Pravastatin in Elderly Individuals at Risk of Vascular Disease Presented at Late Breaking Clinical Trials AHA 2002 PROSPER

www. Clinical trial results.org PROSPER 5,804 high-risk elderly patients  Age 70–82 years  Pre-existing vascular disease (coronary, cerebral, or peripheral)  High-risk for vascular disease (smoking, hypertension, or diabetes)  Total cholesterol 4.0–9.0 mmol/L  Triglyceride < 6.0 mmol/L 5,804 high-risk elderly patients  Age 70–82 years  Pre-existing vascular disease (coronary, cerebral, or peripheral)  High-risk for vascular disease (smoking, hypertension, or diabetes)  Total cholesterol 4.0–9.0 mmol/L  Triglyceride < 6.0 mmol/L Pravastatin 40 mg per day n = 2,891 Pravastatin 40 mg per day n = 2,891 Placebo n = 2,913 Placebo n = 2,913 Endpoints:  Primary – composite of coronary death, non- fatal myocardial infarction, and fatal or non- fatal stroke Endpoints:  Primary – composite of coronary death, non- fatal myocardial infarction, and fatal or non- fatal stroke Lancet 2002; 360: 1623–30 Average follow-up = 3.2 years

www. Clinical trial results.org P=0.014 PROSPER: Clinical Events* Stroke P=0.006 Pravastatin Placebo P=0.047 P=0.043 CV Death / MI / Stroke CV Death / MI * Mean follow-up = 3.2 years Lancet 2002; 360: 1623–30 CV Death Pravastatin Placebo Pravastatin Placebo Pravastatin Placebo

www. Clinical trial results.org P = 0.02 Any New Cancer PROSPER: Safety Events Lancet 2002; 360: 1623–30 Pravastatin Placebo The major safety concern was the increased rate of any new cancer in the pravastatin arm However, in a meta-analysis of statin randomized placebo- controlled trials, treatment with either pravastatin (hazard ratio 1.06, p=0.20) or any statin (HR 1.02, p=0.32) was not associated with an excess risk of cancer The major safety concern was the increased rate of any new cancer in the pravastatin arm However, in a meta-analysis of statin randomized placebo- controlled trials, treatment with either pravastatin (hazard ratio 1.06, p=0.20) or any statin (HR 1.02, p=0.32) was not associated with an excess risk of cancer

www. Clinical trial results.org PROSPER : Summary The PROSPER trial was the first major study to show a benefit with a lipid-lowering agent specifically in high-risk elderly patients –The primary endpoint of CV Death / MI / stroke was reduced significantly in the pravastatin arm –All components of the endpoint except stroke showed a benefit with pravastatin –The major safety concern was the increased rate of any cancer in the pravastatin arm, which was not confirmed in a meta-analysis The PROSPER trial was the first major study to show a benefit with a lipid-lowering agent specifically in high-risk elderly patients –The primary endpoint of CV Death / MI / stroke was reduced significantly in the pravastatin arm –All components of the endpoint except stroke showed a benefit with pravastatin –The major safety concern was the increased rate of any cancer in the pravastatin arm, which was not confirmed in a meta-analysis