VBWG

Growth in heart disease, 2000–2050

Deaths Population

35.0

30.0

25.0

20.0

15.0

10.0

2000 2010 2020 2030 2040 2050

Foot DK et al. J Am Coll Cardiol. 2000;35:1067-81.

Growthby decade

(%)

5.0

Prevalence

0.0

Year

VBWG

Burden of adult hypertensionComparison 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)

1988–1994 1999–2000

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

Primaryoutcome: 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

VBWG

CAMELOT: Baseline characteristics and concomitant medications

Placebo

(n = 655)

Amlodipine

(n = 663)

Enalapril

(n = 673) P

Age, mean (y) 57.2 57.3 58.5 0.02

Men (%) 73.0 76.3 71.9 0.16

White race (%) 89.0 89.4 89.3 0.97

Body mass index, mean (kg/m2) 29.7 29.9 29.7 0.72

LDL-C, mean (mg/dL) 100 104 101 0.04

Blood pressure, mean (mm Hg)

Systolic 128.9 129.5 128.9 0.76

Diastolic 77.6 77.7 77.2 0.54

Concomitant medications

Statin (%) 84.3 83.1 81.7 0.46

Diuretic (%) 33.4 32.1 26.8 0.02

-Blocker (%) 78.8 74.2 74.7 0.11

Aspirin (%) 95.4 94.4 94.7 0.69

Nissen SE et al. JAMA. 2004;292:2217-26.

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CAMELOT: Similar BP reductions frombaseline with amlodipine and enalapril

Nissen SE et al. JAMA. 2004;292:2217-26.

Placebo Amlodipine Enalapril

Diastolic BPSystolic BP

Months Months

72

80

78

76

74

0 1 3 6 9 12 15 18 21 24

122

132

130

128

124

0 1 3 6 9 12 15 18 21 24

126

120

118

mm HgP < 0.001

P < 0.001

VBWG

No. at risk

Placebo 655 588 558 525 488

Enalapril 673 608 572 553 529

Amlodipine 663 623 599 574 535

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

6 12 18 24Months

0.15

0

Placebo AmlodipineEnalapril

31% Relative risk reductionP = 0.003

VBWG

Favors Favors amlodipine placebo RRR (%)

33.9 4.1

22.9 49.3

26.8 42.8

32.2 29.6

30.9

CAMELOT: Reduction in primary outcomewith 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 statinWithout statin

Age, y<65≥65

SexMaleFemale

Systolic BP≤Mean>Mean

All patients

0.25 0.5 0.75 1.0 1.25 1.5

Hazard ratio (95% CI)

P

0.002 0.91

0.07 0.006

0.03 0.03

0.03 0.04

0.003

VBWG

CAMELOT: Slowed progression of atheroma with amlodipine and enalaprilAtheroma 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 0.8

0.5

0.20.0

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

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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 –10 0 10 20

95% CI

Amlodipine and enalapril groups

95% CI

Nissen SE et al. JAMA. 2004;292:2217-26.

Progression

Regression

VBWG

180170160150140

130120110

100

90

80

60

70

0 6 12 18 24 30 36 42 48

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

CAS 11267 8558 8639 7758 7842 5721 3659 1458 796

NCAS 11309 8573 8694 7710 7850 5834 3679 1473 817

Calcium antagonist strategy (CAS) Noncalcium antagonist strategy (NCAS)

No. of patients

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INVEST: Similar reduction in primary outcome with CAS and NCAS in CAD patients

Calcium antagonist strategy (CAS) Noncalcium antagonist strategy (NCAS)

No. at risk

CAS 11,267 10,921 10,716 10,512 10,008 6612 3738 1568 974 393 35

NCAS 11,309 10,991 10,785 10,536 10,048 6604 3706 1563 960 390 33

Cumulativeevents

(%)

25

20

15

10

5

00 6 12 18 24 30 36 42 48 54 60

Months

Primary outcome = first occurrence of death, nonfatal MI, or nonfatal stroke

P = 0.057

Pepine CJ et al. JAMA. 2003;290:2805-15.

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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.