NEW YORK (Reuters Health) – For patients with atrial fibrillation (AF) on long-term warfarin therapy, an interruption in treatment more than doubles the risk of death or a thromboembolic event in the next 90 days, according to a Danish study reported in the European Heart Journal online December 23.
“This underlines the importance of careful and individual consideration of the balance between risk of thrombosis and bleeding before interrupting warfarin treatment,” the authors advise.
Dr. Jakob Raunso, at Copenhagen University Hospital Gentofte, Hellerup, and colleagues point out that patients with AF often do not comply with anticoagulant therapy or discontinue treatment because of apparently stable conversion to sinus rhythm or the need for surgery – but the risk entailed with interruption of ongoing warfarin therapy is unknown.
To investigate, the team analyzed data on 48,989 Danish patients treated with warfarin after hospitalization for AF between 1997 and 2008. Treatment was interrupted for a median duration of 36 days at least once in 35,396 (72%) of these subjects, and 8255 deaths or thromboembolic events (the composite endpoint) occurred during treatment interruption, the researchers report.
The event incidence rate was assessed for successive intervals of 90 days from the point of discontinuation, and showed an early clustering.
Specifically, there were 2717 events during the first 90 days, which translated to an incidence rate of 31.6 per 100 patient-years. The number of occurrences in subsequent 90-day intervals were 835, 500, and 427, and the corresponding incidence rates were 17.7, 12.3, and 11.4 events per 100 patient-years, the data indicate.
Comparing event rates in the first three 90-day intervals to the fourth interval, the authors calculated that the incidence rate ratio was 2.5 for the combined endpoint during the first 90 days of interruption.
In discussing the results, Dr. Raunso and colleagues comment: “It is debatable whether the increase in risk found in the present study is a true rebound effect due to pharmacological properties of warfarin or a ‘catch-up’ effect where the individuals’ inherent thrombotic risk results in events as soon as the anticoagulation effect wears off.”
However, they note that several studies have indicated that levels of clotting factor VII rise above normal levels when anticoagulation is stopped.
Given the findings of their study, they write, “This leads us to conclude that interruption of warfarin treatment frequently occurs and that a sharp increase in incidence of thrombo-embolism or death after interruption of warfarin treatment is evident and may have serious clinical consequences.”
SOURCE:
Eur Heart J 2011.
