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From Duke University Medical Center (L.B.G.), Durham, NC; Denis Diderot University (P.A.), Paris, France; Pfizer (M.S.), New York, NY; Neurologic Consultants (A.C.), Nashville, TN; University of Heidelberg (M.H.), Mannheim, Germany; University of Copenhagen (H.S.), Denmark; University of California (J.A.Z.), San Diego; and Rosalind Franklin University of Medicine and Science (K.M.A.W.), North Chicago, IL.
Address correspondence and reprint requests to Larry B. Goldstein, MD, Box 3651, Duke University Medical Center, Durham, NC 27710 golds004{at}mc.duke.edu
Background: In the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study, atorvastatin 80 mg/day reduced the risk of stroke in patients with recent stroke or TIA. Post hoc analysis found this overall benefit included an increase in the numbers of treated patients having hemorrhagic stroke (n = 55 for active treatment vs n = 33 for placebo).
Methods: We explored the relationships between hemorrhage risk and treatment, baseline patient characteristics, most recent blood pressure, and most recent low-density lipoprotein (LDL) cholesterol levels prior to the hemorrhage.
Results: Of 4,731 patients, 67% had ischemic strokes, 31% TIAs, and 2% hemorrhagic strokes as entry events. In addition to atorvastatin treatment (HR 1.68, 95% CI 1.09 to 2.59, p = 0.02), Cox multivariable regression including baseline variables significant in univariable analyses showed that hemorrhagic stroke risk was higher in those having a hemorrhagic stroke as the entry event (HR 5.65, 95% CI 2.82 to 11.30, p < 0.001), in men (HR 1.79, 95% CI 1.13 to 2.84, p = 0.01), and with age (10y increments, HR 1.42, 95% CI 1.16 to 1.74, p = 0.001). There were no statistical interactions between these factors and treatment. Multivariable analyses also found that having Stage 2 (JNC-7) hypertension at the last study visit before a hemorrhagic stroke increased risk (HR 6.19, 95% CI 1.47 to 26.11, p = 0.01), but there was no effect of most recent LDL-cholesterol level in those treated with atorvastatin.
Conclusions: Hemorrhagic stroke was more frequent in those treated with atorvastatin, in those with a hemorrhagic stroke as an entry event, in men, and increased with age. Those with Stage 2 hypertension at the last visit prior to the hemorrhagic stroke were also at increased risk. Treatment did not disproportionately affect the hemorrhagic stroke risk associated with these other factors. There were no relationships between hemorrhage risk and baseline low-density lipoprotein (LDL) cholesterol level or recent LDL cholesterol level in treated patients.
Abbreviations: DBP = diastolic blood pressure; LDL = low-density lipoprotein; SBP = systolic blood pressure; SPARCL = Stroke Prevention by Aggressive Reduction in Cholesterol Levels.
Supplemental data at www.neurology.org
Editorial, page 2355
e-Pub ahead of print on December 12, 2007, at www.neurology.org.
*SPARCL Investigators are listed in appendix e-1 on the Neurology® Web site at www.neurology.org.
Disclosure: Larry Goldstein has received honoraria from Pfizer during the course of this study. The honoraria did not exceed $10,000/year. Pierre Amarenco has received grants from Pfizer for other research or activities not reported in this research exceeding $10,000/year and honoraria from Pfizer in excess of $10,000/year during the course of this study. Alfred Callahan has received honoraria from Pfizer in excess of $10,000 during the course of this study. Michael Hennerici has received grants from Pfizer for other research or activities not reported in this research/article and honoraria from Pfizer during the course of the study. Neither the grants nor the honoraria exceeded $10,000/year. Henrik Sillesen has received grants from Pfizer for other research or activities not reported in this research/article in excess of $10,000/year and honoraria exceeding $10,000/year during the course of this study. Michael Szarek was a former employee of Pfizer and had an equity or ownership interest in the sponsor of the study. K. Michael Welch has received honoraria from Pfizer during the course of the study in excess of $10,000/year. Justin Zivin has received honoraria from Pfizer during the course of this study. The honoraria did not exceed $10,000/year. The SPARCL trial was funded by Pfizer. Employees of Pfizer contributed to the design and conduct of the study, the collection, management, analysis, and interpretation of the data, and reviewed the manuscript.
Received July 2, 2007. Accepted in final form September 21, 2007.
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