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


Therapeutics

Antihypertensive drugs in stepped doses reduced stroke in elderly patients with isolated systolic hypertension

ACP J Club. 1991 Nov-Dec;115:65. doi:10.7326/ACPJC-1991-115-3-065


Source Citation

SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA. 1991 Jun 26;265:3255-64.


Abstract

Objective

To determine whether antihypertensive drug treatment reduces the risk for stroke (nonfatal and fatal) in men and women ≥ 60 years of age with isolated systolic hypertension.

Design

Randomized, double-blind, placebo-controlled trial over 5 years.

Setting

Community recruitment to 16 tertiary care centers.

Patients

4736 persons with isolated systolic hypertension (mean systolic blood pressure [SBP] ≥ 160 mm Hg and mean diastolic blood pressure [DBP] < 90 mm Hg) were enrolled after screening 447 921 persons. 57% were women; 14% were black; the mean age was 72 years; mean SBP, 170 mm Hg; and mean DBP, 77 mm Hg; 61 % had abnormal ECGs; 33% entered after withdrawal of previous antihypertensive agents. Patients with major medical diseases were excluded. Follow-up was 99.8% and averaged 4.5 years.

Intervention

The goal of therapy was a SBP < 160 mm Hg and a reduction in SBP of at least 20 mm Hg using the lowest possible dose of medicine. BP was monitored monthly, and drug therapy (with active drug or placebo) was adjusted in 4 consecutive steps: chlorthalidone, 12.5 mg/d; increase to chlorthalidone, 25mg/d; addition of atenolol, 25 mg/d, or reserpine, 0.05 mg/d; increase to atenolol, 50 mg/d, or reserpine, 0.1 mg/d. Any patient with sustained SBP > 220 mm Hg or DBP > 90 mm Hg was given active treatment.

Main outcome measures

Fatal and nonfatal stroke, cardiovascular events, and mortality.

Main results

At 5 years, 90% of the study group and 44% of controls were on active treatment. Two thirds of patients assigned to treatment and one third of controls achieved the SBP goal. (65 % to 72% vs 32% to 40%) 103 persons (4%) assigned to treatment had strokes (10 fatal) compared with 159 (7%) in the control group (14 fatal){ P < 0.001}* {This absolute risk reduction (ARR) of 3% means that 43 patients would need to be treated (NNT) with antihypertensive drug treatment (compared with placebo) to prevent 1 additional stroke, 95% CI 27 to 95; the relative risk reduction (RRR) was 35%, CI 17% to 49%}.* Fewer patients in the treatment group had cardiovascular disease {12% vs 17%, P < 0.001; ARR 5%, NNT 19, CI 14 to 31; RRR 30%, CI 20% to 39%}*. Fewer deaths occurred in the treatment group but the difference did not reach statistically significant (9% vs 10%, P = 0.2) {ARR 1%, CI -0.5% to 2.9%}.*

Conclusion

Stepped-care treatment with chlorthalidone, and atenolol or reserpine if required, of persons ≥ 60 years of age with isolated systolic hypertension reduced strokes by 36% and had other favorable cardiovascular effects.

Sources of funding: National Heart, Lung, and Blood Institute and National Institute on Aging.

Address for article reprint: Dr. J. L. Probstfield, Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Federal Building, Room 5C-10B, 7550 Wisconsin Avenue, Bethesda, MD 20892, USA.

*Numbers calculated from data in article.


Commentary

This study is impressive for its size, scientific rigor, and favorable results. Many physicians have been concerned with the risk of treating elderly persons with isolated systolic hypertension, especially because a J- or U-shaped relation between diastolic blood pressure and mortality has been described (1). This study lays those concerns to rest.

The absolute risk reduction of 3% over 5 years might appear unimpressively small. 2 factors, however, need to be taken into account. First, the results compare favorably with other current treatments to prevent stroke or heart disease. On the assumption that event rates would remain constant over the clinically more sensible period of 10 years, the study results suggest that treating 100 elderly patients would prevent 6 strokes, 2 heart attacks, 5 cases of congestive heart failure, and 2 deaths, whereas 7 patients would have intolerable adverse effects from therapy.

The second factor to consider in interpreting these results is that the data were analyzed according to the groups to which patients were assigned, not according to whether patients actually took the medicine or achieved the target blood pressure. At 5 years, 90% of patients in the treatment group were on treatment but only two thirds achieved their blood pressure goal, whereas 44% of patients in the control group were treated and one third were at goal. Thus, the results of this study underestimate the benefits of successfully treating isolated systolic hypertension.

These factors, when combined with the reasonable cost and convenience (once a day), suggest that the stepped-care treatment program is clinically worthwhile.

Arthur T. Evans, MD, MPH
University of North Carolina at Chapel HillChapel Hill, North Carolina, USA


Reference

1. Staessen J, Bulpitt C, Clement D, et al. Relation between mortality and treated blood pressure in elderly patients with hypertension: report of the European Working Party on High Blood Pressure in the Elderly. BMJ. 1989;298:1552-6.