Abstract P623: Lipid-Lowering Therapy and Intracerebral Hemorrhage Risk: Comparative Meta-Analysis of Statins and PCSK9 Inhibitors

Abstract

\n Background:\n Statins were shown to increase intracerebral hemorrhage rates in patients with a first cerebrovascular event in 2006 (SPARCL), likely due to off-target antithrombotic effects, but continued to sometimes be used in elevated ICH risk patients due to absence of alternative agents. Recently, the PCSK9 inhibitors (PCK9is) have become available as potent lipid-lowering class that may not share the hemorrhagic propensity of statins.\n \n \n Methods:\n Systematic comparative meta-analysis assessing ICH rates across all completed statin and PCSK9i RCTs, following PRISMA guidelines. In addition to ICH rates across all trials, causal relation was probed by evaluating for dose-response relationships by agent (low vs high agent dose) and by degree of brain injury at inception (none vs ischemic stroke vs ICH).\n \n \n Results:\n The systematic review identified 33 statin RCTs (203,305 patients) and 4 PCSK9i RCTs (53,253 patients). Across all patient types and all agent doses, statins were associated with increased ICH: relative risk (RR) 1.15, p=0.04; PCSK9is were not (p=0.59). In the agent dose analysis (Table), higher dose statins (7 trials, 62,204 patients) were associated with magnified ICH risk: RR 1.53, p=0.002; higher dose PCSK9is (2 trials, 31,153 patients) were not (p=0.99). In the brain injury dose analysis (Table), for statins, h/o ischemic stroke was associated with a magnified risk of ICH: RR 1.40, p=0.03; and h/o initial ICH was associated with an extremely high effect estimate of risk of recurrent ICH: RR 4.06. For PCSK9is, h/o ischemic stroke was not associated with ICH (p=0.97).\n \n \n Conclusion:\n Statins increase the risk of intracerebral hemorrhage, and the risk is magnified in an agent dose- and brain injury dose-dependent manner; PCSK9is do not ICH risk. PCSK9is may be a preferred lipid-lowering agent class in patients with elevated ICH risk, including patients with intracerebral hemorrhage or multiple covert cerebral microbleeds.\n \n \n \n