Antihypertensive therapy appears to benefit patients who have a clinical history of cardiovascular disease, but who have blood pressures in the normal or prehypertensive range, according to a meta-analysis of data from 25 randomized controlled trials involving more than 64,000 such patients.
Compared with control patients who received placebo, study participants without clinically defined hypertension who received antihypertensive treatment for the secondary prevention of cardiovascular disease events had a 23% reduction in risk of stroke, a 20% reduction in risk of myocardial infarction, a 29% reduction in risk of congestive heart failure, a 15% reduction in risk for composite cardiovascular disease (CVD) events, a 17% reduction in risk for cardiovascular disease mortality, and a 13% reduction in risk for all-cause mortality, Angela M. Thompson of Tulane School of Public Health and Tropical Medicine, New Orleans, and colleagues reported in the March 2 issue of JAMA.
The absolute risk reduction per 1,000 persons was -7.7 for stroke, -13.3 for MI, -43.6 for congestive heart failure events, -27.1 for composite CVD events, -15.4 for CVD mortality, and -13.7 for all-cause mortality, the investigators said (JAMA. 2011;305: 913-22).
All pooled relative risk reductions were statistically significant, but the pooled absolute risk reductions did not achieve statistical significance for myocardial infarction and CVD mortality – a discrepancy that reflects "the increased variance of the absolute measures compared with the variance of the relative measures," they explained.
The investigators conducted a systematic search of MEDLINE, EMBASE, and the Cochrane Collaboration Central Register of Controlled Clinical Trials, as well as a manual examination of references. The 25 trials included represent those that fulfilled all predetermined inclusion and exclusion criteria, and incorporated data from 64,162 participants at least 19 years of age and with blood pressure less than 140 mm Hg systolic or less than 90 mm Hg diastolic. The mean age across the studies ranged from 55 to 68 years; 76% of participants were men, and study duration varied from a mean of 1.5 months to 63 months.
The class and dose of antihypertensive treatments varied, but in most studies it progressively increased to a defined target dose, the investigators noted.
All studies required that participants have a history of cardiovascular disease; clinical evidence of recent MI, congestive heart failure, coronary artery disease, or stroke; or a CVD equivalent such as type 2 diabetes.
No statistically significant benefit of treatment was seen in regard to CVD outcomes and all-cause mortality in trials conducted exclusively in patients with diabetes, but the investigators cautioned that these findings were based on a small number of trials in the analysis.
Previous clinical trials have demonstrated that lowering blood pressure is associated with reduced risk of mortality among patients with hypertension, yet studies in individuals with prehypertension or normal blood pressures have yielded conflicting results, they noted.
The current findings suggest antihypertensive treatment might confer significant benefit.
Existing algorithms for treating hypertension in those with "compelling indications" – those with congestive heart failure, who are post MI, or at high coronary disease risk – call for pharmacologic treatment when blood pressure is not controlled to less than 140/90 mm Hg with lifestyle interventions alone.
"The results of this meta-analysis suggest that persons with these compelling indications, but without hypertension, may also benefit from reduced morbidity and mortality attributable to CVD events when treated with antihypertensive medications," the investigators said.
Since 90% of those aged 40 years and older at have least one above-optimal risk factor, and more than 68% have at least one clinically high-risk factor for heart disease or stroke, it would be economically infeasible to treat everyone at risk. A more reasonable strategy might be to identify groups within the prehypertensive population who would obtain the greatest benefit from early pharmacologic intervention, they suggested.
Additional studies are needed to determine the benefit of treating prehypertension at levels less than 140/90 mm Hg in patients with specific risk factors (elevated lipid levels, smoking history, kidney disease, and minority race or ethnicity), and also to examine the baseline blood pressure level at which treatment should begin in those with CVD or CVD equivalents (such as diabetes), they said.
None of the researchers reported having conflicts of interest. Funding was provided by Tulane University; the National Heart, Lung, and Blood Institute; and the National Institutes of Health.