The Journal of Thoracic and Cardiovascular Surgery

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Accepted Manuscript Scylla versus Charybdis: the eternal dilemma continues Vivek Rao, MD, PhD PII: S0022-5223(18)32088-9 DOI: 10.1016/j.jtcvs.2018.07.092 Reference: YMTC 13320 To appear in: The Journal of Thoracic and Cardiovascular Surgery Received Date: 30 July 2018 Accepted Date: 31 July 2018 Please cite this article as: Rao V, Scylla versus Charybdis: the eternal dilemma continues, The Journal of Thoracic and Cardiovascular Surgery (2018), doi: 10.1016/j.jtcvs.2018.07.092. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

1 Scylla versus Charybdis: the eternal dilemma continues. 2 3 4 5 6 7 8 9 10 Vivek Rao, MD, PhD Chief, Cardiovascular Surgery Peter Munk Cardiac Centre, Toronto General Hospital 200 Elizabeth Street, Toronto, ON. Canada. M5G2C4 Tel: 416 340 3562 Fax: 416 340 3337 E: vivek.rao@uhn.ca

11 12 Anticoagulation has long been viewed as a double edged sword. In patients at high risk for thromboembolic (TE) events, anticoagulation with Vitamin K antagonists such as Warfarin or 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 the newer novel oral anticoagulants (NOAC) has proven to be effective in reducing neurologic events. However, even the NOACs have bleeding complications as a notable side-effect to therapy and thus their use in patients with mechanical heart valves was discontinued. Patients with mechanical heart valves are a particularly challenging patient population as they tend to be young when then receive their valves. Inevitably, as they age they are at risk for common afflictions that often require surgical intervention. These interventions can be elective such as routine orthopaedic procedures or emergent such as acute abdomens. The peri-operative management of mechanical valve anticoagulation for non-cardiac surgery has never been well standardized. In this issue of the Journal, Tan et al have provided an expert commentary describing the evidence (or lack thereof) around bridging vs non-bridging strategies. 1 Their Figure 1 is a nice pictoral illustration of the art and science that becomes necessary when managing anticoagulation in patients with mechanical heart valves. A recent observational study from Italy provided some reassuring data. 2 In a cohort of over 2350 patients in the Italian Federation of Anticoagulation Clinics, the overall rate of thromboembolic events was only 0.67 per 100 patient years. In contrast, the bleeding risk was slightly higher at 1.0 major bleeds per 100 patient years. Interestingly, the adequacy of anticoagulation (as measured by the time in therapeutic range) did not influence the occurrence of TE. Rather, patient factors such as atrial fibrillation, a previous history of TE and a mitral prosthesis were 32 found to be predictive of events. This report further supports the recommendations of Tan and

33 34 colleagues who argue for patient-specific management of anticoagulation considering both clinical risk factors as well as the bleeding risk of the proposed intervention. 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 It is thought-provoking to realize that even in the absence of anticoagulation the risk of a TE event with a mechanical aortic valve ranges from 6-22%. 3 Therefore, even at a 22% risk the daily risk of TE without anticoagulation is 0.06%. Considering that we typically hold warfarin 3 days prior to elective surgery and resume it on postoperative day 1, the cumulative TE risk remains 0.24%. Clearly, patient factors may increase or decrease this risk but the point is, the risk is small compared to a potential life-threatening bleeding complication after major surgery. In a trial of patients with atrial fibrillation, Douketis et al found no benefit to perioperative bridging. 4 While these patients are at lower risk of TE complications compared to those with mechanical heart valves, it provides limited evidence of the lack of efficacy of short term bridging prior to elective surgery. As with Odysseus choice between the serpent Scylla or the whirlpool Charybdis (Figure 1), every patient with a mechanical heart valve faces the risk of TE versus bleeding when contemplating a surgical procedure. As pointed out in their discussion, the field is really in need of prospective data to guide our therapeutic choices. In the interim, the proposed strategy appears logical and would be a useful addition to any anticoagulation clinic.

51 52 References: 53 54 55 56 57 58 59 60 61 62 63 64 65 66 1. Tan CW, Wall M, Rosengart TK, Ghanta RK. How to Bridge? Management of Anticoagulation in Patients with Mechanical Heart Valves undergoing Non-Cardiac Surgery procedures. JTCVS 2018. In press. 2. Poli D, Antonucci E, Pengo V, et al. Mechanical prosthetic heart valves: Quality of anticoagulation and thromboembolic risk. The observational multicenter PLECTRUM study. Int J Cardiol 2018; 267: 68-73 3. Nishimura RA, Otto CM, Bonow RO, et al. 2017 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017 Jul 11;70(2):252-289. 4. Douketis JD, Spyropoulos AC, Kaatz S, Becker RC, Caprini JA, Dunn AS, et al. Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation. N Engl J Med. 2015 Aug 27;373(9):823-33.