Clinicians should consider avoiding statins in patients with intracerebral hemorrhage who are at high risk of recurrence because the risks of the drugs appear to outweigh their benefits, according to a report published online Jan. 10 in Archives of Neurology.
After an increased incidence of intracerebral hemorrhage (ICH) was reported among subjects in a randomized clinical trial that evaluated statin therapy, Dr. M. Brandon Westover of the department of neurology at Massachusetts General Hospital and Harvard Medical School, Boston, and his associates developed a mathematical decision analysis model to assess the "common dilemma facing physicians of patients with a history of prior ICH and indications for statin therapy: Under what clinical circumstances should statin therapy be avoided because of risk of recurrent ICH?"
Their analysis indicates that "for lobar ICH in particular, which has a substantially higher recurrence rate than does deep ICH, statin therapy is predicted to increase the baseline annual probability of recurrence from approximately 14% to approximately 22%, offsetting the cardiovascular benefits for both primary and secondary CV prevention."
The model simulated the effects of statin therapy on quality-adjusted life expectancy for a hypothetical 65-year-old male patient under different clinical circumstances. It incorporated published data on risks and benefits.
In the scenario of a patient with a lobar ICH and no prior history of ischemic cerebrovascular or cardiac events, statin therapy yielded 4.6 quality-adjusted life years (QALYs), whereas avoiding statin therapy yielded 6.8 QALYs. Avoiding statins also proved advantageous in all other primary prevention scenarios run by the simulation model.
Similarly, avoiding statins was the preferable course of action in several secondary prevention scenarios featuring a patient with lobar ICH. "These results indicate that the risk of ICH on statin therapy is not offset by the secondary prevention benefits, even if the cardiovascular risks are artificially forced to be extremely high," Dr. Westover and his colleagues wrote.
The model indicated that the risks of statin therapy were substantially lower in hypothetical patients with deep ICH, but still conveyed a net loss of QALYs when used for either primary or secondary prevention.
"Using the base-case assumptions and measuring over a single year of follow-up, primary prevention with statin therapy is projected to prevent fewer than two deaths from either MI or ischemic stroke per 1,000 patients per year, at the expense of causing 18 lobar ICHs (in patients with prior lobar ICH) or 3 deep ICHs (in patients with prior deep ICH) per 1,000 patients per year.
"From the perspective of disability and resulting loss of quality of life, each year of primary prevention with statin treatment saves 2.6 QALYs from myocardial infarction or 2.2 QALYs from ischemic stroke per 1,000 patients per year, at the expense of 58.6 QALYs for lobar ICH or 9 QALYs for deep ICH," they noted (Arch. Neurol. 2011 Jan. 10 [doi:10.1001/archneurol.2010.356]).
The mechanism by which statins may amplify the risk of hemorrhagic stroke is still unclear, but the drugs are known to have pleiotropic effects independent of their effects on cholesterol levels, which could in turn convey antithrombotic or fibrinolytic changes.
"Mathematical decision analysis of the available data suggests that, because of the high risk of recurrent ICH 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 ICH. 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," the investigators said.
The study was supported by the National Institutes of Health. No financial conflicts of interest were reported.