LDL-C lowering efficacy of inclisiran versus evolocumab
Inclisiran (Leqvio) lowers LDL-C by approximately 50% in phase 3 trials in patients with ASCVD or risk-equivalent conditions. [1],[2],[3] Evolocumab (Repatha) lowers LDL-C by about 60% in the FOURIER trial population on background statin therapy. [4],[5] Head-to-head comparative efficacy data are not available, so relative LDL-C lowering efficacy is inferred from placebo-controlled trial effect sizes. [4],[1]
Cardiovascular outcome evidence for evolocumab
Evolocumab demonstrated a cardiovascular outcomes benefit in FOURIER. [4] Evolocumab reduced the primary composite outcome (cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization) with a hazard ratio of 0.85 versus placebo. [4] Evolocumab reduced the primary outcome event rates from 11.3% to 9.8% over a median follow-up of 26 months (absolute risk reduction 1.5%). [4]
Cardiovascular outcome evidence for inclisiran
Cardiovascular outcomes trials for inclisiran were ongoing at the time of the 2026 ACC/AHA dyslipidemia guideline update, with outcomes data not available as of guideline publication. [6] Accordingly, an evidence-based claim that inclisiran improves cardiovascular outcomes versus evolocumab cannot be made based on completed randomized cardiovascular outcomes trials. [6]
Relative effectiveness for LDL-C lowering
In ORION-10 and ORION-11, inclisiran reduced LDL-C by 52.3% (ORION-10) and 49.9% (ORION-11) at day 510 relative to baseline. [1],[2] In FOURIER, evolocumab achieved a substantially larger placebo-corrected LDL-C lowering effect with clinical outcomes benefit. [4],[5] Direct comparative LDL-C lowering effectiveness between inclisiran and evolocumab has not been established in randomized head-to-head trials. [4],[1]
Relative effectiveness for cardiovascular outcomes
Evolocumab has demonstrated cardiovascular event reduction in a completed cardiovascular outcomes trial. [4] Inclisiran does not have completed cardiovascular outcomes trial results that establish event reduction. [6] Therefore, evolocumab has established cardiovascular outcome efficacy whereas inclisiran has not yet established cardiovascular outcome efficacy. [4],[6]
Clinical selection implications
The 2026 ACC/AHA dyslipidemia guideline indicates that PCSK9-targeting therapies with completed outcomes evidence (e.g., evolocumab and alirocumab) are preferred when significant additional LDL-C lowering is required to reach goal LDL-C. [6] Inclisiran is considered reasonable when a less frequent dosing schedule or other practical considerations influence selection, while outcomes trials remain ongoing. [6]
Practical answer to the comparative question
Inclisiran is effective for LDL-C lowering, with placebo-controlled LDL-C reductions of about 50% in phase 3 trials. [1],[2] Evolocumab is effective for both LDL-C lowering and cardiovascular outcome reduction, with a hazard ratio of 0.85 for the primary composite endpoint and an absolute risk reduction of 1.5% over a median of 26 months in FOURIER. [4] Improved cardiovascular outcomes for inclisiran versus evolocumab cannot be concluded because cardiovascular outcomes results for inclisiran were not yet available. [6]
Evidence-cited conclusion
Inclisiran is not more effective than evolocumab for cardiovascular outcome improvement because evolocumab has demonstrated cardiovascular benefit in completed outcomes testing while inclisiran outcomes evidence remained pending. [4],[6] Inclisiran can be considered similarly effective to evolocumab for LDL-C lowering in the sense that both therapies achieve large LDL-C reductions from baseline in phase 3 trials, but superiority cannot be proven without head-to-head trials. [1],[2],[4]