Effect of PCSK9 Inhibitors on Clinical Outcomes in Patients with Hypercholesterolemia – Meta-Analysis of 35 Randomized Controlled Trials
The authors from several American institutions examined the efficacy and safety of two proprotein convertase subtilisin/kexin type 9 (PCSK9i) inhibitors, alirocumab and evolocumab, in their work. They conducted a systematic meta-analysis of randomized controlled clinical trials comparing the administration of these two PCSK9i with standard treatment.
Analyzed Studies
The meta-analysis included 35 studies involving a total of 45,539 patients. The average age of participants was 61.0 ± 2.8 years, and their average initial LDL cholesterol level was 2.74 ± 0.57 mmol/l. The average follow-up period was 85.5 weeks.
Findings
Compared to patients who did not use PCSK9i, participants treated with PCSK9i showed a lower risk of myocardial infarction (2.3% with PCSK9i vs. 3.6% without PCSK9i; odds ratio [OR] 0.72; 95% confidence interval [CI] 0.64–0.81; p < 0.001), stroke (1.0% with PCSK9i vs. 1.4% without PCSK9i; OR 0.80; 95% CI 0.67–0.96; p = 0.02), and coronary revascularization (4.2% with PCSK9i vs. 5.8% without PCSK9i; OR 0.78; 95% CI 0.71–0.86; p < 0.001).
No significant difference was found in all-cause mortality (OR 0.71; 95% CI 0.47–1.09; p = 0.12) or cardiovascular mortality (OR 1.01; 95% CI 0.85–1.19; p = 0.95). Conversely, a significant association was found between higher initial LDL-c levels and the benefit from PCSK9i treatment in terms of all-cause mortality (p = 0.038).
No significant difference was observed between the PCSK9i-treated and untreated groups regarding neurocognitive adverse events (OR 1.12; 95% CI 0.88–1.42; p = 0.37), incidence of myalgia (OR 0.95; 95% CI 0.75–1.20; p = 0.65), development or worsening of pre-existing diabetes mellitus (OR 1.05; 95% CI 0.95–1.17; p = 0.32), or elevation of creatine kinase (OR 0.84; 95% CI 0.70–1.01; p = 0.06) or hepatic aminotransferases (OR 0.96; 95% CI 0.82–1.12; p = 0.61).
Conclusion
Treatment with PCSK9 inhibitors is well tolerated and improves cardiovascular outcomes. Although no benefit in overall or cardiovascular mortality was observed in this meta-analysis, such a benefit may be achievable in patients with higher baseline LDL cholesterol levels.
(epa)
Source: Karatasakis A., Danek B. A., Karacsonyi J. et al. Effect of PCSK9 inhibitors on clinical outcomes in patients with hypercholesterolemia: a meta-analysis of 35 randomized controlled trials. J Am Heart Assoc 2017; 6 (12): e006910, doi: 10.1161/JAHA.117.006910.
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