Early results from the largest study to date to compare Pradaxa and warfarin indicate that in a real-world setting, Pradaxa causes more complications than decades-old warfarin. The preliminary study results were announced last week, during the 2012 Thrombosis and Hemostasis Summit of North America.
The study was conducted by Mark Wurster, MD, anticoagulation expert and Chief Medical Officer of Standing Stone, Inc., a subsidiary of Alere Inc., a firm that provides anticoagulation monitoring and management services. Entitled “Dabigatran in the Real World,” the study was conducted at a large anticoagulation clinic managing 2,200 patients on oral therapy. Starting in November 2010, all clinic patients whose prescribing physicians requested a switch from warfarin to Pradaxa were tracked prospectively for a one-year period.
Results for each patient were obtained from the first six months of Pradaxa use and compared to the prior six months of treatment on warfarin. A total of 113 patients had evaluable data; the mean exposure times to Pradaxa and warfarin were 3.9 and 6 months, respectively.
While the patients were being treated with warfarin, one patient was hospitalized with the diagnosis of warfarin toxicity. During the Pradaxa period, the following adverse events were recorded:
- one treatment-related death (GI bleed)
- four other bleeding episodes (two GI bleeds, one rectus sheath hemorrhage, one intracranial hemorrhage associated with trauma)
- one episode of deep venous thrombosis
- one atrial thrombus
- one transient ischemic attack
- one skin rash
- four incidents of gastrointestinal symptoms requiring cessation of Pradaxa
Complications related to Pradaxa appeared very early in treatment, with patients reporting issues, on average, after just less than four months of therapy.
“This is the largest series to date that examines how dabigatran is being administered in real-world settings, and I think our findings illustrate some areas of concern with respect to new agents for anticoagulation therapy,” Dr. Wurster said in a press release issued by Alere. “This is not to say that our results indicate that dabigatran is not a good medicine, but we need more information regarding appropriate patient selection and monitoring. As the study progresses, we hope to be able to answer some of these questions.”
Pradaxa, approved by the US. Food & Drug Administration (FDA) in October 2010, is one of a number of new blood thinners that have been positioned as a superior alternative to warfarin, an anti-coagulant that has been marketed for decades. Both warfarin and Pradaxa pose a risk of serious bleeding, a side effect associated with most blood thinners. However, warfarin bleeding can be stopped with the administration of vitamin K or a drug called recombinant factor VIIa. There is currently no practical antidote for Pradaxa bleeding.
Last year, Pradaxa’s maker, Boehringer Ingelheim, acknowledged that since March 2008, it had received 260 reports of bleeding-related deaths in patients taking Pradaxa. In April, the Institute for Safe Medicine Practices (ISMP) reported that Pradaxa was associated with a total 856 reports of serious, disabling or fatal injury, including 117 bleeding deaths, in the second quarter of 2011. In its previous QuarterWatch report, the ISMP had found that more than 500 cases of serious Pradaxa bleeding had been reported to the FDA in the first quarter of 2011.
The FDA launched a review of Pradaxa in December over reports of bleeding-related side effects, while regulators in Europe and Japan have also directed Boehringer Ingelheim to strengthen warnings for the Pradaxa.