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QUARTERLY FOCUS ISSUE: HEART RHYTHM DISORDERS

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

L. Julian Haywood, MD^_*, Charles E. Ford, PhD^,_*, Richard S. Crow, MD, Barry R. Davis, MD, PhD, Barry M. Massie, MD, Paula T. Einhorn, MD^||, Angela Williard, RN, BSN^¶ for the ALLHAT Collaborative Research Group

^_* 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

Manuscript received December 22, 2008; revised manuscript received August 7, 2009, accepted August 18, 2009.

^_* 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 (Email: charles.e.ford{at}uth.tmc.edu).

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

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   AF = atrial fibrillation   AFL = atrial flutter   ARB = angiotensin receptor blocker   ASCVD = atherosclerotic cardiovascular disease   BMI = body mass index   BP = blood pressure   CHD = coronary heart disease   CI = confidence interval   CVD = cardiovascular disease   ECG = electrocardiogram   eGFR = estimated glomerular filtration rate   HR = hazard ratio   LVH = left ventricular hypertrophy   OR = odds ratio   PH = proportional hazards