Design and rationale of Lp(a)HORIZON trial: Assessing the effect of Lipoprotein(a) lowering with Pelacarsen on major cardiovascular events in patients with CVD and elevated Lp(a)
Abstract
BACKGROUND
Lipoprotein(a), abbreviated Lp(a), consists of apolipoprotein B-100 covalently bound to apolipoprotein(a), and represents an independent, genetically-determined, causal risk factor for atherosclerotic cardiovascular disease (CVD) and calcific aortic stenosis. More than 20% of the world CVD population has elevated Lp(a). Currently there are no approved pharmacologic treatments to lower Lp(a) levels, and no randomized trials have demonstrated that lowering Lp(a) reduces CVD risk.
STUDY DESIGN
Lp(a) HORIZON is a phase 3, randomized, placebo-controlled, double-blind, parallel-group, multinational trial in 8,323 patients with established CVD and elevated Lp(a) levels of ≥70 mg/dL (approximately 149 nmol/L), testing the effect of pelacarsen, an antisense oligonucleotide (ASO) on the incidence of major adverse cardiovascular events (MACE). Established CVD is defined as history of myocardial infarction (MI), ischemic stroke or symptomatic peripheral artery disease. The minimum follow-up is required to be 2.5 years. The study will end when 993 CEC confirmed primary CV events have accumulated. Based on the current event accrual trend, the overal study duration is anticipated to be approximately 6 years. Patients were randomized in a 1:1 ratio to receive either monthly subcutaneous (SQ) injections of pelacarsen 80 mg or matching placebo on a background of optimized standard of care therapy for CVD. The primary endpoint is a composite of cardiovascular death, non-fatal MI,…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 8,323 participants or records.
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