Safety and Efficacy of Moderate- vs. High-Intensity Statin Therapy after Nontraumatic Intracerebral Hemorrhage: A...

The optimal intensity of statin therapy after nontraumatic intracerebral hemorrhage (ICH) remains controversial. This study aimed to compare safety and efficacy outcomes between moderate- and high-intensity statin therapy in post-ICH patients using real-world data to inform secondary prevention strategies.

In this retrospective analysis of the TriNetX Global Collaborative Network database (a federated electronic health records platform), patients with nontraumatic ICH who initiated statin therapy ≥7 days post-ICH were identified. Moderate-intensity statin therapy was defined as atorvastatin 10-20 mg, simvastatin 20-40 mg, rosuvastatin 5-10 mg, pravastatin 40-80 mg, lovastatin 40 mg, fluvastatin 40-80 mg, or pitavastatin 2-4 mg. High-intensity therapy included atorvastatin 40-80 mg or rosuvastatin 20-40 mg. Primary outcomes included recurrent ICH, ischemic stroke, composite vascular events, and all-cause mortality. Safety outcomes included rhabdomyolysis and hepatic injury.

After matching, 8,925 patient pairs were well balanced on baseline demographics and comorbidities. Mean follow-up was 283 days (median 365 days) in both groups. Compared with high-intensity statins, moderate-intensity therapy was associated with lower risks of recurrent ICH (23.4% vs. 24.9%; hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.86-0.97; p = 0.002), ischemic stroke (7.1% vs. 10.2%; HR, 0.68; 95% CI, 0.59-0.78; p < 0.001), composite vascular events (15.1% vs. 19.5%; HR, 0.74; 95% CI, 0.66-0.82; p < 0.001), and all-cause mortality (9.0% vs. 10.2%; HR, 0.87; 95% CI, 0.79-0.96; p = 0.004). Rates of rhabdomyolysis (0.3% vs. 0.4%) and hepatic injury (0.5% vs. 0.4%) were low and not significantly different between groups.

In this large, real-world analysis, moderate-intensity statins demonstrated statistically significant but modest reductions in recurrent ICH, ischemic stroke, composite vascular events, and all-cause mortality compared with high-intensity statins, without increased adverse events. These findings may support preferential use of moderate-intensity statin therapy in selected post-ICH patients pending confirmation from randomized trials. While these observational findings suggest potential benefits of moderate-intensity statin therapy in selected post-ICH patients, confirmation from randomized controlled trials is needed before definitive clinical recommendations can be made.