Association between PCSK9 targeted therapy and the risk of stroke and dementia: A meta-analysis of randomized...

Proprotein convertase subtilisin/kexin type 9 (PCSK9) targeted therapies have been shown to reduce low-density lipoprotein cholesterol (LDL-C) levels and circulating PCSK9. However, its effect on cerebrovascular outcomes, especially stroke and dementia, has not been well established to date.

We conducted a systematic literature search of electronic databases for relevant randomized controlled trials (RCTs) from inception through January 2025. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using a random-effect model, and a P-value of < 0.05 was considered statistically significant.

A total of 22 RCTs with 64,116 patients were included in the study. Pooled analysis showed that PCSK9-targeted therapy significantly reduced the risk of all-cause stroke (OR, 0.78 (95% CI: 0.68-0.90), P < 0.001) and ischemic stroke (OR, 0.77 (95% CI: 0.63-0.94), P = 0.01). However, no significant association was observed for the risk of hemorrhagic stroke (OR, 1.16 (95%CI: 0.70-1.93), P = 0.56), transient ischemic attack (OR, 0.98 (95%CI: 0.48-2.06), P = 0.95), dementia (OR, 0.77 (95%CI: 0.14-4.28), P = 0.76), dementia of Alzheimer's type (OR, 0.81 (95%CI: 0.14-4.70), P = 0.82), and Parkinson's disease (OR, 0.82 (95%CI: 0.11-6.37), P = 0.85).

PCSK9 targeted therapies appear to reduce the risk of stroke; however, no significant association was observed for the risk of dementia and Parkinson's disease.