Proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors to treat hypercholesterolemia: Effect on stroke risk

Background/purpose: A reduction of cardiovascular events has been reported in phase 2 and 3 trials of the proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors alirocumab and evolocumab. We aimed to investigate the effect PCSK9 inhibition on stroke risk in a meta-analysis involving data from randomized studies with alirocumab and evolocumab. Methods: Data from pre-specified combined analysis of 4465 patients who completed phase 2 or 3 studies of evolocumab over a period of 1 year and a randomized trial on alirocumab including 2341 patients with hyperlipidemia on maximally tolerated statin who were at high risk for coronary heart disease over a period of 1.5 years were used. Results: The number of patients having an ischemic stroke was small in both trials. PCSK9 inhibition showed no significant effect on stroke rate (risk ratio 1.43; 95% CI, 0.45-4.57, p = 0.55). No significant differences in stroke risk were evident when transient ischemic attacks were included in the analysis (risk ratio 0.65; 95% CI, 0.25-1.68, p = 0.37). No hemorrhagic strokes were reported in either study. Conclusion: Although a benefit towards reduction of cardiovascular events in the overall has been documented, longer exposure is warranted to be able to evaluate the effect on stroke risk. (C) 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.