Effects of Atorvastatin on Stroke in Patients With Unstable Angina or Non-Q Wave Myocardial Infarction. A Myocardial Ischemia Reducation with Aggressive Cholesterol Lowering (MIRACL) Substudy. - MIRACL Stroke Substudy

Description:

The goal of this study was to assess the safety and efficacy of atorvastatin among patients with an acute coronary syndrome (ACS) (the MIRACL study).

Study Design

Study Design:

Mean Follow Up: 16 weeks
Female: 35

Primary Endpoints:

death, nonfatal MI, cardiac arrest and repeat hospitalization with documented ischemia

Secondary Endpoints:

stroke, CHF and need for revascularization

Drug/Procedures Used:

Over 3000 patients with acute coronary syndromes (ACS, unstable angina or non-STEMI) were randomized to atorvastatin 80 mg or placebo between 24 to 96 hours after admission and followed for 16 weeks. Predefined endpoints included death, nonfatal MI, cardiac arrest, and repeat hospitalization with documented ischemia, and secondary endpoints were the incidence of stroke, CHF, and need for revascularization.

Principal Findings:

The average age was 65 years, 65% were men, both arms included approximately 25% smokers, 25% diabetes, and 50% hypertension, and 9% had previous cerebrovascular disease (CVD). Mean baseline cholesterol was 206 mg/dl, LDL-C 124 mg/dl, HDL-C 46 mg/dl, and triglycerides 182 mg/dl. By 16 weeks, the LDL-C increased on placebo to 135 mg/dl (12%) and decreased with atorvastatin to 72 mg/dl (40%). There was no difference in use of medication during and after the hospitalization [about 90% ASA, 75% beta blockers, and 50% ACEi]. Nonfatal and fatal strokes occurred in 24 patients on placebo (1.6%) and 12 on atorvastatin (0.8%) [RR 0.49, 95% CI 0.24-0.98, p =0.04]. The increase in the placebo group was attributable to thrombotic/embolic strokes. Six strokes occurred within 14 days of a coronary intervention. Co-variates associated with stroke included older age, a history of CHF or CVD, and MI, but not baseline lipids. Paradoxically, the stroke rate was lower among smokers, possibly related to their younger age and lower incidence of CRFs.

Interpretation:

Among patients with acute coronary syndromes, intensive cholesterol lowering with atorvastatin was associated with a 50% reduction in the incidence of stroke. The impressive results may be related to the relatively high stroke rate among placebo treated patients, but nevertheless lend further support to the administration of statins at the time of acute coronary events. Other lipid lowering trials have likewise observed a reduction in stroke rates with aggressive lipid lowering, a result that was not prospectively anticipated in early trials. The degree to which reduced hospitalization for ischemic events and stroke in MIRACL is associated with the magnitude of lipid lowering remains to be determined. It is notable that most of the reduction observed was in thrombotic/embolic stroke possibly indicating a favorable interaction with the hematologic milleu and potentially plaque stabilization rather than reducing plaque progression. The relatively high early recurrence and stroke rate in this and other trials of lipid lowering agents is consistent with the concept of diffuse inflammation and a "vulnerable patient" rather than a specific "vulnerable plaque".

References:

Waters DD, Schwartz GG, Olsson AG, et al for the MIRACL Study Investigator. Effects of Atorvastatin on Stroke in Patients With Unstable Angina or Non-Q Wave Myocardial Infarction. A Myocardial Ischemia Reducation with Aggressive Cholesterol Lowering (MIRACL) Substudy. Circulation 2002;106:1690-95.

Clinical Topics: Acute Coronary Syndromes, Arrhythmias and Clinical EP, Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Implantable Devices, SCD/Ventricular Arrhythmias, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Hypertension

Keywords: Inflammation, Stroke, Acute Coronary Syndrome, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Heptanoic Acids, Heart Arrest, Pyrroles, Cholesterol, Triglycerides, Diabetes Mellitus, Hypertension


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