Effects of Alirocumab and Evolocumab on Cardiovascular Mortality and LDL-C: Stratified According to the Baseline LDL-C Levels.

BACKGROUND

A meta-analysis was conducted to determine whether the cardiovascular mortality and lipid-lowering effects of alirocumab and evolocumab are influenced by various baseline low-density lipoprotein cholesterol (LDL-C) levels.

METHODS

We searched for literature published before June 2023. Eligible randomized controlled trials (RCTs) included adults treated with alirocumab or evolocumab and reported LDL-C changes and cardiovascular deaths. The primary endpoints were cardiovascular mortality and percent changes in LDL-C from baseline.

RESULTS

Forty-one RCTs were included in the meta-analysis. Evolocumab did not significantly affect the outcome of cardiovascular mortality whether the baseline data were greater than 100 mg/dL or less than 100 mg/dL. However, the stratified result showed that alirocumab decreased the risk of cardiovascular mortality in patients with a baseline LDL-C level of ≥100 mg/dL (relative risk (RR) 0.45; 95% CI: 0.22 to 0.92; = 0.03). In terms of lipid-lowering efficacy, alirocumab (mean difference (MD) -56.62%; 95% CI: -60.70% to -52.54%; < 0.001) and evolocumab (MD -68.10%; 95% CI: -74.85% to -61.36%; < 0.001) yielded the highest percentage reduction in LDL-C level when baseline levels were 70-100 mg/dL, while the smallest reduction in alirocumab (MD -37.26%; 95% CI: -44.06% to -30.46%; < 0.001) and evolocumab (MD -37.55%; 95% CI: -40.47% to -34.63%; < 0.001) occurred with baseline LDL-C levels of ≥160 mg/dL.

CONCLUSIONS

Alirocumab and evolocumab presented a better lipid-lowering effect when the baseline LDL-C levels were <100 mg/dL. Alirocumab was associated with a significant reduction in cardiovascular mortality at baseline LDL-C levels of ≥100 mg/dL. This finding can have significant implications for the development of personalized drug therapy.

THE PROSPERO REGISTRATION

CRD42023446723, https://www.crd.york.ac.uk/PROSPERO/view/CRD42023446723.