JAMA: Antihypertensives can prolong death

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Treatment of isolated systolic hypertension with chlorthalidone stepped-care therapy for 4.5 years was associated with longer life expectancy at 22 years of follow-up, based on the long-standing SHEP trial published Dec. 21 in the Journal of the American Medical Association.

Antihypertensive drug therapy has been shown to decrease nonfatal and fatal cardiovascular events in controlled clinical trials and meta-analyses. However, long-term data on gain in life expectancy are not available, according to background information in the article.

Chlorthalidone, originally marketed in the U.S. as Hygroton (Novartis Pharmaceuticals), is an antihypertensive diuretic based on thiazide. In the SHEP [Systolic Hypertension in the Elderly Program] trial, conducted between 1985 and 1990, antihypertensive therapy with chlorthalidone-based, stepped-care therapy resulted in a lower rate of cardiovascular events than placebo but effects on mortality were not significant.

In this follow-up study, John B. Kortis, MD, from the Cardiovascular Institute at the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School in New Brunswick, N.J., and colleagues sought to study the gain in life expectancy of participants randomized to active therapy at the 22-year follow-up.

A National Death Index ascertainment of death in the long-term follow-up of a randomized, placebo-controlled, clinical trial of patients aged 60 years or older with isolated systolic hypertension. Recruitment took place between March 1, 1985, and Jan. 15, 1988. After the end of a 4.5-year randomized phase of the SHEP trial, all participants were advised to receive active therapy. The time interval between the beginning of recruitment and the ascertainment of death by National Death Index (Dec. 31, 2006) was approximately 22 years.

At the 22-year follow-up, life expectancy gain, expressed as the area between active (2,365 patients) and placebo (2,371 patients) survival curves, was 105 days for all-cause mortality and 158 days for cardiovascular death. Each month of active treatment was therefore associated with approximately one-day extension in life expectancy. The active treatment group had higher survival free from cardiovascular death vs. the placebo group, but similar survival for all-cause mortality.

There were 1,416 deaths (59.9 percent) in the active treatment group and 1,435 deaths (60.5 percent) in the placebo group.

The authors also found that the active treatment group was associated with higher survival free from cardiovascular death compared with the placebo group (28.3 percent vs. 31 percent, respectively).

Time to 70th percentile survival was 0.56 years longer in the active treatment group versus the placebo group (11.53 vs. 10.98 years) for all-cause mortality and 1.41 years (17.81 years vs. 16.39 years) for survival free from cardiovascular death.

Reporting that each month of antihypertensive therapy was associated with one-day prolongation of life expectancy free from cardiovascular death is a strong message that may result in increased patient adherence to drug therapy and decrease the degree of therapeutic inertia by healthcare providers, the authors concluded.