LDL-C-lowering therapies were associated with a higher risk of hemorrhagic stroke (RR 1.16; 95% CI 1.01-1.32; P=0.03), while triglyceride-lowering therapies showed no clear evidence of increased risk.
Meta-Analysis (n=405,285)
Do lipid-lowering therapies increase the risk of hemorrhagic stroke?
LDL-C-lowering therapies, particularly statins, are associated with a small increased risk of hemorrhagic stroke, with higher risk noted in patients with previous stroke/TIA or age ≥65 years.
Effect estimate: RR 1.16 (95% CI 1.01-1.32)
p-value: p=0.03
Background There is debate over whether statins increase risk of hemorrhagic stroke, so we assessed current evidence, including data from new statin trials and trials of nonstatin low‐density lipoprotein‐cholesterol (LDL‐C)– and triglyceride‐lowering therapies. Methods and Results We performed a systematic review of large randomized clinical trials (≥1000 patients with ≥2 years follow‐up) of LDL‐C–lowering therapy (statin, ezetimibe, and PCSK‐9 proprotein convertase subtilisin/kexin type 9 inhibitor) and triglyceride‐lowering therapy (omega‐3 supplements and fibrate) that reported hemorrhagic stroke as an outcome. We searched MEDLINE, Embase, and Cochrane Library up to July 2, 2021 and updated a meta‐analysis of cardiovascular statin trials published in 2012. Among our several subgroup analyses, we looked at difference depending on stroke status and also depending on age. We identified 37 trials for LDL‐C lowering (284 301 participants) and 11 for triglyceride lowering (120 984 participants). Overall, we found a higher risk of hemorrhagic stroke for LDL‐C lowering, risk ratio (RR) 1.16 (95% CI, 1.01–1.32, P =0.03). For statins (33 trials, 216 258 participants), RR=1.17 (95% CI, 1.01–1.36); for PCSK‐9 inhibitors (2 trials, 46 488 participants), RR=0.86 (95% CI, 0.43–1.74); and for ezetimibe (2 trials, 21 555 participants), RR=1.14 (95% CI, 0.64–2.03). In statin trials of patients with previous stroke/transient ischemic attack, RR was 1.46 (95% CI, 1.05–2.04), and in trials with mean age ≥65 years old, RR=1.34 (95% CI, 1.04–1.73) ( P int =0.14 and P int =0.23 respectively); for triglyceride lowering (11 trials, 120 984 participants), RR=1.05 (95% CI, 0.86–1.30). Conclusions We found evidence for a small increased risk of hemorrhagic stroke events with LDL‐C–lowering therapies but no clear evidence for triglyceride‐lowering therapies. Registration URL: https://www.crd.york.ac.uk/prospero ; Unique identifier: CRD42021275363.
Bétrisey et al. (Wed,) conducted a meta-analysis in Risk of hemorrhagic stroke (n=405,285). LDL-C-lowering and triglyceride-lowering therapies vs. Control was evaluated on Hemorrhagic stroke (RR 1.16, 95% CI 1.01-1.32, p=0.03). LDL-C-lowering therapies were associated with a higher risk of hemorrhagic stroke (RR 1.16; 95% CI 1.01-1.32; P=0.03), while triglyceride-lowering therapies showed no clear evidence of increased risk.