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


In men with hypertension, captopril was associated with better quality of life than enalapril

ACP J Club. 1993 July-Aug;119:5. doi:10.7326/ACPJC-1993-119-1-005

Source Citation

Testa MA, Anderson RB, Nackley JF, Hollenberg NK, and the Quality-of-Life Hypertension Study Group. Quality of life and antihypertension therapy in men: a comparison of captopril with enalapril. N Engl J Med. 1993 Apr 1;328:907-13.



To compare quality-of-life (QoL) scores in men with hypertension who receive enalapril or captopril.


24-week, randomized, double-blind, controlled trial.


25 ambulatory clinical centers.


479 active men with hypertension (diastolic blood pressure [DBP] between 90 and 115 mm Hg) were screened; 379 were studied (mean age 64 y). Exclusion criteria were substantial cardiac, hematologic, renal, hepatic, metabolic, neoplastic, psychiatric, or symptomatic peripheral vascular disease; history of noncompliance; or previous intolerance or hypersensitivity to study medications. Follow-up was 95%.


Patients were randomized to enalapril (n = 187) once daily (5, 10, or 20 mg with or without hydrochlorothiazide) or captopril (n = 192) twice daily (25 or 50 mg with or without hydrochlorothiazide). Study medication was titrated upward to keep DBP < 90 mm Hg; then dosing was kept constant for 16 weeks. Patients were excluded if their DBP was > 100 mm Hg at week 10.

Main outcome measures

QoL was measured using scales for psychological distress (anxiety, depression, loss of behavioral or emotional control); psychological well-being (emotional ties, general positive affect, life satisfaction); general perceived health (vitality, general health status, sleep disturbance); symptom distress; well-being at work or in daily routine; and sexual-symptom distress. DBP was assessed at clinic visits, and life events were monitored.

Main results

Analysis was by intention to treat. The groups did not differ for DBP, withdrawal rates, or major side effects. Men receiving captopril, as compared with enalapril, had higher overall QoL scores (P = 0.04), more positive changes in general health scores (P = 0.01) and vitality (P = 0.007), decreased sleep disturbance scores (P = 0.015), and better emotional or behavioral control (P = 0.029). Baseline scores for QoL were predictive of changes in QoL scores (P < 0.001). Patients with low baseline scores increased their scores. Patients with high baseline scores taking captopril remained stable, and those taking enalapril developed worse QoL scores.


Patients taking enalapril and captopril had similar blood pressure control and adverse effects. Patients receiving captopril had overall higher scores for quality of life compared with those receiving enalapril.

Source of funding: In part, Bristol-Myers Squibb.

For article reprint: Dr. M.A. Testa, Department of Biostatistics, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. FAX 617-237-4407.


Testa and colleagues found captopril and enalapril to be equally effective, and, importantly, observed no differences in side effects or withdrawals because of adverse effects. Differences were found, however, in several QoL measures, suggesting that captopril was associated with improved QoL, whereas enalapril was associated with worse measurements. Stratification showed that the baseline QoL score was of major importance in making the appropriate inferences. Captopril improved the one third of patients who had a low baseline QoL score; enalapril worsened the one third of patients with a high baseline score, although the absolute change in scores that one could expect under placebo conditions is unknown. This lack of consistent effects makes interpretation difficult. The direction of the changes noted (but not the statistical significance) suggests that regression to the mean might be partly responsible. The authors concluded that the changes corresponded to such life events as "major change in work responsibility" or "mortgage foreclosure." How 2 drugs could be associated with such major changes in quality of life but result in similar rates of side effects or discontinuance is interesting. Adjustment for variables such as comorbidity or age might have shown less association between life events and QoL scores.

A recent large study (1) of hypertension showed no difference between an angiotensin-converting enzyme (ACE) inhibitor and a β-blocker in QoL measures; long-acting nifedipine caused more side effects and withdrawals. Other studies with either small sample sizes or short follow-up periods do not show consistent differences in QoL measures between different drugs, perhaps in part because of the different scales that are used. If an ACE inhibitor is indicated, it may be reasonable to discuss potential QoL effects with patients. Without additional confirmatory studies, it would, however, appear to be premature to select or exclude a drug on the basis of this report. Cost-effectiveness studies would provide further information for clinicians.

Richard A. Davidson, MD, MPH
University of FloridaGainesville, Florida, USA


1. Fletcher AE, Bulpitt CJ, Chase DM, et al. Quality of life with three antihypertensive treatments: cilazapril, atenolol, nifedipine. Hypertension. 1992;19:499-507.