Inclisiran and cardiovascular events: a patient-level analysis of phase III trials.
Eur Heart J
; 44(2): 129-138, 2023 01 07.
Article
in En
| MEDLINE
| ID: mdl-36331326
ABSTRACT
BACKGROUND:
Inclisiran, an siRNA administered twice-yearly, significantly reduced LDL cholesterol (LDL-C) in Phase III trials. Whether lowering LDL-C with inclisiran translates into a lower risk of cardiovascular (CV) events is not yet established. METHODS ANDRESULTS:
Patient-level, pooled analysis of ORION-9, -10 and -11, included patients with heterozygous familial hypercholesterolaemia, atherosclerotic CV disease (ASCVD), or ASCVD risk equivalent on maximally tolerated statin-therapy, randomized 11 to receive 284 mg inclisiran or placebo on Days 1, 90, and 6-monthly thereafter for 18 months. Prespecified exploratory endpoint of major cardiovascular events (MACEs) included non-adjudicated CV death, cardiac arrest, non-fatal myocardial infarction (MI), and fatal and non-fatal stroke, evaluated as part of safety assessments using a standard Medical Dictionary for Regulatory Activities basket. Although not prespecified, total fatal and non-fatal MI, and stroke were also evaluated. Mean LDL-C at baseline was 2.88 mmol/L. At Day 90, the placebo-corrected percentage reduction in LDL-C with inclisiran was 50.6%, corresponding to an absolute reduction of 1.37 mmol/L (both P < 0.0001). Among 3655 patients over 18 months, 303 (8.3%) experienced MACE, including 74 (2.0%) fatal and non-fatal MIs, and 28 (0.8%) fatal and non-fatal strokes. Inclisiran significantly reduced composite MACE [OR (95% CI) 0.74 (0.58-0.94)], but not fatal and non-fatal MIs [OR (95% CI) 0.80 (0.50-1.27)] or fatal and non-fatal stroke [OR (95% CI) 0.86 (0.41-1.81)].CONCLUSION:
This analysis offers early insights into the potential CV benefits of lowering LDL-C with inclisiran and suggests potential benefits for MACE reduction. These findings await confirmation in the larger CV outcomes trials of longer duration.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cardiovascular Diseases
/
Anticholesteremic Agents
Type of study:
Clinical_trials
Limits:
Humans
Language:
En
Journal:
Eur Heart J
Year:
2023
Type:
Article
Affiliation country:
United kingdom