The Effect of PCSK-9 Inhibitors on Incidence of Stroke: A Systematic Review and Meta-analysis
Esraa Elsayed1, Md Manjurul Islam Shourav1, Bhrugun Anisetti1, James Meschia1, Michelle Lin1
1Mayo Clinic
Objective:

To perform a systematic review and meta-analysis to assess the efficacy and safety of PCSK9 inhibitors in preventing stroke among patients at high risk for ASCVD.

Background:
The addition of a PCSK9 inhibitor to statins has been shown to further lower LDL-C levels and cardiovascular events in patients at risk for atherosclerotic cardiovascular disease (ASCVD). However, the effect of PCSK9 inhibitors on ischemic stroke prevention remains unclear. 
Design/Methods:

A systematic search of PubMed, EMBASE, Cochrane and Clinicialtrials.gov was conducted from inception to September 2023, using pre-specified keywords. RCTs that compared the use of PCSK9 inhibitor to standard of care and reported incidence of stroke were selected. Random-effects estimation based on Mantel-Haenszel method was used to calculate pooled relative risks with 95% confidence intervals of stroke and intracranial hemorrhage (ICH). I-squared statistic was used to test for heterogeneity.

Results:

Seventeen RCTs with 88,086 patients at high risk for ASCVD were included. Of these, 45,487 patients received PCSK9 inhibitors, and 42,599 patients received standard of care. Median follow-up was 1.5 years (range 0.1 to 2.8 years). The mean age was 61.4 years, 28.5% were women, 72.8% had hypertension, 36.5% had type 2 diabetes. Baseline characteristics were balanced across groups. The incidence of stroke was 0.8% (395/45381) in the intervention group and 1.2% (515/42692) in the control group (RR 0.76; 95% CI 0.66-0.86; P<0.001; I²=0%). Of the 2 studies that reported intracranial hemorrhage, there was no difference in the risk of ICH (RR 0.86; 95% CI 0.43-1.74; p=0.68; I²=53%). There was no significant heterogeneity across studies.

Conclusions:

PCSK9 inhibitor significantly reduce the risk of ischemic stroke without increasing the risk of intracranial hemorrhage in patients at high risk for ASCVD. These findings suggest that PCSK9 inhibitors may have an additive benefit to statin in stoke prevention in this population.

10.1212/WNL.0000000000205773