Feasibility of Treating Prehypertension with an Angiotensin-Receptor Blocker
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., M. Anthony Schork, Ph.D., for the Trial of Preventing Hypertension (TROPHY) Study Investigators
Background Prehypertension is considered a precursor of stage1 hypertension and a predictor of excessive cardiovascular risk.We investigated whether pharmacologic treatment of prehypertensionprevents or postpones stage 1 hypertension.
Methods Participants with repeated measurements of systolicpressure of 130 to 139 mm Hg and diastolic pressure of 89 mmHg or lower, or systolic pressure of 139 mm Hg or lower anddiastolic pressure of 85 to 89 mm Hg, were randomly assignedto receive two years of candesartan (Atacand, AstraZeneca) orplacebo, followed by two years of placebo for all. When a participantreached the study end point of stage 1 hypertension, treatmentwith antihypertensive agents was initiated. Both the candesartangroup and the placebo group were instructed to make changesin lifestyle to reduce blood pressure throughout the trial.
Results A total of 409 participants were randomly assigned tocandesartan, and 400 to placebo. Data on 772 participants (391in the candesartan group and 381 in the placebo group; meanage, 48.5 years; 59.6 percent men) were available for analysis.During the first two years, hypertension developed in 154 participantsin the placebo group and 53 of those in the candesartan group(relative risk reduction, 66.3 percent; P<0.001). After fouryears, hypertension had developed in 240 participants in theplacebo group and 208 of those in the candesartan group (relativerisk reduction, 15.6 percent; P<0.007). Serious adverse eventsoccurred in 3.5 percent of the participants assigned to candesartanand 5.9 percent of those receiving placebo.
Conclusions Over a period of four years, stage 1 hypertensiondeveloped in nearly two thirds of patients with untreated prehypertension(the placebo group). Treatment of prehypertension with candesartanappeared to be well tolerated and reduced the risk of incidenthypertension during the study period. Thus, treatment of prehypertensionappears to be feasible. (ClinicalTrials.gov number, NCT00227318
[ClinicalTrials.gov]
.)
Source Information
From the University of Michigan, Ann Arbor (S.J., N.K., M.A.S.); University of Texas Southwestern Medical Center at Dallas, Dallas (S.D.N.); Medical University of South Carolina, Charleston (B.M.E.); the State University of New York Downstate College of Medicine, Brooklyn (M.A.W.); AstraZeneca, Wilmington, Del. (E.L.M.); Rush University Medical Center, Chicago, (H.R.B.); Hennepin County Medical Center, Minneapolis, (R.H.G.); St. Luke's–Roosevelt Hospital Center, New York (F.H.M.); and University of Alabama at Birmingham, Birmingham (S.O.). This article was published at www.nejm.org on March 14, 2006.
Address reprint requests to Dr. Julius at the University of Michigan, Department of Internal Medicine, Division of Cardiovascular Medicine, 24 Frank Lloyd Wright Dr., Lobby M, 3rd Fl., Ann Arbor, MI 48106, or at sjulius{at}umich.edu.
Treating Prehypertension
Grassi D. G., Lopez-Plasencia Y., Amela-Peris R., Garcia-Delgado Y., Conen D., Martina B., Baumann M., van den Born B.-J., Julius S., Nesbitt S. D., Egan B. M.
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N Engl J Med 2006;
355:416-418, Jul 27, 2006.
Correspondence
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