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DOI: 10.2337/dc05-2415
© 2006 by the American Diabetes Association
Clinical Care/Education/Nutrition |
Efficacy and Safety of Atorvastatin in the Prevention of Cardiovascular End Points in Subjects With Type 2 Diabetes
The Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-Insulin-Dependent Diabetes Mellitus (ASPEN)
1 Department of Medicine and the Northwest Lipid Research Clinic, University of Washington School of Medicine, Seattle, Washington
2 Department of Medicine, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia
3 Department of Internal Medicine, Refaja-Hospital, Stadskanaal, the Netherlands
4 Medical Statistics Unit, London School of Hygiene and Tropical Medicine, London, U.K.
Address correspondence and reprint requests to Chief Robert H. Knopp, Harborview Medical Center, 325 Ninth Ave., #359720, Seattle, WA 98104-2499. E-mail: rhknopp{at}u.washington.edu
OBJECTIVE—Cardiovascular disease (CVD) risk is increased in type 2 diabetes. The purpose of this study was to assess the effect of 10 mg of atorvastatin versus placebo on CVD prevention in subjects with type 2 diabetes and LDL cholesterol levels below contemporary guideline targets.
RESEARCH DESIGN AND METHODS—Subjects were randomly assigned to receive 10 mg of atorvastatin or placebo in a 4-year, double-blind, parallel-group study. The composite primary end point comprised cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, recanalization, coronary artery bypass surgery, resuscitated cardiac arrest, and worsening or unstable angina requiring hospitalization.
RESULTS—A total of 2,410 subjects with type 2 diabetes were randomized. Mean LDL cholesterol reduction in the atorvastatin group over 4 years was 29% versus placebo (P < 0.0001). When we compared atorvastatin versus placebo, composite primary end point rates were 13.7 and 15.0%, respectively (hazard ratio 0.90 [95% CI 0.73–1.12]). In the subset of 1,905 subjects without prior myocardial infarction or interventional procedure, 10.4% of atorvastatin- and 10.8% of placebo-treated subjects experienced a primary end point (0.97 [0.74–1.28]). In the 505 subjects with prior myocardial infarction or interventional procedure, 26.2% of atorvastatin- and 30.8% of placebo-treated subjects experienced a primary end point (0.82 [0.59–1.15]). Relative risk reductions in fatal and nonfatal myocardial infarction were 27% overall (P = 0.10) and 19% (P = 0.41) and 36% (P = 0.11) for subjects without and with prior myocardial infarction or interventional procedure, respectively.
CONCLUSIONS—Composite end point reductions were not statistically significant. This result may relate to the overall study design, the types of subjects recruited, the nature of the primary end point, and the protocol changes required because of changing treatment guidelines. For these reasons, the results of the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-Insulin-Dependent Diabetes Mellitus (ASPEN) did not confirm the benefit of therapy but do not detract from the imperative that the majority of diabetic patients are at risk of coronary heart disease and deserve LDL cholesterol lowering to the currently recommended targets.
Abbreviations: ALLHAT, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial • ASCOT, Anglo-Scandinavian Cardiac Outcomes Trial • ASPEN, Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-Insulin-Dependent Diabetes Mellitus • CARDS, Collaborative Atorvastatin Diabetes Study • CHD, coronary heart disease • CVD, cardiovascular disease • DSMB, Data and Safety Monitoring Board • FIELD, Fenofibrate Intervention and Event Lowering in Diabetes • ITT, intent-to-treat • NCEP, National Cholesterol Education Program
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