Over Time Additional Risk Factors Can Progress: Effect of Cholesterol and BP on CHD Risk in MRFIT Trial < Cholesterol quintile (mg/dL) SBP quintile (mm Hg) < < Deaths/10,000 patient-years 245+ N = 316,099 BP = blood pressure; CHD = coronary heart disease. Neaton JD et al. Arch Intern Med. 1992;152: Increasing Risk
ASCOT LLA Trial of Statin in Hypertensive Patients With Additional Risk Factors: Patient Population 3 All patients in ASCOT have hypertension plus 3 risk factors for CHD Sever PS et al. J Hypertens. 2001;19: Patients With Risk Factor, % Peripheral vascular disease Previous cerebrovascular events LVH Certain ECG abnormalities Plasma TC:HDL-C ≥6 Type 2 diabetes Family history of coronary disease Smoker Microalbumin/proteinuria Male Age ≥55 years Hypertension
ASCOT LLA Primary End Point: Nonfatal MI and Fatal CHD 4 Sever PS et al. Lancet. 2003;361: % relative risk reduction HR = 0.64 (95% CI, 0.50 – 0.83) Atorvastatin 10 mg Placebo P =.0005 Years Cumulative Incidence, % Number of Events 100 Number of Events 154
ASCOT LLA Secondary End Point: Fatal and Nonfatal Stroke 5 Sever PS et al. Lancet. 2003;361: % relative risk reduction HR = 0.73 (0.56 – 0.96)P = Years Cumulative Incidence, % Atorvastatin 10 mg Placebo Number of Events 89 Number of Events 121
HPS: Effects of Statin on Major Coronary Events and Stroke in Diabetic and Nondiabetic Patients 6 SimvastatinPlaceboRate ratio & 95% CI Statin betterPlacebo better Vascular event & disease group (10269)(10267) Major coronary events Diabetes279377(9.4%)(12.6%) No diabetes (8.5%)(11.5%) All patients (8.7%)(11.8%) 27% (95% CI 21-33) reduction (P<0.0001) Strokes Diabetes149193(5.0%)(6.5%) No diabetes (4.0%)(5.4%) All patients444585(4.3%)(5.7%) 25% (95% CI 15-34) reduction (P<0.0001) Collins et al. Lancet 2003;361:
CARDS: Effect of Atorvastatin on the Primary End Point—Major CV Events Including Stroke 7 Colhoun HM et al. Lancet 2004;364: Cumulative Hazard, % Years Relative Risk Reduction 37% (95% CI, 17–52) P = Placebo Atorvastatin Placebo 127 events Atorvastatin 83 events
CARDS: Component End Points 8 21 (1.5%) 24 (1.7%) 51 (3.6%) 83 (5.8%) Atorva* 48% (11-69) 39 (2.8%) Stroke 31% (–16-59) 34 (2.4%) Coronary revascularization 36% (9-55) 77 (5.5%) Acute coronary events 37% (17-52) p= (9.0%) Primary end point Hazard Ratio Risk Reduction (95% CI) Placebo* Event * N (% randomized) Favors Atorvastatin Favors Placebo Colhoun HM et al. Lancet. 2004;364: