Atrial Fibrillation at Baseline and During Follow-Up in ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial)

Received 22 December 2008; received in revised form 7 August 2009; accepted 18 August 2009.

Objectives

The ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) determined that treatment with amlodipine, lisinopril, or doxazosin was not superior to thiazide-like diuretic (chlorthalidone) in preventing coronary heart disease (CHD) or other cardiovascular events. This subanalysis examines baseline prevalence and in-trial incidence of new-onset atrial fibrillation (AF) or atrial flutter (AFL) and their influence on clinical outcomes.

Background

Limited information is available on whether atrial fibrillation incidence is affected differentially by different classes of antihypertensive medications or treatment with statins.

Methods

AF/AFL was identified from baseline and follow-up electrocardiograms performed biannually. Analyses were performed to identify characteristics associated with baseline AF/AFL and its subsequent incidence.

Results

AF/AFL was present at baseline in 423 participants (1.1%), more frequent in men (odds ratio: 1.72; 95% confidence interval [CI]: 1.37 to 2.17) and nonblacks (odds ratio: 2.09; 95% CI: 1.58 to 2.75). Its prevalence increased with age (p < 0.001) and was associated with CHD, cardiovascular disease, obesity, and high-density lipoprotein cholesterol <35 mg/dl. New-onset AF/AFL was associated with the same baseline risk factors plus electrocardiogram left ventricular hypertrophy. It occurred in 641 participants (2.0%) and, excluding doxazosin, did not differ by antihypertensive treatment group or, in a subset of participants, by pravastatin versus usual care. Baseline AF/AFL was associated with increased mortality (hazard ratio [HR]: 2.82; 95% CI: 2.36 to 3.37; p < 0.001), stroke (HR: 3.63; 95% CI: 2.72 to 4.86; p < 0.001), heart failure (HR: 3.17; 95% CI: 2.38 to 4.25; p < 0.001), and fatal CHD or nonfatal myocardial infarction (HR: 1.64; 95% CI: 1.22 to 2.21; p < 0.01). There was a nearly 2.5-fold increase in mortality risk when AF/AFL was present at baseline or developed during the trial (HR: 2.42; 95% CI: 2.11 to 2.77; p < 0.001).

Conclusions

In this high-risk hypertensive population, pre-existing and new-onset AF/AFL were associated with increased mortality. Excluding doxazosin, treatment assignment to either antihypertensive drugs or pravastatin versus usual care did not affect AF/AFL incidence. (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial [ALLHAT]; NCT00000542)

Key Words: hypertension, atrial fibrillation, clinical trial, chlorthalidone, amlodipine, lisinopril, doxazosin, pravastatin

⁎ Los Angeles County/University of Southern California Medical Center, Los Angeles, California

† University of Texas Health Science Center at Houston, School of Public Health, Houston, Texas

‡ University of Minnesota, Minneapolis, Minnesota

§ San Francisco Veterans Affairs Medical Center, San Francisco, California

∥ Division of Prevention and Population Sciences, National Heart, Lung, and Blood Institute, Bethesda, Maryland

¶ Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana

Reprint requests and correspondence: Dr. Charles E. Ford, The University of Texas School of Public Health, 1200 Herman Pressler Drive, E-827, Houston, Texas 77030

This research was supported by Health and Human Services contract number N01-HC-35130 from the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, Maryland. Additional financial support was provided by Pfizer, Inc. Study medications were supplied by Pfizer, Inc. (amlodipine and doxazosin), AstraZeneca (atenolol and lisinopril), and Bristol-Myers Squibb (pravastatin). Dr. Davis is on the Data Safety Monitoring Board of Takeda Pharmaceuticals.

PII: S0735-1097(09)02924-6

doi:10.1016/j.jacc.2009.08.020

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