No Relationship of Lipid-Lowering Agents to Hematoma Growth

Lipid-lowering therapy with 3-hydroxy-3methyl-glutarylCoA enzyme (HMG-CoA) reductase inhibitors (statins) is a proven effective treatment for prevention of ischemic vascular events. Controversy persists over whether statins increase the risk of intracerebral hemorrhage (ICH). A recent systematic overview of randomized trials found no association of statins and the risk of ICH, but less evidence exists for populations with high rates of ICH. Statins do not seem to increase risks of poor functional outcomes in ICH, but no study has examined their association with hematoma growth which may be promoted by ancillary mechanisms, such as inhibition of platelet aggregation and thrombogenesis. We examined associations of lipid-lowering therapy, mainly with statins, and hematoma growth and clinical outcomes in participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials (INTERACT). Methods Details of the INTERACT 1 and 2 studies are outlined elsewhere. In summary, these were international, multicenter, open, blinded end point, randomized controlled trials with a common protocol that collectively compromised 3243 patients with spontaneous ICH (<6 hours of onset) and elevated systolic blood pressure (150–220 mm Hg) randomly allocated to receive intensive or guideline-based blood pressure management. In predefined computed tomographic substudies, 1310 consecutive patients underwent 24 hour repeat computed tomography. Demographics, clinical characteristics, and medical history including current medications including use of any lipid-lowering therapy including statins, were recorded at the time of enrollment. ICH severity was measured using the Glasgow Coma Scale and National Institutes of Health Stroke Scale at baseline, 24 hours, and day 7 (or earlier on hospital discharge). The primary clinical outcome was death or major disability (or dependency), defined as a score of 3 to 6 on the modified Rankin Score Background and Purpose—Controversy persists over statins and risk of intracerebral hemorrhage. We determined associations of premorbid lipid-lowering therapy and outcomes among participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials (INTERACT). Methods—The pooled data of INTERACT 1 and 2 (international, multicenter, prospective, open, blinded end point, randomized controlled trials of patients with intracerebral hemorrhage [<6 hours] and elevated systolic blood pressure) were analyzed with regard to associations of baseline lipid-lowering treatment and clinical outcomes of 3184 participants in a multivariate model. Associations of lipid-lowering therapy and hematoma growth (baseline to 24 hours) in computed tomographic substudies participants (n=1310) were estimated in ANCOVA. Results—Among 204 patients (6.5%) with baseline lipid-lowering treatment, 90-day clinical outcomes were not significantly different after adjustment for confounding variables including region and age. In the computed tomographic substudy, 24-hour hematoma growth was greater in 124 patients (9%) with, compared with those without, prior lipid-lowering therapy. However, this association was not significant between groups (9.2 versus 6.8 mL; P<0.13), after adjustment for prior antithrombotic therapy. Conclusions—No independent associations were found between lipid-lowering medication and adverse outcomes in patients with intracerebral hemorrhage. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00226096 and NCT00716079. (Stroke. 2015;46:857-859. DOI: 10.1161/STROKEAHA.114.007664.)