1. VBWG IDEAL: The Incremental Decrease in End Points Through Aggressive Lipid Lowering Study

2. VBWG IDEAL: Study design Objective: To compare intensive vs less-intensive lipid-lowering therapies Design: Prospective, randomized, open-label, blinded end-point evaluation ( PROBE) Population: N = 8888 with previous MI Treatment: Atorvastatin 80 mg, simvastatin 20-40 mg/d Primary outcome: Coronary death, nonfatal MI, resuscitated cardiac arrest Secondary outcomes: Major CVD (primary event, stroke), CHD (primary event, coronary revascularization, hospitalization for UA), any CVD (any of the above, PAD, hospitalization for CHF), all-cause mortality Follow-up: Median 4.8 years Pedersen TR et al. JAMA. 2005;294:2437-45. Incremental Decrease in End Points Through Aggressive Lipid Lowering

3. VBWG IDEAL: Reduction in primary endpoint Pedersen TR et al. JAMA. 2005;294:2437-45. Cumulative hazard (%) Major coronary event* Time from randomization (years) No. at risk Simvastatin444942934165403739171200 Atorvastatin443942854170405339401182 16 12 8 4 0 123450 Simvastatin Atorvastatin 11% RRR HR = 0.89 (95% CI, 0.78–1.01) P = 0.07 *Death from CAD, nonfatal MI, cardiac arrest with resuscitation Incremental Decrease in End Points Through Aggressive Lipid Lowering

4. VBWG IDEAL: Reduction in secondary endpoints Pedersen TR et al. JAMA. 2005;294:2437-45. Cumulative hazard (%) Any coronary heart disease* Time from randomization (years) No. at risk Simvastatin444939373920352733701002 Atorvastatin443939843799363234961032 40 30 20 10 0 123450 Any cardiovascular disease † Time from randomization (years) 44493841358033383127908 44393902367134693299963 40 30 20 10 0 123450 Simvastatin Atorvastatin Simvastatin Atorvastatin * Major coronary event, hospitalization for UA, coronary revascularizations † CHD endpoints, peripheral vascular disease, hospitalization for nonfatal CHF Incremental Decrease in End Points Through Aggressive Lipid Lowering 16% RRR HR = 0.84 (95% CI, 0.76–0.91) P < 0.001 16% RRR HR = 0.84 (95% CI, 0.78–0.91) P < 0.001

5. VBWG IDEAL: Summary High-dose atorvastatin vs usual-dose simvastatin in post-MI patients: Trend to benefit in primary outcome (11% RRR) Significant reductions in composite secondary outcomes (13% to 16%) No difference between groups in all-cause or CV mortality No difference between groups in serious adverse events – Incidence of liver enzyme elevation with atorvastatin was <1% and comparable with results of other trials 4 studies now support aggressive lipid lowering to reduce CV events in high-risk patients: IDEAL, PROVE IT-TIMI 22, A to Z, TNT Pedersen TR et al. JAMA. 2005;294:2437-45. Cannon CP. JAMA. 2005;294:2492-4. Incremental Decrease in End Points Through Aggressive Lipid Lowering