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Findings published in Circulation demonstrate that Pradaxa®(dabigatran etexilate) is associated with a substantially shorter interruption of oral anticoagulation therapy than warfarin in patients with atrial fibrillation (AF)1 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 than 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% for dabigatran 150mg bid/110mg bid vs. 11% for warfarin, p<0.001).
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, 4591 patients underwent at least one surgical
procedure, which represented 24.7% of patients receiving Pradaxa® 110mg bid, 25.4% receiving Pradaxa® 150mg bid and 25.9% receiving warfarin.
The most common reasons for surgical procedures were pacemaker/defibrillator insertion (10.3%), dental procedures (10.0%) and diagnostic procedures (10.0%).
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 with warfarin (110mg bid: RR=0.83, 95% CI: 0.59–1.17, p=0.28/ 150mg bid: RR=1.09, 95% CI: 0.80‐1.49, p=0.58)
- Substantially lower rates of major bleeding were seen with both doses of Pradaxa® compared with warfarin when surgery was performed within a 48 hour period:
o 24‐48 hrs interruption: 110mg bid: RR= 0.35, 95% CI: 0.16‐0.80,
p= 0.01/ 150mg bid: RR=0.36, 95% CI: 0.16‐0.82, p=0.01
o < 24 hrs interruption: 110mg bid: RR=0.18 95% CI: 0.07‐0.50,
p<0.001/ 150mg bid: RR=0.44, 95% 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).
