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Figure.
Kaplan-Meier Estimates for Discontinuation of Warfarin Therapy
Kaplan-Meier Estimates for Discontinuation of Warfarin Therapy

Kaplan-Meier curves for the discontinuation of warfarin therapy among patients with nonvalvular atrial fibrillation who did or did not undergo electrical cardioversion (ECV) or radiofrequency ablation (RFA). The estimated 1-year discontinuation rates are 51.2% for patients who underwent ECV or RFA and 27.8% for patients who did not.

Table.  
Unadjusted and Multivariable Predictors of Discontinuation of Warfarin Therapy Within 1 Year
Unadjusted and Multivariable Predictors of Discontinuation of Warfarin Therapy Within 1 Year
1.
Zalesak  M, Siu  K, Francis  K,  et al.  Higher persistence in newly diagnosed nonvalvular atrial fibrillation patients treated with dabigatran versus warfarin.  Circ Cardiovasc Qual Outcomes. 2013;6(5):567-574.PubMedGoogle ScholarCrossref
2.
Rosendaal  FR, Cannegieter  SC, van der Meer  FJ, Briët  E.  A method to determine the optimal intensity of oral anticoagulant therapy.  Thromb Haemost. 1993;69(3):236-239.PubMedGoogle Scholar
3.
Lip  GY, Nieuwlaat  R, Pisters  R, Lane  DA, Crijns  HJ.  Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation.  Chest. 2010;137(2):263-272.PubMedGoogle ScholarCrossref
4.
January  CT, Wann  LS, Alpert  JS,  et al; ACC/AHA Task Force Members.  2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society.  Circulation. 2014;130(23):e199-e267.PubMedGoogle ScholarCrossref
5.
Castellucci  LA, Shaw  J, van der Salm  K,  et al.  Self-reported adherence to anticoagulation and its determinants using the Morisky medication adherence scale.  Thromb Res. 2015;136(4):727-731.PubMedGoogle ScholarCrossref
Research Letter
March 2017

Discontinuation of Warfarin Therapy for Patients With Atrial Fibrillation: The Michigan Anticoagulation Quality Improvement Initiative Experience

Author Affiliations
  • 1Frankel Cardiovascular Center, University of Michigan Health System, Ann Arbor
  • 2Henry Ford Hospital, Detroit, Michigan
  • 3Huron Valley Sinai-Cardiology and Vascular Associates, Commerce Township, Michigan
JAMA Cardiol. 2017;2(3):341-343. doi:10.1001/jamacardio.2016.5041

The use of warfarin significantly reduces the risk of stroke among patients with atrial fibrillation (AF). Unfortunately, up to 60% of patients discontinue therapy within the first year.1 Prior studies did not assess the quality of warfarin therapy or the occurrence of electrical cardioversion (ECV) or radiofrequency ablation (RFA) as predictors of discontinuation of warfarin therapy.

Methods

Within the Michigan Anticoagulation Quality Improvement Initiative, a 6-center Blue Cross Blue Shield of Michigan/Blue Care Network–sponsored collaborative of anticoagulation management services, we explored the discontinuation rate of warfarin therapy among a randomly sampled, diverse inception cohort of unselected patients with AF. Institutional review board approval was gained at all 6 Michigan Anticoagulation Quality Improvement Initiative sites, and informed consent was waived because the data was collected retrospectively. For each patient, we calculated the Rosendaal time in the therapeutic range and the Congestive Heart Failure, Hypertension, Age, Diabetes Mellitus Stroke or Systemic Embolism, Vascular Disease, and Sex Characteristic (CHA2DS2-VASc) score for stroke risk.2,3 The statistical significance for all P values was set at .05. We explored the predictive ability of these measures and the scheduling of an ECV or RFA based on discontinuation rates among patients enrolled in warfarin therapy from August 2011 to December 2013 and followed up through June 2015.

Results

Of the 734 patients initiating warfarin therapy for nonvalvular AF between August 2011 and December 2013, 270 (36.8%) discontinued therapy within 1 year of initiation (118 of 218 patients [54.1%] with ECV or RFA and 152 of 516 patients [29.5%] without ECV or RFA; P < .001). The Kaplan-Meier estimated probability that a patient would discontinue warfarin therapy within the first year was 34.8% and was greater for patients with ECV or RFA (P < .001) (Figure).

Patients who discontinued warfarin therapy within the first year were more likely than patients who continued therapy to have undergone ECV or RFA (43.7% vs 21.6%; P < .001), a lower CHA2DS2-VASc score (mean [SD] score, 3.0 [1.9] vs 3.7 [1.6]; P < .001), and a lower time in the therapeutic range in the first year (mean [SD], 51.2% [22.7%] vs 65.5% [15.2%]; P < .001). Race/ethnicity was not a statistically significant predictor of discontinuation of warfarin therapy. In the multivariable model (Table), predictors of discontinuation of warfarin therapy within the first year include having undergone ECV or RFA (hazard ratio, 1.86; 95% CI, 1.32-2.61), CHA2DS2-VASc risk group (hazard ratio, 3.89; 95% CI, 2.05-7.36 for low score [0] vs high score [2-9]), and low time in the therapeutic range (hazard ratio, 1.45; 95% CI, 1.33-1.58 for each 10% decrease).

Discussion

The association of ECV or RFA with discontinuation of warfarin therapy is an important consideration given the lack of consensus around long-term stroke risk following ECV or RFA. Guidelines suggest at least 4 to 8 weeks of anticoagulation following ECV but do not specify if stopping anticoagulation is appropriate after that initial period.4 Conclusive data are needed regarding the efficacy of extended prophylaxis with warfarin beyond 4 to 8 weeks after a successful ECV or RFA.

Identifying poor-quality warfarin control as a predictor of discontinuation has important implications given the abundance of alternative therapies. For some clinicians, poor warfarin therapy control indicates a need to change anticoagulant therapy. While it may seem appealing to use a direct oral anticoagulant for patients with poorly controlled warfarin therapy, there are many situations in which switching is not recommended. Early reports indicate that patients with AF prescribed direct-acting oral anticoagulants for stroke prevention have rates of discontinuation similar to those of warfarin-treated patients.5

The strengths of this analysis include using an unselected inception cohort of warfarin-treated patients at 6 health centers and medical record–abstracted data instead of billing codes for analysis. Our study’s limitations include the potential for unmeasured confounders in observational studies, the inability to characterize index AF diagnoses (eg, postoperative and paroxysmal), and the single-state location of all of the clinics.

Despite these limitations, our study demonstrates a high rate of discontinuation of warfarin therapy within the first year, especially among patients undergoing ECV or RFA. This suggests a need to better define which patients with AF undergoing ECV or RFA should continue anticoagulation. Additionally, we identified poor-quality warfarin care as a strong predictor of medication discontinuation, without transition to another oral anticoagulant. Further efforts are needed to increase the use and persistence of anticoagulation therapy among patients with nonvalvular AF and to understand the implications of ECV or RFA as an indication for anticoagulation therapy.

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Article Information

Corresponding Author: Geoffrey D. Barnes, MD, MSc, Frankel Cardiovascular Center, University of Michigan Medical Health System, 2800 Plymouth Rd, Bldg 14, Room G101, Ann Arbor, MI 48109-2800 (gbarnes@umich.edu).

Published Online: January 4, 2017. doi:10.1001/jamacardio.2016.5041

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Barnes received research support from Bristol-Myers Squib/Pfizer, grant T32-HL007853 (from the National Heart, Lung, and Blood Institute), and consulting fees from Portola and Aralez. Dr Kaatz received consulting fees from Boehringer Ingelheim, Janssen, Daiichi Sankyo, Bristol-Myers Squibb, and Pfizer and served on the speaker’s bureau for Janssen, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, and CSL Behring. Dr Froehlich received consulting fees from Merck, Bristol-Myers Squibb, Pfizer, Sanofi-Aventis, and Janssen and grants from Bristol-Myers Squibb/Pfizer. No other disclosures are reported.

Funding/Support: The Michigan Anticoagulation Quality Improvement Initiative is funded by Blue Cross Blue Shield of Michigan.

Role of the Funder/Sponsor: Blue Cross Blue Shield of Michigan had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Previous Presentation: This study was presented in part at the American Heart Association Scientific Sessions; November 19, 2013; Dallas, Texas.

Additional Contributions: We acknowledge the contributions of Steve Almany, MD, William Beaumont Hospital Michigan Heart Group, Royal Oak, to this project.

References
1.
Zalesak  M, Siu  K, Francis  K,  et al.  Higher persistence in newly diagnosed nonvalvular atrial fibrillation patients treated with dabigatran versus warfarin.  Circ Cardiovasc Qual Outcomes. 2013;6(5):567-574.PubMedGoogle ScholarCrossref
2.
Rosendaal  FR, Cannegieter  SC, van der Meer  FJ, Briët  E.  A method to determine the optimal intensity of oral anticoagulant therapy.  Thromb Haemost. 1993;69(3):236-239.PubMedGoogle Scholar
3.
Lip  GY, Nieuwlaat  R, Pisters  R, Lane  DA, Crijns  HJ.  Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation.  Chest. 2010;137(2):263-272.PubMedGoogle ScholarCrossref
4.
January  CT, Wann  LS, Alpert  JS,  et al; ACC/AHA Task Force Members.  2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society.  Circulation. 2014;130(23):e199-e267.PubMedGoogle ScholarCrossref
5.
Castellucci  LA, Shaw  J, van der Salm  K,  et al.  Self-reported adherence to anticoagulation and its determinants using the Morisky medication adherence scale.  Thromb Res. 2015;136(4):727-731.PubMedGoogle ScholarCrossref
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