Association between PCSK9 targeted therapy and the risk of stroke and dementia: A meta-analysis of randomized controlled trials.
Vikash Jaiswal, Novonil Deb, Fakhar Latif et al.
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In 30 seconds
This meta-analysis pooled randomized controlled trials to assess cerebrovascular and neurodegenerative outcomes with PCSK9-targeted therapy. Across 22 trials involving 64,116 patients, treatment was associated with lower odds 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). No statistically significant associations were found for hemorrhagic stroke, transient ischemic attack, dementia, dementia of Alzheimer's type, or Parkinson's disease. The findings support a stroke-risk reduction signal but do not establish an effect on dementia or Parkinson's disease.
Key findings
- PCSK9-targeted therapy was associated with lower odds of all-cause stroke (OR, 0.78 (95% CI: 0.68-0.90), P < 0.001).
- Odds of ischemic stroke were lower with therapy (OR, 0.77 (95% CI: 0.63-0.94), P = 0.01).
- No significant association was observed for hemorrhagic stroke (OR, 1.16 (95%CI: 0.70-1.93), P = 0.56) or transient ischemic attack (OR, 0.98 (95%CI: 0.48-2.06), P = 0.95).
- Dementia, dementia of Alzheimer's type, and Parkinson's disease showed no significant associations with treatment.
Why it matters
Stroke is a clinically important outcome in populations receiving lipid-lowering therapy. This synthesis of randomized trial evidence suggests PCSK9-targeted therapy may reduce all-cause and ischemic stroke, while the available pooled results do not demonstrate protection against dementia or Parkinson's disease. Distinguishing these outcomes helps frame the cerebrovascular evidence without extending it to unproven neurocognitive benefits.
What to keep in mind
The abstract does not report outcome-specific event counts or follow-up duration; estimates for dementia and Parkinson's disease have wide confidence intervals, limiting precision.