missing data is imputed using "non-responder" (i.e., "negative" outcome) imputation.

Outcome measures

Outcome measures
Measure	Inclisiran First n=225 Participants Inclisiran sodium 300 mg 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=225 Participants Treating physicians were recommended to treat patients in accordance with the 2018 ACC/AHA guidelines
Percentage of Participants Achieving ≥ 50% Reduction From Baseline in LDL-C	69.8 Percentage of participants	5.3 Percentage of participants

SECONDARY outcome

Timeframe: Day 330

Population: Full Analysis Set (FAS) comprised of all randomized patients. Only a subset of participants with LDL-C \>=100 mg/dL at baseline were included in the analysis.

Percentage of participants achieving Low-Density Lipoprotein Cholesterol (LDL-C) \< 100 mg/dL (among the subset of participants with LDL-C \>=100 mg/dL at baseline) of an "inclisiran first" implementation strategy compared to usual care at Day 330. Missing data is imputed using "non-responder" (i.e., "negative" outcome) imputation.

Outcome measures

Outcome measures
Measure	Inclisiran First n=77 Participants Inclisiran sodium 300 mg 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=81 Participants Treating physicians were recommended to treat patients in accordance with the 2018 ACC/AHA guidelines
Percentage of Participants Achieving LDL-C < 100 mg/dL.	80.5 Percentage of participants	32.1 Percentage of participants

SECONDARY outcome

Timeframe: Day 330

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

Percentage of participants achieving Low-Density Lipoprotein Cholesterol (LDL-C) \< 70 mg/dL of an "inclisiran first" implementation strategy compared to usual care at Day 330. Missing data is imputed using "non-responder" (i.e., "negative" outcome) imputation.

Outcome measures

Outcome measures
Measure	Inclisiran First n=225 Participants Inclisiran sodium 300 mg 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=225 Participants Treating physicians were recommended to treat patients in accordance with the 2018 ACC/AHA guidelines
Percentage of Participants Achieving LDL-C < 70 mg/dL	81.8 Percentage of participants	22.2 Percentage of participants

SECONDARY outcome

Timeframe: Day 330

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

Percentage of participants achieving Low-Density Lipoprotein Cholesterol (LDL-C) \< 55 mg/dL of an "inclisiran first" implementation strategy compared to usual care at Day 330. Missing data is imputed using "non-responder" (i.e., "negative" outcome) imputation.

Outcome measures

Outcome measures
Measure	Inclisiran First n=225 Participants Inclisiran sodium 300 mg 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=225 Participants Treating physicians were recommended to treat patients in accordance with the 2018 ACC/AHA guidelines
Percentage of Participants Achieving LDL-C < 55 mg/dL	71.6 Percentage of participants	8.9 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Day 330

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

Percent change in plasma lipids, lipoproteins and triglycerides in participants receiving an "inclisiran first" implementation strategy compared to usual care at Day 330

Outcome measures

Outcome measures
Measure	Inclisiran First n=208 Participants Inclisiran sodium 300 mg 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=178 Participants Treating physicians were recommended to treat patients in accordance with the 2018 ACC/AHA guidelines
Percent Change in Lipids and Other Lipoproteins From Baseline Total Cholesterol	-34.1 Percent change Interval -36.7 to -31.6	-4.1 Percent change Interval -6.8 to -1.4
Percent Change in Lipids and Other Lipoproteins From Baseline HDL Cholesterol	8.5 Percent change Interval 6.5 to 10.6	2.0 Percent change Interval -0.2 to 4.2
Percent Change in Lipids and Other Lipoproteins From Baseline Non-HDL Cholesterol	-49.3 Percent change Interval -52.7 to -46.0	-5.1 Percent change Interval -8.7 to -1.6
Percent Change in Lipids and Other Lipoproteins From Baseline VLDL Cholesterol	-10.1 Percent change Interval -14.8 to -5.4	6.8 Percent change Interval 1.8 to 11.9
Percent Change in Lipids and Other Lipoproteins From Baseline Triglycerides	-10.6 Percent change Interval -15.3 to -5.9	7.2 Percent change Interval 2.1 to 12.2
Percent Change in Lipids and Other Lipoproteins From Baseline Apolipoprotein B	-46.4 Percent change Interval -49.7 to -43.1	-3.8 Percent change Interval -7.3 to -0.3
Percent Change in Lipids and Other Lipoproteins From Baseline Lipoprotein(a)	-19.6 Percent change Interval -22.2 to -16.9	2.3 Percent change Interval -0.5 to 5.2

SECONDARY outcome

Timeframe: Baseline, Day 330

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

Absolute change in plasma lipids, lipoproteins and triglycerides in participants receiving an "inclisiran first" implementation strategy compared to usual care at Day 330

Outcome measures

Outcome measures
Measure	Inclisiran First n=208 Participants Inclisiran sodium 300 mg 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=178 Participants Treating physicians were recommended to treat patients in accordance with the 2018 ACC/AHA guidelines
Absolute Change in Lipids and Other Lipoproteins From Baseline HDL Cholesterol	3.5 mg/dL Interval 2.6 to 4.4	0.3 mg/dL Interval -0.6 to 1.3
Absolute Change in Lipids and Other Lipoproteins From Baseline Total Cholesterol	-59.6 mg/dL Interval -63.8 to -55.5	-9.7 mg/dL Interval -14.1 to -5.2
Absolute Change in Lipids and Other Lipoproteins From Baseline Non-HDL Cholesterol	-63.0 mg/dL Interval -66.9 to -59.1	-10.5 mg/dL Interval -14.7 to -6.4
Absolute Change in Lipids and Other Lipoproteins From Baseline VLDL Cholesterol	-4.6 mg/dL Interval -5.9 to -3.4	0.0 mg/dL Interval -1.4 to 1.3
Absolute Change in Lipids and Other Lipoproteins From Baseline Triglycerides	-25.4 mg/dL Interval -31.9 to -18.9	-0.1 mg/dL Interval -7.0 to 6.8
Absolute Change in Lipids and Other Lipoproteins From Baseline Apolipoprotein B	-43.6 mg/dL Interval -45.9 to -41.3	-7.3 mg/dL Interval -9.8 to -4.8
Absolute Change in Lipids and Other Lipoproteins From Baseline Lipoprotein(a)	-9.8 mg/dL Interval -11.1 to -8.4	-1.0 mg/dL Interval -2.5 to 0.4

SECONDARY outcome

Timeframe: Baseline, Day 330

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

Percentage of participants with decrease in dose, no change in dose or increase in dose to assess changes in background lipid-lowering therapy in participants receiving an "inclisiran first" implementation strategy compared to usual care at Day 330

Outcome measures

Outcome measures
Measure	Inclisiran First n=215 Participants Inclisiran sodium 300 mg 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=199 Participants Treating physicians were recommended to treat patients in accordance with the 2018 ACC/AHA guidelines
Percentage of Participants by Intensity of Lipid Lowering Therapy Increase in statin intensity	0.5 Percentage of participants	2.5 Percentage of participants
Percentage of Participants by Intensity of Lipid Lowering Therapy Decrease in statin intensity	2.3 Percentage of participants	4.5 Percentage of participants
Percentage of Participants by Intensity of Lipid Lowering Therapy No change in statin intensity	97.2 Percentage of participants	93.0 Percentage of participants

SECONDARY outcome

Timeframe: Up to 330 Days

Population: Full Analysis Set (FAS) comprised of all randomized patients. Participants with missing baseline LDL-C are excluded from the regression analysis.

Proportion of days covered refers to the total number of days on either statin, ezetimibe, bempedoic acid or PCSK9 inhibiting monoclonal antibody therapies taken during the study divided by total number of study days, calculated for each participant; If a participant did not take any of the four medications then the total number of days will be assumed to be zero.

Outcome measures

Outcome measures
Measure	Inclisiran First n=224 Participants Inclisiran sodium 300 mg 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=224 Participants Treating physicians were recommended to treat patients in accordance with the 2018 ACC/AHA guidelines
Proportion of Days Covered by Medication	0.894 proportion of days covered Standard Error 0.0169	0.902 proportion of days covered Standard Error 0.0169

SECONDARY outcome

Timeframe: Day 90, Day 180, Day 270 and Day 330

Population: Full Analysis Set (FAS) comprised of all randomized patients. Number of participants analyzed corresponds to the number of subjects who had available values at each timepoint.

Visit-to-visit LDL-C variability from Day 90 until Day 330 of an "inclisiran first" implementation strategy compared to usual care. It was assessed using two measures of variability: standard deviation and coefficient of variation.

Outcome measures

Outcome measures
Measure	Inclisiran First n=213 Participants Inclisiran sodium 300 mg 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=201 Participants Treating physicians were recommended to treat patients in accordance with the 2018 ACC/AHA guidelines
LDL-C Measures of Variability - Standard Deviation Day 270	46.2 mg/dL Standard Deviation 31.22	88.4 mg/dL Standard Deviation 32.16
LDL-C Measures of Variability - Standard Deviation Day 90	42.6 mg/dL Standard Deviation 27.21	94.3 mg/dL Standard Deviation 38.33
LDL-C Measures of Variability - Standard Deviation Day 180	41.1 mg/dL Standard Deviation 28.39	91.2 mg/dL Standard Deviation 31.61
LDL-C Measures of Variability - Standard Deviation Day 330	38.8 mg/dL Standard Deviation 25.33	86.8 mg/dL Standard Deviation 35.47

SECONDARY outcome

Timeframe: Day 90, Day 180, Day 270 and Day 330

Population: Full Analysis Set (FAS) comprised of all randomized patients. Number of participants analyzed corresponds to the number of subjects who had available values at each timepoint.

Outcome measures

Outcome measures
Measure	Inclisiran First n=213 Participants Inclisiran sodium 300 mg 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=201 Participants Treating physicians were recommended to treat patients in accordance with the 2018 ACC/AHA guidelines
LDL-C Measures of Variability - Coefficient of Variation Day 90	63.90 Coefficient of Variation	40.65 Coefficient of Variation
LDL-C Measures of Variability - Coefficient of Variation Day 180	69.00 Coefficient of Variation	34.67 Coefficient of Variation
LDL-C Measures of Variability - Coefficient of Variation Day 270	67.56 Coefficient of Variation	36.38 Coefficient of Variation
LDL-C Measures of Variability - Coefficient of Variation Day 330	65.34 Coefficient of Variation	40.89 Coefficient of Variation

Adverse Events

Inclisiran First

Serious events: 27 serious events

Other events: 64 other events

Deaths: 2 deaths

Usual Care

Serious events: 29 serious events

Other events: 53 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Inclisiran First n=234 participants at risk Inclisiran sodium 300 mg 1.5 ml (equivalent to 284 mg of inclisiran) + usual care	Usual Care n=216 participants at risk Treating physicians were recommended to treat patients in accordance with the 2018 ACC/AHA guidelines
General disorders Injection site pain	7.7% 18/234 • 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 or until resolution. All safety analyses were conducted in the Safety Set.	0.00% 0/216 • 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 or until resolution. All safety analyses were conducted in the Safety Set.
Infections and infestations COVID-19	7.7% 18/234 • 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 or until resolution. All safety analyses were conducted in the Safety Set.	6.5% 14/216 • 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 or until resolution. All safety analyses were conducted in the Safety Set.
Infections and infestations Urinary tract infection	3.4% 8/234 • 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 or until resolution. All safety analyses were conducted in the Safety Set.	3.2% 7/216 • 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 or until resolution. All safety analyses were conducted in the Safety Set.
Injury, poisoning and procedural complications Fall	1.3% 3/234 • 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 or until resolution. All safety analyses were conducted in the Safety Set.	4.2% 9/216 • 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 or until resolution. All safety analyses were conducted in the Safety Set.
Investigations Blood creatine phosphokinase increased	4.3% 10/234 • 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 or until resolution. All safety analyses were conducted in the Safety Set.	6.0% 13/216 • 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 or until resolution. All safety analyses were conducted in the Safety Set.
Investigations Glycosylated haemoglobin increased	3.8% 9/234 • 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 or until resolution. All safety analyses were conducted in the Safety Set.	2.3% 5/216 • 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 or until resolution. All safety analyses were conducted in the Safety Set.
Metabolism and nutrition disorders Type 2 diabetes mellitus	3.4% 8/234 • 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 or until resolution. All safety analyses were conducted in the Safety Set.	4.6% 10/216 • 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 or until resolution. 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