TROPHY TRial Of Preventing HYpertension

High-normal BP increases CV risk Vasan RS et al. N Engl J Med. 2001;345: Incidence of CV events in women Cumulative incidence (%) and 95% CI High-normal BP 130–139/85–89 mm Hg Normal BP 120–129/80–84 mm Hg Optimal BP <120/<80 mm Hg 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:

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: *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: Candesartan 16 mg qd n = 391 Patients with untreated prehypertension Ages 30–65 years N = 772 Placebo n = 381 Placebo Years 3 & 4 Study end points: Development of HTN at years 2 and 4 Randomized Double-blind Years 1 & 2

TROPHY: Baseline characteristics Candesartan n = 391 Placebo n = 381 Age (years) Male (%) Race (%) White Black Other BMI (kg/m 2 ) N = 772 Julius S et al. N Engl J Med. 2006;354:

Candesartan n = 391 Placebo n = 381 Blood pressure (mm Hg)133.9/ /84.8 Total-C (mg/dL) Triglycerides (mg/dL) HDL-C (mg/dL) Glucose (mg/dL) TROPHY: Baseline laboratory values N = 772 Julius S et al. N Engl J Med. 2006;354:

TROPHY: Reduction in new-onset hypertension  66%*  16%* Candesartan vs PlaceboPlacebo only *Relative risk reduction † P < 0.001; ‡ P = Julius S et al. N Engl J Med. 2006;354: † ‡ N = 772

TROPHY: Reduction in new-onset hypertension N = 772 Cumulative incidence (%) Julius S et al. N Engl J Med. 2006;354: RRR 16% HR = 0.84 (0.75–0.95) P = RRR 66% HR = 0.34 (0.25–0.44) P < Number of patients without HTN Candesartan Placebo PlaceboCandesartan 16 mg qd Candesartan vs placebo Placebo only 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: Placebo Candesartan SBP (mm Hg) Difference (mm Hg) Time (months) Candesartan vs PlaceboPlacebo only SBP difference

TROPHY: Incidence of adverse events Adverse events (AE) Candesartan n = 396 (%) Placebo n = 391 (%) Any serious AE14 (3.5)23 (5.9) Cardiovascular1 (0.3)6 (1.5) Gastrointestinal4 (1.0)2 (0.5) Headache85 (21.5)74 (18.9) Dizziness41 (10.4)33 (8.4) Hypotension4 (1.0)2 (0.5) Angioedema01 (0.3) Julius S et al. N Engl J Med. 2006;354:

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:

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: