{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:07:45Z","timestamp":1790744865715,"version":"4.1.0"},"reference-count":89,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2024,2,20]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">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\u2010density lipoprotein\u2010cholesterol (LDL\u2010C)\u2013\u00a0and triglyceride\u2010lowering therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      We performed a systematic review of large randomized clinical trials (\u22651000 patients with \u22652\u2009years follow\u2010up) of LDL\u2010C\u2013lowering therapy (statin, ezetimibe, and PCSK\u20109 [proprotein convertase subtilisin\/kexin type 9] inhibitor) and triglyceride\u2010lowering therapy (omega\u20103 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\u2010analysis 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\u2010C lowering (284\u2009301 participants) and 11 for triglyceride lowering (120\u2009984 participants). Overall, we found a higher risk of hemorrhagic stroke for LDL\u2010C lowering, risk ratio (RR) 1.16 (95% CI, 1.01\u20131.32,\n                      <jats:italic>P<\/jats:italic>\n                      =0.03). For statins (33 trials, 216\u2009258 participants), RR=1.17 (95% CI, 1.01\u20131.36); for PCSK\u20109 inhibitors (2 trials, 46\u2009488 participants), RR=0.86 (95% CI, 0.43\u20131.74); and for ezetimibe (2 trials, 21\u2009555 participants), RR=1.14 (95% CI, 0.64\u20132.03). In statin trials of patients with previous stroke\/transient ischemic attack, RR was 1.46 (95% CI, 1.05\u20132.04), and in trials with mean age \u226565\u2009years old, RR=1.34 (95% CI, 1.04\u20131.73) (\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>int<\/jats:sub>\n                      =0.14 and\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>int<\/jats:sub>\n                      =0.23 respectively); for triglyceride lowering (11 trials, 120\u2009984 participants), RR=1.05 (95% CI, 0.86\u20131.30).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">We found evidence for a small increased risk of hemorrhagic stroke events with LDL\u2010C\u2013lowering therapies but no clear evidence for triglyceride\u2010lowering therapies.<\/jats:p>\n             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