Current issues of ACP Journal Club are published in Annals of Internal Medicine


Low-dose hydrochlorothiazide lowered blood pressure in older men with isolated systolic hypertension

ACP J Club. 1992 Mar-April;116:36. doi:10.7326/ACPJC-1992-116-2-036

Source Citation

Cushman WC, Khatri I, Materson BJ, et al. Treatment of hypertension in the elderly. III. Response of isolated systolic hypertension to various doses of hydrochlorothiazide: results of a Department of Veterans Affairs Cooperative Study. Arch Intern Med. 1991 Oct;151:1954-60.



To evaluate the blood pressure (BP) lowering effects of various doses of hydrochlorothiazide (HCTZ) in elderly men with isolated systolic hypertension.


Randomized, double-blind, controlled trial.


7 ambulatory care centers in the United States.


51 compliant men > 60 years of age (mean, 69 years) with systolic BP between 160 and 239 mm Hg (mean, 171 mm Hg) and diastolic BP below 90 mm Hg (mean, 84 mm Hg). 59% were black. Patients with serious illness and those on BP-altering medication were excluded.


After a 4- to 10-week single-blind, placebo baseline period to determine eligibility and compliance, patients were randomized to 25 mg/d (lower-dose group) or 50 mg/d (higher-dose group) of HCTZ. During the titration period (maximum of 5 biweekly visits), the dose could be increased to twice daily to achieve goal BP: systolic BP < 160 mm Hg and > 10 mm Hg lower than baseline. Patients who reached their BP goals were classified as responders and advanced to a 6-month maintenance phase.

Main outcome measures

Proportion of patients achieving their BP goals; side effects, including cognitive, behavioral, and mood changes.

Main results

During the titration phase, goal BPs were reached by 13 of the 23 patients (57%) originally assigned to 25 mg HCTZ; 5 additional patients (22%) in this group responded to 50 mg HCTZ/d. 18 of 28 patients (64%) in the higher-dose group responded to 50 mg/d and 7 (25%) responded to 100 mg HCTZ/d. Mean decreases in BP were similar (25/7 vs 29/7 mm Hg, P > 0.2), whereas mean serum potassium level changes were -0.17 mmol/L for the lower-dose group compared with -0.57 mmol/L for the higher-dose group (P = 0.01). BP and potassium level did not change significantly among the responders during the maintenance period. Side effects and changes in behavioral functioning in both groups were minimal and were no more frequent than during the pretitration (single-blind) placebo period.


Low-dose hydrochlorothiazide lowered blood pressure and was well tolerated in older men with isolated systolic hypertension.

Source of funding: Veterans Affairs Cooperative Studies Program.

Address for article reprint: Dr. W.C. Cushman, Hypertension Section (111E5), Department of Veterans Affairs Medical Center, 1030 Jefferson Avenue, Memphis, TN 38104, USA.


Medical treatment of hypertension in the elderly is now based on solid evidence. The impressive results of the Swedish STOP-Hypertension trial in "old" elderly persons with diastolic hypertension confirm earlier studies and suggest that the benefits of treatment persist to the age of 84 years. (SeeAntihypertensive treatment reduced morbidity and mortality in elderly patients with hypertension.) For those who always regretted the historically derived emphasis on diastolic compared with systolic BP, there is also good news: Treatment of those with an arbitrarily defined disproportionate elevation of systolic pressure (> 160 mm Hg with diastolic pressure < 90 mm Hg) is also beneficial, as shown by the results of the SHEP trial (1).

Unanswered questions include whether the SHEP results can be extrapolated to a less healthy population (many excluded subjects had other serious disease) and which drug regimen provides the optimal benefit-to-risk ratio in elderly patients.

The study by Cushman and coworkers provides data on the latter question by studying HCTZ monotherapy in elderly men (including 59% black men) with isolated systolic hypertension. Previous work suggested a "ceiling" benefit of HCTZ at 25 mg/d with additional toxicity, including hypokalemia, at higher doses. From this study, because 1 group started with 50 mg/d and all patients could receive increases above 25 mg/d, it is unclear how many patients could ultimately have been controlled at 25 mg/d. The hypokalemic effect of high-dose diuretics is of concern to many practitioners although it is not linked to excess cardiovascular mortality.

This study should encourage clinicians to continue to rely on low-dose, once daily thiazide as first-line therapy for elderly hypertensive patients. The ongoing European Syst-Eur trial is addressing the comparisons among thiazide, calcium antagonists, and ACE-inhibitors in patients with isolated systolic hypertension.

Gert Van Montfrans, MD, PhD
University of AmsterdamAmsterdam, The Netherlands

Gert Van Montfrans, MD, PhD
University of Amsterdam
Amsterdam, The Netherlands


1. SHEP Cooperative Research Group. JAMA. 1991;265:3225-64.