Study Title:

Statins Increase Risk of a Second Stroke

Study Abstract

Context Statins are widely prescribed for primary and secondary prevention of ischemic cardiac and cerebrovascular disease. Although serious adverse effects are uncommon, results from a recent clinical trial suggested increased risk of intracerebral hemorrhage (ICH) associated with statin use. For patients with baseline elevated risk of ICH, it is not known whether this potential adverse effect offsets the cardiovascular and cerebrovascular benefits.

Objective To address the following clinical question: Given a history of prior ICH, should statin therapy be avoided?

Design A Markov decision model was used to evaluate the risks and benefits of statin therapy in patients with prior ICH.

Main Outcome Measure Life expectancy, measured as quality-adjusted life-years. We investigated how statin use affects this outcome measure while varying a range of clinical parameters, including hemorrhage location (deep vs lobar), ischemic cardiac and cerebrovascular risks, and magnitude of ICH risk associated with statins.

Results Avoiding statins was favored over a wide range of values for many clinical parameters, particularly in survivors of lobar ICH who are at highest risk of ICH recurrence. In survivors of lobar ICH without prior cardiovascular events, avoiding statins yielded a life expectancy gain of 2.2 quality-adjusted life-years compared with statin use. This net benefit persisted even at the lower 95% confidence interval of the relative risk of statin-associated ICH. In patients with lobar ICH who had prior cardiovascular events, the annual recurrence risk of myocardial infarction would have to exceed 90% to favor statin therapy. Avoiding statin therapy was also favored, although by a smaller margin, in both primary and secondary prevention settings for survivors of deep ICH.

Conclusions Avoiding statins should be considered for patients with a history of ICH, particularly those cases with a lobar location.

From press release:

Statin drugs could cause more harm than good for some patients at risk for stroke.
Though the medications are used to lower cholesterol and prevent cardiovascular disease and stroke, researchers warn the widely used drugs may could be risky for patients with a history of stroke from intracerebral hemorrhage, or bleeding in the brain.

Many patients at risk for brain bleeding that causes stroke are also given statins to reduce co-morbidities from cardiovascular disease, but researchers writing in the Archives of Neurology say widespread use of cholesterol lowering drugs are concerning because of "the increased incidence of intracerebral hemorrhage observed among subjects randomized to statin therapy in a clinical trial of secondary stroke prevention."

M. Brandon Westover, M.D., Ph.D., of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues conducted an analysis of the risk and benefits of statin therapy using a Markov (mathematical) decision model.

According to Westover, the findings showed patients with a history of intracerebral hemorrhage were found to have an increased risk of intracerebral hemorrhage that increased from 14 percent to approximately 22 percent, "offsetting the cardiovascular benefits for both primary and secondary cardiovascular prevention." The researchers don't know the reasons statin drugs increase the chances of a second stroke from bleeding.

"Our analysis indicates that in settings of high recurrent intracerebral hemorrhage risk, avoiding statin therapy may be preferred," the authors write. They found that in cases of deep intracerebral hemorrhage the risk of recurrence was lower, advising, "...the optimal treatment option may vary with specific circumstances."

Larry B. Goldstein, M.D., of Duke University and Durham VA Medical Center, Durham, N.C writes in an accompanying editorial, "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 - 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."

The authors say the decision about prescribing statins for patients with a history of intracerebral hemorrhage is difficult, but without clinical trials that compare dosing of the cholesterol lowering drugs and risk of recurrent brain hemorrhage among the specific types of medications available, the mathematical analysis could be used for clinical guidance.

Study Information

M. Brandon Westover; Matt T. Bianchi; Mark H. Eckman; Steven M. Greenberg
Statin Use Following Intracerebral Hemorrhage: A Decision Analysis
Archives of Neurology
2011 January
Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts.

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