Key result
Evolocumab plus statin cuts 3-point MACE ~41% in high-risk primary prevention.
Why the study?
The comparative effectiveness across different lipid-lowering drug classes for primary cardiovascular prevention remained uncertain.
What is the comparative effectiveness of different lipid-lowering drug classes and statin intensities in reducing major adverse cardiovascular events in adults without a prior coronary event?
Meta-Analysis (n=218,657)
Randomised trials
What is the comparative effectiveness of different lipid-lowering drug classes and statin intensities in reducing major adverse cardiovascular events in adults without a prior coronary event?
In primary cardiovascular prevention, clinical benefit tracks with statin intensity rather than drug class, with evolocumab providing incremental benefit when added to statins and bempedoic acid serving as an effective alternative for statin-intolerant high-risk patients.
Supports risk-stratified regimen selection in primary prevention; extends RCT network evidence across ASCVD risk levels.
Background Comparative effectiveness across lipid-lowering drug classes in primary prevention remains uncertain. Methods We conducted a random-effects network meta-analysis of randomised trials of lipid-lowering therapy in adults without a prior coronary event, stratified by baseline atherosclerotic cardiovascular disease (ASCVD) risk. MEDLINE and EMBASE were searched from inception to July 25, 2026; included trials were published 1984–2026. Statin-containing regimens were classified by intensity, with no lipid-lowering therapy as reference. Findings 29 trials (218,657 unique participants) were included; hazard ratios are shown with 95% CIs. At high ASCVD risk, evolocumab plus statin (0.59, 0.49–0.71), bempedoic acid (0.64, 0.48–0.85) and high-intensity statin (0.80, 0.69–0.92) reduced 3-point major adverse cardiovascular events (MACE) vs. no lipid-lowering therapy. Against its statin comparator, evolocumab retained benefit (0.74, 0.65–0.83), whereas eicosapentaenoic acid (EPA) (0.81, 0.62–1.06) and fibrates (4-point MACE, low-to-moderate risk; 1.04, 0.80–1.36) did not. At low-to-moderate risk, benefit was graded by statin intensity (high 0.53, 0.37–0.75; moderate 0.76, 0.64–0.91); for 4-point MACE, ezetimibe (0.66, 0.50–0.87) and fibrates (0.81, 0.70–0.94) also reduced events. Heterogeneity was moderate in the 2-point and 3-point networks (I 2 59–62%) and no network contained a closed loop, precluding consistency testing. Two trials were at high risk of bias; certainty was low or very low for 23 of 27 comparisons. No comparison contained enough trials to test for small-study effects. Interpretation Benefit in primary prevention tracked statin intensity rather than drug class. Evolocumab added to a statin conferred further benefit over that statin, whereas EPA and fibrates did not, and bempedoic acid is an option where statins are not tolerated.
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Gnanavelou et al. (2026) conducted a meta-analysis in Primary cardiovascular prevention (adults without a prior coronary event) (n=218,657). Lipid-lowering therapies (statins, evolocumab, bempedoic acid, ezetimibe, fibrates, EPA) vs. No lipid-lowering therapy or statin comparator was evaluated on 3-point major adverse cardiovascular events (MACE) at high ASCVD risk (evolocumab plus statin vs. no therapy) (HR 0.59, 95% CI 0.49-0.71). Evolocumab plus statin (HR 0.59; 95% CI 0.49-0.71), bempedoic acid (HR 0.64), and high-intensity statins (HR 0.80) reduced 3-point MACE vs no therapy in high-risk primary prevention.
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