Atorvastatin in stroke: a review of SPARCL and subgroup analysis

Abstract

Statin therapy in patients with cardiovascular disease is associated with reduced incidence of stroke. The Stroke Prevention by Aggressive Reduction of Cholesterol Levels (SPARCL) trial showed daily treatment with 80 mg of atorvastatin in patients with a recent stroke or transient ischemic attack (TIA) reduced the incidence of fatal or nonfatal stroke by 16%. Several post hoc analyses of different subgroups followed the SPARCL study. They have not revealed any significant differences when patients were sorted by age, sex, presence of carotid disease or type of stroke, with the exception of intracranial hemorrhage as the entry event. Lower low-density lipoprotein cholesterol levels in addition to possible neuroprotective mechanisms due to atorvastatin treatment correlate with improved risk reduction. Although not predefined subgroups and subject to an insufficient power, these post hoc studies have generated new clinical questions. However, clinicians should avoid denying therapy based on such subgroup analysis. At this point, the best evidence powerfully demonstrates stroke and TIA patients should be prescribed high dose statin therapy for secondary stroke prevention.

Keywords: carotid stenosis; intracranial hemorrhage; neuroprotection; outcome; prevention; statins; transient ischemic attack.

Figure 1

Kaplan-Meier curves for the first occurrence of primary endpoint (fatal or nonfatal stroke). Reproduced with permission from The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355:549–559. Copyright © 2006 Massachusetts Medical Society. All rights reserved. Abbreviations: HR, hazard ratio; CI, confidence interval.

Figure 2

Primary endpoint (fatal or nonfatal stroke) by different patient subgroups showing the treatment hazard ratios from the Cox regression model. *Type of event at entry study. Abbreviations: CS, carotid stenosis; CI, confidence interval; C-LDL, low-density lipoprotein cholesterol; TIA, transient ischemic attack.

Figure 3

Stroke severity after 90 days measured by modified Rankin Score (mRS) from subjects who had only ischemic stroke during the trial. P = 0.067 Using Cochran-Mantel-Haenszel test. From data of Goldstein et al.