Is the Verdict Out? A Systematic Review of Pharmacotherapy for Hypertension in the Elderly

PURPOSE: To quantify long-term effects of antihypertensive drug treatment on overall mortality and cardiovascular-specific morbidity and mortality in older people with mild to moderate systolic or diastolic hypertension and in older people with isolated systolic hypertension. To characterize the comorbid risk profiles of all trial participants and specify cardiovascular morbidity/mortality rates among control groups in different trials. To quantify adverse drug effects observed in longterm trials of antihypertensive drug therapy in older people with hypertension. BACKGROUND: The number of older people and their percentage of the population is growing, and hypertension is highly prevalent in this age group. It is estimated that 50% of people aged 65 and older are hypertensive. 1 Increased arterial stiffness, weight gain, reduced physical activity, and increased insulin resistance all contribute to the development of laterlife hypertension, which not only increases the risk of heart attack and stroke, but is also an antecedent of congestive heart failure, chronic occlusive peripheral vascular disease, aortic aneurysm, and renal failure. 2 Randomized trials have provided conclusive evidence that lowering blood pressure levels in older people safely and effectively decreases cerebrovascular and cardiovascular morbidity and mortality rates. 3 It has also been reported that the absolute number of cardiovascular events prevented per 1,000 patients treated is higher in older people with hypertension than younger people with hypertension. 4 A recent Cochrane review examined the use of antihypertensive medication in older people. This paper is a critical analysis of the systematic review from a geriatrician’s perspective. SEARCH STRATEGY: Randomized controlled trials of at least 1 year’s duration in hypertensive older people ( 60) assessing efficacy of antihypertensive drug therapy and providing morbidity and mortality data were sought by electronic search of register of the Blood Pressure–Lowering Treatment Trialists’ Collaboration of the World Health Organization International Society of Hypertension (August 1997), The Cochrane Library (1997; Issue 1), MEDLINE (1966 to April 1997), and two Japanese databases (JMEDICINE, 1981–1995, and JAPIC-DOC, 1973–1995); references from reviews, trials, and 10 previously published meta-analyses; and experts. STUDY SELECTION CRITERIA: Only randomized controlled trials of at least 1 year’s duration providing morbidity and mortality data were acceptable for review. Trials must have included a control group that received a placebo, no hypertension therapy, or nonspecific antihypertensive therapy from their personal physician. Trials that compared two specific antihypertensives were excluded. Trials must have been limited to persons aged 60 and older or separately reported data on subgroups of persons aged 60 and older. Participants must have had hypertension defined as systolic blood pressure of at least 140 mmHg or diastolic blood pressure of at least 90 mmHg. Outcome measures that were assessed in the study were total mortality, including death from all causes; cardiovascular (coronary heart disease and cerebrovascular) morbidity and mortality; and dropout rates due to side effects of treatment. DATA EXTRACTION AND ANALYSIS: This review of 15 randomized controlled trials with 21,908 older subjects is based on two previously published meta-analyses. 5,6 These meta-analyses employed similar data abstraction techniques: development of a standard data abstraction form, dual abstraction of data from the original reports of trial results byt wo independent reviewers, and disagreements resolved by discussion. A fifth reviewer compared the published results of these two meta-analyses. A quality-scoring scheme was not used; instead, key trial characteristics were detailed in tabular form. Potential parameters of methodological quality listed in the table include whether randomization was completed in an appropriate and blinded manner; whether patients, providers, and outcome assessors were blinded to assigned therapy; whether the control group received a placebo; percentage of participants who did not complete follow-up (dropouts); and percentage of participants not on assigned active or placebo therapy at study completion (cross-over). From the University Medical Center at SUNY, Stony Brook, NY