Statin therapy did not raise the risk of intracerebral hemorrhage among older survivors of ischemic stroke in a large observational study published online Sept. 12 in Archives of Neurology.
"At present, more than 80% of patients discharged from the hospital with a diagnosis of ischemic stroke are prescribed statin therapy. ... 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," wrote Dr. Daniel G. Hackam of the department of clinical neurologic sciences, University of Western Ontario, London, and his associates.
After clinical practice guidelines recommended statin therapy as protective against recurrent ischemic stroke in 2006, exploratory analyses in two clinical trials suggested that the drugs may actually raise the risk of hemorrhagic stroke. These reports prompted uncertainty and controversy over whether the known benefits of statin therapy in this patient population outweighed the possible risks.
Dr. Hackam and his colleagues performed a retrospective, population-based cohort study to examine the association between statin therapy and intracerebral hemorrhage in older survivors of ischemic stroke. They assessed the medical records of 17,872 patients 66 years and older (mean age, 78 years) who were treated at any Ontario hospital for ischemic stroke between 1994 and 2008 and whose records were available through 2010 to track the development of intracerebral hemorrhage.
The investigators compared the outcomes of 8,936 study subjects who began taking statins within 120 days of hospital discharge with the same number of control subjects who did not take statins. The two groups were matched on the basis of 75 patient characteristics.
During a median follow-up of 4 years, there were 213 episodes of intracerebral hemorrhage. The rate was slightly lower among patients taking statins (2.94/1,000 patient-years) than among controls (3.71/1,000 patient-years).
"The hazard ratio for statin exposure was 0.87, indicating no association between statins and intracerebral hemorrhage," the investigators wrote (Arch. Neurol. 2011 Sept. 12 [doi:10.1001/archneurol.2011.228]).
There were no associations between statin therapy and hemorrhage across numerous subgroups of patients; the risks were the same regardless of patient age, sex, socioeconomic status, major comorbidities, use of antiplatelet therapy, and use of anticoagulants.
In addition, unexposed control subjects had the same risks as did patients taking low doses of statins and patients taking high doses, so no dose-response relationship was observed.
There also were no differences in the use of statin therapy in the subgroup of study subjects who developed fatal hemorrhagic stroke during follow-up.
And in an analysis excluding "crossover" subjects – patients in the statin group who were nonadherent and patients in the control group who began statin therapy during follow-up – the results showed a significantly lower rate of intracranial hemorrhage in those who actually took statins compared with those who did not.
Furthermore, the researchers examined the use of several unrelated medical and surgical procedures in the study population, in an effort to adjust for the possibility that statin users might simply be more health conscious or heavier users of the health care system than nonusers. "As anticipated, we found no association between statin exposure and any of these events ... [which] argues against healthy user bias or screening bias in our cohort," Dr. Hackam and his associates wrote.
They cautioned that a recent study suggested that people with a history of lobar hemorrhage might be at particular risk from statin therapy. Since their study "could not test this important subset" of stroke survivors, clinicians should remain cautious about prescribing statins for such patients, the researchers said.
This study was supported by the Physicians’ Services Incorporated Foundation (a nonprofit medical research charity), the Canadian Institutes for Health Research, the Heart and Stroke Foundation of Ontario, the Canadian Stroke Network, the Institute for Clinical Evaluative Sciences, and the Ontario Ministry of Health and Long-Term Care. One of Dr. Hackam’s associates reported ties to Pfizer, Eli Lilly, Novartis, GlaxoSmithKline, and Boehringer Ingelheim.