Statin risks may outweigh benefits for patients with a history of brain hemorrhage

A computer decision model suggests that for patients with a history of bleeding within the brain, the risk of recurrence associated with statin treatment may outweigh the benefit of the drug in preventing cardiovascular disease, according to a report posted online today that will appear in the May print issue of Archives of Neurology, one of the JAMA/Archives journals.

The benefits of statins for reducing the risk of heart disease and stroke are well established, but more widespread use of statin therapy remains controversial, according to background information in the article. "A particular subgroup of patients for whom the advisability of statin use is unclear are those at high risk for intracerebral hemorrhage," or a stroke caused by bleeding within the brain, the authors write. "The reason for added concern is the increased incidence of intracerebral hemorrhage observed among subjects randomized to statin therapy in a clinical trial of secondary stroke prevention."

"Because intracerebral hemorrhage sufferers commonly have co-morbid [co-occurring] cardiovascular risk factors that would otherwise warrant cholesterol-lowering medication, it is important to weigh the risks and benefits of statin therapy in this population," write M. Brandon Westover, M.D., Ph.D., of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues. The researchers used a Markov decision model to evaluate these benefits and risks. Based on prior research, simulated patients were assigned to states that correspond to disease risk and could then experience any combination of events which may lead to the increased risk of stroke or heart disease, change in quality of life or death.

"Our analysis indicates that in settings of high recurrent intracerebral hemorrhage risk, avoiding statin therapy may be preferred," the authors write. "For lobar intracerebral hemorrhage [bleeding in the cerebrum] in particular, which has a substantially higher recurrence rate than does deep intracerebral hemorrhage, statin therapy is predicted to increase the baseline annual probability of recurrence from approximately 14 percent to approximately 22 percent, offsetting the cardiovascular benefits for both primary and secondary cardiovascular prevention."

In the case of deep intracerebral hemorrhage, a type of stroke due to bleeding deep within the brain that has a lower risk of recurrence, the benefits and risks of statin use were more evenly balanced. "Consequently, the optimal treatment option may vary with specific circumstances," the authors write.

The mechanism by which statins might increase the risk of hemorrhagic stroke are unknown, the authors note. The association may be due to an increased risk of brain bleeding among those with lower cholesterol levels, or potential anti-clotting properties of statins.

"In summary, mathematical decision analysis of the available data suggests that, because of the high risk of recurrent intracerebral hemorrhage in survivors of prior hemorrhagic stroke, even a small amplification of this risk by use of statins suffices to recommend that they should be avoided after intracerebral hemorrhage," the authors conclude. "In the absence of data from a randomized clinical trial (ideally comparing various agents and doses), the current model provides some guidance for clinicians facing this difficult decision."

(Arch Neurol. Published online January 10, 2011. doi:10.1001/archneurol.2010.356. Available pre-embargo to the media at www.jamamedia.org.)

Editor's Note: This work was supported by a grant from the National Institutes of Health. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

"The question prompting the decision analysis model reported by Westover et al epitomizes a common conundrum faced by clinicians—the need to make a therapeutic decision for a given patient in the absence of guidance from specific, high-quality clinical trial data," writes Larry B. Goldstein, M.D., of Duke University and Durham VA Medical Center, Durham, N.C., in an accompanying editorial.

"In this case, exploratory data from two clinical trials (Heart Protection Study and SPARCL) suggest, but do not prove, a statin-associated increased risk of brain hemorrhage that may reduce the overall benefit of treatment in patients with a history of cerebrovascular disease."

The available data are "generally consistent with the conclusion of the decision analysis—the risk of statin therapy likely outweighs any potential benefit in patients with (at least recent) brain hemorrhage and should generally be avoided in this setting," Dr. Goldstein writes. "Until and unless there are data to the contrary, or warranted by specific clinical circumstances, the use of statins in patients with hemorrhagic stroke should be guided by the maxim of nonmaleficence—Primum non nocere."

(Arch Neurol. Published online January 10, 2011. doi:10.1001/archneurol.2010.349. Available pre-embargo to the media at www.jamamedia.org.)

Editor's Note: This work was supported by a grant from the National Institutes of Health. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

To contact corresponding author Steven M. Greenberg, M.D., Ph.D., call Mike Morrison at 617-724-6425 or e-mail mdmorrison@partners.org. To contact editorial author Larry B. Goldstein, M.D., call Melissa Schwarting at 919-660-1303 or e-mail melissa.schwarting@duke.edu.

For more information, contact JAMA/Archives Media Relations at 312/464-JAMA (5262) or e-mail mediarelations@jama-archives.org.