VBWG Growth in heart disease, 2000–2050 Deaths Population Foot DK et al. J Am Coll Cardiol. 2000;35: Growth by decade (%) 5.0 Prevalence 0.0 Year

VBWG Burden of adult hypertension Comparison of NHANES data 1988–1994 and 1999–2000 *US adults with SBP ≥140 mm Hg, DBP ≥90 mm Hg, or using antihypertensive medication (conventional definition) **US adults not classified by conventional definition but told at least twice by a healthcare professional that they had high BP Fields LE et al. Hypertension. 2004;44: Hypertensive* History of hypertension** Hypertensive adults (millions) 1988– –2000 P < 0.001

VBWG Study design:Randomized, double-blind, multicenter, 24-month trial in patients with angiographically documented CAD (N = 1991) Treatment:Amlodipine (10 mg), enalapril (20 mg), or placebo added to background therapy with  -blockers and/or diuretics Primary outcome: Incidence of CV events for amlodipine vs placebo IVUS substudy:Measurement of atherosclerosis progression using IVUS (n = 274) Outcome:Change in percent atheroma volume Nissen SE et al. JAMA. 2004;292: CAMELOT: Optimal BP control in CAD patients

VBWG CAMELOT: Baseline characteristics and concomitant medications Placebo (n = 655) Amlodipine (n = 663) Enalapril (n = 673)P Age, mean (y) Men (%) White race (%) Body mass index, mean (kg/m 2 ) LDL-C, mean (mg/dL) Blood pressure, mean (mm Hg) Systolic Diastolic Concomitant medications Statin (%) Diuretic (%)  -Blocker (%) Aspirin (%) Nissen SE et al. JAMA. 2004;292:

VBWG CAMELOT: Similar BP reductions from baseline with amlodipine and enalapril Nissen SE et al. JAMA. 2004;292: PlaceboAmlodipineEnalapril Diastolic BPSystolic BP Months mm Hg P < 0.001

VBWG No. at risk Placebo Enalapril Amlodipine CAMELOT: 31% Reduction in primary outcome with amlodipine compared to standard care Nissen SE et al. JAMA. 2004;292: Primary outcome = incidence of CV events Cumulative CV events (proportion) Months PlaceboAmlodipineEnalapril 31% Relative risk reduction P = 0.003

VBWG FavorsFavors amlodipineplacebo RRR (%) CAMELOT: Reduction in primary outcome with amlodipine, by subgroup Nissen SE et al. JAMA. 2004;292: Box size indicates proportion of total study population (ie, smaller boxes have fewer patients relative to other subgroups). Lipid-lowering therapy With statin Without statin Age, y <65 ≥65 Sex Male Female Systolic BP ≤Mean >Mean All patients Hazard ratio (95% CI) P

VBWG CAMELOT: Slowed progression of atheroma with amlodipine and enalapril Atheroma volume measured using IVUS at baseline and 24 months (n = 274) Nissen SE et al. JAMA. 2004;292: *P = vs baseline † P < vs baseline Change in percent atheroma volume vs baseline (%) P = 0.02 Placebo (n = 95) Enalapril (n = 88) Amlodipine (n = 91) Placebo (n = 49) Enalapril (n = 40) Amlodipine (n = 47) † * Baseline systolic BP > meanAll patients

VBWG CAMELOT : Continuous relationship between rate of atheroma progression and change in SBP LOWESS = locally weighted scatterplot smoothing LOWESS plot for combined amlodipine and enalapril drug-treatment groups Change in percent atheroma volume (%) Change in systolic BP (mm Hg) –1.0 –0.5 –1.5 –2.0 –30–40–20– % CI Amlodipine and enalapril groups 95% CI Nissen SE et al. JAMA. 2004;292: Progression Regression

VBWG INVEST: Similar BP control with CAS and NCAS in hypertensive CAD patients Systolic BP (mm Hg) Diastolic BP (mm Hg) Pepine CJ et al. JAMA. 2003;290: Months CAS NCAS Calcium antagonist strategy (CAS) Noncalcium antagonist strategy (NCAS) No. of patients

VBWG INVEST: Similar reduction in primary outcome with CAS and NCAS in CAD patients Calcium antagonist strategy (CAS) Noncalcium antagonist strategy (NCAS) No. at risk CAS11,26710,92110,71610,51210, NCAS11,30910,99110,78510,53610, Cumulative events (%) Months Primary outcome = first occurrence of death, nonfatal MI, or nonfatal stroke P = Pepine CJ et al. JAMA. 2003;290:

VBWG CAMELOT: Conclusions In CAD patients with “normal” BP, amlodipine demonstrated a significant reduction in ischemia-related CV events. IVUS substudy showed that progression of coronary atherosclerosis may be minimized or slowed when BP is further reduced below the so-called normal level. Results suggest optimal BP range for CAD patients may be substantially lower than indicated by current guidelines. Nissen SE et al. JAMA. 2004;292: