Published Online
on October 25, 2007

A more recent version of this article appeared on December 1, 2007

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Submitted on May 8, 2007
Accepted on May 16, 2007

Effects of Intense Low-Density Lipoprotein Cholesterol Reduction in Patients With Stroke or Transient Ischemic Attack. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Trial

Pierre Amarenco MD^*; Larry B. Goldstein MD; Michael Szarek MS; Henrik Sillesen MD, MSc; Amy E. Rudolph PhD; Alfred Callahan III MD; Michael Hennerici MD, PhD; Lisa Simunovic MS; Justin A. Zivin MD, PhD; K. Michael A. Welch MBChB, FRCP; SPARCL Investigators

From the Department of Neurology and Stroke Centre, Bichat University Hospital, Denis Diderot University and Medical School, Paris, France.

^* To whom correspondence should be addressed. E-mail: amarenco{at}ccr.jussieu.fr.

Background and Purpose—The intention-to-treat analysis of data from the placebo-controlled Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial found 80 mg atorvastatin per day reduced the risk of stroke and major coronary events in patients with recent stroke or transient ischemic attack. This benefit was present despite only a 78% net difference in adherence to randomized treatment over the course of the trial. In this exploratory analysis, our aim was to evaluate the benefit and risks associated with achieving a 50% low-density lipoprotein cholesterol (LDL-C) reduction from baseline.

Methods—This post hoc analysis was based on 55 045 LDL-C measurements among the 4731 patients enrolled in SPARCL (average, 11.6 measurements per patient) during a mean follow-up of 4.9 years. At each postrandomization LDL-C assessment, percent change in LDL-C from baseline for each patient was classified as no change or increase from baseline (32.7% of measurements), <50% LDL-C reduction (39.4%), or 50% reduction (27.9%).

Results—Compared with no change or an increase in LDL-C, analysis of time-varying LDL-C change showed that patients with 50% LDL-C reduction had a 31% reduction in stroke risk (hazard ratio, 0.69, 95% CI, 0.55 to 0.87, P=0.0016), a 33% reduction in ischemic stroke (P=0.0018), no statistically significant increase in hemorrhagic stroke (P=0.8864), and a 37% reduction in major coronary events (P=0.0323). There was no increase in the incidence of myalgia or rhabdomyolysis. Persistent liver enzyme elevations were more frequent in the group with 50% LDL-C reduction.

Conclusions—As compared with having no change or an increase in LDL-C, achieving a 50% lowering was associated with a greater reduction in the risk of stroke and major coronary events with no increase in brain hemorrhages.

Key words: lipids • prevention • statins • stroke

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