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TROPHY
TRial Of Preventing HYpertension
High-normal BP increases CV risk
Vasan RS et al. N Engl J Med. 2001;345:1291-7.
Incidence of CV events in women
Cumulative incidence (%)
and 95% CI
High-normal BP130–139/85–89 mm Hg
Normal BP 120–129/80–84 mm Hg
Optimal BP <120/<80 mm Hg
10
8
6
4
2
0
0 2 4 6 8 10 12
Time (years)
Framingham Heart Study
TROPHY: Background
• Framingham, MRFIT, and other studies indicate that prehypertension is a strong predictor of excessive cardiovascular risk
• These data illustrate the need to identify and potentially treat patients with prehypertension
• Hypertension (HTN) is a progressive and self-accelerating condition
• Vascular abnormalities occur long before the onset of clinical disease
Julius S et al. N Engl J Med. 2006;354:1685-97.
TROPHY: Study objectives
• TROPHY evaluated 2 years of treatment with candesartan in individuals with prehypertension*
• Primary objective:– Determine if the incidence of HTN can be reduced for up to
2 years after discontinuation of active treatment
• Secondary objective:– Evaluate the incidence of HTN during 2 years of treatment
with candesartan or placebo
Julius S et al. N Engl J Med. 2006;354:1685-97.*Average BP 130–139/≤89 mm Hg; or ≤139/85–89 mm Hg
TROPHY: Study design
Julius S et al. N Engl J Med. 2006;354:1685-97.
Candesartan 16 mg qd
n = 391
Patients with untreated prehypertensionAges 30–65 years
N = 772
Placebo n = 381
PlaceboYears 3 & 4
Study end points: Development of HTN at years 2 and 4
RandomizedDouble-blindYears 1 & 2
TROPHY: Baseline characteristics
Candesartann = 391
Placebon = 381
Age (years) 48.6 48.3
Male (%) 59.1 60.1
Race (%)
White 79.8 84.3
Black 12.3 8.1
Other 7.9 7.6
BMI (kg/m2) 29.9 30.0
N = 772
Julius S et al. N Engl J Med. 2006;354:1685-97.
Candesartann = 391
Placebon = 381
Blood pressure (mm Hg) 133.9/84.8 134.1/84.8
Total-C (mg/dL) 202.9 205.7
Triglycerides (mg/dL) 145.8 159.8
HDL-C (mg/dL) 48.9 49.2
Glucose (mg/dL) 95.5 95.9
TROPHY: Baseline laboratory values
N = 772
Julius S et al. N Engl J Med. 2006;354:1685-97.
40.4
63.0
13.6
53.2
0
20
40
60
80
Year 2 Year 4
Patients (%)
Placebo Candesartan 16 mg qd
TROPHY: Reduction in new-onset hypertension
66%*
16%*
Candesartan vs Placebo Placebo only
*Relative risk reduction†P < 0.001; ‡P = 0.007 Julius S et al. N Engl J Med. 2006;354:1685-97.
†
‡
N = 772
TROPHY: Reduction in new-onset hypertension
N = 772
Cumulative incidence
(%)
Julius S et al. N Engl J Med. 2006;354:1685-97.
RRR 16%HR = 0.84 (0.75–0.95)P = 0.007
RRR 66%HR = 0.34 (0.25–0.44)P < 0.001
Number of patients without HTN
391381
356269
309184
191118
CandesartanPlacebo
12785
Placebo Candesartan 16 mg qd
Candesartan vs placebo
Placebo only
100
80
60
40
20
0
0 1 2 3 4
Study year
TROPHY: Blood pressure by treatment group
• After 2 years:↓SBP ~10 mm Hg
• At study end: ↓SBP 2.0 mm Hg (P = 0.037)
Julius S et al. N Engl J Med. 2006;354:1685-97.
PlaceboCandesartan
SBP (mm Hg)
Difference (mm Hg)
00 6 12 18 24 30 36 42 48
Time (months)
140
130
120
90
30
0
-10
-20Candesartan vs Placebo Placebo only
SBP difference
TROPHY: Incidence of adverse events
Adverse events (AE)
Candesartan n = 396
(%)
Placebon = 391
(%)
Any serious AE 14 (3.5) 23 (5.9)
Cardiovascular 1 (0.3) 6 (1.5)
Gastrointestinal 4 (1.0) 2 (0.5)
Headache 85 (21.5) 74 (18.9)
Dizziness 41 (10.4) 33 (8.4)
Hypotension 4 (1.0) 2 (0.5)
Angioedema 0 1 (0.3)
Julius S et al. N Engl J Med. 2006;354:1685-97.
TROPHY: Summary
• Efficacy– Candesartan significantly delayed new-onset HTN vs placebo:
• Relative risk reduction: 66% (year 2); 16% (year 4)• Absolute reduction of new-onset HTN: 26.8% (year 2); 9.8% (year 4)• New-onset HTN at 2 years: 13.6% vs 40.4%
• Safety– Candesartan was safe and well tolerated– Serious AE rates: 3.5% (candesartan) vs 5.9% (placebo)
Julius S et al. N Engl J Med. 2006;354:1685-97.
TROPHY: Implications
• Vascular abnormalities occur long before the onset of clinical disease
• Aggressive BP-lowering with candesartan can reduce the incidence of HTN in prehypertensive patients at risk for CV disease
Julius S et al. N Engl J Med. 2006;354:1685-97.
