Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 15325833 · doi:10.1016/S0140-6736(04)16895-5
What was done
A multicentre, randomised, placebo-controlled trial in 132 centres across the UK and Ireland assigned 2,838 patients aged 40-75 years with type 2 diabetes and no prior history of cardiovascular disease to atorvastatin 10 mg daily (n=1,428) or placebo (n=1,410). Participants had baseline LDL-cholesterol 4.14 mmol/L or less, fasting triglycerides 6.78 mmol/L or less, and at least one risk factor: retinopathy, albuminuria, current smoking, or hypertension. The primary endpoint was time to first occurrence of acute coronary heart disease events, coronary revascularisation, or stroke, analysed by intention to treat.
What was found
The trial stopped 2 years early due to meeting prespecified efficacy stopping rules after a median follow-up of 3.9 years (IQR 3.0-4.7). Major cardiovascular events occurred in 83 patients on atorvastatin (1.54 per 100 person-years) versus 127 on placebo (2.46 per 100 person-years), reflecting a 37% rate reduction (95% CI -52 to -17, p=0.001). Assessed separately, acute coronary heart disease events were reduced by 36% (95% CI -55 to -9), coronary revascularisations by 31% (95% CI -59 to 16), and stroke by 48% (95% CI -69 to -11). Death rate was reduced by 27% (95% CI -48 to 1, p=0.059). No excess of adverse events was noted in the atorvastatin group.
Why it matters
This trial demonstrates that statin therapy significantly lowers major cardiovascular events and stroke in type 2 diabetes patients even without elevated baseline LDL-cholesterol, arguing against using arbitrary LDL-cholesterol thresholds to guide statin initiation.
Limits
The trial was stopped early for efficacy, which can overestimate effect sizes. All participants had at least one cardiovascular risk factor (hypertension, smoking, albuminuria, or retinopathy), limiting generalisability to diabetes patients without additional risk factors. All-cause mortality reduction did not reach statistical significance (p=0.059), and only a single 10 mg daily dose was assessed.
Cited by
- supports A major clinical trial reported a 46% relative risk reduction in strokes with statins, which translated to an absolute risk reduction of 1.3% (13 fewer strokes per 1,000 people over 4 years).