Summary

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• This summary is based on the review of 31 systematic review(s)/meta-analysis(es). ^[1-31]
• Low-Density Lipoprotein (LDL-C) Reduction: Evolocumab significantly reduced LDL-C levels by -61.09% to -63.67% compared to placebo over a median of 24 weeks, with the 140 mg once every 2 weeks (Q2W) dosage showing the highest efficacy at -69.13%. Alirocumab showed reductions ranging from -46.35% to -59.75% in various studies.
• Cardiovascular Outcomes: Evolocumab reduced the risk of myocardial infarction (odds ratio (OR) 0.72, 95% confidence interval (CI): 0.64-0.81, p<0.01), stroke (OR 0.79, 95% CI: 0.66-0.94, p=0.01), and overall major adverse cardiovascular events (MACE) (OR 0.85, 95% CI: 0.80-0.89, p<0.01). Alirocumab was associated with a significant reduction in cardiovascular mortality (OR 0.35, 95% CI: 0.16-0.77, p=0.01) and all-cause mortality (OR 0.60, 95% CI: 0.43-0.84, p<0.01).
• Subgroup Analysis: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors effectively reduced LDL-C and MACE in various subgroups, including patients with diabetes mellitus, where a reduction in MACE by 18% was noted. No significant differences in LDL-C reduction were found based on racial or ethnic backgrounds, although Asian participants with type 2 diabetes showed a larger reduction.
• Chronic Kidney Disease (CKD): PCSK9 inhibitors demonstrated safety and efficacy in lowering LDL-C levels in patients with CKD, but further investigation is required for severe and end-stage CKD populations.
• General Safety Profile: PCSK9 inhibitors, including evolocumab, alirocumab, and inclisiran, demonstrated favorable safety profiles with no significant increase in the incidence of adverse events (AEs) or severe adverse events (SAEs) compared to placebo. There were no significant differences noted in rates of diabetes, neurocognitive disorders, or serious infections.
• Injection-Site Reactions and Specific Concerns: Injection-site reactions were more frequently reported with alirocumab, inclisiran, and tafolecimab, while evolocumab did not show an increased risk of sepsis or severe infections. Additionally, alirocumab was associated with a reduction in serious adverse events and diabetes-related adverse events compared to controls.
• Subgroup Analysis: Among patients with familial hypercholesterolemia, there was no significant difference in treatment-emergent adverse events (TEAEs) and SAEs compared to placebo. However, evolocumab exhibited a slightly higher event rate of AEs in patients with impaired kidney function.
• Diverse Patient Populations: PCSK9 inhibitors, including evolocumab and alirocumab, effectively reduced LDL-C and MACE in various populations, such as patients with atherosclerotic cardiovascular disease (ASCVD) and those with diabetes mellitus, achieving an 18% reduction in MACE. Both drugs demonstrated efficacy in familial hypercholesterolemia (FH) patients, with no significant differences between heterozygous and homozygous forms, while Asian participants with type 2 diabetes showed larger reductions in LDL-C levels.