1. 1 SECOND AUSTRALIAN NATIONAL BLOOD PRESSURE STUDY (ANBP-2) Enalapril/ACEI vs. HCTZ, n = 6,083 Randomized, open-label (blinded endpoint review) All CV events or death from any cause –HR = 0.89 (0.79-1.00), p=0.05 First events –CVD: HR = 0.88 (0.77-1.01), p = 0.07 –CHD: HR = 0.86 (0.70-1.06), p = 0.16 –Stroke: HR = 1.02 (0.78-1.33), p = 0.91 –HF: HR = 0.85 (0.62-1.18), p = 0.33 NEJM 2003;348:583-92

2. 2 SECOND AUSTRALIAN NATIONAL BLOOD PRESSURE STUDY (ANBP-2) Results by Gender NEJM 2003;348:583-92 HR (95% CI)p p for interaction All CVD / Total Mortality Men0.83 (0.71-0.97)0.02 0.15 Women1.00 (0.83-1.21)0.98 1 st CVD / Total Mortality Men0.83 (0.71-0.97)0.02 0.14 Women1.00 (0.83-1.20)0.98

3. 3 ALLHAT vs. ANBP2 Baseline Characteristics ALLHATANBP2 N24,3096,083 Women, %4751 Black, %35-- Mean age, years66.971.9 Baseline BP, mm Hg*146 / 84168 / 91 Previous treatment, %9062 BMI, kg/m 2 3027 Current smoking, %227 Diabetes, %367 * ALLHAT: no washout, ANBP2: after washout

4. 4 ALLHAT vs. ANBP2 Blood Pressure & Endpoints ALLHAT Total ANBP2 N (ACE / diuretic)9,054 / 15,2553,044 / 3,039 1-year BP delta (ACE - diuretic) 3 / 12 / 0 1 st CVD / Total Mortality 1.07 (1.03-1.12) p=.002 0.89 (0.79-1.01) p=.06 1 st CHD1.05 (0.98-1.11) p=.18 0.86 (0.70-1.06) p=.16 Heart Failure1.19 (1.07-1.31) p<.001 0.85 (0.62-1.18) p=.85 Stroke1.15 (1.02-1.30) p=.02 1.02 (0.78-1.33) p=.91

5. 5 ALLHAT vs. ANBP-2 Randomized double-blind vs. PROBE design ACEI vs. thiazide-type diuretic, n = 24,309 vs. 6,083 Number of patients with events –CVD: n = 6,455 vs. 823 –CHD: n = 3,956 vs. 368 –Stroke: n = 1,132 vs. 219 –Heart failure: n = 1,482 vs. 147 Treatment differences consistent across gender subgroup vs. differences noted only in men SBP slightly lower with diuretic in both trials

6. 6 CONCLUSIONS – ALLHAT vs. ANBP2 ALLHAT had 4 times the number of participants, 5-10 times more endpoints, and a double-blinded design Even so, the upper 95% CI of ANPB2 compatible with ALLHAT point estimates of relative risk: –Coronary events –Stroke –Heart failure ALLHAT - no ACE advantage for any outcomes in either men or women, and heart failure outcomes were worse compared to the diuretic. While the aggregate analyses will have to await those planned by the Blood Pressure Lowering Treatment Trialists’ Collaboration, the totality of trial evidence from ALLHAT and other individual trials favors the diuretic.