Association between PCSK9 targeted therapy and the risk of stroke and dementia: A meta-analysis of randomized controlled trials.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 42551778 · doi:10.1016/j.amjmed.2026.06.034
What was done
Authors conducted a systematic review and meta-analysis of electronic databases through January 2025 for randomized controlled trials assessing the effect of PCSK9-targeted therapies on stroke and neurodegenerative outcomes. Pooled odds ratios and 95% confidence intervals were calculated using a random-effects model across 22 RCTs encompassing 64,116 patients.
What was found
PCSK9-targeted therapy significantly decreased 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). No statistically significant associations were observed for 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), Alzheimer's-type dementia (OR 0.81, 95% CI: 0.14-4.70, P = 0.82), or Parkinson's disease (OR 0.82, 95% CI: 0.11-6.37, P = 0.85).
Why it matters
This meta-analysis confirms that PCSK9 inhibitors confer a meaningful reduction in ischemic stroke risk without an observed increase in hemorrhagic stroke or early neurodegenerative events.
Limits
The cognitive and neurodegenerative endpoints showed extremely wide confidence intervals due to low event rates, limiting certainty. The abstract lacks information on trial follow-up durations (which may be too brief to capture dementia incidence), specific PCSK9 drug types, and patient baseline characteristics.
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