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Original Investigation
August 2016

Effect of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) on Conduction System Disease

Author Affiliations
  • 1Knight Cardiovascular Institute, Oregon Health and Science University, Portland
  • 2Department of Epidemiology and Prevention, Section of Cardiology, Wake Forest School of Medicine, Winston-Salem, North Carolina
  • 3Department of Internal Medicine, Section of Cardiology, Wake Forest School of Medicine, Winston-Salem, North Carolina
  • 4Section of Cardiovascular Medicine, Boston University School of Medicine, Boston, Massachusetts
  • 5Department of Biostatistics, University of Texas School of Public Health, Houston
  • 6Division of Cardiovascular Medicine, Keck School of Medicine, University of Southern California, Los Angeles
  • 7Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis
  • 8Center for Arrhythmia Prevention, Division of Preventive Medicine and Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
  • 9Section of Electrophysiology, Division of Cardiology, Department of Medicine, University of California, San Francisco

Copyright 2016 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.

JAMA Intern Med. 2016;176(8):1085-1092. doi:10.1001/jamainternmed.2016.2502

Importance  Cardiac conduction abnormalities are associated with an increased risk for morbidity and mortality, and understanding factors that accelerate or delay conduction system disease could help to identify preventive and therapeutic strategies. Antifibrotic and anti-inflammatory properties of angiotensin-converting enzyme inhibitors and treatment for hyperlipidemia may reduce the risk for incident conduction system disease.

Objective  To identify the effect of pharmacologic therapy randomization and clinical risk factors on the incidence of conduction system disease.

Design, Setting, and Participants  This secondary analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) investigation acquired data from 623 North American centers. A total of 21 004 ambulatory individuals 55 years or older with hypertension and at least 1 other cardiac risk factor were included in the analysis.

Interventions  Participants were randomly assigned to receive amlodipine besylate, lisinopril, or chlorthalidone. Individuals with elevated fasting low-density lipoprotein cholesterol levels were also randomized to pravastatin sodium vs usual care.

Main Outcomes and Measures  An electrocardiogram (ECG) was obtained at study enrollment and every 2 years of follow-up. The development of incident first-degree atrioventricular block, left anterior fascicular block, incomplete left bundle branch block (LBBB), LBBB, incomplete right bundle branch block (RBBB), RBBB, or intraventricular conduction delay was assessed by serial ECGs.

Results  The 21 004 participants (11 758 men [56.0%]; 9246 women [44.0%]; mean [SD] age, 66.5 [7.3] years) underwent a mean (SD) follow-up of 5.0 (1.2) years. Among the 1114 participants who developed any conduction defect, 389 developed LBBB, 570 developed RBBB, and 155 developed intraventricular conduction delay. Compared with chlorthalidone, randomization to lisinopril was associated with a significant 19% reduction in conduction abnormalities (hazard ratio [HR], 0.81; 95% CI, 0.69-0.95; P = .01). Treatment with amlodipine, however, was not associated with a significant difference in conduction outcome events (HR, 0.94; 95% CI, 0.81-1.09; P = .42). Similarly, pravastatin treatment was not associated with a reduced adjusted risk for incident disease compared with usual hyperlipidemia treatment (HR, 1.13; 95% CI, 0.95-1.35; P = .18). Increased age (HR, 1.47; 95% CI, 1.34-1.63; P < .001), male sex (HR, 0.59; 95% CI, 0.50-0.73; P < .001), white race (HR, 0.59; 95% CI, 0.50-0.70; P < .001), diabetes (HR, 1.23; 95% CI, 1.07-1.42; P = .003), and left ventricular hypertrophy (HR, 3.20; 95% CI, 2.61-3.94; P < .001) were also independently associated with increased risk for conduction system disease.

Conclusions and Relevance  Incident conduction system disease is significantly reduced by lisinopril therapy and is independently associated with multiple clinical factors. Further studies are warranted to determine whether pharmacologic treatment affects conduction abnormality outcomes, including pacemaker implantation.

Trial Registration Identifier: NCT00000542