Among patients who have had an ischemic stroke, use of cholesterol-lowering statin medications is not associated with subsequent intracerebral hemorrhage (bleeding in the brain), according to a report published Online First by Archives of Neurology, one of the JAMA/Archives journals.1
According to background information in the article, after stroke or transient ischemic attack, patients are at increased risk for recurrent events. Results from the Stroke Prevention by Aggressive Lowering of Cholesterol Levels (SPARCL) trial and the Heart Protection Study (HPS) were used to develop clinical practice guidelines which recommend therapy with statins to prevent further cerebrovascular problems. The authors note that this treatment appears to be associated with a reduced risk of ischemic stroke in those patients. However, they add, “together these two trials suggest a sizable increase in hemorrhagic stroke related to statin therapy in patients with a history of stroke or transient ischemic attack, a finding reported in two widely cited systematic reviews.”
Daniel G. Hackam, M.D., Ph.D., from the University of Western Ontario, London, Ontario, Canada, and colleagues, conducted a retrospective study of six Canadian health care databases. They included 17,872 patients age 66 years and older who were admitted to Ontario hospitals for acute ischemic stroke from July 1994 to March 2008. Equal numbers of patients did not receive statins (control group) and did receive statins (intervention group). Patients were followed from 120 days after hospital discharge until they developed intracerebral hemorrhage (ICH), died or reached the March 31, 2010 endpoint of the study; the median (midpoint) follow-up time was 4.2 years.
Researchers found 213 episodes of ICH; the rate was slightly lower in patients treated with statins (2.94 vs. 3.71 episodes per 1,000 patient-years, respectively), but the difference was not statistically significant. Strokes were hemorrhagic in 10.09 percent of patients receiving statins and 10.23 percent of patients in the control group. Analysis of patient subgroups and statin dosage, and of screening tests that could indicate a healthy user bias or differences in quality of care, also did not demonstrate an association between medication use and ICH.
“At present, more than 80 percent of patients discharged from the hospital with a diagnosis of ischemic stroke are prescribed statin therapy,” note the authors. “In a large North American jurisdiction, we found no evidence that such patients are at higher risk for cerebral bleeding than individuals who do not receive statins. Physicians should continue to adhere to current treatment guidelines recommending statin therapy for most patients with a history of ischemic stroke.”
In an editorial2, Philip B. Gorelick, M.D., M.P.H., from the University of Illinois College of Medicine, Chicago, discusses the results of the study by Hackam and colleagues in the context of other research about the effects of statin therapy on stroke and brain hemorrhage. “In clinical practice, the controversy over the administration of statins after stroke centers on the subsequent risk of brain hemorrhage in patients who might benefit from a reduction in major ischemic vascular events with statin therapy,” he writes. Next, Gorelick outlines the results of other research addressing this question: “The HPS and SPARCL trial results suggest that there may be a signal of increased risk of brain hemorrhage with statin administration after stroke, whereas the Hackam et al findings diverge from this message.” Gorelick suggests that differences in and limitations of the various study designs may help explain the discrepancy.
“Until we have additional, high-level evidence to clarify the statin-ICH [intracerebral hemorrhage] risk relationship, I recommend careful control of modifiable risks for brain hemorrhage such as blood pressure in those who are treated with a statin,” Gorelick recommends. “The clinical decision to administer a statin following ICH remains a challenging one with available evidence tilting in the direction of withholding such therapy, especially when there is a history of lobar brain hemorrhage.” Input from patients and family members who have been informed of the risks may help in deciding whether to pursue treatment with statins, he adds.
1. (Arch Neurol. Published online September 12, 2011. doi:10.1001/archneurol.2011.228.
2. (Arch Neurol. Published online September 12, 2011. doi:10.1001/archneurol.2011.234.