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).