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Managing Chronic Atrial Fibrillation: A Markov Decision Analysis Comparing Warfarin, Quinidine, and Low-Dose Amiodarone

Dennis L. Disch, MD; Mark L. Greenberg, MD; Peter T. Holzberger, MD; David J. Malenka, MD; and John D. Birkmeyer, MD
[+] Article, Author, and Disclosure Information

From the Department of Veterans Affairs Medical Center, White River Junction, Vermont; Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. Request for Reprints: Dennis L. Disch, MD, Cardiovascular Division, Washington University School of Medicine, 660 South Euclid Avenue, Box 8086, St. Louis, MO 63110. Acknowledgments: The authors thank Drs. H. Gilbert Welch, Robert A. Nease, and Harold C. Sox, Jr., for their helpful critiques of the decision model and the manuscript. Grant Support: Dr. Disch was supported by the Veterans Affairs fellowship in ambulatory care. Dr. Birkmeyer was supported by a training grant from the National Library of Medicine (NIH 5 T15 LM07044).

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1994;120(6):449-457. doi:10.7326/0003-4819-120-6-199403150-00001
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Objective: To compare the relative risks and benefits of several clinical strategies for managing patients with chronic atrial fibrillation.

Design: Five recent randomized, controlled trials of warfarin in atrial fibrillation, 6 randomized, controlled trials of quinidine, and 13 longitudinal studies of low-dose amiodarone were used. A MEDLINE search was also done (1966 to present).

Measurements: A Markov decision analysis model was used to assess outcomes in large, hypothetical cohorts of patients with atrial fibrillation followed from 65 to 70 years of age within four clinical strategies: 1) no treatment; 2) warfarin; 3) electrical cardioversion followed by quinidine to maintain normal sinus rhythm; and 4) electrical cardioversion followed by low-dose amiodarone.

Results: In this hypothetical cohort, fewer patients had disabling events with amiodarone (1.4%) than with quinidine (1.8%), warfarin (2.6%), or no treatment (7.4%). Amiodarone appeared to be associated with the lowest 5-year mortality (13.6%) when compared with warfarin (14.4%), quinidine (15.2%), and no treatment (18.2%). In terms of quality-adjusted life-years, amiodarone had the highest expected value (4.75 years), followed by warfarin (4.72 years), quinidine (4.68 years), and no treatment (4.55 years). Amiodarone remained the preferred strategy using the most plausible scenarios of risks associated with atrial fibrillation. Choices among warfarin, quinidine, and no treatment depended on estimates of bleeding rates with warfarin, stroke rates after discontinuing warfarin, quinidine-related mortality, and the quality of life with warfarin.

Conclusion: Cardioversion followed by low-dose amiodarone to maintain normal sinus rhythm appears to be a relatively safe and effective treatment for patients with chronic atrial fibrillation.


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Figure 1.
Schematic of the decision model.Table 1

The square is a “decision node” of which treatment strategy to use. The circles are “chance nodes” at which each patient faces several chance events. Each “disabled” state above represents several states in the actual model (for example, disabled from stroke, disabled from bleeding event). The asterisks indicate that the model was not sensitive to the corresponding variable when its value was varied over the plausible range reported in . See Methods for a full description of the Markov model. AF = atrial fibrillation; CV = cardioversion; NSR = normal sinus rhythm.

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Figure 2.
Risk profiles for each of the four treatment strategies after 5 years.

The analysis is based on a simulated cohort of hypothetical patients who enter the model at 65 years of age, 50% of whom are men. AF = atrial fibrillation; NSR = normal sinus rhythm.

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Figure 3.
The effect on the choice of therapy of varying assumptions about the quality of life for patients receiving warfarin.

As the perceived quality of life declines for patients receiving warfarin (more quality-of-life adjustment is made from right to left), the expected value of the warfarin strategy decreases substantially. In the baseline analysis, no quality adjustment is made for patients receiving warfarin. QALYs = quality-adjusted life-years.

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