ASCOT and Steno-2: Aggressive risk reduction benefits two different patient populations *Composite of CV death, nonfatal MI or stroke, revascularization, and amputation, P < † Fatal CHD and nonfatal MI (including silent MI), P < * † Gaede P et al. N Engl J. Med. 2003;348: 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

ASCOT: Patients had hypertension and ≥3 other risk factors, fitting a common clinical profile Sever PS et al. J Hypertens. 2001;19: Sever PS et al. Lancet. 2003;361: LVH = left ventricular hypertrophy Patients with risk factor (%) 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

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

ASCOT: Risk reductions with the amlodipine/perindopril regimen Secondary endpoints Nonfatal MI (excluding silent) fatal CHD Total coronary endpoint Total CV events and procedures All-cause mortality CV mortality Fatal/nonfatal stroke Fatal/nonfatal HF Tertiary endpoints Development of diabetes Development of renal impairment Rate/1000 patient-years Amlodipine-based* (n = 9639) Atenolol-based † (n = 9618) <0.05 <0.01 < < <0.001 NS < <0.05 P Amlodipine-based better Atenolol-based better Dahlöf B et al. Lancet. 2005;366: *Amlodipine 5–10 mg ± perindopril 4–8 mg † Atenolol 50–100 mg ± bendroflumethiazide 1.25–2.5 mg Unadjusted hazard ratio

CAFE asked whether newer vs older BP treatments have differing effects on central aortic BP N = 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: *Newer antihypertensive regimen † Older antihypertensive regimen

CAFE: Central aortic pressure is lower with the amlodipine/perindopril regimen Amlodipine ± perindopril Atenolol ± bendroflumethiazide Time (years) mm Hg Brachial SBP Central aortic SBP CAFE Investigators. Circulation. 2006;113:

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

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) ( ) ≥231 (≥6.0) Sever PS et al. Lancet. 2003;361:

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) Events/1000 patient-years NS P < P (interaction between lipid and BP lowering) = *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 † P = 0.015