1. Collaborative Atorvastatin Diabetes Study CARDS Dr Sachin Kadoo

2. CARDS The Rationale Type 2 diabetes is associated with elevated cardiovascular risk The role of lipid-lowering particularly with statins for secondary prevention of CHD is clear More data on the benefits of lipid-lowering for the primary prevention of CHD and stroke are needed The effectiveness and safety of lipid lowering for primary prevention in patients with low levels of LDL-C is unclear Lancet. 2004 Aug 21;364(9435):685-96

3. Aim of CARDS To evaluate the effectiveness and safety of atorvastatin 10mg daily versus placebo in the primary prevention of cardiovascular disease (major coronary events, revascularisation and stroke) in patients with type 2 diabetes without raised cholesterol levels

4. 6 week pre-randomisation placebo run in phase then visits at month 1, 3, 6 and 6 monthly Atorvastatin 10mg Placebo 2838 patients CARDS Design Placebo Lancet. 2004 Aug 21;364(9435):685-96

5. CARDS Eligibility Criteria Type 2 diabetes Males or females 40-75 years of age No clinical history of coronary, cerebrovascular or severe peripheral vascular disease LDL-C  4.14 mmol/L (  160 mg/dL) TG  6.78 mmol/L (  600 mg/dL) One of : –Hypertension defined as receiving antihypertensive treatment or SBP  140 mm Hg or DBP  90 mm Hg –Retinopathy –Microalbuminuria or macroalbuminuria –Current smoking

6. CARDS Endpoints Acute CHD death Non-fatal MI including silent MI Hospitalised unstable angina Resuscitated cardiac arrest Coronary revascularisation Stroke Major coronary events Primary Efficacy Parameters Secondary Efficacy Parameters Total mortality Any cardiovascular endpoint Lipid and lipoproteins

7. Cumulative Hazard for Primary Endpoint Relative Risk Reduction 37% (95% CI: 17-52) Years 328 305 694 651 1074 1022 1361 1306 1392 1351 Atorva Placebo 1428 1410 Placebo 127 events Atorvastatin 83 events Cumulative Hazard (%) 0 5 10 15 012344.75 P=0.001

8. Cumulative Hazard for Any CVD Endpoint Relative Risk Reduction= 32% (95% CI 15-45) p=0.001 Years 306 287 663 621 1040 992 1337 1275 1372 1334 Atorva Placebo 1428 1410 Placebo 189 events Atorvastatin 134 events Cumulative Hazard (%) 0 5 10 15 20 012344.75

9. Cumulative Hazard for All Cause Mortality Relative Risk Reduction 27% (95%CI: -1-48) p=0.059 Cumulative Hazard (%) Years Atorva Placebo 82 deaths Atorvastatin 61 deaths 351 332 730 709 1110 1094 1401 1370 1418 1395 1428 1410 12344.75 0 2 4 6 8 10 0

10. Summary Trial terminated about 2 years earlier than anticipated, because a highly significant reduction in the Primary End Point was observed at the 2 nd interim analysis 37% reduction in major CVD events 48% reduction in stroke 27% reduction in all cause mortality of borderline statistical significance Consistent effect regardless of age, sex, lipids and complications (hypertension, smoking, retinopathy or macro/microalbuminuria) at baseline Atorvastatin 10mg was well tolerated with no cases of rhabdomyolysis and no differences in muscle and liver adverse effects