Increased Short-Term Risk of Thrombo-Embolism or Death After Interruption of Warfarin Treatment in Patients With Atrial Fibrillation

Study Questions:

What is the risk and timing of thromboembolic events associated with interruptions of warfarin treatment in atrial fibrillation?


The authors reported the results of a retrospective nationwide cohort study of all patients in Denmark treated with warfarin for atrial fibrillation, using the Danish National Patient Registry. Analysis included patients with nonvalvular atrial fibrillation, greater than age 30, after a first hospitalization for atrial fibrillation with subsequent use of warfarin as documented through the Danish Registry of Medicinal Product Statistics. Warfarin use interruption was assumed to start when a patient ran out of available warfarin tablets, as calculated based on prescription claims. Incident rate ratios (IRRs) were calculated using Poisson regression for estimates of thromboembolic events and all-cause mortality.


Between 1997 and 2008, 48,980 atrial fibrillation patients were identified, of which 35,396 had one estimated warfarin interruption, among whom there were 8,255 deaths or thromboembolic events associated with treatment interruption. The timing of these events was clustered as follows: 2,717, 835, 500, and 427 events occurred during 0-90, 91-180, 181-270, and 271-360 days after warfarin treatment interruption, respectively. The corresponding crude incident rates were 31.6, 17.7, 12.3, and 11.4 events per 100 patient-years. By multivariable analysis, the initial 90-day interval after treatment interruption was associated with a markedly higher risk of death or thromboembolism (IRR, 2.5; 95% confidence interval, 2.3-2.8) versus the interval between 271 and 360 days after warfarin treatment interruption.


The authors concluded that, in patients with atrial fibrillation, an interruption of warfarin treatment is associated with a significantly increased short-term risk of death with thromboembolic events within the first 90 days after treatment interruption.


Although extensive data exist documenting the degree to which patients with atrial fibrillation are at risk for thromboembolic events on an annual basis, very little is known with much accuracy about the interpolated risk that patients face over shorter periods of time. The answer to this question is critical to the frequently faced clinical dilemma of when warfarin therapy can be interrupted, and for how long. This current study exploits the opportunity of the comprehensive nature of medical and health care information provided by the Danish national health care system to establish the statistical risk of thromboembolic events and death associated with interruptions of warfarin therapy. The study does not evaluate elective interruptions of therapy (such as those associated with surgical procedures), but rather identifies warfarin treatment interruption by identifying periods of time when supply of medication ran out. Furthermore, the median duration of treatment interruptions was 36 days, significantly exceeding the usual elective interruption for an invasive procedure. In spite of these limitations, the data are extremely useful, and suggest that the risk of thromboembolism or death is more than doubled within 90 days after warfarin treatment interruption for a median of 36 days.

Clinical Topics: Anticoagulation Management

Keywords: Thromboembolism, Risk, Warfarin, Denmark

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