1. VBWG Growth in heart disease, 2000–2050 Deaths Population 35.0 30.0 25.0 20.0 15.0 10.0 200020102020203020402050 Foot DK et al. J Am Coll Cardiol. 2000;35:1067-81. Growth by decade (%) 5.0 Prevalence 0.0 Year

2. 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;44:398-404. 7.7 6.0 50.0 65.2 0 10 20 30 40 50 60 70 80 42.3 59.2 Hypertensive* History of hypertension** Hypertensive adults (millions) 1988–19941999–2000 P < 0.001

3. 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;292:2217-26. CAMELOT: Optimal BP control in CAD patients

4. VBWG CAMELOT: Baseline characteristics and concomitant medications Placebo (n = 655) Amlodipine (n = 663) Enalapril (n = 673)P Age, mean (y)57.257.358.50.02 Men (%)73.076.371.90.16 White race (%)89.089.489.30.97 Body mass index, mean (kg/m 2 )29.729.929.70.72 LDL-C, mean (mg/dL)1001041010.04 Blood pressure, mean (mm Hg) Systolic128.9129.5128.90.76 Diastolic77.677.777.20.54 Concomitant medications Statin (%)84.383.181.70.46 Diuretic (%)33.432.126.80.02  -Blocker (%) 78.874.274.70.11 Aspirin (%)95.494.494.70.69 Nissen SE et al. JAMA. 2004;292:2217-26.

5. VBWG CAMELOT: Similar BP reductions from baseline with amlodipine and enalapril Nissen SE et al. JAMA. 2004;292:2217-26. PlaceboAmlodipineEnalapril Diastolic BPSystolic BP Months 72 80 78 76 74 013691215182124 122 132 130 128 124 0136912151821 24 126 120 118 mm Hg P < 0.001

6. VBWG No. at risk Placebo655588558525488 Enalapril673608572553529 Amlodipine663623599574535 CAMELOT: 31% Reduction in primary outcome with amlodipine compared to standard care Nissen SE et al. JAMA. 2004;292:2217-26. Primary outcome = incidence of CV events Cumulative CV events (proportion) 0 0.25 0.20 0.10 0.05 612 1824 Months 0.15 0 PlaceboAmlodipineEnalapril 31% Relative risk reduction P = 0.003

7. VBWG FavorsFavors amlodipineplacebo RRR (%) 33.9 4.1 22.9 49.3 26.8 42.8 32.2 29.6 30.9 CAMELOT: Reduction in primary outcome with amlodipine, by subgroup Nissen SE et al. JAMA. 2004;292:2217-26. 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 0.250.50.751.01.251.5 Hazard ratio (95% CI) P 0.002 0.91 0.07 0.006 0.03 0.04 0.003

8. 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;292:2217-26. *P = 0.001 vs baseline † P < 0.001 vs baseline 1.3 2.3 0.8 0.5 0.2 0.0 0.5 1.0 1.5 2.0 2.5 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

9. 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 (%) 2.5 2.0 1.0 Change in systolic BP (mm Hg) 1.5 0.5 0 –1.0 –0.5 –1.5 –2.0 –30–40–20–1001020 95% CI Amlodipine and enalapril groups 95% CI Nissen SE et al. JAMA. 2004;292:2217-26. Progression Regression

10. VBWG 180 170 160 150 140 130 120 110 100 90 80 60 70 0612182430364248 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;290:2805-15. Months CAS112678558863977587842572136591458796 NCAS113098573869477107850583436791473817 Calcium antagonist strategy (CAS) Noncalcium antagonist strategy (NCAS) No. of patients

11. 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 CAS11,26710,92110,71610,51210,00866123738156897439335 NCAS11,30910,99110,78510,53610,04866043706156396039033 Cumulative events (%) 25 20 15 10 5 0 06121824303642485460 Months Primary outcome = first occurrence of death, nonfatal MI, or nonfatal stroke P = 0.057 Pepine CJ et al. JAMA. 2003;290:2805-15.

12. 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;292:2217-26.