Collaborative Atorvastatin Diabetes Study (CARDS)
From Pubdrug
| Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial | |
| Authors | Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, et al. |
| Journal | Lancet |
| Year/Volume(Issue)/Pages | 2004;364(9435):685-696 |
| Original Article Abstract | |
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Contents |
Quick Summary
- This trial was performed to assess the role of atorvastatin 10mg daily in the primary prevention of major cardiovascular events in type 2 diabetic patients who did not have high LDL cholesterol values.
- The participants randomized to atorvastatin experienced a 37% reduction in the incidence of major cardiovascular events.
- The trial was stopped 2 years early due to the statistical significance seen between the treatment and placebo groups.
- There was no difference in adverse events seen between groups.
Hypothesis/Objectives
Previous studies including diabetic patients (the Heart Protection Study (HPS) and the Anglo-Scandinavian Cardiac Outcomes Trial - Lipid Lowering Arm (ASCOT-LLA)) had shown that treatment with statins led to a reduced risk of cardiovascular disease. The objective of this trial was to assess the effectiveness of atorvastatin 10 mg daily versus placebo in the primary prevention of cardiovascular disease in patients with type 2 diabetes.
Methods/Design
| Y | Randomized? | ||
| Y | Controlled? | ||
| Y | Placebo-controlled? | ||
| Y | Prospective? | ||
| Y | Double-blind? | ||
| *U = not reported | |||
Inclusion criteria
- Men and women aged 40-75
- Type 2 diabetes mellitus diagnosed at least 6 months prior to study entry
- At least one or more of the following:
- history of hypertension (receiving antihypertensive treatment or systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg on at least two successive occasions)
- retinopathy
- microalbuminuria
- macroalbuminuria
- currently smoking
Exclusion criteria
- Any past history of:
- myocardial infarction
- angina
- coronary vascular surgery
- cerebrovascular accident
- severe peripheral vascular disease
- LDL cholesterol <160 mg/dL (4.14 mmol/L)
- Triglycerides <600 mg/dL (6.78 mmol/L)
- Plasma creatinine >1.7 mg/dL (150 micromol/L)
- A1C >12%
- Less than 80% compliance with placebo
Design
Participants meeting inclusion criteria were randomized to placebo or atorvastatin 10mg daily. This included 2,838 participants. If additional lipid-lowering therapy was necessary, specificed additional therapy could be added on in addition to the study drug. Participants were seen each month for the first 3 months, then at 6 months, then every 6 months thereafter. Information regarding adverse events, weight, and blood pressure were taken at each visit.
Results
Baseline characteristics
Participants were mostly of white ethnic origin (94%), mostly male (68%), and had an average age of 62 years. The treatment groups were matched for age, sex, baseline cardiovascular disease risk factors, and diabetes-specific factors.
Primary endpoint results
The primary endpoint was defined as the first incidence of the following events: acute coronary heart disease (including myocardial infarction, unstable angina, acute coronary heart disease death, and resuscitated cardiac arrest), coronary revascularization procedures, or stroke. Patients in the atorvastatin arm had a 37% relative reduction in the risk of a primary endpoint event (95% CI -52% to -17%, p=0.001). This finding included a 36% reduction in acute coronary events, 31% reduction in coronary revascularization events, and 48% reduction in stroke. This finding was associated with an incidence of major cardiovascular disease events of 15.4 per 1,000 person-years in the atorvastatin group, compared to 24.6 events per 1,000 person-years in the placebo group.
Other
Other findings included a non-significant 27% reduction in all-cause mortality (p=0.059), and a 32% reduction of any acute cardiovascular disease event (hazard ratio 0.68 [95% CI 0.55-0.85], p=0.001). LDL cholesterol levels were decreased by 40% in the atorvastatin arm [95% CI -41% to -39%, p<0.0001]. There was no difference in the frequency of adverse events between the two arms, and there were no reports of rhabdomyolysis. The trial was originally intended to last four years, but was terminated after two years due to statistically significant findings in favor of atorvastatin.
Limitations
- The results of this study show that 27 patients would have to be treated for 4 years to prevent one event.
- It may be a financial burden for patients to be on a statin if they are within their goal cholesterol range.
- Since this study included almost entirely participants of white ethnic origin the findings may not be applicable to diabetic patients of other ethnic origins.
- The study was sponsored in part by Pfizer, the manufacturer of brand name atorvastatin (Lipitor).
- Several of the authors received reimbursement or payments from Pfizer for speaking at meetings.
