On 4 May, Alere announced, at the 2012 Thrombosis and Hemostasis Summit of North America (3–5 May, Chicago, USA), preliminary results from the largest study to date comparing warfarin (Coumadin) and dabigatran (Pradaxa) therapies administered in a real-world setting.
The study was performed by Mark Wurster, anticoagulation expert and chief medical officer of Standing Stone, an Alere subsidiary. Findings reveal that complications necessitating therapy discontinuation occurred more frequently with dabigatran than with warfarin. Additionally, complications related to dabigatran appeared very early in treatment, with patients reporting issues, on average, after just less than four months of therapy.
Dabigatran is the first oral thrombin/Xa inhibitor cleared for use by the FDA in the United States. Commercially available since November 2010, the medication is intended for the prevention of thromboembolic complications related to atrial fibrillation. While pre-approval studies are numerous, reporting on the use of dabigatran after commercial release in real-world settings has generally been limited to individual cases. Moreover, little information is available about the frequency of side effects or complications for patients on dabigatran, especially in comparison to patients receiving warfarin therapy administered by organised anticoagulation clinics.
The “Dabigatran in the real world” study was conducted at a large anticoagulation clinic managing 2,200 patients on oral therapy. Beginning in November 2010, all clinic patients whose prescribing physicians requested a switch from warfarin to dabigatran were tracked prospectively for a one-year period. Each patient served as his or her own control, and primary outcome measures focused on clinical events that led to the discontinuation of dabigatran or warfarin. These include episodes of thrombosis, bleeding, treatment-related death and any other events that required therapy with either agent to be discontinued.
Results for each patient were obtained from the first six months of dabigatran 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 dabigatran and warfarin were 3.9 and 6 months, respectively. During the warfarin treatment period, primary outcomes included one hospitalisation with the diagnosis of warfarin toxicity. During the dabigatran treatment period, primary outcomes included: one treatment-related death (GI bleed); four other bleeding episodes (two GI bleeds, one rectus sheath haemorrhage, one intracranial haemorrhage associated with trauma); one episode of deep vein thrombosis; one atrial thrombus; one transient ischaemic attack; one skin rash; and four incidents of gastrointestinal symptoms requiring cessation of dabigatran. The frequency of primary outcomes during the warfarin treatment phase was 0.88%, compared to 11.5% during the dabigatran treatment phase (p 0.0014).
Commenting on the preliminary results of the trial, Wurster said, “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. 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.”
The “Dabigatran in the real world” study remains active, and the final report will include information on possible contributing factors like renal function, co-morbid conditions, and concomitant medication use. Meanwhile, results of the study to date support the conclusion that warfarin remains an affordable, effective, and safe option for many patients.