Trial of Preventing Hypertension - TROPHY

Description:

The goal of the trial was to evaluate treatment with candesartan compared with placebo on the incidence of new hypertension among patients with prehypertension.

Study Design

Study Design:

Patients Screened: 1,904
Patients Enrolled: 809
Mean Follow Up: 4 years
Mean Patient Age: Mean age 48 years
Female: 40

Patient Populations:

Age 30-65 years with blood pressure at study entry in the high-normal range (systolic blood pressure [SBP] 130-139 mm Hg and diastolic blood pressure [DBP] ≤89 mm Hg, or SBP ≤139 mm Hg and DBP 85-89 mm Hg) and not currently treated

Primary Endpoints:

Incidence of hypertension for up to 2 years after the discontinuation of active treatment with candesartan

Secondary Endpoints:

Incidence of hypertension during 2 years of treatment with candesartan or placebo

Drug/Procedures Used:

Patients were randomized in a double-blind manner to treatment with candesartan (16 mg daily; n = 391) or matching placebo (n = 381) for 2 years. After 2 years, all patients were treated with placebo for 2 additional years. Antihypertensive medication was started if a patient met the criteria for hypertension during the study.

Principal Findings:

Blood pressure measured at baseline at the clinic was 131/85 mm Hg. Hypertension developed less frequently during the first 2 years of the study in patients randomized to candesartan (13.6% vs. 40.4%, relative risk [RR] 0.34, p < 0.001). Likewise, at the 4-year visit when all patients were treated with placebo, hypertension had developed less frequently in the group initially randomized to candesartan (53.2% vs. 63.0%, RR 0.84, p = 0.007) for an overall trial relative risk of hypertension of 0.58 for candesartan (p < 0.001).

Results were similar across several key subgroups. The median time to onset of hypertension was 3.3 years in the candesartan group and 2.2 years in the placebo group. Blood pressure in the candesartan group was reduced by study end for both systolic (2.0 mm Hg reduction, p = 0.037) and diastolic (1.1 mm Hg, p = 0.073). Serious adverse events were low in both groups (3.5% for candesartan vs. 5.9% for placebo).

Interpretation:

Among patients with prehypertension, treatment with the angiotensin receptor blocker candesartan was associated with a reduction in the development of hypertension through 4 years compared with placebo, although the reduction was most evident during the 2 years that patients were on active therapy.

The findings of the present trial of reducing new onset hypertension are provocative, but the widespread clinical implications are unknown. Larger trials would be needed to further evaluate safety, as well as to look at longer term use of these medications in patients with prehypertension. Reductions in blood pressure were observed in the candesartan group, but it is unclear if these reductions account for all of the improvements in new hypertension shown in the trial or if other pleotropic effects may have played a role.

References:

Presented by Dr. Stevo Julius at the March 2006 ACC Annual Scientific Session, Atlanta, GA.

Julius S, Nesbitt SD, Egan BM, et al. Feasibility of treating prehypertension with an angiotensin-receptor blocker. N Engl J Med 2006;354:1685-97.

Clinical Topics: Prevention, Vascular Medicine, Novel Agents, Hypertension

Keywords: Risk, Angiotensin II Type 1 Receptor Blockers, Benzimidazoles, Prehypertension, Blood Pressure, Tetrazoles, Hypertension


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