Boehringer Ingelheim has announced that the new findings published demonstrate that Pradaxa (dabigatran etexilate) is associated with a substantially shorter interruption of oral anticoagulation therapy compared to warfarin in patients with atrial fibrillation (AF) who require surgery, allowing patients to undergo procedures more quickly and reducing the time of reduced protection against stroke. Additionally, the study found that discontinuing Pradaxa within 48 hours of surgery was associated with a lower risk of peri-operative bleeding compared to similar discontinuation times with warfarin.

The new analysis of the RE-LY trial highlights that significantly more patients treated with Pradaxa were able to undergo surgery within 48 hours of stopping therapy, compared to patients taking warfarin (46 per cent for dabigatran 150mg bid/110mg bid vs. 11 per cent for warfarin, p < 0.001)1. This is primarily due to the specific pharmacokinetic characteristics of Pradaxa including a short half life (12-17 hours vs. approx. 36 hours for warfarin) and much faster on- and off-set of anticoagulant effect offered by this novel oral anticoagulant treatment.

Overall, similar rates of bleeding and thrombotic events were observed in patients treated with Pradaxa and warfarin who were undergoing surgery or invasive procedures, including those requiring urgent or major surgery.

Dr. Jeff Healey, McMaster University, Hamilton, Canada, commented, “Surgical or invasive procedures are commonly required in patients with atrial fibrillation taking anticoagulant medications. This analysis provides reassurance that dabigatran is as safe as warfarin with regards to perioperative bleeding and thromboembolic events in patients undergoing surgery or invasive procedures, irrespective of whether interventions were minor or major. In addition, nearly half of all patients using dabigatran were able to have their procedure performed within 48 hours of the discontinuation of treatment with the anticoagulant, ensuring a shorter interruption of protection from thromboembolic complications than with warfarin, while still ensuring adequate haemostasis at the time of surgery.”

In the RE-LY trial, 4,591 patients underwent at least one surgical procedure, which represented 24.7 per cent of patients receiving Pradaxa 110mg bid, 25.4 per cent receiving Pradaxa 150mg bid and 25.9 per cent receiving warfarin. The most common reasons for surgical procedures were pacemaker/defibrillator insertion (10.3 per cent), dental procedures (10.0 per cent), and diagnostic procedures (10.0 per cent). Key results from the analysis showed:

There was no significant difference in the rates of peri-procedural major bleeding with either dose of Pradaxa® compared to warfarin (110mg bid: RR=0.83, 95 per cent CI: 0.59-1.17, p=0.28/ 150mg bid: RR=1.09, 95 per cent CI: 0.80-1.49, p=0.58).

Substantially lower rates of major bleeding were seen with both doses of Pradaxa compared to warfarin when surgery was performed within a 48 hour period:

24-48 hrs interruption: 110mg bid: RR= 0.35, 95 per cent CI: 0.16-0.80, p= 0.01/ 150mg bid: RR=0.36, 95 per cent CI: 0.16-0.82, p=0.01.

< 24 hrs interruption: 110mg bid: RR=0.18 95 per cent CI: 0.07-0.50, p<0.001/ 150mg bid: RR=0.44, 95 per cent CI: 0.21-0.92, p=0.027.

The incidence of stroke and all other thromboembolic complications, including cardiovascular death, systemic embolism, myocardial infarction or pulmonary embolism were low and not significantly different between treatment groups.

The advantage of Pradaxa with regard to the incidence of haemorrhagic stroke was again confirmed in the present analysis where four peri-operative haemorrhagic strokes were seen within the well-controlled warfarin group versus none with either dose of Pradaxa (p<0.05 for both doses of Pradaxa compared to warfarin).

In the analysis, recommendations developed during the RE-LY study to establish the optimal timing of discontinuation of Pradaxa prior to invasive procedures were reviewed. The recommendations take into account the bleeding risk of the surgery itself and renal function of the patient, due to Pradaxa being 80 per cent renally excreted. The analysis reconfirmed the application of these recommendations, which are reflected in the labelling information such as the European Summary of Product Characteristics, and provide specific guidance on the discontinuation time for Pradaxa in patients at varying degrees of renal impairment based on a standard or high risk of bleeding associated with the planned surgery or intervention.

“Emergency surgery is a frightening proposition for any patient taking an anticoagulant given the increased risk of bleeding encountered,” commented Eve Knight, co-founder and chief executive of AntiCoagulation Europe (ACE). “This data is encouraging for patients as it demonstrates that with Pradaxa shorter therapy interruptions with no increase in bleeding risk are possible.”

The effectiveness and favourable safety profile of Pradaxa have been proven within an extensive clinical trial programme, passing independent regulatory scrutiny and approval worldwide.

Dabigatran etexilate is at the forefront of a new generation of oral anticoagulants/direct thrombin inhibitors (DTIs) targeting a high unmet medical need in the prevention and treatment of acute and chronic thromboembolic diseases.

Potent antithrombotic effects are achieved with direct thrombin inhibitors by specifically blocking the activity of thrombin (both free and clot-bound), the central enzyme in the process responsible for clot (thrombus) formation. In contrast to vitamin-K antagonists, which variably act via different coagulation factors, dabigatran etexilate provides effective, predictable and consistent anticoagulation with a low potential for drug-drug interactions and no drug-food interactions, without the need for routine coagulation monitoring or dose adjustment.