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Collaborative Atorvastatin Diabetes Study - CARDS
Description:
The goal of the Collaborative Atorvastatin Diabetes Study (CARDS) trial was to determine the effectiveness of the lipid-lowering agent atorvastatin in reducing cardiovascular events and death among diabetic patients with at least one heart disease risk factor, but without elevated cholesterol.
Hypothesis:
Atorvastatin therapy will reduce the rate of coronary events compared with placebo in diabetic patients with at least one heart disease risk factor.
Study Design
Study Design:
Patients Screened: 4,053
Patients Enrolled: 2,838
Mean Follow Up: 3.9 years
Mean Patient Age: Age range 40-75 years (mean 62 years)
Female: 32
Patient Populations:
Patients age 40-75 years with noninsulin-dependent diabetes mellitus, LDL cholesterol <4.14 mmol/l (<160 mg/dl) and triglycerides <6.78 mmol/l (<600 mg/dl), and ≥1 of the following risk factors: retinopathy, micro-/macroalbuminuria, current smoker, or hypertension
Exclusions:
Type I and secondary diabetes, MI, severe peripheral vascular disease, percutaneous coronary intervention or coronary artery bypass graft, unstable angina, heart failure, or uncontrolled hypertension
Primary Endpoints:
Time to first of acute CHD death, MI (including silent MI), coronary revascularization, unstable angina, stroke, and resuscitated cardiac arrest
Secondary Endpoints:
Total mortality, angina, nonfatal cerebrovascular events, peripheral vascular disease, other nonfatal cardiovascular events, and lipid levels
Drug/Procedures Used:
Patients were randomized to atorvastatin 10 mg/day (n=1,428) or placebo (n=1,410).
Principal Findings:
The trial was discontinued two years earlier than scheduled due to a significantly lower rate of fatal and nonfatal coronary events, stroke, and coronary revascularization procedures in the atorvastatin arm at the second interim analysis.
Baseline characteristics were similar in both arms, with 37% obese (body mass index >30) and a median duration of diabetes of 7.8 years. Baseline total cholesterol was 207 mg/dl and low-density lipoprotein (LDL) cholesterol was 118 mg/dl in the placebo arm and 119 mg/dl in the atorvastatin arm. Total cholesterol was reduced by 54 mg/dl and LDL by 46 mg/dl in the atorvastatin arm (p<0.0001 each).
The primary endpoint occurred significantly less frequently in the atorvastatin arm versus placebo (5.8% vs. 9.0%, relative risk reduction [RRR] 37%, p=0.001), as did acute coronary events (3.6% vs. 5.5%, RRR 36%), and stroke (1.5% vs. 2.8%, RRR 48%). There was no evidence of heterogeneity by any of the subgroups for the primary endpoint. Any cardiovascular disease event was lower in the atorvastatin arm (RRR 32%, p=0.001), while all-cause mortality trended lower (RRR 27%, p=0.059). There were no cases of rhabdomyolysis in either arm and no difference in serious adverse effects between treatment groups.
Interpretation:
Among diabetic patients with at least one heart disease risk factor, but without elevated cholesterol, treatment with atorvastatin 10 mg was associated with a reduction in the primary endpoint of acute coronary heart disease (CHD) death, nonfatal myocardial infarction (MI), hospitalized unstable angina, resuscitated cardiac arrest, coronary revascularization, or stroke compared with placebo, as well as reductions in the secondary endpoint of any cardiovascular disease event.
The current American Diabetes Association guidelines have target LDL levels of <100 mg/dl, with statin therapy recommended if LDL is above 130 mg/dl. The presenter stated that the data from the present study suggests there should be no threshold level of LDL to determine which type 2 diabetic patients should be treated with statins, but that the overall cardiovascular risk should be the guiding principal. In the Heart Protection Study, major vascular events were reduced 28% with simvastatin in the subgroup of diabetics with no history of CHD, further supporting the use of statins as a class in diabetic patients.
References:
Colhoun HM, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicenter randomised placebo-controlled trial. Lancet 2004;364:685-96.
Presented by Prof. Helen Colhoun at the 2004 American Diabetes Association Scientific Sessions, Orlando, FL.
Trial design: Colhoun HM, Thomason MJ, Mackness MI, et al. Design of the Collaborative AtoRvastatin Diabetes Study (CARDS) in patients with Type 2 diabetes. Diabet Med 2002;19:201-11.
Keywords: Myocardial Infarction, Stroke, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Diabetes Mellitus, Type 2, Risk Factors, Heptanoic Acids, Heart Arrest, Hypercholesterolemia, Simvastatin, Rhabdomyolysis, Pyrroles, Cholesterol, Body Mass Index, Triglycerides, Hypertension
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