1. LIPID: Long-term Intervention with Pravastatin in Ischemic Disease Purpose To determine whether pravastatin will reduce coronary mortality and morbidity in patients with AMI or unstable angina pectoris and broad range of initial cholesterol levels Reference LIPID Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998;339:1349–57.

2. LIPID: Long-term Intervention with Pravastatin in Ischemic Disease - TRIAL DESIGN - Design Randomized, double-blind, placebo-controlled Patients 9014 patients with AMI or hospitalization 3–36 months previously for unstable angina pectoris; baseline cholesterol 155-271 mg/dL (4–7 mmol/L) Follow up and primary endpoint Follow up mean 6.1 years. Primary endpoint death from CHD Treatment Pravastatin 40 mg daily or placebo. Dietary counseling for both groups

3. LIPID: Long-term Intervention with Pravastatin in Ischemic Disease - RESULTS - Significant reduction in overall mortality, death from CHD and all other pre-specified cardiovascular events Total plasma cholesterol 21% lower than in placebo group at 6 months, falling to 13% at 6.1 years due to discontinuation of treatment in pravastatin group and commencement of open-label therapy in placebo group Pravastatin well tolerated: no significant differences in cancers, accidents, violence, suicide (11 vs. 6 deaths due to trauma or suicide) or myopathy (8 vs. 10 cases) in pravastatin group compared with placebo

4. LIPID: Long-term Intervention with Pravastatin in Ischemic Disease - RESULTS continued - Years after randomization 0 0 36912161821 5 10 20 LIPID Study Group.N Engl J Med 1998;339:1349–57. Death from all causes and CHD Placebo Pravastatin Death due to CHD Death from all causes Pravastatin (% of patients) Placebo (% of patients) Relative reduction in risk (%) 95% CI P Death due to CHD Death from all causes 6.4 8.3 24 12–35 <0.001 11.0 14.1 22 13–31 <0.001

5. LIPID: Long-term Intervention with Pravastatin in Ischemic Disease - RESULTS continued - LIPID Study Group.N Engl J Med 1998;339:1349–57. Relative reduction in risk of cardiovascular outcomes Outcome Relative reduction in risk with pravastatin* (%) * 95% CI, P<0.001 for all except stroke (P = 0.048) CHD mortality Overall mortality MI Stroke Coronary revascularization 24 22 29 24 19 20 Placebo n=4502 (%) Pravastatin n=4512 (%) 8.3 14.1 10.3 15.9 4.5 15.7 6.4 11.0 7.4 12.3 3.7 13.0 Non-fatal MI or death due to CHD

6. LIPID: Long-term Intervention with Pravastatin in Ischemic Disease - SUMMARY - As seen in other studies, cholesterol-lowering therapy significantly reduced all major cardiovascular events; however, study also specifically demonstrated that pravastatin: —reduced both mortality due to CHD and overall mortality —had benefit for patients with unstable angina On basis of differences in proportions of patients with an event, for every 1000 patients assigned pravastatin: —death from any cause avoided in 30 patients —death due to CHD avoided in 19 —non-fatal MI/death due to CHD avoided in 35 —death due to stroke avoided in 8