Effects of Intense Low-Density Lipoprotein Cholesterol Reduction in Patients With Stroke or Transient Ischemic Attack
- From: Marilyn Mann <mannm@xxxxxxxxxxx>
- Date: Fri, 7 Dec 2007 15:39:09 -0800 (PST)
(Stroke. 2007;38:3198.)
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 on behalf of the SPARCL
Investigators
From the Department of Neurology and Stroke Centre, Bichat UniversityHospital, Denis Diderot University and Medical School, Paris, France.
Correspondence to Pierre Amarenco, MD, Department of Neurology and
Stroke Centre, Bichat University Hospital, Denis Diderot University
and Medical School, 46, rue Henri Huchard, 75018, Paris, France. E-
mail amarenco@xxxxxxxxxxxxxx
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.
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