Hypertension Treatment: Results from Clinical Trials

There is now no question that a significant reduction in cardiovascular and cerebrovascular morbidity and mortality results from treatment to reduce blood pressure in older hypertensive patients. Several randomized clinical trials of antihypertensive therapy in older populations have provided compelling evidence that treatment is effective in reducing cardiovascular (e.g., chronic congestive heart failure) and cerebrovascular (e.g., stroke) morbidity and mortality. A meta-analysis of outcome trials in systolic hypertension demonstrated that treatment was associated with significant reductions in overall mortality, cardiovascular events, and stroke.

The treatment effect was largest in men, in those over the age of 70 years, and in those who had larger pulse pressures. Similarly, another meta-analysis of nine treatment trials confirmed that treatment of hypertension in the older population is associated with significant benefits: the treatment group had significant reductions in all-cause mortality [odds ratio, 0.88; 95% confidence interval (CI), 0.80-0.97], stroke mortality (0.64; CI, 0.49-0.82), and morbidity (0.65; CI, 0.55-0.76), as well as cardiac mortality (0.75; CI, 0.64-0.88) and morbidity (0.85; 0.73-0.99). Based in part on these data, an analysis of the effectiveness of antihypertensive therapy utilizing data derived from the NHANES I survey suggested that the number needed to treat (assuming a 12 mmHg reduction in SBP for 10 years) to prevent cardiovascular events and deaths or all-cause mortality decreased as a function of the initial blood pressure reading and of increasing risk strata (derived from JNC-VI definitions); the prevention of 1 all-cause death required that 81 patients in the lowest risk grouping be treated compared to 9 patients in the highest risk group.

In addition to the demonstrated efficacy of antihypertensive therapy with respect to cardiovascular and stroke outcomes, it is worth noting that there may be other benefits. An analysis of data from the SHEP study identified that the relative risk of developing congestive heart failure among the treatment group was approximately one-half that of the control group. Other studies have focused on a possible relationship between hypertension and the risk of developing cognitive impairment. Results from a vascular dementia project designed as part of the Syst-Eur trial suggest that the rate of the development of dementia was significantly lower (approximately one-half) in the active treatment compared with the control group. It should be noted, however, that the dementia incidence was small (7.7 and 3.8 cases per 1000 patient-years in control and treated groups, respectively), and this observation has not yet been replicated.

Although the results from these randomized clinical trials have provided convincing support for the beneficial effects of treatment of hypertension in older patients, there nevertheless are several unanswered questions. The majority of these trials focused on those with simple hypertension and, for example, excluded those with significant comorbidities such as diabetes or a history of prior stroke or heart disease. The extent to which these results are applicable to frail older patients with multi-ple coexisting diseases is not known.