Secondary Prevention of CVD Events among Persons without Hypertension

Cardiovascular disease (CVD) represents 30% of all deaths worldwide and is the leading cause of death in the United States. Studies have shown a strong, graded, and independent association between blood pressure levels and the risk of CVD, stroke, and premature death. In people with prehypertension, 90% have at least 1 risk factor above optimal levels for heart disease or stroke and 68% had at least 1 clinically high risk factor for heart disease or stroke. The risk of CVD increases beginning at systolic blood pressure levels of 115 mm Hg. There have been clinical trials showing that lowering blood pressure reduces cardiovascular mortality in people with hypertension. Trials of lowering blood pressure for the prevention of CVD among people with prehypertension or normal blood pressure have had conflicting results. Researchers recently conducted a mega-analysis to evaluate the association between antihypertensive treatment and secondary prevention of CVD events and all-cause mortality among people without clinically defined hypertension (≥140 mm Hg systolic or ≥90 mm Hg diastolic and/or use of antihypertensive medications or history of hypertension). Results of the mega-analysis were reported in the Journal of the American Medical Association [2011;305(9):913-922]. The initial literature search found 874 potentially relevant studies; of those, 25 were included in the meta-analysis. There was variation between the studies in the class and dose of medication administered in the antihypertensive treatment group, but for most studies, it progressively increased to a defined target dose. Duration of the studies ranged from 1.5 to 63 months. All 25 studies required a history of CVD; clinical evidence of recent myocardial infarction (MI), congestive heart failure (CHF), coronary artery disease, or stroke; or CVD equivalent such as type 2 diabetes. In total, the studies incorporated data from 64,162 participants, 76% of whom were male; the mean age of participants ranged from 55.0 to 68.0 years. There was variation between the studies in participants’ clinical history of MI, CHF, diabetes, stroke, and coronary artery disease at baseline. Overall, compared with controls, the pooled relative risk (RR) for stroke among participants receiving antihypertensive medications was 0.77 (95% confidence interval [CI], 0.61-0.98). For MI, the pooled RR was 0.80 (95% CI, 0.69-0.93); for CHF, the pooled RR was 0.71 (95% CI, 0.65-0.77); for composite CVD events, the pooled RR was 0.85 (95% CI, 0.80-0.90); for CVD mortality, the pooled RR was 0.83 (95% CI, 0.69-0.99); and for all-cause mortality from random effects models, the pooled RR was 0.87 (95% CI, 0.80-0.95). The corresponding absolute risk reductions per 1000 persons were −7.7 (95% CI, −15.2 to −0.3) for stroke; −13.3 (95% CI, −28.4 to 1.7) for MI; −43.6 (95% CI, −65.2 to −22.0) for CHF events; −27.1 (95% CI, −40.3 to −13.9) for composite CVD events; −15.4 (95% CI, −32.5 to 1.7) for CVD mortality; and −13.7 (95% CI, −24.6 to −2.8) for all-cause mortality. There were no differences in results based on trial characteristics or subgroups defined by clinical history. The primary limitation to the study cited by the researchers was the dearth of studies that reported the outcomes of interest for normotensive and prehypertensive participants; few studies included the results by baseline blood pressure levels and treatment regimen; therefore, it was not possible to determine the dose-response relationship between baseline blood pressure and the risk of first occurrence or recurrence of CVD events in participants with blood pressure <140/90 mm Hg. In conclusion, the researchers summarized the results of the meta-analysis, stating, “Among patients with a clinical history of CVD but without hypertension, antihypertensive treatment was associated with decreased risk of stroke, CHF, composite CVD events, and all-cause mortality.” They added their opinion that “additional randomized trial data are necessary to assess these outcomes in patients without CVD clinical recommendations.”