Lp(a)HORIZON

Lipoprotein(a) Lowering With Pelacarsen on Major Cardiovascular Events in Patients With Established Cardiovascular Disease

Patient / Population Intervention / Exposure Comparison Outcome

In 8,323 patients with established cardiovascular disease and Lp(a) ≥70 mg/dL, pelacarsen 80 mg monthly did not reduce cardiovascular death, myocardial infarction, stroke or urgent revascularisation compared with placebo.

8,323

Design

Randomised, double-blind, placebo-controlled, multicentre trial. Pelacarsen 80 mg subcutaneously monthly versus placebo, on guideline-directed therapy. Two co-primary populations: Lp(a) ≥70 and ≥90 mg/dL. Median follow-up about four years.

Endpoint

Expanded MACE: cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or urgent coronary revascularisation requiring hospitalisation.

Relevance

ResultPrimary endpoint not met. Lp(a) was lowered but cardiovascular events were not. No effect estimate, confidence interval or p-value has been released; a topline company announcement only (4 September 2026).

Novartis media release, 4 Sept 2026 (topline). Design: Cho L, et al. Am Heart J. 2025;287:1-9. 10.1016/j.ahj.2025.03.019

Discussion & critique

The first cardiovascular outcomes trial of Lp(a) lowering, and it is negative — which weighs on the causal case built from genetics and epidemiology. Read with care: nothing is public beyond a press release, so the size of the miss, the ≥90 mg/dL co-primary and the safety data are all unknown until the congress presentation.