Key result
Evolocumab carries the lowest risk of adverse muscle effects among PCSK9 inhibitors and inclisiran.
Why the study?
Findings regarding the impact of PCSK9 inhibitors and siRNA on muscle symptoms have been inconsistent despite promising clinical trials.
Do different PCSK9 inhibitors and inclisiran vary in their risk of incident muscle symptoms and creatine kinase elevation in patients with hyperlipidemia?
Meta-Analysis (n=100,193)
Do different PCSK9 inhibitors and inclisiran vary in their risk of incident muscle symptoms and creatine kinase elevation in patients with hyperlipidemia?
Effect estimate: RR 1.05 (95% CI 0.97-1.14)
p-value: p=0.94
In a network meta-analysis of over 100,000 patients, evolocumab demonstrated the most favorable safety profile regarding muscle symptoms and creatine kinase elevations compared to alirocumab and inclisiran.
Favors evolocumab to minimize muscle symptom risk in hyperlipidemia; extends network safety comparisons among PCSK9 inhibitors and inclisiran.
Background: Atherosclerotic cardiovascular disease (ASCVD), a leading cause of global fatalities, has inconsistent findings regarding the impact of muscle symptoms despite promising clinical trials involving PCSK9 inhibitors (PCSK9i) and siRNA as potential therapeutic options. Methods: The databases EMBASE, PubMed, Web of Science, Cochrane, and ClinicalTrials.gov were thoroughly searched without any restrictions on language. Review Manager 5.3 software was utilized to calculate relative risks with 95% confidence intervals (CIs) for dichotomous data and mean differences or standardized mean differences with 95%CIs for continuous data. To evaluate publication bias, Egger's test was employed using Stata/SE software. Results: This analysis included 26 studies comprising 28 randomized controlled trials (RCTs) involving a total of 100,193 patients, and 4 different lipid-lowering therapy combinations. For events with creatine kinase >3ULN, evolocumab and alirocumab demonstrated significant advantages compared to inclisiran. Evolocumab showed the best results in terms of both new muscle symptom events and creatine kinase >3ULN. Conclusions: Based on this network meta-analysis (NMA) results, evolocumab has emerged as a promising treatment option for patients with hyperlipidemia and muscle disorders compared to other PCSK9 inhibitors and inclisiran. Systematic Review Registration: PROSPERO [CRD42023459558].
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Li et al. (2024) conducted a meta-analysis in Hyperlipidemia (n=100,193). PCSK9 inhibitors and inclisiran vs. Placebo was evaluated on New muscle symptoms (evolocumab vs placebo) (RR 1.05, 95% CI 0.97-1.14, p=0.94). Evolocumab demonstrated the lowest likelihood of causing adverse muscle effects compared to other PCSK9 inhibitors and inclisiran in patients with hyperlipidemia.
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