Cardiology · 4 h ago
PCSK9-targeting therapies associated with lower mortality in trial meta-analysis
A systematic review and random-effects meta-analysis pooled 32 randomized trials involving 77,178 participants treated with alirocumab, evolocumab or inclisiran. PCSK9-targeting therapy was associated with lower all-cause mortality and fewer ischemic events, although evidence was dominated by large trials of PCSK9 antibodies in people with known atherosclerosis.
- Meta-analysis included 32 trials and 77,178 participants.
- All-cause mortality IRR was 0.88 (95% CI 0.82–0.95).
- Most mortality evidence came from antibody trials in atherosclerosis.
- Survival benefit remains uncertain for inclisiran and unselected populations.
Researchers reviewed randomized trials comparing alirocumab, evolocumab or inclisiran with placebo or active control in stable or clinically stabilized populations. The PROSPERO-registered review included 32 trials and 77,178 participants; the primary outcome was all-cause mortality. Treatment effects were pooled as incidence rate ratios using random-effects models. Atherosclerosis status was classified by trial enrollment criteria, not individual participant data.
PCSK9-targeting treatment was associated with lower all-cause mortality (IRR 0.88, 95% CI 0.82–0.95). Estimates also favored treatment in trials requiring known atherosclerosis (IRR 0.90, 95% CI 0.83–0.98) and those without that requirement (IRR 0.78, 95% CI 0.62–0.97), with no evidence of a subgroup difference (interaction p=0.21). Treatment was also associated with lower rates of myocardial infarction, stroke and coronary revascularization. Leave-one-out analyses were directionally consistent.
The authors caution that large cardiovascular outcome trials in populations with known atherosclerosis contributed most of the mortality evidence. The results therefore do not establish a survival benefit in populations not selected for atherosclerosis or for each individual therapy, particularly inclisiran. The abstract reports associations from pooled randomized trials; full-text details were unavailable in the supplied source.
In practice
Across 32 randomized trials, PCSK9-targeting therapies were associated with lower all-cause mortality and fewer ischemic events, but the pooled estimate should not be taken as proof of a survival benefit for every agent or patient group. Most mortality evidence came from large cardiovascular outcome trials enrolling people with known atherosclerosis and using PCSK9 antibodies. The review notes that individual atherosclerosis status could not be determined and that evidence is especially limited for inclisiran and populations not selected for atherosclerosis; these findings alone do not establish a reason to change treatment selection.
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European Journal of Preventive Cardiology: PCSK9-Targeting Therapies and Mortality: A Systematic Review and Meta-Analysis of Randomized Trials ↗This is an automated AI-condensed summary that has not yet been reviewed by an editor. Always consult the full item at the original source.