Diuretic-based antihypertensive therapy is associated with the development of diabetes
but with improved clinical outcomes. It has been proposed that the duration of clinical
trials has been too short to detect the adverse effects of diabetes. We assessed the
long-term mortality rate of subjects in the Systolic Hypertension in the Elderly Program
(n = 4,732) who were randomized to stepped-care therapy with 12.5 to 25.0 mg/day of
chlorthalidone or matching placebo. If blood pressure remained above the goal, atenolol
or matching placebo was added. At a mean follow-up of 14.3 years, cardiovascular (CV)
mortality rate was significantly lower in the chlorthalidone group (19%) than in the
placebo group (22%; adjusted hazard ratio [HR] 0.854, 95% confidence interval [CI]
0.751 to 0.972). Diabetes at baseline (n = 799) was associated with increased CV mortality
rate (adjusted HR 1.659, 95% CI 1.413 to 1.949) and total mortality rate (adjusted
HR 1.510, 95% CI 1.347 to 1.693). Diabetes that developed during the trial among subjects
on placebo (n = 169) was also associated with increased CV adverse outcome (adjusted
HR 1.562, 95% CI 1.117 to 2.184) and total mortality rate (adjusted HR 1.348, 95%
CI 1.051 to 1.727). However, diabetes that developed among subjects during diuretic
therapy (n = 258) did not have significant associations with CV mortality rate (adjusted
HR 1.043, 95% CI 0.745 to 1.459) or total mortality rate (adjusted HR 1.151, 95% CI
0.925 to 1.433). Diuretic treatment in subjects who had diabetes was strongly associated
with lower long-term CV mortality rate (adjusted HR 0.688, 95% CI 0.526 to 0.848)
and total mortality rate (adjusted HR 0.805, 95% CI 0.680 to 0.952). Thus, chlorthalidone-based
treatment improved long-term outcomes, especially among subjects who had diabetes.
Subjects who had diabetes associated with chlorthalidone had no significant increase
in CV events and had a better prognosis than did those who had preexisting diabetes.
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Article info
Publication history
Accepted:
August 24,
2004
Received:
July 7,
2004
Footnotes
This study was supported in part by contracts with the National Heart, Lung, and Blood Institute, Bethesda, Maryland, and the National Institute on Aging, Bethesda, Maryland; and a grant from the Robert Wood Johnson Foundation, Princeton, New Jersey.
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Copyright
© 2005 Excerpta Medica Inc. Published by Elsevier Inc. All rights reserved.
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