Relationship of antihypertensive treatment regimens and change in blood pressure to risk for heart failure in hypertensive patients randomly assigned to doxazosin or chlorthalidone: further analyses from the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial.
BACKGROUND
The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial reported that treatment initiated with doxazosin compared with chlorthalidone doubled the risk for heart failure in high-risk hypertensive patients (relative risk, 2.04 [95% CI, 1.79 to 2.32]). Patients assigned to doxazosin therapy had a mean in-trial systolic/diastolic blood pressure 3/0 mm Hg higher than that in patients assigned to chlorthalidone. Sixty-eight percent (6167 of 9061) of the former patients and 59% (9081 of 15 256) of the latter patients were given additional medications to achieve a target blood pressure of less than 140/90 mm Hg.


OBJECTIVE
To ascertain the influence of open-label antihypertensive drugs and subsequent blood pressure on relative risk for heart failure.


METHODS
Randomized, double-blind, active-controlled clinical trial.


METHODS
623 sites in the United States and Canada.


METHODS
Hypertensive patients 55 years of age or older with at least one additional risk factor for cardiovascular disease.


METHODS
Chlorthalidone (12.5 to 25 mg/d) or doxazosin (2 to 8 mg/d) for a planned follow-up of 4 to 8 years.


METHODS
Data on blood pressure, medication, and incident heart failure (treated outside hospital, hospitalized, or fatal) from February 1994 through December 1999.


RESULTS
After the treatment groups were categorized as having no exposure to open-label medications (monotherapy) or exposure to open-label therapy, the relative risk for heart failure with doxazosin versus chlorthalidone was 3.10 (CI, 2.51 to 3.82) and 1.42 (CI, 1.20 to 1.69), respectively. After adjustment for follow-up systolic/diastolic blood pressure, the overall relative risk was 2.00 (CI, 1.72 to 2.32).


CONCLUSIONS
In high-risk patients with hypertension, the higher risk for heart failure while taking doxazosin compared with chlorthalidone is attenuated but not eliminated by adding other antihypertensive drugs. The small observed difference in systolic blood pressure does not explain this increased risk.
Davis
Barry R
BR
The University of Texas School of Public Health, 1200 Herman Pressler Street, Houston, TX 77030, USA. bdavis@sph.uth.tmc.edu
Cutler
Jeffrey A
JA
Furberg
Curt D
CD
Wright
Jackson T
JT
Farber
Michael A
MA
Felicetta
James V
JV
Stokes
John D
JD
D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D002303:Cardiac Output, Low / Q000209:etiology / Q000517:prevention & control*; D002752:Chlorthalidone / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D017292:Doxazosin / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D017292:Doxazosin; D002752:Chlorthalidone