Influence of Prevalent and Incident Atrial Fibrillation on Post-Trial Major Events in ALLHAT

J Natl Med Assoc. 2017 Autumn;109(3):172-181. doi: 10.1016/j.jnma.2017.02.005. Epub 2017 Mar 18.


Aims: Limited information is available on long-term antihypertensive and lipid-lowering therapy effects on hypertensive patients with atrial fibrillation/flutter (AF/AFL) compared to those without. AF/AFL at baseline or during the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) (mean follow-up 4.9 years) markedly increased risk of stroke, heart failure, CHD, and all-cause mortality. We aimed to determine if AF/AFL continued to impact outcomes during post-trial follow-up (mean 3.8 years).

Methods: Patients were randomized to chlorthalidone, amlodipine, or lisinopril, and to pravastatin vs. usual care in the lipid-lowering trial (LLT). Of 31,473 available subjects, AF/AFL occurred in 854; 383/14,371 chlorthalidone (2.7%), 247/8565 amlodipine (2.9%), and 224/8537 lisinopril (2.6%). Post-hoc analyses utilized administrative databases for post-trial data. Individuals with AF/AFL were compared to those without during post-trial. Outcomes were analyzed by treatment groups for the antihypertensive and LLT trials.

Results: Among 854 AF/AFL participants, 491 (57.5%) died: 220 in-trial, 271 post-trial. Ten-year all-cause mortality rates for those with in-trial AF/AFL were similar for chlorthalidone and lisinopril, but lower for amlodipine (68, 66, and 49 per 100 persons, respectively); adjusted HR for amlodipine vs. chlorthalidone was 0.68 (95% CI, 0.54-0.87). Ten-year all-cause mortality rates were 57 vs. 65 per 100 persons (pravastatin vs. usual care); non-CVD mortality rates, 18 vs. 39 per 100 persons (pravastatin vs. usual care) (adjusted HR = 0.46, 95% CI, 0.24-0.86).

Conclusion: Post-trial follow-up revealed continued deleterious AF/AFL effects. The amlodipine (ALLHAT) and pravastatin (ALLHAT-LLT) treatment groups showed lower all-cause and non-CVD mortality compared to the chlorthalidone and usual-care groups, respectively.

Keywords: Antihypertensive therapy; Atrial fibrillation; Heart failure; Stroke.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antihypertensive Agents / therapeutic use*
  • Atrial Fibrillation / complications*
  • Atrial Fibrillation / epidemiology
  • Case-Control Studies
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Hyperlipidemias / complications
  • Hyperlipidemias / drug therapy*
  • Hyperlipidemias / mortality
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Hypertension / mortality
  • Hypolipidemic Agents / therapeutic use*
  • Incidence
  • Male
  • Middle Aged
  • Prevalence
  • Risk Factors
  • Treatment Outcome


  • Antihypertensive Agents
  • Hypolipidemic Agents