(Hypertension. 1995;25:1052.)
© 1995 American Heart Association, Inc.
Articles |
Thiazides and Hypertension in the Elderly
From the Department of Nephrology and Hypertension, Cleveland (Ohio) Clinic Foundation (R.W.G.), and the Department of Internal Medicine, Southwestern Medical Center, Dallas, Tex (N.M.K.).
Correspondence to Ray W. Gifford, Jr, MD, Department of Nephrology and Hypertension, Desk A101, The Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195.
Key Words: aging • diuretics • elderly • epidemiology • antihypertensive agents
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Introduction |
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 Top Introduction References |
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The declining use of diuretics in the treatment of elderly hypertensive patients described in the report by Monane and colleagues in this issue of Hypertension is lamentable but understandable. Lamentable because meta-analyses of randomized clinical trials in elderly hypertensive patients have shown that diuretic-based treatment leads to an impressive reduction in morbidity and mortality from stroke and coronary heart disease, as well as all-cause mortality.1 2 Elderly patients with isolated systolic hypertension (
160/<90 mm Hg) enjoy the same benefit from
diuretic-based therapy as patients with elevations of both systolic and
diastolic pressures.3 Lamentable because these randomized
clinical trials have influenced most of the recent national guidelines
that recommend prescribing a diuretic in a low dose preferentially in
the initiation of antihypertensive therapy, especially for elderly
hypertensive patients.4 5 Understandable because most of the randomized trials that have convincingly demonstrated the benefit of diuretics in managing hypertension in elderly patients, and the guidelines that were subsequently developed, have been published since 1988, when the observations by Monane and colleagues concluded. Understandable because earlier randomized trials that used diuretics in large doses (50 to 100 mg/d of hydrochlorothiazide or chlorthalidone) in young and middle-aged patients had failed to achieve the expected reduction in coronary events,6 leading to speculation that the metabolic side effects of diuretic therapy might have a counterproductive effect with regard to coronary disease. Without the massive marketing provided for newer agents, generic diuretics were easy targets for the trade-name alternatives included in the recommendations for initial therapy in the 1982 and 1993 Joint National Committee reports.7 8 Having lost their patents, diuretics had no constituency except for the randomized trials cited above.
The likely explanation for the more convincing effect of diuretics in decreasing coronary events in the recent trials compared with earlier ones lies not only in the lower doses used in the recent trials, thereby minimizing metabolic side effects, but also in the concentration on the elderly population in current trials as opposed to younger subjects of the earlier studies. Elderly patients are at greater risk for coronary events than are younger patients, and consequently, a randomized trial limited to 3 to 5 years of observation is more likely to reach a statistically significant conclusion with regard to coronary end points, because there will be more end points. To reach a statistically significant conclusion in a trial of young and middle-aged patients would require a longer trial, more participants, or both. This may be why extended observations in the Multiple Risk Factor Intervention Trial (MRFIT)9 and the Hypertension Detection and Follow-up Program (HDFP)10 showed a more impressive reduction in coronary events in the special intervention groups than did the original observations at the end of the 5-year trials.
"Expected" reductions in coronary events were calculated from long-term observational studies that extended for 10 to 30 years, whereas the randomized clinical trials were concluded after 5 years at most.6 Consequently, the surprising conclusion of the earlier clinical trials was that the reduction in strokes met expectations, not that the reduction in coronary events failed to do so.
We hope physicians have by now received the good news about the benefits of treating elderly hypertensive patients with low-dose diuretics. Whether the newer agents will be as effective, more effective, or less effective in reducing cardiovascular risk in elderly hypertensive patients will not be known until the results of the Antihypertensive Lipid-Lowering Heart Attack Trial (ALLHAT) are available some time after the year 2000. In the meantime, the data presented by Monane and colleagues provide a benchmark by which we can judge how quickly research can be translated into clinical practice.
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Footnotes |
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The opinions expressed in this editorial comment are not necessarily those of the editors or of the American Heart Association.
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References |
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TopIntroductionReferences |
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1. Insua JT, Sacks HS, Lau TS, Lau J, Reitman D, Pagano D, Chalmers TC. Drug treatment of hypertension in the elderly: a meta-analysis. Ann Intern Med. 1994;121:355-362.
2.
Mulrow CD, Cornell JA, Herrera CR, Kadri A, Farnett L,
Aguilar C. Hypertension in the elderly: implications and
generalizability of randomized trials. JAMA. 1994;272:1932-1938.
3.
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;265:3255-3264.
4. Alderman MN, Cushman WC, Hill MN, Krakoff LR. International roundtable discussion of national guidelines for the detection, evaluation, and treatment of hypertension. Am J Hypertens. 1993;6:974-981. [Medline] [Order article via Infotrieve]
5.
National High Blood Pressure Education Program
Working Group. National High Blood Pressure Education Program
Working Group Report on Hypertension in the Elderly.
Hypertension. 1993;23:275-285.
6. MacMahon S. Antihypertensive drug treatment: the potential, expected and observed effect on vascular disease. J Hypertens. 1990;8(suppl 7):S239-S244.
7.
Moser M, Blaufox MD, Freis E, Gifford RW Jr,
Kirkendall W, Langford H, Shapiro A, Sheps S. Who really
determines your patients' prescriptions? JAMA. 1991;265:498-500. Commentary.
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Alderman MH. Which antihypertensive drugs
first—and why! JAMA. 1992;267:2786-2787.
Commentary.
9.
The Multiple Risk Factor Intervention Trial Research
Group. Mortality rates after 10.5 years for participants in the
Multiple Risk Factor Intervention Trial: findings related to a priori
hypotheses of the trial. JAMA. 1990;263:1795-1801.
10.
Hypertension Detection and Follow-up Program
Cooperative Group. Persistence of reduction in blood pressure
and mortality of participants in the Hypertension Detection and
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