New RE-LY sub-analyses demonstrate safety and efficacy of Pradaxa in patients with heart failure and those undergoing surgery


A new post hoc sub-analysis of the RE-LY trial found Boehringer Ingelheim’s oral anticoagulant Pradaxa (dabigatran etexilate) 150mg bid significantly reduced the risk of stroke compared to well-controlled warfarin (median time in therapeutic range (TTR) 67.3%) in patients with non-valvular atrial fibrillation and symptomatic heart failure. Importantly, the benefit for Pradaxa compared to well-controlled warfarin with regard to major bleeding was maintained, irrespective of symptomatic heart failure. The results were presented on 14 November at the American Heart Association (AHA) Scientific Sessions 2011.

The landmark RE-LY trial was a global, phase III, prospective, randomised, open-label with blinded endpoint evaluation trial of 18,113 patients enrolled in over 900 centres in 44 countries. The trial was designed to compare two fixed doses of the oral direct thrombin inhibitor dabigatran (110mg and 150mg bid) each administered in a blinded manner, with well controlled (INR 2.0-3.0, median TTR 67%) open label warfarin.

Stuart Connolly, director, Division of Cardiology at McMaster University and member of The Population Health Research Institute, Hamilton, Canada, commented, “This post hoc sub-analysis shows that atrial fibrillation patients with symptomatic heart failure benefit from treatment with Pradaxa consistently with the overall results of the RE-LY trial. Pradaxa150mg bid significantly reduced the risk of stroke and intracranial bleeds compared to well-controlled warfarin, with similar rates of major bleeds. This is an important clinical finding given patients with symptomatic heart failure and atrial fibrillation are at high risk of suffering a stroke, and require effective and safe anticoagulation to prevent these potentially disabling and fatal events.”

Main findings from the post hoc RE-LY sub-analysis were:

  • Pradaxa 150mg bid reduced the risk of stroke in atrial fibrillation patients with or without symptomatic heart failure compared to well-controlled warfarin (HR = 0.75 vs. 0.61; p-value for interaction = 0.66)
  • Rates of intracranial bleeding were significantly lower with both doses of Pradaxa compared to well-controlled warfarin, irrespective of whether patients had symptomatic heart failure or not (Pradaxa 110mg bid: HR=0.34 vs. 0.28, Pradaxa 150mg bid: HR = 0.39 vs. 0.42; p-value for interaction = 0.80)
  • Annual rates of stroke or systemic embolism were higher overall for patients with symptomatic heart failure (Pradaxa 110mg bid: 1.90%, Pradaxa 150mg bid: 1.44%, warfarin: 1.92%) than those without this condition (Pradaxa 110mg bid: 1.41%, Pradaxa150mg bid: 1.00%, warfarin: 1.64%)
  • There were no significant interactions for major bleeding events between patients with symptomatic heart failure and those without – i.e. no signal for an increase in major bleeding events was detected in patients with symptomatic heart failure (Pradaxa 110mg bid: HR=0.83 vs. 0.79, Pradaxa 150mg bid: HR = 0.79 vs. 0.99; p-value for interaction = 0.21).

A second sub-analysis presented at the AHA Scientific Sessions 2011 assessed the risk of bleeding with Pradaxa compared to well-controlled warfarin in patients undergoing surgery (n = 4,615). The analysis showed that there was no increased risk of peri-operative bleeding with both doses of Pradaxa compared to well-controlled warfarin, even among patients having emergency or major surgery.

Key findings were:

  • There was no significant difference in the risk of bleeding, including major (RR = 1.08; p = 0.64), minor (RR = 1.15; p = 0.25), fatal (RR = 1.01; p = 0.99), bleeding requiring re-operation (RR = 1.39; p = 0.32) and bleeding requiring red blood cell transfusion (RR = 0.85; p = 0.37), between patients receiving Pradaxa 150mg bid compared to warfarin.
  • Emergency surgery was associated with more major bleeds across all treatment groups compared to those having elective surgery (Pradaxa 110mg: 17.5% vs. 2.7%, Pradaxa 150mg: 17.4% vs. 3.8%, warfarin: 21.7% vs. 3.3%; p<0.001 for all).
  • Major bleeding was more common for major compared to minor surgery with both doses of Pradaxa compared to warfarin (Pradaxa 110mg: 6.3% vs. 1.9%, Pradaxa 150mg: 6.4% vs. 3.2%, warfarin: 8.0% vs. 1.8%; p<0.01 for all). However, there were no significant differences between treatment arms.

Jeff Healey, McMaster University, Hamilton, Canada, commented, “This sub-study highlights that patients taking Pradaxa who require surgery or invasive procedures have no increased risk of bleeding complications compared to patients treated with warfarin, even when these procedures are major or are performed on an emergency basis. This is important as one-quarter of RE-LY patients underwent an invasive procedure or surgery over a two-year period. Patients receiving Pradaxa required a shorter period of interruption of their anticoagulation.”

Pradaxa has been approved for the prevention of stroke in atrial fibrillation in more than 50 countries worldwide (including the USA, Canada, Japan and the member states of European Union). Since the first launch of Pradaxa in this new indication in October 2010, more than 450,000 patients have already been prescribed the novel oral anticoagulant.