Summary

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• This summary is based on the review of 23 systematic review(s)/meta-analysis(es). ^[1-23]
• Low-Density Lipoprotein (LDL-C) Reduction: Alirocumab reduced LDL-C by 46.35% (95% CI (confidence interval): -51.75 to -41.13, p<0.01) and evolocumab by 61.09% (95% CI: -64.81 to -57.38, p<0.01) over 24 weeks, with evolocumab demonstrating the highest efficacy among the treatments. Inclisiran showed dose-dependent efficacy, reducing LDL-C by 54.83% at 284 mg (95% CI: -59.04 to -50.62, p=0.05) and 43.11% at 300 mg (95% CI: -52.42 to -33.80, p=0.01).
• Reduction in Apolipoprotein B and Lipoprotein(a): Tafolecimab showed the greatest reductions in ApoB (-61.70%) and Lp(a) (up to -43%), while both alirocumab and evolocumab were effective in lowering Lp(a) levels in familial hypercholesterolemia patients, with a weighted mean difference (WMD) of -20.10% (95% CI: -25.59% to -14.61%).
• Major Adverse Cardiovascular Events (MACE): Alirocumab significantly reduced myocardial infarction (OR (odds ratio) 0.57, 95% CI: 0.38 to 0.86, p=0.01), cardiovascular mortality (OR 0.35, 95% CI: 0.16 to 0.77, p=0.01), and all-cause mortality (OR 0.60, 95% CI: 0.43 to 0.84, p<0.01). Evolocumab showed benefits in reducing myocardial infarction, revascularization, stroke, and overall MACE, with ORs ranging from 0.72 for MI (95% CI: 0.64 to 0.81, p<0.01) to 0.85 for overall MACE (95% CI: 0.80 to 0.89, p<0.01).
• Comparative Effectiveness: All PCSK9 inhibitors (alirocumab, evolocumab, inclisiran) provided significant reductions in LDL-C when compared to placebo or ezetimibe, with evolocumab exhibiting the most pronounced LDL-C reduction. Alirocumab was noted for a significant reduction in all-cause mortality relative to evolocumab, while the safety profiles for PCSK9 inhibitors were comparable to ezetimibe.
• Adverse Events (AEs): Across PCSK9 inhibitors, no significant increase in adverse events, severe adverse events, or adverse events leading to treatment discontinuation was observed compared to placebo. However, injection-site reactions were noted as a potential risk with alirocumab, inclisiran, and tafolecimab.
• Muscle Symptoms and Creatine Kinase Levels: Alirocumab and evolocumab showed benefits in reducing incidents of elevated creatine kinase levels (CK >3 ULN) when compared to inclisiran, suggesting a lower risk of muscle-related events for these agents.
• Comparative Safety: Alirocumab and evolocumab had similar safety profiles with the exception of injection-site reactions, which were more frequent with alirocumab. Both agents showed no significant differences in systemic allergic reactions, neurocognitive events, ophthalmologic events, or new/worsening diabetes.
• Both heterozygous and homozygous familial hypercholesterolemia (FH) patients experienced effective LDL-C and Lp(a) reductions with alirocumab and evolocumab, with similar response levels observed between these subtypes. Additionally, PCSK9 inhibitors showed significant benefits for patients at high cardiovascular risk, especially those with recent acute coronary syndrome, and were effective in reducing LDL-C levels in patients with chronic kidney disease, though further evaluation is needed for severe CKD.