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


Therapeutics

Review: Antihypertensive drugs reduce stroke in patients 80 years of age or older

ACP J Club. 1999 Sept-Oct;131:29. doi:10.7326/ACPJC-1999-131-2-029


Source Citation

Gueyffier F, Bulpitt C, Boissel J-P, et al., for the INDANA Group. Antihypertensive drugs in very old people: a subgroup meta-analysis of randomised controlled trials. Lancet. 1999 Mar 6;353:793-6.


Abstract

Question

What is the effectiveness of antihypertensive drug treatment for persons ≥ 80 years of age?

Data sources

{Studies were identified by searching MEDLINE, the Cochrane Library, the World Health Organization International Society of Hypertension Blood Pressure Lowering Treatment Trialists' Collaboration register, and 2 Japanese databases; contacting experts; and reviewing bibliographies of articles.}*

Study selection

Studies were selected if they were randomized controlled trials that included persons ≥ 80 years of age with hypertension and compared antihypertensive treatment with placebo, no treatment, or a lower dosage of the study drug.

Data extraction

Data were extracted on hypertension treatments, inclusion criteria, length of follow-up, loss to follow-up, baseline patient characteristics, and clinical history. Primary outcomes were fatal and nonfatal stroke (excluding transient ischemic attack). Secondary outcomes included all-cause mortality, fatal and nonfatal major coronary events, fatal and nonfatal major cardiovascular events (stroke, major coronary events, and cardiovascular deaths), and congestive heart failure.

Main results

Individual data on 1670 patients (76% women) were available from 7 trials (the European Working Party on High Blood Pressure in the Elderly trial, the Coope and Warrender trial, the Systolic Hypertension in the Elderly Program Pilot, the Systolic Hypertension in the Elderly Program, the Swedish Trial in Old Patients with Hypertension, the Cardiovascular Study of the Elderly trial, and the Syst-Eur trial). Meta-analysis using a fixed-effects model showed that antihypertensive treatment reduced the risk for stroke (6 studies), major cardiovascular events (6 studies), and heart failure (6 studies) (Table) but did not affect major coronary events or fatal outcomes.

Conclusion

Among persons ≥ 80 years of age, antihypertensive treatment reduces stroke, cardiovascular events, and heart failure but does not reduce all-cause or cardiovascular mortality or major coronary events.

Sources of funding: Association pour la Promotion de la Recherche et de l'Evaluation au Thérapeutique; the Société Francaise d'Hypertension Artérielle; the Fondation pour la Recherche médicale; the Hospices Civils de Lyon.

For correspondence: Dr. F. Gueyffier, EA 643, Service de Pharmacologie Clinique, BP 3041, 69394 Lyon, Cedex 03, France. FAX 33-47-853-1030.

*Information provided by author.


Table. Antihypertensive drugs vs control (placebo, no treatment, or lower dosage) for persons ≥ 80 years of age†

Outcomes at mean 3.5 y Weighted event rates RRR (95% CI) NNT (CI)
Antihypertensive drugs Control
Stroke 7.5% 1-.8% 33% (7 to 52) 30 (17 to 238)
Cardiovascular events 17.2% 22.2% 23% (6 to 37) 21 (12 to 86)
Heart failure 6.9% 9.0% 40% (13 to 59) 48 (24 to 668)†

†Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.
P = 0.07


Commentary

Treatment of hypertension in very elderly persons (≥ 80 y of age) has not been clearly addressed in any clinical trial. Although a study is under way in Europe (i.e., the Hypertension in the Very Elderly Trial) (1), results are not yet available. In this systematic review, Gueyffier and colleagues analyzed subgroup data on 1670 patients ≥ 80 years of age taken from 7 trials. The authors of this paper include 1 investigator from each of the included studies. The drug therapy used in the studies tended to be simple (thiazides or β-blockers in 5 of 7 studies), and most patients had predominantly systolic hypertension. Diabetes was the most important comorbid condition. Studies varied considerably in the degree of blood pressure control. Primary end points (fatal and nonfatal stroke) were clearly defined.

Because of the varied trial designs and small numbers of patients in the subgroup analyses, the authors acknowledge that a single study of proper design could potentially render their results nonsignificant. Antihypertensive treatment reduced the risk for stroke (although the benefit was restricted to nonfatal stroke) and heart failure. The mortality rate did not improve with treatment. If only double-blind, controlled trials were included, the mortality rate would have actually increased in treated patients, raising concerns about the adverse effects of treatment.

Although the analysis concluded that even very elderly persons seem to have a reduced risk for stroke with antihypertensive treatment, a properly controlled, randomized, double-blind trial will be necessary before any firm conclusions can be included in clinical practice guidelines.

Jean Gray, MD
Queen Elizabeth II Health Sciences CentreHalifax, Nova Scotia, Canada


Reference

1. Bulpitt CJ, Fletcher AE, Amery A, et al. The Hypertension in the Very Elderly Trial (HYVET). J Hum Hypertens. 1994;8:631-2.