Warfarin resumption after GI tract bleeding associated with lower thrombosis risk

Issue: November 10, 2012

The resumption of warfarin therapy after an episode of gastrointestinal tract bleeding was associated with lower risk for thrombosis and death, according to study results.

Daniel M. Witt

Daniel M. Witt, PharmD, FCCP, BCPS, senior manager of clinical pharmacy services at Kaiser Permanente Colorado, and colleagues determined the incidence of thrombosis (stroke, systemic embolism and venous thromboembolism), recurrent gastrointestinal (GI) tract bleeding and death, as well as time until warfarin therapy was resumed during the 90 days after a GI bleeding event.

Researchers used administrative and clinical databases from Kaiser Permanente Colorado in their retrospective cohort study. Their analysis comprised 442 patients with a warfarin-associated index GI tract bleeding.

“The results highlight the clinical dilemma of managing warfarin therapy following a hospitalization or ED visit for GI tract bleeding,” Witt and colleagues wrote. “Although we observed a numerical increase in recurrent GI tract bleeding associated with not interrupting or resuming warfarin therapy in the 90 days after the index GI tract bleeding, this increase was not statistically significant. However, a decision not to resume warfarin therapy was associated with a significantly increased risk of both thrombosis and death from any cause.”

Following the index bleed, 260 patients (58.8%) resumed warfarin therapy, including 41 patients whose therapy was never stopped. Median time to resume therapy was 4 days.

Resuming warfarin therapy was associated with a lower risk for thrombosis (HR=0.05; 95% CI, 0.01-0.58) and lower risk for death (HR=0.31; 95% CI, 0.15-0.62). Further, resuming therapy lowered these risks without significantly increasing the risk for recurrent GI tract bleeding (HR=1.32; 95% CI, 0.5-3.57), according to the study results.

Among the 260 patients who resumed warfarin, there was one thrombotic event, 26 episodes of recurrent GI tract bleeding and 15 deaths in the 90 days after the initial GI tract bleeding event. Among the 182 patients who did not resume warfarin, there were 10 thrombotic events, 10 episodes of recurrent GI tract bleeding and 37 deaths.

“Our analysis suggests that, for many patients who have experienced GI tract bleeding, the benefits of resuming warfarin therapy will outweigh the risks,” the researchers wrote. “Further research will be needed to identify the optimal duration of warfarin interruption after a GI tract bleeding event and the patients for whom a more prolonged interruption can be justified.”

Daniel J. Brotman

In an accompanying editorial, Daniel J. Brotman, MD, director of the hospitalist program at Johns Hopkins Hospital in Baltimore, and Amir K. Jaffer, MD, associate professor at the University of Miami Miller School of Medicine, said the findings demonstrate that physicians and patients often are willing to resume anticoagulation after gastrointestinal tract bleeding.

Amir K. Jaffer

“On the basis of these observations, and in the absence of other studies providing competing data, we believe that most patients with warfarin-associated GI bleeding and indications for continued long-term antithrombotic therapy should resume anticoagulation within the first week following the hemorrhage,” they wrote.

“Although not specifically addressed in this study, we would hesitate to continue concurrent antiplatelet therapy in these patients without a compelling indication to do so — such as a recent coronary stent — and also would caution against extrapolating these findings to newer anticoagulants, such as dabigatran and rivaroxaban, that may be associated with more GI bleeding than warfarin when used long-term and whose effects are not easily reversed,” they added.

Reference:

Witt DM. Arch Intern Med. 2012;doi:10.1001/archinternmed.2012.4261.

Disclosure:

CSL Behring provided funding for the study.