Primary and secondary prevention of stroke and cardiovascular events using evolocumab and alirocumab: Meta-analysis of randomized controlled trials

Objectives: Although the clinical role of protein convertase subtilisin kexin type 9 (PCSK9) inhibitors for cholesterol management is increasing, the post-marketing period of use is short compared to other lipid-lowering drugs, so there is still insufficient evidence for their efficacy and safety. In this meta-analysis, we evaluated preventive effects of stroke and cardiovascular (CV) events using evolocumab and alirocumab. Materials and methods: We assessed the relative risk of stroke and CV events after alirocumab or evolocumab treatment in individuals with or without clinical CV diseases compared with that in controls. In addition, we evaluated the relative risk of hemorrhagic stroke. Results: A total of 25 articles were included (median of study duration = 52 weeks). The risk of stroke was significantly decreased after treatment with alirocumab or evolocumab (primary prevention in patients without CV diseases: RR = 0.733; 95% CI, 0.618 – 0.870; secondary prevention in patients with CV diseases: RR = 0.703; 95% CI, 0.562 – 0.880). The risk of CV events also significantly decreased in patients treated with alirocumab or evolocumab (primary prevention: RR = 0.818; 95% CI, 0.777 – 0.861; secondary prevention: RR = 0.725; 95% CI, 0.578 – 0.910). The relative risk of hemorrhagic stroke was not significantly different between PCSK9 inhibitor-treated patients and controls (RR = 1.041; 95% CI, 0.690 – 1.573). Conclusion: Our findings indicate that evolocumab and alirocumab are significantly effective without increasing the risk of hemorrhagic stroke. Based on this, the PCSK9 inhibitors can be highly recommended for cholesterol management.