Lp(a) After
Lp(a)HORIZON:
From Causal
Biomarker to
Unproven
Therapeutic
Target

Sep 16, 2026

Peter A. McCullough, MD, MPH

The first major Lp(a)-lowering outcomes trial fails its primary endpoint, and the entire class — olpasiran, lepodisiran, zerlasiran, muvalaplin — must now answer a harder question than it expected.

In a result that will reshape clinical lipidology for a decade, Novartis announced on September 4 that its flagship antisense oligonucleotide (ASO), pelacarsen, failed to meet its primary endpoint in the pivotal Lp(a)HORIZON trial. Across more than 8,300 patients with elevated Lp(a) and established cardiovascular disease, pelacarsen did lower lipoprotein(a) — potently, and as designed — but that reduction did not translate into fewer heart attacks, strokes, cardiovascular deaths, or urgent revascularizations.

https://open.substack.com/pub/petermcculloughmd/p/lpa-after-lpahorizon-from-causal?utm_source=share&utm_medium=android&r=o554c

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