1. Lipid Lowering Substudy Trial of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial JAMA 2002;288:2998-3007 ALLHAT- LLT

2. www. Clinical trial results.org 10,355 patients with moderate hypercholesterolemia  All patients enrolled in the ALLHAT antihypertensive trial  Fasting LDL-C level of 120-189 mg/dL with no known CHD or 100-129 mg/dL with known CHD  Fasting triglyceride levels <350 mg/dL  NHLBI funded trial 10,355 patients with moderate hypercholesterolemia  All patients enrolled in the ALLHAT antihypertensive trial  Fasting LDL-C level of 120-189 mg/dL with no known CHD or 100-129 mg/dL with known CHD  Fasting triglyceride levels <350 mg/dL  NHLBI funded trial Endpoints:  Primary – All-cause mortality Fatal coronary heart disease and nonfatal MI  Secondary – Fatal coronary heart disease and nonfatal MI, stroke, CHF, cancer  Mean follow-up 4.8 years Endpoints:  Primary – All-cause mortality Fatal coronary heart disease and nonfatal MI  Secondary – Fatal coronary heart disease and nonfatal MI, stroke, CHF, cancer  Mean follow-up 4.8 years ALLHAT- LLT JAMA 2002;288:2998-3007 Pravastatin 40 mg/day (n=5,170) Pravastatin 40 mg/day (n=5,170) Usual Care at discretion of primary care physician (n=5,185) Usual Care at discretion of primary care physician (n=5,185)

3. www. Clinical trial results.org All Cause Mortality RR = 0.99 p = 0.88 All Cause Mortality RR = 0.99 p = 0.88 ALLHAT- LLT: Clinical Endpoints Pravastatin Usual Care Fatal Heart Disease or Nonfatal MI RR = 0.91 p = 0.16 Fatal Heart Disease or Nonfatal MI RR = 0.91 p = 0.16 Stroke RR = 0.91 p = 0.31 Stroke RR = 0.91 p = 0.31 JAMA 2002;288:2998-3007 Pravastatin Usual Care Pravastatin Usual Care

4. www. Clinical trial results.org Pravastatin  17.2% Pravastatin  17.2% ALLHAT- LLT: Total Cholesterol Baseline 4 Year Follow-up Usual Care  7.6% Usual Care  7.6% mg/dL Baseline 4 Year Follow-up JAMA 2002;288:2998-3007 mg/dL

5. www. Clinical trial results.org Pravastatin  27.7% Pravastatin  27.7% ALLHAT- LLT: LDL Cholesterol Baseline 4 Year Follow-up Usual Care  11.0% Usual Care  11.0% mg/dL Baseline 4 Year Follow-up JAMA 2002;288:2998-3007 mg/dL

6. www. Clinical trial results.org ALLHAT- LLT: Summary Despite moderate reduction in cholesterol with pravastatin, there was no difference in mortality, CHD or stroke compared with usual care for moderate hypercholesterolemia –High crossover rate from usual care to statin treatment (8% at year 2 and 17% at year 4) may explain the only moderate difference in cholesterol reduction and the lack of clinical benefit between the two arms –A greater benefit was observed in blacks than in nonblacks with pravastatin for fatal heart disease or nonfatal MI endpoint (RR 0.73 vs 1.02, p=0.03) –Lack of clinical benefit with statin therapy contrasts with other large statin trials (4S, CARE, LIPID, and PROSPER) –Meta-analysis of 9 large statin trials including ALLHAT-LLT shows CHD events  27% and mortality  14% with statin therapy Despite moderate reduction in cholesterol with pravastatin, there was no difference in mortality, CHD or stroke compared with usual care for moderate hypercholesterolemia –High crossover rate from usual care to statin treatment (8% at year 2 and 17% at year 4) may explain the only moderate difference in cholesterol reduction and the lack of clinical benefit between the two arms –A greater benefit was observed in blacks than in nonblacks with pravastatin for fatal heart disease or nonfatal MI endpoint (RR 0.73 vs 1.02, p=0.03) –Lack of clinical benefit with statin therapy contrasts with other large statin trials (4S, CARE, LIPID, and PROSPER) –Meta-analysis of 9 large statin trials including ALLHAT-LLT shows CHD events  27% and mortality  14% with statin therapy