May was National High Blood Pressure Awareness month but perhaps we should devote the entire year to it. It is estimated that over 76,000,000 adults in the United States ≥ 20 years of age have hypertension (HTN) leading to direct and indirect costs exceeding $50 billion annually.1 The age adjusted prevalence of HTN was 75% for older women and 65% for older men based on national health statistics.2 Unfortunately, among patients ≥ 80 years of age, only 38% of men and 23% of women had blood pressures that met targets.3 It is not known why the control rate is so low; is it related to resistant HTN or is it related to reluctance to treat HTN in the very elderly?
The results of the Hypertension in the Very Elderly Trial (HYVET) have been previously published.4 Briefly, this was a randomized, double blind, placebo controlled trial conducted in 195 centers in 13 countries in western and eastern Europe, China, Australasia, and Tunisia. Participants had to be aged 80 years or greater and have a sustained systolic blood pressure (SBP) of 160 mm Hg or higher. Patients were assigned to receive indapamide SR 1.5 mg daily (Step I), indapamide plus perindopril 2 mg daily (Step II), or indapamide SR plus perindopril 4 mg daily (Step III) or corresponding matching placebos. Drug titration was encouraged in order to achieve a target SBP < 150 mm Hg. In the active treatment arm 25% of patients were on Step I, 28% on Step II, and 45% on Step III. At the end of the trial the mean sitting blood pressure was 145.0/76.6 mm Hg in patients on active treatment compared to 159.3/80.8 mm Hg in those on placebo (P<0.001). The study was stopped early with a median follow-up of 1.8 years because clear evidence of active treatment was found. Total mortality was reduced by 21% (95% confidence interval 4% to 35%; P=0.019) and cardiovascular events by 34% (18% to 47%; P<0.001).
At the end of the trial patients still on double-blind treatment and had not reached a study endpoint were eligible for a one-year open-label extension study. Patients provided a written consent prior to starting the follow-up trial. Patients were seen at three-month intervals. The same endpoint data used in the main trial were collected. At the end of the main HYVET trial 1009 patients were receiving active therapy and 873 were on matching placebo. Of this cohort, 924 patients taking active treatment and 788 taking placebo entered the extension trial. All patients were restarted at Step I therapy with indapamide regardless of their final therapy in the main trial. At six months there was not a statistical difference in the blood pressures of the two groups; 145.3/76 mm Hg in patients on previous active therapy versus 146.6/76.6 mm Hg previously on placebo.
At the end of the extension there were no differences in the primary outcome of fatal and non-fatal stroke or for heart failure or a composite of cardiovascular events. However, patients originally assigned to active therapy had lower total mortality (hazard ratio 0.48, 0.26 to 0.87; P=0.02) and cardiovascular mortality (0.19, 0.04 to 0.87; P=0.03). The investigators concluded that the cardiovascular benefits of treating HTN in the very elderly are seen early in the course of treatment. Some benefits such as total and cardiovascular mortality may take longer. The data also demonstrated that most patients > 80 years of age can achieve a SBP < 140 mm Hg with combination therapy. The benefits of this indapamide/perindopril regimen should not be extrapolated to other thiazide-type diuretics such as hydrochlorothiazide. Another large randomized controlled trial in elderly patients ≥ 60 years of age, the Systolic Hypertension in Elderly Persons (SHEP) trial used a chlorthalidone-based regimen which resulted in a significant decrease in major cardiovascular events.6
1. Fields LE, Burt VL, Cutler JA, et al. The burden ...