Chlorthalidone, antenolol, and weight-loss diet lowered diastolic blood pressure
ACP J Club. 1991 May-June;114:69. doi:10.7326/ACPJC-1991-114-3-069
Langford HG, Davis BR, Blaufox D, et al. Effect of drug and diet treatment of mild hypertension on diastolic blood pressure. Hypertension. 1991;17:210-7.
To assess treatment of mild hypertension with a thiazide (chlorthalidone), a β-blocker (atenolol), a weight-loss diet, and a low-sodium/high-potassium diet, alone and in combination.
Randomized controlled trial (the Trial of Antihypertensive Interventions and Medications [TAIM]), with data reported from the initial 6 months of treatment. Medications were given double-blind.
Volunteers were recruited from communities near the 3 participating U.S. medical school clinics.
10 148 volunteers between 21 and 65 years old were screened. Entry criteria included an untreated diastolic blood pressure between 90 and 100 mm Hg and weight between 110% and 160% of ideal weight. Exclusion criteria were evidence of myocardial infarction, stroke, or bronchial asthma; creatinine level ≥ 180 µmol/L; insulin-dependent diabetes; allergy to thiazide or β-blocker; pregnancy; and probable noncompliance. 878 people were randomly assigned to treatment.
Each patient was assigned to 1 of 3 drug regimens (chlorthalidone, 25 mg; atenolol, 50 mg; placebo) and to 1 of 3 diet groups (weight-loss diet, low-sodium/high-potassium diet, usual diet), for a total of 9 intervention groups.
Main outcome measure
6-month change in diastolic blood pressure.
A P value < 0.0036 was considered to be significant. 787 patients (90%) had data available on blood pressure at 6 months. Patients in the weight-loss-diet group lost an average of 4.7 kg. Patients in the low-sodium/high-potassium diet group had an average decrease in urinary sodium of 27 mmol/d and an average increase in urinary potassium of 11 mmol/d. The weight-loss diet lowered blood pressure more than usual diet (P = 0.001), but the low-sodium/high-potassium diet did not (P = 0.3). Both chlorthalidone and atenolol lowered blood pressure more than placebo (for both P < 0.001), but neither was better than the other (P = 0.4). Atenolol reduced blood pressure more than a low-sodium diet (P = 0.001). When combined with weight loss, chlorthalidone therapy lowered diastolic blood pressure more than chlorthalidone alone (P = 0.002).
Diastolic blood pressure was lowered by chlorthalidone or atenolol compared with placebo and by weight-loss diet compared with usual diet. Weight loss augmented the effect of chlorthalidone, but not that of atenolol. The low-sodium/high-potassium diet was not effective in this trial.
Sources of funding: National Heart, Lung, and Blood Institute and ICI Americas, Inc.
Address for reprint: Dr. B.R. Davis, The University of Texas, School of Public Health, 1200 Herman Pressler Street, Suite 801, Houston, TX 77030, USA.
The lead author, Herb Langford, died before this first report of the TAIM study was published. He made many important contributions to our understanding of the management of hypertension and will be missed by his students and friends around the world.
In this ambitious study, 9 separate groups were studied in a factorial design. When executed as planned, such studies provide information about single interventions, their relative effects, and, most important, their combinations. The validity of these studies, however, depends on 2 factors. First, no interactions should occur between the treatment groups (for example, the combined effect of atenolol and weight-loss diet should not differ from the sum of their individual effects). Second, participants should comply with their assigned treatments. No important interaction was detected in the study, but the sample size was small for detecting such interactions. 20% of the participants assigned to placebo, but only 3% of patients receiving active medication, required additional medication by 6 months. This imbalance would underestimate the differences in treatment effects, a bias that is acceptable when the results are positive, as in this study.
This early report has 2 messages. First, a weight-reduction program for overweight patients enhances the antihypertensive effect of diuretics and, in a regression analysis, appears to lower blood pressure on its own. (Other studies differ in their conclusions about the value of weight reduction alone.) Second, a low-sodium/high-potassium diet program is not worthwhile (at least, not among patients with relatively low sodium intake to begin with, as in this study). If the number of patients who need additional medication does not increase too much, the longer-term results of this study will be of great interest.
R. Brian Haynes, MD, PhD
McMaster UniversityHamilton, Ontario, Canada
Addendum added in 1996:
Results of Phase II of the TAIM study, including longer-term follow-up, have been reported (1, 2). In 1 of the reports (1), weight reduction was effective as monotherapy or in combination with either thiazide diuretics or β-blockers. In the second report (2), sole use of a low-sodium/high-potassium diet was of no benefit. Unfortunately, follow-up in the Phase II study was complete for only 77% of patients, missing the 80% cut off for abstracting in ACP Journal Club.
1. Davis BR, Blaufax D, Oberman A, et al. Reduction in long-term antihypertensive medication requirements. Effects of weight reduction by dietary intervention in overweight persons with mild hypertension. Arch Intern Med. 1993;153:1773-82.
2. Davis BR, Aberman A, Blaufax MD, et al. Lack of effectiveness of a low-sodium/high-potassium diet in reducing antihypertensive medication requirements in overweight persons with mild hypertension. Am J Hypertens. 1994;7:926-32.