Clinical Briefs
How Long Should We Treat with Warfarin for Symptomatic Venous Thromboembolism?
SOURCE: Middeldorp S, Hutten BA. Long-term vs short-term therapy with vitamin K antagonists for symptomatic venous thromboembolism. JAMA 2015;314:72-73.
After a symptomatic episode of acute venous thromboembolism, duration of treatment must be individualized. For leg thromboses, the most recent guidelines on antithrombotic therapy by the American College of Chest Physicians (AT9) suggest the decision for duration of warfarin treatment depends on whether the thrombosis is proximal or distal, whether it is provoked (e.g., surgery, trauma) or unprovoked, and whether the level of bleeding risk is low-moderate or high.
Middeldorp and Hutten summarized the evidence by reviewing a meta-analysis of 10 randomized trials (n = 1771) that compared short-term anticoagulation (1-3 months) vs long-term anticoagulation (3-48 months) for the outcome of recurrent venous thrombosis (DVT). Although warfarin was the most commonly employed anticoagulant in this meta-analysis, some trials used acenocoumarol, fluindione, or dicoumarol. For rate of recurrent DVT, no clinical trial indicated superior outcomes for short-term treatment.
Overall, long-term anticoagulation was associated with about an 80% reduction in recurrent venous thromboembolic events compared to short-term anticoagulation (30 events/1771 persons vs 155 events/1765 persons, respectively).
Despite the confirmed risk reduction, clinicians must still take baseline bleeding risk into consideration, since the risk-benefit balance shifts as bleeding risk increases.
Extending the Window of Anticoagulation After Pulmonary Embolus
SOURCE: Couturaud F, et al. Six months vs extended oral anticoagulation after a first episode of pulmonary embolism: The PADIS-PE randomized clinical trial. JAMA 2015;314:31-40.
Utilization of anticoagulation in patients who have suffered an unprovoked pulmonary embolus (PE) is a complex issue. The most recent edition of the guidelines for antithrombotic therapy issued by the American College of Chest Physicians (AT9) suggests that after a minimum of 3 months’ anticoagulation post-PE, treatment decisions must be individualized based on bleeding risk. If bleeding risk is considered “low-moderate,” then indefinite anticoagulant therapy (with periodic reassessment) is suggested. But are there good outcomes data to support such a recommendation?
Couturaud et al performed a double-blind, placebo-controlled trial in 371 PE patients ascertaining risk of recurrent thromboembolism or major bleeding associated with extended anticoagulation. Patients who had already been treated with 6 months of warfarin were randomized to an additional 18 months of warfarin or placebo. Extended anticoagulation reduced recurrent thromboembolism by 85% (3 events vs 25 events). This benefit was counterbalanced by an increased incidence of major bleeding (4 patients in the warfarin group, 1 in the placebo group). There was no between-group difference in mortality.
After the initial 6-month treatment of PE, extended anticoagulation of up to 18 months dramatically reduces risk of recurrence at the expense of more episodes of major bleeding. Based on patient priorities and preferences, treatment will have to be individualized.
Stroke Accelerates Long-term Process of Cognitive Decline
SOURCE: Levine DA, et al. Trajectory of cognitive decline after incident stroke. JAMA 2015;314:41-51.
It would likely come as no surprise that acute stroke can lower cognitive function. It might, however, come as a surprise that post-stroke incidence of cognitive impairment (that is, onset of cognitive impairment significantly after the period of acute stroke, rather than immediately post-stroke) is higher, and that once cognitive impairments ensue, the rate of further cognitive decline is faster in persons post-stroke than in controls.
These insights emerged from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke, n = 30,239), which collected data on baseline cognitive function in adults > 45 years of age prior to incident stroke. Hence, the impact of stroke on cognition, as well as the impact on longer-term cognitive decline, is measurable within this data set. In this publication, persons with pre-existing cognitive impairment (that is, pre-stroke) were excluded from analysis.
Following an acute stroke, executive function declined significantly — more steeply than in controls; encouragingly, the capacity for new learning post-stroke did not decline.
Stroke is associated not only with acute cognitive decline in the immediate post-stroke period, but also with a more rapid slope of cognitive function decline over the long-term.
Treating symptomatic venous thromboembolism with warfarin; extending the window of anticoagulation after pulmonary embolus; and stroke accelerates long-term process of cognitive decline.
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