December 26, 2011

First Data to Show Antihypertensive Therapy Prolongs Life

December 20, 2011 (New Brunswick, New Jersey) — The first long-term data from a high-blood-pressure study, the Systolic Hypertension in the Elderly Program (SHEP), show that each month of chlorthalidone-based therapy was associated with approximately one day of extension in life, free from cardiovascular death [1].

"The main findings are that after 22 years of follow-up, when about 60% of the participants in SHEP were dead, we saw a prolonged life expectancy in those who took the active treatment for 4.5 years, and that is the first time this has been reported in studies of hypertension, because you have to wait a long time to find out differences in life expectancy," lead author Dr John B Kostis (UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ) told heartwire. "In hypertension trials, by the time everybody dies, the investigators have died," he added.

The study "is a strong message that may result in increased patient adherence to drug therapy and decrease the degree of therapeutic inertia by healthcare providers," he and his colleagues say in their paper in the December 21, 2011 issue of the Journal of the American Medical Association.
Kostis cautions, however, that the gains relate primarily to CVD avoidance and that "everyone has to die from something," but he points out that other benefits of antihypertensive treatment, such as preventing strokes, could arguably be even more important than prolonging life.

SHEP Participants Were 72, on Average, When They Entered the Trial

The SHEP trial was conducted between March 1985 and January 1988, and just over 4700 patients aged, on average, 72 years were randomized to active treatment with chlorthalidone--with atenolol added if antihypertensive control was not sufficient--or placebo for 4.5 years. After this time, all patients were asked to go on active therapy.

At 22 years later, life-expectancy gain--expressed as the area between the active and placebo survival curves--was 105 days for all-cause mortality and 158 days for cardiovascular death.

The active-treatment group had higher survival free from cardiovascular death vs the placebo group (hazard ratio 0.89; p=0.03), but similar survival for all-cause mortality (HR 0.97; p=0.42).

There were 1416 deaths (59.9%) in the active-treatment group and 1435 in the placebo group (60.5%). But cardiovascular death was lower in the active-treatment group--669 deaths (28.3%) vs 735 deaths (31.0%) in the placebo group (p=0.03).

Time to 70th-percentile survival was 0.56 years longer in the active-treatment vs the placebo group for all-cause mortality and 1.41 years for survival free from CV death.

Stroke Prevention One of Key Messages

Kostis stresses, therefore, that the gains in life expectancy relate mainly to CVD. "If you do not die from CVD then you have more chance to die from other conditions. We found the CVD benefit was much higher than the overall benefit, because non-CV causes [of death] were more common in people treated [with antihypertensive therapy] at the beginning of SHEP.

"We all die, and if you don't die from heart disease you have the opportunity of dying from something else. Immortality hasn't been achieved yet in humans," he noted.
But, he believes, "it's better to live an extra year, then die from cancer." And he points out that other benefits of antihypertensive therapy, such as preventing strokes, are perhaps even more important. "Preventing one stroke has many implications other than life expectancy; stroke is a terrible thing."

Another key message from this trial is that the earlier therapy is started the better, says Kostis. "These patients happened to be elderly; they were 72, on average, when they were enrolled in this trial. But if you start treatment earlier you would have even better benefit. If you start therapy early and live 20 more years, you will be productive and enjoy life."

Kostis reported receiving grant support and travel to meetings from the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute on Aging (NIA). Disclosures for the coauthors are listed in the paper.

References
  1. Kostis, JB, Cabrera J, Cheng JQ et al. Association between chlorthalidone treatment of systolic hypertension and long-term survival. JAMA 2011; 306:2588-2593.

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