Statin after ischemic stroke does not raise ICH risk

Megan Brooks

September 13, 2011

Chicago, IL - New research does not support an association between statin use and intracerebral hemorrhage (ICH) in patients with prior ischemic stroke, as was suggested in two recent post hoc analyses of clinical trials [1].

Currently, more than 80% of patients with ischemic stroke leave the hospital with a statin prescription, Dr Daniel G Hackam (University of Western Ontario, London) and colleagues note.

In a large retrospective study, they found no evidence that these patients are at higher risk for ICH than patients 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," they conclude.

Their work is published online September 12, 2011 in the Archives of Neurology.

ICH rate slightly lower with statin

Using six Canadian healthcare databases, the researchers identified 17 872 patients who were admitted to Ontario hospitals for acute ischemic stroke between July 1994 and March 2008. Half received statins at discharge and half did not. The mean age of subjects was 78 years, and 53% were women.

During a median follow-up of 4.2 years, 213 episodes of ICH occurred. In the primary analysis comparing statin users with nonusers, there was no association between statin therapy and ICH (hazard ratio 0.87; 95% CI 0.65-1.17).

The rate of ICH was actually slightly lower in the statin users, at 2.94 vs 3.71 episodes per 1000 patient-years, respectively, but the difference was not statistically significant, the investigators note.

"This lack of harmful association," they point out, "was consistent regardless of analytic technique (propensity-based matching or multivariable adjustment in the parent cohort), maintained across subgroup analyses, and irrespective of statin dosing." There was also no evidence that statin users were healthier or received more healthcare than nonusers.

There was no between-group difference in the breakdown by stroke type, whether ischemic or hemorrhagic. Strokes were hemorrhagic in roughly 10% of patients in both groups.

The statin-ICH controversy

Patients with stroke or transient ischemic attack (TIA) are at increased risk for recurrent events. Clinical practice guidelines currently recommend statin therapy for most patients with a history of ischemic cerebrovascular events.

This recommendation is based largely on data from the Stroke Prevention by Aggressive Lowering of Cholesterol Levels (SPARCL) trial [2] and the Heart Protection Study (HPS) [3], which showed significant reductions in recurrent ischemic stroke with statin therapy.

However, as Hackam's team points out in their report, post hoc analyses of both trials suggested a "sizable" increase in hemorrhagic stroke related to statin therapy in patients with a history of stroke or TIA, a finding reported in two widely cited systematic reviews [4][5].

The current study provides no evidence that statin therapy following ischemic stroke raises the risk of ICH, the researchers note.

Unlike this new report, "previous studies have been much smaller and/or lumped together primary intracerebral hemorrhage (the main type of hemorrhagic stroke) with hemorrhagic transformation of ischemic stroke," Hackam commented in an interview.

"In addition, previous studies did not evaluate a diverse range of statins as used in clinical practice but rather studied very high doses of specific potent statins," he said.

In an accompanying commentary [6], Dr Philip Gorelick (University of Illinois College of Medicine, Chicago) suggests that the discrepancy may be explained, at least in part, by the differences in and the potential limitations of the respective study designs.

He also notes that in both the SPARCL trial and the HPS, analyses related to brain hemorrhage were "exploratory in nature and detailed clinical information about the etiology of brain hemorrhage (eg, subarachnoid hemorrhage and intraparenchymal hemorrhage) might be lacking."

Advice for clinicians

Until additional, high-level evidence to clarify the statin-ICH risk relationship becomes available, Gorelick recommends "careful control of modifiable risks for brain hemorrhage such as blood pressure in those who are treated with a statin."

Other statin-associated risks for ICH, such as history of ICH or use of antithrombotic therapy and possibly the presence of cerebral microbleeds, "should be carefully considered in the clinical decision-making process," he adds.

"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," Gorelick writes.

In his experience, "input from patients and their family members after they have been informed about the possible bleeding risks of statin therapy as they relate to the individual patient may be useful in making the final decision for that patient."

Th e study was supported by a peer- reviewed grant-in-aid from the nonprofit medical research charity Physicians ' Services Incorporated Foundation . Hackam has no relevant disclosures. Disclosures for the coauthors are listed in the paper. Gorelick has disclosed that he has served as a consultant to A straZeneca and Pfizer.

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