PCSK9-Targeting Therapies and Mortality: A Systematic Review and Meta-Analysis of Randomized Trials
In brief
PCSK9-targeting therapies were linked to 12% lower mortality across trials
In a meta-analysis of 32 randomized trials involving 77,178 participants, PCSK9-targeting therapies were associated with 12% lower all-cause mortality and fewer heart attacks, strokes, and coronary procedures. Most mortality evidence came from large trials of PCSK9 antibodies in people with known atherosclerosis, so a survival benefit in other populations, or with inclisiran specifically, remains uncertain.
- Journal
- European journal of preventive cardiology (Q1)
- Published
- 2 November 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Eliano P Navarese, Eleonora Ruscio, Haixiang Zheng, Felicita Andreotti, Victor Aboyans, Jacek Kubica, et al.
- PMID
- 42968334
- DOI
- 10.1093/eurjpc/zwag575
Why clinicians should know about it
- Picked for Cardiology and Cardiovascular Medicine (paper of the day, 3 November 2026): Meta-analysis evaluates PCSK9 therapies and cardiovascular outcomes
Abstract
AIMS: To evaluate the association of PCSK9-targeting therapies with mortality and cardiovascular events in stable or clinically stabilized randomized trial populations. METHODS: We systematically reviewed randomized trials comparing alirocumab, evolocumab or inclisiran with placebo or active control. The review was registered in PROSPERO (CRD420261395609). Treatment effects were pooled as incidence rate ratios (IRRs) using random-effects models. The primary outcome was all-cause mortality. Prespecified subgroup analyses were based on trial-level known atherosclerosis status, as defined by enrollment criteria. RESULTS: Thirty-two trials enrolled 77,178 participants. Individual atherosclerosis status could not be determined beyond trial-level eligibility criteria. Mortality estimates were predominantly informed by large cardiovascular outcome trials. All-cause mortality was lower with PCSK9-targeting therapy (IRR 0.88, 95% CI 0.82-0.95). Estimates favored PCSK9-targeting treatment in both trials requiring known atherosclerosis for enrollment (IRR 0.90, 95% CI 0.83-0.98) and trials without such an enrollment requirement (IRR 0.78, 95% CI 0.62-0.97; interaction p = 0.21). PCSK9-targeting treatment additionally reduced myocardial infarction, stroke, and coronary revascularization rates. Leave-one-out estimates remained directionally consistent. CONCLUSION: PCSK9-targeting therapies were associated with lower all-cause mortality and fewer ischemic events across trial populations. The predominant contribution of large cardiovascular outcome trials enrolling populations with known atherosclerosis and using PCSK9 antibodies limits the ability to infer a survival benefit in populations not selected on the basis of atherosclerosis status and across individual therapies, particularly inclisiran.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.