Treatment of hypertension in the very old reduces all-cause mortality

May 4, 2008 By Benjamin A. Olenchock, M.D. Ph.D. [mailto:bolenchock@partners.org]

Results from the Hypertension in the Very Elderly Trial (HYVET) have been published in the New England Journal of Medicine. This randomized, double-blind, placebo-controlled trial demonstrated that treatment of stage II hypertension in patients over 80 years of age reduces the incidence of fatal stroke and all-cause mortality.

Controversy exists regarding whether hypertension should be aggressively treated in patients over the age of 80. In this age group, the risks from medication side effects, poly-pharmacy, hypotension and falls could be greater than any cardiovascular benefit from good blood pressure control. Some previous retrospective studies seemed to support this conclusion, as treatment of hypertension has been associated with fewer strokes but higher mortality in this age group. Other data support the conclusion that while the relative benefit of blood pressure control is clearly less in older individuals than in younger patients, the absolute benefit is equal or greater in the elderly as baseline cardiovascular risk is so high in this group.

The HYVET study randomized patients over the age of 80 with stage II hypertension (systolic pressure >160) to indapamide (1.5 mg) or placebo. The goal blood pressure was 150/80, and perindopril (2 or 4 mg) or placebo could be added to reach this goal blood pressure. The primary end point was fatal of nonfatal stroke. Secondary end points included all-cause mortality, cardiovascular death, and death from stroke. Major exclusion criteria included secondary hypertension, recent hemorrhagic stroke, heart failure, dementia, and nursing home residents. Data were analyzed by intention to treat. This trial was conducted in Europe, China, Australasia and Tunisia, with the majority of patients enrolled in Eastern Europe and China.

Over 3800 patients underwent randomization, and baseline characteristics were similar between treatment arms. The average patient age was 83 years old, and baseline blood pressures were 173/90 in both study arms. In the intention to treat analysis, systolic/diastolic blood pressures had fallen by 14.5/6.6 mm in the placebo arm and 29.5/12.9 in the study arm at 2 years follow up. At that time, most patients (74%) in the active treatment arm were being treated with indapamide and either 2 or 4 mg perindopril. There were 51 strokes in the active treatment arm and 69 in the placebo arm, for a relative risk reduction of 30% (OR 0.70, CI 0.49-1.01, p=0.06). There was a 21% reduction in the risk of death (OR 0.79, CI 0.65-0.95, p=0.02), and a 39% reduction in death from stroke (OR 0.61, CI 0.38-0.99, p=0.046) in the active treatment arm. Rates of heart failure (OR 0.36, CI 0.22-0.58, p<0.001), defined by clinical criteria, were dramatically reduced by active treatment. Adverse events were very few in this study, with only 5 total events (2 of which were in the active treatment arm) thought to be due to study drug.

The authors were surprised by the reduction in all-cause mortality, and note that a mortality benefit is rare among trials of antihypertensive trials. One plausible explanation for this finding is the higher rates of fatal stroke in this population. The study population was a healthy elderly population, which might limit generalizability. Also, the trial medications are not commonly used in the USA. Indapamide is a non-thiazide diuretic, and preparations exist that combine indapamide with the ACE inhibitor perindopril. These caveats aside, HYVET demonstrates that achieving modest blood pressure control in very old patients has significant mortality benefits.