December 19, 2011 (San Diego, CA) — Data from the RECOVER II study confirms the safety and efficacy of dabigatran (Pradaxa, Boehringer Ingelheim) when compared with warfarin for the treatment of patients with acute venous thromboembolism (VTE) . The new study included significantly more Asian patients than the 2500-patient RECOVER trial, note investigators, and the rates of recurrent VTE and bleeding were similar in these patients and non-Asian patients.
RECOVER II, presented last week at the American Society of Hematology 2011 Annual Meeting, led by Dr Sam Schulman (McMaster University, Hamilton, ON), was designed to replicate the results of RECOVER, given the low rate of the primary outcome--a composite of recurrent VTE or fatal pulmonary embolism (PE)--in the original trial. Also, studies that have tested the newer oral anticoagulants have recently expanded, including approximately 7000 patients in the rivaroxaban (Xarelto, Bayer/Johnson & Johnson) VTE trials and more than 5000 patients treated with apixaban (Eliquis, Bristol-Myers Squibb/Pfizer), making the original RECOVER study with dabigatran small in comparison.
"It's because the event rate is quite low nowadays, we felt 2500 was kind of small," said Schulman, referring to the first RECOVER trial. "And we also felt that a second study would be important in order to be able to get information about subgroups. Even with one study, although we can get enough information regarding the primary end point, we often can't say much about subgroup analyses."
In RECOVER II, 1279 patients were randomized to dabigatran 150 mg twice daily and 1289 patients randomized to warfarin. Regarding the primary outcome, recurrent VTE or PE occurred in 2.4% of patients treated with the new anticoagulant and in 2.2% of patients treated with warfarin, a difference that met the prespecified noninferiority margin (p < 0.0001). In RECOVER, the primary end point occurred in 2.4% of patients treated with dabigatran and 2.1% of patients treated with warfarin. Subgroup analyses, including in the 537 Asian patients, all showed that dabigatran was noninferior to warfarin.
Major bleeding events occurred in 15 patients treated with dabigatran and 22 patients treated with warfarin, a statistically nonsignificant difference in the treatment arms. Rates of any bleeding favored dabigatran, with 200 bleeding events in dabigatran-treated patients and 285 bleeding events in the warfarin group (hazard ratio 0.67; 95% CI 0.56–0.81). There was no difference in mortality rates and no difference in the rate of serious adverse events.
Similar to RECOVER, there were two more definite or likely acute coronary syndromes in the dabigatran-treated patients compared with those who received warfarin (five ACS events vs three ACS events, respectively).
"We think that dabigatran will be quite useful for patients with venous thromboembolism, acknowledging that in both studies it had a lead-in period with treatment," said Schulman. "The other two drugs, rivaroxaban and apixaban, don't have this in their VTE studies. However, if you ask around, a lot people don't feel this five days of [treatment with] low-molecular-weight heparin, nowadays usually injected at home by the patient, is a burden. It is a good alternative to warfarin because it does relieve the patient of the burden of frequent monitoring and dose adjustments."
Dabigatran is currently approved for use in Europe for VTE prophylaxis after hip- and knee-replacement surgery but is not approved in the US. The Food and Drug Administration and European regulators have approved rivaroxaban (Xarelto, Bayer/Johnson & Johnson) for the prevention of VTE in the setting of knee- or hip-replacement surgery, while Europe recently approved the drug for the treatment of VTE. Apixaban has also been approved in Europe for the prevention of DVT following hip and knee surgery. Edoxaban (Lixiana, Daiichi Sankyo), another direct factor Xa inhibitor, is currently approved in Japan.
Heartwire from Medscape © 2011 Medscape, LLC
Cite this: RECOVER II Confirms Benefit of Dabigatran in Treatment of VTE - Medscape - Dec 21, 2011.