Wednesday, December 23, 2015

How long should we treat with oral anticoagulants after VTE?

This question has been asked many times and in many ways through the years. Despite that, as the authors of a new study open their paper:

Importance The optimal duration of anticoagulation after a first episode of unprovoked pulmonary embolism is uncertain.

More from the paper:

Design, Setting, and Participants Randomized, double-blind trial (treatment period, 18 months; median follow-up, 24 months); 371 adult patients who had experienced a first episode of symptomatic unprovoked pulmonary embolism (ie, with no major risk factor for thrombosis) and had been treated initially for 6 uninterrupted months with a vitamin K antagonist were randomized and followed up between July 2007 and September 2014 in 14 French centers.

Interventions Warfarin or placebo for 18 months.

Main Outcomes and Measures The primary outcome was the composite of recurrent venous thromboembolism or major bleeding at 18 months after randomization. Secondary outcomes were the composite at 42 months (treatment period plus 24-month follow-up), as well as each component of the composite, and death unrelated to pulmonary embolism or major bleeding, at 18 and 42 months.

Results After randomization, 4 patients were lost to follow-up, all after month 18, and 1 withdrew due to an adverse event. During the 18-month treatment period, the primary outcome occurred in 6 of 184 patients (3.3%) in the warfarin group and in 25 of 187 (13.5%) in the placebo group (hazard ratio [HR], 0.22; 95% CI, 0.09-0.55; P = .001). Recurrent venous thromboembolism occurred in 3 patients in the warfarin group and 25 patients in the placebo group (HR, 0.15; 95% CI, 0.05-0.43); major bleeding occurred in 4 patients in the warfarin group and in 1 patient in the placebo group (HR, 3.96; 95% CI, 0.44 to 35.89). During the 42-month entire study period (including the study treatment and follow-up periods), the composite outcome occurred in 33 patients (20.8%) in the warfarin group and in 42 (24.0%) in the placebo group (HR, 0.75; 95% CI, 0.47-1.18). Rates of recurrent venous thromboembolism, major bleeding, and unrelated death did not differ between groups.

Conclusions and Relevance Among patients with a first episode of unprovoked pulmonary embolism who received 6 months of anticoagulant treatment, an additional 18 months of treatment with warfarin reduced the composite outcome of recurrent venous thrombosis and major bleeding compared with placebo. However, benefit was not maintained after discontinuation of anticoagulation therapy.

From a related piece in ACP Hospitalist Weekly:

The authors noted that their primary outcome included 2 outcome measures that may not have been clinically equivalent, that newer anticoagulants were not examined, and that D-dimer levels were not used to guide therapy, among other limitations. However, they concluded that an additional 18 months of warfarin treatment in patients with first unprovoked PE improves outcomes versus placebo, although the improvement was not sustained after anticoagulant treatment was discontinued.

"Our results suggest that patients such as those who participated in our study require long-term secondary prophylaxis measures," the authors wrote. "Whether these should include systematic treatment with vitamin K antagonists, new anticoagulants or aspirin, or be tailored according to patient risk factors (including elevated D-dimer levels) needs further investigation."

1 comment:

james gaulte said...

I tend to think of "unprovoked"VTE as provoked by one or more unknown factors, which is consistent with the notion that medical conditions have basic underlying processes most of which remain to be determined.Having said that the concept of provoked versus unproved is well established and seems to have utility. This concept has significant limbic valence for me as I am on Apixban for 3 months after a pacemaker implantation.
The catheter manipulations in the subclavian artery sure seems like a likely provoker, though symptomatic PE post PM insertion is said to be quite rare. Given a PE I am relieved that a likely provoking incident is available to blame Rather than some mysterious, unidentified precipitating factor predisposing me to inappropriately form clots in the venous system which might sentence me to possibly lifelong anticoagulation.
And as the momentum to use NOACs instead of warfarin grows the relevance of still another article on the use of warfarin in DVT diminishes.