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Apixaban, dabigatran found effective, safe for extended post-VTE therapy

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Weigh risks, benefits of extended anticoagulation

Balancing the risks and benefits of extended anticoagulation is difficult, and deciding whether or when to stop the treatment remains a challenge, said Dr. Jean M. Connors.

Neither apixaban nor dabigatran are approved for short-term or extended treatment of VTE; rivaroxaban is the first of the new anticoagulants to gain such approval. However, the finding that apixaban was as effective in a low dose as it was at the full therapeutic dose, with the same bleeding risk, "may tip the risk-to-benefit ratio in favor of extended treatment for this patient population."

"The crux of using the new oral anticoagulants in clinical practice ... lies in the selection of appropriate patients. Patients in these studies were younger (average age, 56 years), with fewer coexisting diseases and a lower bleeding risk than patients typically seen in practice," and they had no strong indications for continuing anticoagulation, such as cancer or antiphospholipid syndrome.

Patients at the greatest risk of VTE recurrence are the ones who stand to benefit most from extended anticoagulation. Better risk-stratification strategies are needed to identify these patients, she said.

Dr. Connors is in the hematology division, department of medicine, at Brigham and Women’s Hospital, Boston. She reported no financial conflicts of interest. These remarks were taken from her editorial accompanying Dr. Agnelli’s and Dr. Schulman’s reports (N. Engl. J. Med. 2013 Feb. 21 [doi:10.1056/NEJMe1215678]).


 

FROM THE NEW ENGLAND JOURNAL OF MEDICINE

In RE-MEDY, this outcome occurred in 1.8% of the dabigatran group and 1.3% of the warfarin group, thus meeting the criteria for noninferiority to warfarin in preventing recurrent or fatal VTE.

In RE-SONATE, this outcome occurred in 0.4% of the dabigatran group, compared with 5.6% of the placebo group, so the drug was significantly more effective than placebo at preventing recurrent or fatal VTE.

Dabigatran was associated with markedly fewer major bleeding events (0.9% vs. 1.8%) and clinically relevant bleeding events (5.6% vs. 10.2%) than was warfarin. However, the drug was associated with more major or clinically relevant bleeding events than was placebo (5.3% vs 1.8%).

In addition, there was a higher rate of acute coronary events with dabigatran (0.9%) than with warfarin (0.2%), although the number of affected patients was small. A recent meta-analysis of seven noninferiority trials also showed a significantly higher risk of MI or acute coronary syndromes with dabigatran than with the comparators. "Whether dabigatran increases the risk of MI is therefore still unclear," Dr. Schulman and his associates said.

AMPLIFY-EXT was funded by Bristol-Myers Squibb (BMS) and Pfizer; Dr. Agnelli reported ties to Bayer, Boehringer Ingelheim (BI), Daiichi Sankyo, BMS, and Sanofi-Aventis, and his associates reported ties to numerous industry sources. RE-MEDY and RE-SONATE were funded by BI; Dr. Schulman and his associates reported ties to numerous industry sources.

UPDATED 2/21: An earlier version of this article transposed the trial names in this instance only. The names were correct in all other instances.

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