Pharmacologic Prevention of Incident Atrial Fibrillation: Long-Term Results From the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial)

Circ Arrhythm Electrophysiol. 2017 Dec;10(12):e005463. doi: 10.1161/CIRCEP.117.005463.


Background: Although atrial fibrillation (AF) guidelines indicate that pharmacological blockade of the renin-angiotensin system may be considered for primary AF prevention in hypertensive patients, previous studies have yielded conflicting results. We sought to determine whether randomization to lisinopril reduces incident AF or atrial flutter (AFL) compared with chlorthalidone in a large clinical trial cohort with extended post-trial surveillance.

Methods and results: We performed a secondary analysis of the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), a randomized, double-blind, active-controlled clinical trial that enrolled hypertensive individuals ≥55 years of age with at least one other cardiovascular risk factor. Participants were randomly assigned to receive amlodipine, lisinopril, or chlorthalidone. Individuals with elevated fasting low-density lipoprotein cholesterol levels were also randomized to pravastatin versus usual care. The primary outcome was the development of either AF or AFL as diagnosed by serial study ECGs or by Medicare claims data. Among 14 837 participants without prevalent AF or AFL, 2514 developed AF/AFL during a mean 7.5±3.2 years of follow-up. Compared with chlorthalidone, randomization to either lisinopril (hazard ratio, 1.04; 95% confidence interval, 0.94-1.15; P=0.46) or amlodipine (hazard ratio, 0.93; 95% confidence interval, 0.84-1.03; P=0.16) was not associated with a significant reduction in incident AF/AFL.

Conclusions: Compared with chlorthalidone, treatment with lisinopril is not associated with a meaningful reduction in incident AF or AFL among older adults with a history of hypertension.

Clinical trial registration: URL: Unique identifier: NCT00000542.

Keywords: antihypertensive agents; atrial fibrillation; atrial flutter; primary prevention; renin-angiotensin system.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Amlodipine / adverse effects
  • Amlodipine / therapeutic use*
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / epidemiology
  • Atrial Fibrillation / physiopathology
  • Atrial Fibrillation / prevention & control*
  • Atrial Flutter / diagnosis
  • Atrial Flutter / epidemiology
  • Atrial Flutter / physiopathology
  • Atrial Flutter / prevention & control*
  • Chlorthalidone / adverse effects
  • Chlorthalidone / therapeutic use*
  • Double-Blind Method
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hypertension / diagnosis
  • Hypertension / drug therapy*
  • Hypertension / epidemiology
  • Hypertension / physiopathology
  • Incidence
  • Lisinopril / adverse effects
  • Lisinopril / therapeutic use*
  • Male
  • Middle Aged
  • Myocardial Infarction / diagnosis
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / prevention & control*
  • Primary Prevention / methods*
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • United States / epidemiology


  • Antihypertensive Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Amlodipine
  • Lisinopril
  • Chlorthalidone

Associated data