Association between PCSK9 targeted therapy and the risk of stroke and dementia: A meta-analysis of randomized controlled trials
Recommended Citation
Jaiswal V, Deb N, Latif F, Shrestha AB, Garimella V, Shama N, Jitta SR, Naz S, Kumar T, Khan S, Perone F, Mattumpuram J, Ang SP. Association between Pcsk9 Targeted Therapy and the Risk of Stroke and Dementia: A Meta-Analysis of Randomized Controlled Trials. Am J Med. 2026;139(12):1640-1652.
Document Type
Article
Publication Date
12-1-2026
Publication Title
The American journal of medicine
Keywords
Humans, Randomized Controlled Trials as Topic, Proprotein Convertase 9, Stroke, Dementia, PCSK9 Inhibitors, Cholesterol, LDL
Abstract
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSION: 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.
Medical Subject Headings
Humans; Randomized Controlled Trials as Topic; Proprotein Convertase 9; Stroke; Dementia; PCSK9 Inhibitors; Cholesterol, LDL
PubMed ID
42551778
ePublication
ePub ahead of print
Volume
139
Issue
12
First Page
1640
Last Page
1652
