Status:
Complete. Recruitment started November 1998. Enrollment of 4732 patients was completed in March 2001. Patient follow-up was for an average of 5 years. Results published August 2006.
Purpose:
To assess the efficacy of statins in preventing vascular events in patients with recent previous stroke or transient ischemic attack (TIA) but no history of coronary heart disease (CHD).
Interventions:
Atorvastatin
Competitive inhibitor of HMG-CoA reductase; lowers cholesterol and lipids
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Location(s):
North America, South America, Africa, Asia, Europe
Year Started:
1998
Year Finished:
2005
Year Presented:
2007
Design:
Double-blind, randomized, placebo-controlled trial.
Inclusion Criteria
Patients who presented within 1 - 6 months of TIA or stroke, who had an LDL-C level between 100 mg/dL and 190 mgl/dL, and who had a modified Rankin scale (MRS) score =< 3, were eligible for this study.
Exclusion Criteria
Females who were pregnant or breast-feeding, and persons who were under 18 years of age, who had any evidence of CAD, including a history of myocardial infarction (MI), coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, angina, abnormal stress testing, and abnormal angiography, who had atrial fibrillation or took medication for atrial fibrillation, who had prosthetic heart valves or clinically significant mitral stenosis, who had hepatic dysfunction, defined by alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 X the upper limit of normal (ULN), who had a hematologic condition predisposing towards thrombus formation, whose strokes were caused by trauma, a revascularization procedure, or subarachnoid hemorrhage, who had an endarterectomy within 1 month of randomization, who had severe renal dysfunction, whose creatine phosphokinase (CPK) was > 5 X the ULN, who were deemed unreliable (e.g. severe psychiatric illness or substance abuse), who had sinus node dysfunction, a history of peripheral vascular disease, or claudication, who had uncontrolled hypertension, who were taking niacin, probucol, fibrates, bile-acid-sequestering resins, other statins, fish oils, immunosuppressive agents, azole antifungals, any drugs that could interact with statins or affect laboratory parameters (e.g. intermittent systemic steroids, iso-t- retinoin), or any drugs known to cause rhabdomyolysis with statins (e.g. cyclosporine, erythromycin), or who had any comorbid condition that could affect their safety and participation, were excluded from the study.
Patient Involvement:
Eligible patients were randomized to receive either atorvastatin 80 mg/day or placebo. Patients in both groups will be assessed at 1, 3, and 6 months, and every 6 months thereafter for 5 years.
Primary Outcome:
First nonfatal or fatal stroke.
Secondary Outcome:
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), individual components of the composite end points and death from any cause.
Results:
80 mg of atorvastatin per day reduced the overall incidence of strokes and of cardiovascular events, despite a small increase in the incidence of hemorrhagic stroke. During followup, 265 patients (11.2 percent) receiving atorvastatin and 311 patients (13.1 percent) receiving placebo had a fatal or nonfatal stroke (5-year absolute reduction in risk, 2.2 percent; P = 0.03), with the atorvastatin group having 218 ischemic strokes and 55 hemorrhagic strokes, compared to the placebo group with 274 ischemic strokes and 33 hemorrhagic strokes. The atorvastatin group had 216 deaths, compared to the placebo rate of 211 (P = 0.98).
Elevated liver enzyme values were a concern with persistent elevation of alanine or aspartate aminotransferase (>3 times the upper limit of the normal group on two consecutive occasions) more frequent in the atorvastatin group (51 patients, or 2.2 percent) than in the placebo group (11 patients, or 0.5 percent; P<0.001), but there were no cases of liver failure.
Sub study of 781 patients with metabolic syndrome showed a slightly reduced risk of stroke of 12% and major coronary events by 26% (both insignificant) while reducing the risk of coronary heart disease events by 43%.
Sub study with results reported in "Stroke" in October 2007, using a post hoc analysis of 55,045 LDL-C measurements among the 4731 patients enrolled in SPARCL to determine the benefit and risks associated with achieving a >/=50% low-density lipoprotein cholesterol (LDL-C) reduction from baseline during a mean follow-up period of 4.9 years showed that patients with >/=50% LDL-C reduction had a 31% reduction in stroke risk (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).
A post-hoc analysis of changes in kidney function performed after the close of the study, revealed that those post-stroke or mini-stroke patients treated with 80 mg Lipitor had significantly improved kidney function compared to placebo group.
Source of Information:
Presented at the 29th International Stroke Conference [February 2004].
Cerebrovascular Diseases. 2003;16:389-395.
N Engl J Med 2006;355:549-59.
Presented at the 67th Annual Scientific Sessions of the American Diabetes Association [June 2007].
Presented at the 2008 International Stroke Conference (February 2008).
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