Management of Anticoagulation during Device Implants; Coumadin to Novel Agents

Transcription

1 Management of Anticoagulation during Device Implants; Coumadin to Novel Agents DR D Birnie Invited Faculty Core Curriculum Heart Rhythm Society May 8 th 2014

2 Disclosures Boehringer Ingleheim Research Support (Moderate)

3 Background Between 14% and 35% of patients receiving arrhythmia devices require chronic oral anticoagulation Perhaps 30-50% are on chronic anti-platelet therapy their periprocedural management presents a dilemma to physicians. This is particularly true for the subset of patients at moderate-to-high risk of thromboembolic events. 1 Douketis JDet al. Perioperative management of antithrombotic therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 Suppl):e326S-e350S.

4 Balance of risks Prevent bleeding Tamponade Hemothorax Device pocket hematoma Prevent thrombosis Stroke and systemic embolism

5 Stroke and Systemic Embolism Data on general peri-operative experience in the NOAC trials have been published; the key points from these two studies are: 1. Temporary interruptions for procedures/surgery are common (between 10 and 15% of patients per year). 2. About 10% of temporary interruptions are for pacemaker or defibrillator surgery. 3. Even brief temporary interruptions, carefully controlled in the environment of clinical trials, are associated with an approximately 3-fold increase in stroke/systemic embolism. Healey JS et al. Periprocedural bleeding and thromboembolic events with dabigatran compared with warfarin: results from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) randomized trial. Circulation 2012 July 17;126(3): Patel MR, Het al. Outcomes of discontinuing rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: analysis from the ROCKET AF trial J Am Coll Cardiol 2013 February 12;61(6):651-8.

6 Device Pocket Hematoma

7 Talk Outline Why prevent hematomas? Infection How to manage peri-operative Anti-coagulation Warfarin NOACS Anti-platelets Other factors

8 1. Why prevent

9 Why prevent? Device pocket hematomas can have very serious consequences for patients: they can necessitate prolonged cessation of AC with the attendant risk of ATE they can significantly increase hospitalization and cost (by a mean of 3.1 days and US$6995 in one study) sometimes re-operation is required.

10 Why prevent? In BRUISE CONTROL Clinically significant hematomas occurred in 66/681 (9.7%) of patients Five patients (7.6%) with hematomas developed subsequent device system infection, This compares to system infection occurring in 3/615 (0.50%) of patients without hematomas (p<0.001). Of the 5 patients with infections after a hematoma, 2 had had reintervention (evacuation of the hematoma) prior to developing infection. 15 fold increase risk of infection!!

11 Why prevent? In the REPLACE registry Patients with infections were more likely to have had postoperative hematomas (five of 22 [22.7%] vs. 17 of 1,722 [0.98%], P = fold increase risk of infection!!

12 2. How to prevent Management of peri-operative anticaogulation

13 May 2013

14 Background Recent guidelines recommended interruption of warfarin and bridging with intravenous or low-molecular-weight heparin around the time of surgery. However, there are a number of potential drawbacks to bridging with heparin Bridging with heparin consumes considerable healthcare resources. Bridging with heparin also involves a short period of normal coagulability with associated risk of thromboembolism. Case series have fund a substantial, risk of device pocket hematoma when heparin bridging is used.

15 Background In response to these issues, some centers have started performing device surgery without interruption of warfarin However, there have been little clinical trial data to support the safety and efficacy of this approach and two small randomized trials have been inconclusive. In the first of these, four of 51 patients (7.8%) in the heparin-bridging arm and four of 50 (8.0%) in the warfarin arm developed pocket hematomas following implantation. 2 In the second trial, only seven patients received heparin bridging. 3 We sought to resolve this dilemma with an adequately powered randomized clinical trial. 2 Tolosana JM,. Eur Heart J 2009;30(15): Cheng A, et al. Heart Rhythm 2011;8(4):

16 Methods Multicenter single-blind randomized controlled trial Patients were eligible if they had a 5% annual predicted risk of thromboembolism, were taking warfarin, and were undergoing nonemergency device surgery. 4 4 Birnie D, Healey JS, Krahn A et al. Bridge or continue Coumadin for device surgery: a randomized controlled trial rationale and design. Curr Opin Cardiol 2009;24(1):82-87.

17 Methods Treatment groups In the continued-warfarin arm, the INR on the day of surgery was targeted to be 3.0 or lower, except for patients with mechanical valves, for whom an INR of 3.5 or lower was permitted. Patients in the heparin-bridging arm discontinued warfarin 5 days before the procedure and started full therapeutic dosages of lowmolecular-weight heparin or intravenous heparin three days before the procedure. Patients restarted LMWH or IV heparin 24 hours after the procedure and continued until a therapeutic INR was achieved.

18 Methods - Primary Outcome The primary outcome was clinically significant hematoma Defined as a hematoma requiring re-operation and/or resulting in prolongation of hospitalization and/or requiring interruption of all anticoagulation for > 24 hours

19 Methods - Blinding To permit investigator blinding, each center was required to identify two patient-care teams. The unblinded team had knowledge of treatment allocation and was responsible for device implantation and follow-up of only The blinded team had no knowledge of treatment allocation and was responsible for diagnosing, following, and making decisions about hematomas.

20 Results

21 Early Termination We enrolled patients at 17 centers in Canada and one in Brazil. Data on 668 patients were reviewed by the DSMB at the second prespecified interim analysis on February 27 th 2013, at which time they recommended study termination. All randomized patients who had device surgery before this date were followed until study completion. We therefore report data on 681 patients enrolled between October 2009 and February 2013.

22 Randomized N = 681 Exited Study Before Surgery N = 12 6 pts withdrew consent 1 pt withdrawn by physician 2 pts declined device implant 3 pts had change in clinical status surgery no longer indicated Heparin Bridging N = 338 Underwent Surgery N = 326 Continued Warfarin N = 343 Underwent Surgery N = 335 Exited Study Before Surgery N = 8 3 pts died before surgery 1 pt withdrew consent 1 pt withdrawn by physician 3 pts declined device implant Lost to Follow-up N = 1 Died After Surgery But Before Final Follow-up N = 1 Completed Follow-up N = 325 Completed Follow-up N = 334

23 there was no significant differences in any variable

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25 Results Primary Outcome

26 Results Primary Outcome

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28 Secondary Outcomes There were no embolic events in the heparin-bridging arm and two in the continued-warfarin arm. Both patients with embolic events had non-valvular atrial fibrillation and a high risk of stroke as determined by CHADS 2 score. In both cases the INR had become subtherapeutic (not intentional). There was one episode of cardiac tamponade requiring pericardiocentesis in the heparin-bridging arm. Patients in the continued-warfarin arm had greater satisfaction with their perioperative anticoagulation management (p<0.001)

29 Conclusions In this large randomized trial we evaluated performing device surgery without interruption of warfarin in patients with an annual risk of stroke of 5% We found that this strategy is associated with a significant reduction in the rate of device pocket hematoma compared to heparin bridging (from 16.0% to 3.5%). We also found that operating with continued warfarin, with a median INR of 2.3 was not associated with any major perioperative bleeding events and was favored by patients. These results suggest that continuation of warfarin during pacemaker or defibrillator surgery may be preferable to heparin bridging, at least for patients like those enrolled in our trial. Unclear what is best to do for lower risk patients Either continue warfarin or temporary hold it DON T BRIDGE!!

30 What about NOAC management?

31 Do we really need another clinical trial..surely Bruise Control applies to NOACs too??

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34 Why we need more data because the NOACs are very different drugs that we are just starting to understand

35 The trial was terminated prematurely after the enrollment of 252 patients because of an excess of thromboembolic and bleeding events among patients in the dabigatran group. Ischemic or unspecified stroke occurred in 9 patients (5%) in the dabigatran group and in no patients in the warfarin group; major bleeding occurred in 7 patients (4%) and 2 patients (2%), respectively. The results of RE-ALIGN showing that, in valve patients, there is less bleeding and fewer strokes with warfarin rather than dabigatran is exactly the opposite result to the findings from the studies in AF.

36 2 BRUISE CONTROL -2 A randomized controlled trial to investigate whether a strategy of Continued versus Interrupted Dabigatran at the time of device surgery, in patients with moderate to high risk of arterial thromboembolic events, leads to a reduction in the incidence of clinically significant hematoma

37 Why BC-2? We speculate that the temporary cessation of Dabigatran may have similar downsides to bridging anti-coagulation therapy. That is, a period of normal coagulability for 48 to 72 hours; and the potential for significant rates of pocket hematoma with associated morbidity and cost.

38 What to do with NOACs meantime Pre-op Device implant considered a low bleeding risk procedure Follow product monographs Post-op No data In patients, with an annual risk of TE > 5%, reasonable to give the first dose of NOAC 24 hours after surgery. In patients with lower risk of TE (< 5%) reasonable to give the first dose of NOAC 48 hours after surgery

39 2. How to prevent anti-platelets

40 Univariate Analysis for Presence of Clinically Significant Hematoma

41 Multivariable Logistic Regression Model for Presence of Clinically Significant Hematoma

42 Analysis in the continued Warfarin group

43 Other data - antiplatelets

44 So how to manage anti-platelets peri-op

45 Other suggested algorithm

46 2. How to prevent Other factors

47 Hemostat into pocket

48 Other factors Operator experience Meticulous cautery Tamponade pocket with gauze during lead implantation Wound drains Pressure dressings NO DATA

49 How to manage? No data No expert guidelines

50 How to manage? No data No expert guidelines What about antibiotics

51 Conclusions Per-operative management of anti-coagulation and anti-platelets is complex and needs to be individualized The key is to balance the risk of thrombosis (primarily stroke) and bleeding (primarily hematoma) Good news is that lots of data to guide us Good news is bad things can usually be prevented by careful planning