Stroke Prevention by Aggressive Reduction in Cholesterol Levels - SPARCL

Description:

The goal of the trial was to evaluate the effect of intensive lipid-lowering therapy with atorvastatin compared with placebo among patients with prior stroke or transient ischemic attack (TIA).

Hypothesis:

Treatment with atorvastatin 80 mg daily would reduce the risk of fatal or nonfatal stroke among patients with a history of stroke or TIA.

Study Design

Study Design:

Patients Screened: 6,670
Patients Enrolled: 4,731
Mean Follow Up: Median follow-up 4.9 years
Mean Patient Age: Mean age 63 years
Female: 40

Patient Populations:

Age >18 years; ischemic or hemorrhagic stroke or a TIA 1-6 months prior to randomization; ambulatory, with a modified Rankin score of ≤3; and LDL cholesterol 100-190 mg/dl

Exclusions:

Atrial fibrillation, other cardiac sources of embolism, and subarachnoid hemorrhage

Primary Endpoints:

Stroke (fatal or nonfatal)

Secondary Endpoints:

Stroke or TIA; major coronary event (death from cardiac causes, nonfatal myocardial infarction, or resuscitation after cardiac arrest); major cardiovascular event (stroke plus any major coronary event); acute coronary event (major coronary event or unstable angina); any coronary event (acute coronary event plus a coronary revascularization procedure, unstable angina, or angina or ischemia requiring emergency hospitalization); revascularization procedure (coronary, carotid, or peripheral); and any cardiovascular event (any of the former plus clinically significant peripheral vascular disease)

Drug/Procedures Used:

Patients were randomized in a double-blind manner to treatment with atorvastatin (80 mg daily, n = 2,365) or placebo (n = 2,366). Patients were followed for a median of 4.9 years.

Principal Findings:

Prior stroke had occurred in 69% of patients and TIA in 31%. Mean baseline low-density lipoprotein (LDL) level was 133 mg/dl. By 1 month, LDL levels were reduced to 61.3 mg/dl in the atorvastatin group (p < 0.0001 vs. baseline), but did not change in the placebo group (133.5 mg/dl).

The primary endpoint of fatal or nonfatal stroke was lower in the atorvastatin group compared with placebo (11.2% vs. 13.1%, p = 0.05). There were also reductions in the secondary endpoints of TIA (6.5% vs. 8.8%, p = 0.004), major coronary event (3.4% vs. 5.1%, p = 0.006), major cardiovascular event (14.1% vs. 17.2%, p = 0.005), and any cardiovascular event (22.4% vs. 29.0%, p < 0.001). There was no difference in all-cause mortality (9.1% for atorvastatin vs. 8.9% for placebo, p = 0.77) or cardiac death (1.7% vs. 1.6%, p = 0.90).

Serious adverse events occurred in 41.8% of the atorvastatin group and 41.2% of the placebo group. Persistent alanine or aspartate aminotransferase elevations occurred more frequently in the atorvastatin group (2.2% vs. 0.5%, p < 0.001). There were two cases of rhabdomyolysis in the atorvastatin group and three cases in the placebo group.

Interpretation:

Among patients with prior stroke or TIA, treatment with atorvastatin was associated with a reduction in recurrent stroke through a median of 4.9 years of follow-up compared with placebo. Reductions in major coronary events associated with atorvastatin therapy were also evident, despite excluding patients at baseline with known coronary disease.

Prior studies such as 4S, CARE, and CARDS have demonstrated reductions in coronary events with statins among patients with coronary heart disease. Data from the present trial extend these findings to the setting of cerebrovascular disease. Additional information on the prior TIA, prior stroke, and type of stroke subgroups would provide insight as to the consistency of benefit across the syndrome.

References:

Amarenco P, Bogousslavsky J, Callahan A III, et al., on behalf of 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;355:549-9.

Presented by P. Amarenco, European Society of Cardiology Scientific Congress, September 2006.

Clinical Topics: Dyslipidemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins

Keywords: Lipoproteins, LDL, Pyrroles, Stroke, Follow-Up Studies, Ischemic Attack, Transient, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Coronary Disease, Heptanoic Acids, Rhabdomyolysis


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