One of the biggest breakthroughs in heart medicine works for a reason scientists didn't even expect.
April 15, 2026
Original Paper
Corrective Re-analysis of the Alirocumab ODYSSEY Outcomes Trial Suggests the Clinical Importance of Lipoprotein(a) Remain Substantially Underestimated
medRxiv · 2025.10.29.25338763
The Takeaway
For years, cardiologists have been prescribing drugs to lower 'bad' LDL cholesterol and prevent heart attacks. But a re-analysis of a major clinical trial found that 70% of the benefit didn't come from lowering LDL at all. Instead, the drug was primarily working by reducing a much more mysterious and dangerous particle called Lipoprotein(a). This is a massive paradigm shift because it suggests we’ve been focusing on the wrong target for heart disease prevention. It means that Lipoprotein(a)—which is largely genetic and ignored by most standard tests—is actually the real 'silent killer' that we need to be measuring. We might have been winning the war on heart disease for the wrong reason.
From the abstract
Although Lp(a) is an established risk factor for ASCVD, our analysis indicates its importance remains substantially underestimated. Reanalyzing cardiovascular outcomes trial (CVOT) data for the PCSK9 antibody alirocumab stratified by Lp(a) quartiles, we find that approximately 70% of the observed benefit is attributable to absolute reductions in Lp(a), rather than to lowering of LDL-C. This result aligns with a prior post hoc analysis of the PCSK9 antibody evolocumab, which attributed 57% of the