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Treating Prehypertension with an Angiotensin-Receptor Blocker Reduces the Development of Hypertension

April 26, 2006

By: Jennifer Tartaglia MS and Asher Kimchi M.D.

Ann Arbor, Michigan Prehypertension is considered a precursor of hypertension. The Trial of Preventing Hypertension (TROPHY) in the United States investigated whether two years of treatment with candesartan could reduce the incidence of hypertension in prehypertensive patients. The trial found that candesartan treatment reduced the incident hypertension in the prehypertensive participants. These results were published in the April 20, 2006 issue of the New England Journal of Medicine.

The study was a randomized, double-blind, placebo-controlled trial that collected data on 772 participants. Enrolled participants were 30 65 years of age with high-normal blood pressure at the time of enrollment. These participants were randomly assigned to receive candesartan (16mg daily) for two years followed by placebo for two years or to receive placebo for all four years. Endpoint was established hypertension at which time participants were offered antihypertensive medications. Cumulative incidence of hypertension was analyzed at two and four years into the treatment.

The primary study findings were that 13.6% of patients in the candesartan group developed hypertension as compared to 40.1% in the placebo group during the first two years (relative risk, 0.34; 95% confidence interval, 0.25-0.44; P<0.001). After four years, 208 patients (53.2%) in the candesartan group developed hypertension, while 240 participants (63.0%) in the placebo group progressed to hypertension (relative risk 0.84; 95% confidence interval, 0.75-0.95; P=0.007). In addition, rates of serious adverse events were low with 3.5% of participants in the candesartan group and 5.9% of participants in the placebo group experiencing adverse effects in the first two years.

The increase in blood pressure from prehypertension to established hypertension is facilitated by evolving arteriolar hypertrophy and endothelial dysfunction. Angiotensin-receptor blockers have been reported to cause regression of arteriolar hypertrophy, and thus were thought by the investigators to be helpful in preventing or prolonging the incidence of hypertension in prehypertensive patients.

The findings presented in this study suggest that monotherapy with candesartan in prehypertensive individuals suppresses new onset hypertension. However, the authors do not recommend candesartan treatment for people with prehypertension until long-term studies and cost evaluations have been performed.

Authors: Stevo Julius, M.D., Sc.D., Shawna D. Nesbitt, M.D., Brent M. Egan, M.D., Michael A. Weber, M.D., Eric L. Michelson, M.D., Niko Kaciroti, Ph.D., Henry R. Black, M.D., Richard H. Grimm, Jr., M.D., Ph.D., Franz H. Messerli, M.D., Suzanne Oparil, M.D., and M. Anthony Schork, Ph.D., for the Trial of Preventing Hypertension (TROPHY) Study Investigators.


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