Statins May Hike Risk of Hemorrhagic Second Stroke
By Judith Groch, Senior Writer, MedPage Today
DURHAM, N.C., Dec. 12 -- Patients taking statins after a stroke or a TIA were five times more likely than controls to have a second, hemorrhagic stroke if their initial stroke had been hemorrhagic, researchers here reported.
These negative findings came from a secondary analysis of the generally positive results in a clinical trial known as Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL).
That trial found that atorvastatin (Lipitor) at 80 mg a day produced a 16% reduction in fatal and nonfatal stroke in patients with a recent stroke or TIA and no known coronary heart disease, Larry B. Goldstein, M.D., of Duke University here, and colleagues reported in the Dec. 12 online issue of Neurology.
However, the researchers said, their post hoc analysis found that despite the overall reduction in stroke and other coronary events, there was an increase in stroke among atorvastatin-treated patients who had had a hemorrhagic stroke (55 for active treatment versus 33 for placebo, HR: 1.68, 95% CI: 1.09 to 2.59, P=0.02).
The findings came from the SPARCL trial of 4,731 patients with no history of heart disease, in which half the participants received atorvastatin and half a placebo. Of these, 67% had had ischemic strokes, 31% TIAs, and 2% hemorrhagic strokes within six months of study entry.
The patients were then followed for a mean of 4.5 years. At the end of follow-up, overall statin treatment reduced stroke in these patients (HR: 0.84, 95% CI: 0.71 to 0.99, P=0.03).
However, of those randomized to atorvastatin, 2.3% had a hemorrhagic stroke during the study compared with 1.4% of those randomized to placebo.
At the same time, the researchers found a 21% reduction in ischemic stroke among those taking atorvastatin.
Cox multivariable analyses showed that the hemorrhagic stroke risk was more than five times higher for those with hemorrhagic stroke as their entry event (HR: 5.65, 95% CI: 2.82 to 11.30, P<0.001).
Men were nearly twice as likely to have a hemorrhagic stroke (HR: 1.79, 95% CI: 1.13 to 2.84, P=0.01), while the risk also increased with age (10-year increments, HR: 1.42, 95% CI: 1.16 to 1.74, P=0.001).
There were no statistical interactions between these factors and treatment, the investigators said.
Multivariable analyses also found that having Stage 2 hypertension at the last study visit before a hemorrhagic stroke increased the stroke risk more than sixfold (HR: 6.19, 95% CI: 1.47 to 26.11, P=0.01).
These data support the need for aggressive management of hypertension, the researchers said.
Finally, they said, there was no effect for baseline LDL-cholesterol level or the most recent level in those treated with atorvastatin.
Anticoagulants and some antiplatelet regimens may be associated with an increased risk of post-stroke brain hemorrhage, the researchers said. However, they found no overall effect of these drugs on the risk of brain hemorrhage in SPARCL.
Unlike patients with an ischemic stroke upon study entry, there is no evidence that those with an original hemorrhagic stroke benefited from treatment, Dr. Goldstein and his colleagues said.
It is, however, important to re-emphasize the exploratory nature of these analyses, they said. They are useful for generating hypotheses, but cannot be conclusive.
Hemorrhagic strokes occurred in no more than 2% of the study population. The observation was found in a post hoc analysis, and the exploratory statistical models accounted for only a small proportion of bleeding, the investigators said.
Therefore, in making therapeutic decisions, they wrote, the increase in the risk of hemorrhagic stroke must be balanced against the benefit of statin treatment in reducing the overall risk of stroke, as well as other cardiovascular events.
The SPARCL trial was funded by Pfizer, maker of atorvastatin (Lipitor). Pfizer employees contributed to the design and conduct of the study, the collection, management, analysis, and interpretation of the data, as well as review of the manuscript.
Dr. Goldstein reported receiving honoraria from Pfizer during the course of this study. Various co-authors have received grants and honoraria from Pfizer for this study or for other research or activities not reported in this research.
Primary source: Neurology
Source reference:Goldstein LB, et al "Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels study" Neurology 2007; DOI: 10.1212/01.wnl.00002296277.63350.77.
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