Do novel anticoagulant agents increase the risk of perioperative complications during implantable cardiac rhythm device insertion?

BEST EVIDENCE TOPIC – ADULT CARDIAC Interactive CardioVascular and Thoracic Surgery 24 (2017) 126–128 doi:10.1093/icvts/ivw282 Advance Access publication 5 September 2016 Cite this article as: Davies RA, Perera NK, Orr Y. Do novel anticoagulant agents increase the risk of perioperative complications during implantable cardiac rhythm device insertion? Interact CardioVasc Thorac Surg 2017;24:126–8. Do novel anticoagulant agents increase the risk of perioperative complications during implantable cardiac rhythm device insertion? Reece A. Daviesa,b,*, Nisal K. Pereraa and Yishay Orra a b Department of Cardiothoracic Surgery, Westmead Hospital, Sydney, Australia Faculty of Medicine, University of Sydney, Sydney, Australia * Corresponding author. Department of Cardiothoracic Surgery, Westmead Hospital, 2145 Westmead, NSW, Australia. Tel: +61-2-98457994; e-mail: reece_davies@ yahoo.com.au (R.A. Davies). Received 10 January 2016; received in revised form 11 July 2016; accepted 29 July 2016 Abstract A best evidence topic was written according to a structured protocol. The question addressed was ‘In patients requiring an implanted cardiac rhythm device, do novel oral anticoagulant agents lead to increased rates of peri-procedural complications?’ Altogether 1228 papers were found using the reported search, of which 5 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The novel oral anticoagulant agents (NOACs) assessed in the included studies were dabigatran (a direct thrombin inhibitor) and rivaroxaban (a Factor Xa inhibitor). Dabigatran was included in all five studies and showed bleeding complication rates of 0–4%. Rivaroxaban was included in one study and had bleeding complication rates of 4%. Warfarin was a comparator agent in three studies and had bleeding complication rates of 4.6–8%. The incidence rate of thromboembolic complications was 0–1% with dabigatran and 0% with rivaroxaban and warfarin in all studies. Based on the available studies, there is no evidence of significantly increased risk of bleeding or thromboembolic events with NOACs compared with warfarin when used at the time of cardiac rhythm device implantation. However, not all patients in the studies were actually receiving the specified NOAC at the time of device implantation, thereby limiting the available evidence. Keywords: Cardiac pacemaker • Implantable defibrillator • Dabigatran • Rivaroxiban • Novel anticoagulant INTRODUCTION A best evidence topic was written according to a structured protocol. This is fully described in the ICVTS [1]. regarding the risk of bleeding complications with continuation of NOACs at the time of cardiac rhythm device implantation. SEARCH STRATEGY In [patients requiring an implantable cardiac rhythm device] do [novel oral anticoagulant agents] lead to [increased rates of periprocedural complications]? The literature search was performed in Medline from 1950 to June 2016 using the PubMed interface. [Pacemaker OR pacing OR implant OR defibrillator OR resynchronisation] AND [NOAC OR Anticoagulant OR Factor Xa Inhibitor OR Antithrombin OR apixaban OR rivaroxaban OR dabigatran]. CLINICAL SCENARIO SEARCH OUTCOMES An 80-year old man is referred to you for consideration of a permanent pacemaker. He has paroxysmal atrial fibrillation and sinus node dysfunction and is on a novel oral anticoagulant (NOAC). Due to his history of diabetes, hypertension, previous stroke and consequently high CHADS2 score, the referring cardiologist wishes to maintain the patient on anticoagulation in the perioperative period. Recent studies have shown a decreased risk of bleeding complications with continued warfarin as opposed to heparin bridging [2, 3]. You decide to evaluate the available evidence Overall 1228 papers were identified using the reported search. From these, five papers were identified that provided the best evidence to answer the question (Table 1). THREE-PART QUESTION RESULTS Madan et al. [4] compared warfarin (86 patients) to interrupted dabigatran (47 patients) in patients undergoing surgery for © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. R.A. Davies et al. / Interactive CardioVascular and Thoracic Surgery 127 Table 1: Best evidence papers Author (date), journal, country study type (level of evidence) Patient groups Outcomes Results Other comments Madan et al. (2016), Cardiovasc Diagn Ther, USA [4] 47 receiving interrupted dabigatran Major complication/mortality 86 receiving continuous warfarin (mean INR 2.3 ± 0.7) Device-related pocket haematoma 0% in the dabigatran group versus 1.2% in the warfarin group 0% in the dabigatran group versus 7% in the warfarin group (P = 0.09) 0% in both groups Dabigatran was ceased a mean of 23.3 h (range 12–91 h) preoperatively and was recommenced a mean of 21.0 h (range 9–54 h) postoperatively 3% in the dabigatran group versus 8% in the warfarin group (P = 0.075) 0% in the dabigatran group versus 1% in the warfarin group (P = 0.156) 5% in the dabigatran group versus 10% in the warfarin group (P = 0.092) 1% in the dabigatran group versus 0% in the warfarin group (P = 0.316) 2.5 ± 2.3 days in the dabigatran group versus 3.8 ± 4.1 day in the warfarin group (P = 0.002) Nil significant differences in complications but shorter LoS with dabigatran 2.1% on uninterrupted dabigatran versus 0% on interrupted dabigatran versus 4.6% on uninterrupted warfarin (P = 0.69) 0 in all three groups No significant differences between groups for complications, but antiplatelet use was associated with increased bleeding complications 2% in the dabigatran group versus 5% in the rivaroxaban group (P = 0.330) 0% in the dabigatran group versus 4% in the rivaroxaban group (P = 0.064) 1% in the dabigatran group versus 0% in the rivaroxaban group (P = 0.343) 2 (IQR 1–3) days vs 2 (IQR 1–3) days (P = 0.722) 74% of dabigatran patients were on the drug prior to the procedure, and it was ceased 24 h prior 26 ± 16 h in withholding patients versus 5 ± 3 h in continuing patients (P = 0.0003) 27 ± 19 h in withholding patients versus 8 ± 3 h in continuing patients (P = 0.003) 0 Very low rates of complications irrespective of continuing or withholding dabigatran Thromboembolic events Kosiuk et al. (2014), Circ J, Germany [5] 118 receiving dabigatran periprocedurally Device-related pocket haematomas Case control (level 3) 118 receiving warfarin uninterrupted [mean INR 2.1 (IQR 1.5– 2.4)] Revision surgery for bleeding Hb change > 10% Thromboembolic events Length of hospital stay Jennings et al. (2013), J Cardiovasc Electrophysiol, USA [6] Cohort (level 3) 48 patients received uninterrupted dabigatran 14 patients received dabigatran withheld on the morning of the procedure Bleeding comp (...truncated)