Characteristics and long-term follow-up of participants with peripheral arterial disease during ALLHAT.

BACKGROUND: Hypertension is a major risk factor for peripheral artery disease (PAD). Little is known about relative efficacy of antihypertensive treatments for preventing PAD.

OBJECTIVES: To compare, by randomized treatment groups, hospitalized or revascularized PAD rates and subsequent morbidity and mortality among participants in the Antihypertensive and Lipid-Lower Treatment to Prevent Heart Attack Trial (ALLHAT).

DESIGN: Randomized, double-blind, active-control trial in high-risk hypertensive participants.

PARTICIPANTS: Eight hundred thirty participants with specified secondary outcome of lower extremity PAD events during the randomized phase of ALLHAT.

INTERVENTIONS/EVENTS: In-trial PAD events were reported during ALLHAT (1994-2002). Post-trial mortality data through 2006 were obtained from administrative databases. Mean follow-up was 8.8 years.

MAIN MEASURES: Baseline characteristics and intermediate outcomes in three treatment groups, using the Kaplan-Meier method to calculate cumulative event rates and post-PAD mortality rates, Cox proportional hazards regression model for hazard ratios and 95 % confidence intervals, and multivariate Cox regression models to examine risk differences among treatment groups.

KEY RESULTS: Following adjustment for baseline characteristics, neither participants assigned to the calcium-channel antagonist amlodipine nor to the ACE-inhibitor lisinopril showed a difference in risk of clinically advanced PAD compared with those in the chlorthalidone arm (HR, 0.86; 95 % CI, 0.72-1.03 and HR, 0.98; 95 % CI, 0.83-1.17, respectively). Of the 830 participants with in-trial PAD events, 63 % died compared to 34 % of those without PAD; there were no significant treatment group differences for subsequent nonfatal myocardial infarction, coronary revascularizations, strokes, heart failure, or mortality.

CONCLUSIONS: Neither amlodipine nor lisinopril showed superiority over chlorthalidone in reducing clinically advanced PAD risk. These findings reinforce the compelling need for comparative outcome trials examining treatment of PAD in high-risk hypertensive patients. Once PAD develops, cardiovascular event and mortality risk is high, regardless of type of antihypertensive treatment.