Treatment of systolic
hypertension with chlorthalidone associated with long-term improvement
in life expectancy
Patients with systolic hypertension who were
treated with the diuretic chlorthalidone for 4.5 years as part of
a clinical trial had a significantly lower rate of death and a gain
in life expectancy free from cardiovascular death about 20 years
later compared to patients who received placebo, according to a
study in the December 21 issue of JAMA.
"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.
John B. Kostis, M.D., of the UMDNJ-Robert Wood Johnson Medical
School, New Brunswick, N.J., and colleagues conducted a study to
examine the effect of blood pressure (BP) lowering on long-term
outcomes such as life expectancy. The researchers obtained long-term
mortality data for participants in the Systolic Hypertension in
the Elderly Program (SHEP) trial, which was a randomized, placebo-controlled,
clinical trial designed to assess the effect of antihypertensive
drug treatment (chlorthalidone) in reducing the risk of stroke in
patients with isolated systolic hypertension. Recruitment for SHEP
was between March 1985 and January 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 (December 2006) was
approximately 22 years (21 years 10 months). Of the 4,736 participants
enrolled in the SHEP trial, 2,365 (49.9 percent) were randomized
to active treatment therapy and 2,371 (50.1 percent) were randomized
to placebo. The average age of participants was 72 years, 57 percent
were women, and 14 percent were black.
At the end of follow-up, 2,851 of the 4,736 randomized patients
(60.2 percent) had died, with 1,416 deaths (59.9 percent) in the
active treatment group and 1,435 deaths (60.5 percent) in the placebo
group. The researchers found that both life expectancy and time
to the 70th percentile survival at the end of follow-up were longer
for the SHEP participants who were randomized to the active group
compared with those randomized to the placebo group. Life expectancy
gain at 22 years was 158 days for cardiovascular death and 105 days
for death from all causes. The gain in life expectancy free from
cardiovascular death corresponds with 1 day (0.89 days) gained per
month of treatment. For all-cause mortality, the gain in life expectancy
from 1 month of antihypertensive drug treatment was estimated at
a half day (0.59 days).
The authors also found that the active treatment group was associated
with higher survival free from cardiovascular death compared with
the placebo group (669 deaths [28.3 percent] vs. 735 deaths [31
percent], respectively).
"Reporting that each month of antihypertensive therapy was
associated with 1 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 health care providers," the authors write.
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