This study re-examined data from large Phase 3 trials involving patients with atherosclerotic cardiovascular disease (ASCVD) who were treated with PCSK9 inhibitors like alirocumab and evolocumab. The researchers focused on how much of the observed health benefit was actually due to lowering lipoprotein(a), a specific type of cholesterol particle. They compared the total benefit seen with the specific reduction in Lp(a) levels to separate out the effects. The sample size and specific setting of the original trials were not reported in this re-analysis. The study did not report new safety concerns or adverse events because it used existing data from completed trials.
The main finding was that approximately 70% of the benefit from alirocumab and 57% of the benefit from evolocumab could be attributed to the reduction in Lp(a). The researchers also projected that future therapies targeting Lp(a) directly might reduce the risk of major cardiovascular events by roughly 50% to 60%. Additionally, they noted that setting a goal to reduce major cardiovascular events by 15% to 20% could benefit about 40% of patients in secondary prevention. These numbers help explain how much of the drug effect is tied to this specific cholesterol marker.
Readers should be careful not to assume a simple linear relationship between lowering cholesterol and clinical benefit, especially at lower levels. The study authors warn that the widely accepted idea that every drop in LDL-C leads to a proportional drop in risk may not hold true below 80 mg/dL. There is also a concern about collider bias in these specific patient groups, which might lead to underestimating the true risk linked to Lp(a). This research offers a new perspective on how these drugs work but does not change current medical advice or practice guidelines.