1. ASCOT and Steno-2: Aggressive risk reduction benefits two different patient populations *Composite of CV death, nonfatal MI or stroke, revascularization, and amputation, P < 0.001 † Fatal CHD and nonfatal MI (including silent MI), P < 0.0001 * † Gaede P et al. N Engl J. Med. 2003;348:383-93. Sever PS et al. Circulation. 2005; 112(suppl II):II-134. Abstract 730. Relative risk reduction (%) Steno-2: Diabetes + microalbuminuria Intensive target-driven reduction of BP, total-C, TG, A1C vs usual care 7.8 years ASCOT-LLA: Hypertension + ≥3 CV risk factors, total-C ≤250 mg/dL Amlodipine/perindopril + atorvastatin vs placebo 3.5 years Steno-2ASCOT-LLA

2. ASCOT: Patients had hypertension and ≥3 other risk factors, fitting a common clinical profile Sever PS et al. J Hypertens. 2001;19:1139-47. Sever PS et al. Lancet. 2003;361:1149-58. LVH = left ventricular hypertrophy Patients with risk factor (%) 0102030405060708090100 Hypertension Aged ≥55 years Male Microalbuminuria/proteinuria Smoker Family history of CHD Plasma total-C:HDL-C ≥6 Type 2 diabetes Certain ECG abnormalities LVH Prior cerebrovascular events Peripheral vascular disease

3. ASCOT-BPLA: Reduction in primary outcome (nonfatal MI and fatal CHD) Proportion of events (%) 6 2 4 0 1234 8 10 560 Time since randomization (years) RRR = 10% HR = 0.90 (95% CI, 0.79–1.02) P = 0.1052 Atenolol-based regimen* Amlodipine-based regimen † Dahlöf B et al. Lancet. 2005;366:895-906. *Atenolol 50–100 mg ± bendroflumethiazide 1.25–2.5 mg † Amlodipine 5–10 mg ± perindopril 4–8 mg

4. ASCOT: Risk reductions with the amlodipine/perindopril regimen Secondary endpoints Nonfatal MI (excluding silent)7.4 8.5 + fatal CHD Total coronary endpoint14.6 16.8 Total CV events and procedures 27.4 32.8 All-cause mortality13.9 15.5 CV mortality4.9 6.5 Fatal/nonfatal stroke6.2 8.1 Fatal/nonfatal HF2.5 3.0 Tertiary endpoints Development of diabetes11.0 15.9 Development of renal impairment7.7 9.1 Rate/1000 patient-years Amlodipine-based* (n = 9639) Atenolol-based † (n = 9618) <0.05 <0.01 <0.0001 <0.05 0.001 <0.001 NS <0.0001 <0.05 P Amlodipine-based better Atenolol-based better 0.500.751.001.502.00 Dahlöf B et al. Lancet. 2005;366:895-906. *Amlodipine 5–10 mg ± perindopril 4–8 mg † Atenolol 50–100 mg ± bendroflumethiazide 1.25–2.5 mg Unadjusted hazard ratio

5. CAFE asked whether newer vs older BP treatments have differing effects on central aortic BP N = 2199 5 UK ASCOT centers N = 2073 Evaluable for tonometry n = 126 Excluded: HR irregularity Poor waveforms n = 1042 Amlodipine ± perindopril* n = 1031 Atenolol ± bendroflumethiazide † n = 1042 Intent-to-treat n = 1038 Complete information n = 1031 Intent-to-treat n = 1030 Complete information CAFE Investigators. Circulation. 2006;113:1213-25. *Newer antihypertensive regimen † Older antihypertensive regimen

6. CAFE: Central aortic pressure is lower with the amlodipine/perindopril regimen Amlodipine ± perindopril Atenolol ± bendroflumethiazide 140 135 130 125 120 115 00.511.522.533.544.555.56 Time (years) mm Hg Brachial SBP Central aortic SBP CAFE Investigators. Circulation. 2006;113:1213-25.

7. CAFE: Lesser ability of β-blockers to reduce augmentation wave P < 0.0001 Amlodipine ± perindopril Atenolol ± bendroflumethiazide CAFE Investigators. Circulation. 2006;113:1213-25.

8. ASCOT: Lipid lowering is beneficial regardless of baseline cholesterol level Total-C range mg/dL (mmol/L) Hazard ratio for primary endpointP value <193 (<5.0)0.630.098 193-230 (5.0-5.99)0.620.011 ≥231 (≥6.0)0.690.084 Sever PS et al. Lancet. 2003;361:1149-58.

9. Fatal CHD and nonfatal MI ASCOT: Greater gain with statin + CCB/ACE inhibitor vs statin + β-blocker/diuretic Atenolol* Amlodipine + Atorvastatin (10 mg) - Atorvastatin (+ placebo) 9 9.8 7.5 4.6 0 1 2 3 4 5 6 7 8 9 10 Events/1000 patient-years NS P < 0.0001 P (interaction between lipid and BP lowering) = 0.025 *Atenolol ± bendroflumethiazide † Amlodipine ± perindopril Sever PS et al. Circulation. 2005; 112(suppl II):II-134. Abstract 730. Sever PS et al. AHA Scientific Sessions. Nov 2005. † P = 0.015