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Perioperative management of anticoagulation in patients on warfarin therapy undergoing surgery for cardiac implantable electronic devices
Journal of Arrhythmia 29 (2013) 162–167
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Review
Perioperative management of anticoagulation in patients on warfarin therapy undergoing surgery for cardiac implantable electronic devices Dennis Weixi Zhu MD, FACC, FHRSn, Imdad Ahmed MD Regions Hospital and HealthPartners Medical Group, University of Minnesota, Saint Paul, MN, United States
a r t i c l e i n f o
a b s t r a c t
Article history: Received 6 December 2012 Received in revised form 8 January 2013 Accepted 9 January 2013 Available online 17 March 2013
Many patients on chronic warfarin therapy are undergoing surgery for permanent pacemakers and implantable defibrillators, collectively known as cardiac implantable electronic device (CIED). The perioperative management of anticoagulation in these patients is a challenging clinical situation that requires balance between the risk of acute thrombosis and perioperative hemorrhage. This issue however, is inadequately addressed in the guidelines published by professional organizations. Increasing evidence suggests that temporarily interrupting anticoagulation is associated with a small but real thromboembolic risk, whereas cessation of warfarin with heparin bridging anticoagulation frequently leads to a higher incidence of pocket hematoma. Continuing warfarin with a therapeutic international normalized ratio appears to be a safe and cost-effective approach for CIED surgery in most patients with moderate to high thromboembolic risk. An algorithm is proposed for the practical management of anticoagulation and antiplatelet therapy in these patients during the perioperative period. & 2013 Japanese Heart Rhythm Society. Published by Elsevier B.V. All rights reserved.
Keywords: Anticoagulation Warfarin Pocket hematoma Pacemaker/defibrillator Thromboembolism
Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2. Perioperative risk assessment of thromboembolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3. Current management options . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4. Risk of thromboembolism with short-term interruption of warfarin therapy. . . . . . . . . . . . . . . . . . 5. Risk of pocket hematoma on bridging therapy with heparin or LMWH . . . . . . . . . . . . . . . . . . . . . . 6. Safety of continuation of warfarin during the perioperative period of pacemaker and defibrillator 7. Safety of cardiac resynchronization therapy device implantation with continuation of warfarin . . 8. Risk of bleeding complications with dual antiplatelet agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9. Empirical approaches to reduce the perioperative bleeding complications. . . . . . . . . . . . . . . . . . . . 10. Practical management of perioperative anticoagulation and antiplatelet therapy in CIED surgery . Conflict of interest. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Introduction The optimal management of perioperative anticoagulation in patients on warfarin therapy undergoing cardiac implantable electronic device (CIED) surgery is not yet established.
n Correspondence to: Cardiology 11102H, HealthPartners Medical Group, Regions Hospital, University of Minnesota, 640 Jackson Street, Saint Paul, MN 55101. Tel.: þ1 651254 0829; fax: þ1 651254 4129. E-mail address: [email protected] (D.W. Zhu MD, FACC, FHRS).
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Neither the recent American Heart Association/American College of Cardiology nor European Society of Cardiology guidelines mentioned device surgery in patients on chronic anticoagulation therapy. The 2008 guidelines from the American College of Chest Physicians (ACCP) have recommended the use of bridging anticoagulation with therapeutic dose of subcutaneous low-molecularweight heparin (LMWH) or intravenous heparin in patients with mechanical heart valves, atrial fibrillation, or venous thromboembolism who are at moderate or high risk for thromboembolic events [1]. This recommendation, however, was largely based on
1880-4276/$ - see front matter & 2013 Japanese Heart Rhythm Society. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.joa.2013.01.010
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Table 1 Risk stratification for perioperative thromboembolism. Risk group Mechanical heart valve High
Moderate
Low
Atrial fibrillation
VTE
CHADS2 score of 5 or 6 VTE r3months Stroke or TIAr 3 months Severe thrombophilia (deficiency of protein C, protein S or antithrombin; antiphospholipid Stroke or TIAr 6 months Rheumatic valvular heart disease Aortic valve prosthesis CHADS2 score of 2 to 4 VTE within3–12 months Nonsevere thrombophilia (e.g., heterozygous factor Leiden) Recurrent VTE Active cancer CHADS2 score of 0 to 1 VTE 412 months and no other risk factors
Mitral valve prosthesis
CHADS2¼ congestive heart failure, hypertension, ageZ 75 years, diabetes mellitus, and stroke or transient ischemic attack. TIA¼ transient ischemic attack, VTE ¼ venous thromboemolic event.
expert opinion. The new ACCP 2012 guidelines considered CIED surgery to be a procedure associated with an increased bleeding risk during perioperative antithrombotic administration [2]. CIED implantation in which separation of infraclavicular fascial layers and lack of suturing of unopposed tissues within device pocket may predispose to hematoma development. However, the updated guidelines did not provide specific recommendations on the management of this patient population. Recent surveys in Canada and United Kingdom revealed a lack of consensus among the CIED implanting physicians on whether to withhold anticoagulation and whether to use bridging therapy [3,4]. As increasing data are emerging during the last decade, we are here to provide an updated literature review and to offer our suggestions on the practical management of this important clinical issue.
In the second strategy, bridging therapy with intravenous heparin or subcutaneous LMWH is used to minimize the time before and after the procedure during which INR is subtherapeutic in patients with moderate to high risk of thromboembolic events. Bridging therapy, however, has been associated with an increased incidence of pocket hematoma and other bleeding complications, higher costs, and complexity of procedure scheduling. In the third strategy, CIED surgery is performed without cessation or reduction of oral anticoagulation to keep the INR in the therapeutic range during the perioperative period. In the past, continuing anticoagulation throughout the perioperative period was perceived to increase the risk of bleeding complications. Recent studies, however, have challenged this concern and suggested that there was no greater risk of bleeding by maintaining therapeutic warfarin than simply withholding warfarin during the implantation period.
2. Perioperative risk assessment of thromboembolism The current thromboembolic risk stratification is largely based on indirect evidence from studies outside of the perioperative setting involving patients with a mechanical heart valve, chronic atrial fibrillation or venous thromboembolism who either did not receive anticoagulation ( i.e., placebo-treated group in atrial fibrillation trials) or received less-effective treatment (e.g., aspirin-treated group in mechanical heart valve trials) [2]. Table 1 is a simplified risk stratification scheme for perioperative thromboembolism. Patients are classified as high risk (annual risk410%), moderate risk (annual risk 5% to 10%), and low risk (annual risko5%) for thromboembolism. An estimate of individual patient risk for perioperative thromboembolism is subjective but should consider both the baseline risk and the individual patient factors. For patients who are already on chronic warfarin therapy, most of them should have been considered by their physicians as moderate to high risk for thromboembolism.
3. Current management options Three strategies in the management of anticoagulation during the perioperative period of CIED surgery are frequently used in the current clinical practice. In the first strategy, device implantation in patients on warfarin therapy is often postponed until the International Normalized Ratio (INR) has decreased to a nontherapeutic or ‘‘safe’’ level by withholding warfarin, with or without administration of coagulation factors (fresh frozen plasma) or vitamin K. Several days may be needed to reestablish therapeutic anticoagulation after the procedure. Although the period of subtherapeutic anticoagulation is short, exposing patients to potential thromboembolic complications is a concern, especially in those deemed to be moderate or high risk.
4. Risk of thromboembolism with short-term interruption of warfarin therapy A systematic review of perioperative anticoagulation suggested that risk of stroke for patients in whom warfarin was withheld might be substantially higher than would be predicted based on annual thromboembolic rates of patients with atrial fibrillation or a mechanical heart valve [5]. In a prospective, observational cohort study, 1293 episodes of warfarin therapy interruption in 1024 patients for an outpatient invasive procedure were included [6]. Warfarin therapy was withheld for r5 days in 83.8% of the episodes. Seven patients (0.7%) experienced postprocedural thromboembolic events. All those patients with arterial events were in atrial fibrillation with CHADS2 score of Z2. In our study, 114 patients on chronic warfarin therapy had anticoagulation temporarily interrupted for CIED surgery without bridging therapy. Among them, 4 patients with atrial fibrillation and CHADS score Z3 experienced a transient ischemic attack (TIA) even though these patients continued to receive aspirin [7]. Although it is generally safe for low risk patients, a short period of interruption of warfarin therapy during the periprocedural period in patients with moderate to high risk factors could potentially expose them to a small, but real thromboembolic threat.
5. Risk of pocket hematoma on bridging therapy with heparin or LMWH A substantial risk of pocket hematoma related to bridging therapy with therapeutic dose of heparin or LMWH has been consistently observed in patients undergoing device surgery. In a retrospective cohort study, Wiegand et al. reported that patients who received bridging therapy, with a therapeutic dose of heparin,
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had a higher incidence of pocket hematoma as compared to the group who did not receive such treatment (10.7% vs. 2.9%; po0.001) [8]. In a randomized trial, Michaud et al. demonstrated up to 10-fold greater risk of pocket hematoma after device implantation in patients who received intravenous heparin than in patients who did not receive such therapy [9]. The risk was similar whether heparin therapy was initiated 6 h or 24 h after surgery. Marquie et al. confirmed that the postoperative use of heparin of any type conferred a 14-fold increased risk for pocket hematoma [10]. Similar findings were reported by us and other authors [7,11]. Robinson et al. showed that omission of LMWH the night before procedure did not reduce hematoma rates, but omission of postoperative LMWH dramatically reduced the occurrence of hematoma [12]. Several studies also demonstrated that bridging therapy is associated with a longer hospital stay after the procedure [7,13,14]. This finding is expected, as a patient on bridging therapy with intravenous heparin must be kept in the hospital until their INR reaches the therapeutic range. Although subcutaneous LMWH could be self-administered, many of these patients were unable to do so and required transfer to a transitional facility. In addition, patients who developed a pocket hematoma stayed in the hospital longer for observation, transfusion, or surgical evacuation [15]. More importantly. the development of pocket hematoma often lead to withhold anticoagulation therapy for a prolonged time and thus potentially increase the risk for thromboembolism in these patients.
6. Safety of continuation of warfarin during the perioperative period of pacemaker and defibrillator surgery An increasing body of literature has suggested that pacemaker and defibrillator implantation without cessation of oral anticoagulation is safe and feasible. Goldstein et al. were among the first to report their experience implanting devices in 37 patients continued on warfarin with a mean INR of 2.5 at the time of device surgery and compared to 113 patients who did not receive warfarin. The incidence of pocket hematoma in warfarin continuation group was not significantly different from the controls [16]. Al-Khadra reported similar findings in 47 patients with a mean INR 2.3 at device implantation [17]. Only 1 patient in his study had a small hematoma, which resolved spontaneously. The largest observational study was provided by Giudici et al. who assessed the risk of major bleeding complications in 1025 patients undergoing pacemaker or ICD implantation, 470 of whom were continued on warfarin therapy (mean INR 2.5, range 1.5 to 7.5) [18]. They found similar complication rates between patients continued on warfarin therapy and patients who had a normal INR while warfarin was
Table 2 Postoperative hemorrhagic and thromboembolic complications in 459 patients on chronic warfarin therapy managed by three perioperative strategies Outcome
Continued warfarin (n ¼222)
Bridging (n¼123)
Anticoagulation withheld (n¼ 114)
Hematoma
1 (0.45%)
Transient ischemic attack
0
7 (5.7%) p¼ .004 1 (0.8%)
2 (1.75%) p ¼ .26 4 (3.5%)
p¼ .35 1.33 70.20 1.1–1.7
p ¼ .01 1.35 7 0.32 1.0–1.6
Mean INR ( 7SD) 2.577 0.49 INR range 1.5–4.7
INR ¼ International normal ratio. Source: Table reproduced with permission from Heart Rhythm Society.
withheld. Cheng et al. randomized 100 patients undergoing pacemaker and defibrillator implantation into a warfarin continued group and a warfarin interrupted group [19]. Of warfarin interrupted group, 7 patients received bridging with heparin and 43 patients received no bridging therapy. Two patients developed pocket hematoma in bridging group and one patient had TIA in no bridging group. No events were noted in warfarin continued group. Li et al. retrospectively studied 766 patients on chronic warfarin therapy who underwent device-related procedures [13]. Patients were divided into three groups: discontinued warfarin, continued warfarin, and discontinued warfarin with heparin bridging. Bleeding events occurred more often in the heparin bridging group (7.0%) than the discontinued warfarin group (2.1%) or continued warfarin group (3.7%, p¼0.029). Concurrent aspirin use with warfarin significantly increased bleeding risk than warfarin alone (5.6% vs. 1.4%, p¼0.02). We performed a retrospective analysis of 459 consecutive patients on chronic warfarin therapy who underwent CIED surgery [7]. Warfarin was continued in 222 patients, discontinued with heparin or LMWH bridging in 123 patients, and temporarily discontinued without bridging therapy in 114 patients. The perioperative pocket hematoma and thromboembolic complications in these patients are shown in Table 2. Patients who continued warfarin had a lower incidence of pocket hematoma than did patients in the bridging group. Holding warfarin without bridging was associated with a higher incidence of transient ischemic attacks than those on continued warfarin. Similar findings were observed by other authors [20]. Only two small studies failed to show a negative impact of bridging therapy [21,22]. Two recent articles used a meta-analysis to compare various strategies in the perioperative management of anticoagulation therapy in patients undergoing CIED surgery. Bernard et al. analyzed bleeding complications of 5978 patients from 11 studies and found that the estimated odds of bleeding increased by 8.3 times in patients with heparin bridging, 5 times for dual antiplatelet therapy (DAPT) compared to 1.6 times for continued oral anticoagulation [23]. The authors concluded that continuation of oral anticoagulation did not increase bleeding events compared to no anticoagulation therapy. The meta-analysis by Ghanbari et el evaluated 2321 patients undergoing implantation of CIED from 8 studies and found that continuation of therapeutic warfarin therapy was associated with lower risk of bleeding compared to heparin-based bridging therapy without increasing risk for thromboembolic events [24].
7. Safety of cardiac resynchronization therapy device implantation with continuation of warfarin Many patients requiring cardiac resynchronization therapy (CRT) are on chronic warfarin therapy. Although previous studies have suggested that placement of pacemaker or implantable defibrillator in patients with continuation of oral anticoagulation is safe, the safety of this approach in patients for CRT device surgery has not been well established. A specific concern is the potential serious bleeding consequence if coronary sinus (CS) dissection or perforation occurred during placement of a left ventricular (LV) lead. Fortunately, coronary venous perforation during the procedure is rare [25]. We retrospectively analyzed 90 consecutive patients on chronic warfarin therapy who underwent CRT device implantation at our institution [26]. Warfarin therapy was continued in 65 patients, interrupted with bridging in 10 patients and without bridging in 15 patients. A LV lead was successfully implanted in 92% of patients. Pre-procedural mean INR was 2.5 70.38 in patients with continued warfarin. CS dissection occurred in four patients: 3 in patients with continued warfarin and 1 with warfarin discontinued without bridging. CS
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dissection during the procedure did not interfere with LV lead placement nor did it lead to pericardial effusion or tamponade even when INR were in the therapeutic range. Clinically significant pocket hematoma occurred in two patients: one was on heparin bridging and one without bridging but was on DAPT. One patient with discontinued warfarin had a TIA. None of the 65 patients on continued warfarin therapy had bleeding or thromboembolic events. Ghanbari et al. reported the incidence of pocket hematoma in patients undergoing CRT device implantation was 5% in the 20 patients with uninterrupted warfarin as compared to 20.7% in the 29 patients who received bridging therapy (p¼0.03) [27]. No patient had pericardial effusion. Although published data are limited, CRT device implantation with continuation of warfarin appears to be safe, with a low risk of bleeding complications [28].
8. Risk of bleeding complications with dual antiplatelet agents Dual antiplatelet therapy (DAPT) with combined aspirin and clopidogrel has become a standard treatment after percutaneous coronary intervention (PCI). Recent studies have examined the impact of such therapy on the incidence of bleeding complications after CIED surgery. Dreger et al. did not notice an increased risk of clinically relevant hematoma when a drainage system was applied [29]. However, several other studies have demonstrated a consistently higher risk of bleeding complications in these patients. Wiegand et al. reported that the use of DAPT was highly predictive for intraoperative bleeding and pocket hematoma in patients who have undergone pacemaker and defibrillator implantation, while aspirin monotherapy did not appear to have a significant impact on bleeding complications [8]. Tompkins et al. demonstrated that patients on DAPT had a significantly increased bleeding risk as compared with controls (7.2% vs. 1.6%; p¼0.004), while bleeding risk was only marginally higher in patients taking aspirin alone (3.9% vs. 1.6%, p¼0.078) [11]. Thal et al. noted that more patients with hematoma were on DAPT than warfarin therapy alone, and those with the highest incidence of hematoma (40%) were on DAPT combined with warfarin [30]. Kutinsky et al. reported the incidence of pocket hematoma after CIED surgery: aspirin 4.2%, warfarin 6.9%, warfarinþaspirin 10.3%, clopidogrel11.1%, DAPT 24.2%, and warfarinþDAPT 9.5% [31]. Clopidogrel use was one of the predictors of pocket hematoma, while aspirin monotherapy did not seem to have a significant impact on bleeding complications. In the meta-analysis by Bernard et al., bleeding event rates were 2.2% for no therapy, 2.5% for warfarin held, 2.8% for warfarin continued, 3.9% for single antiplatelet therapy, 9.4% for DAPT and 14.6% for heparin bridging strategy (Fig. 1) [23].
Fig. 1. Meta-analysis of unadjusted, pooled rates of bleeding complications associated with CIED implantation. AC = anticoagulant; SAPT = single antiplatelet therapy; DAPT = dual antiplatelet therapy; HBS = heparin bridging strategy (Reproduced with permission of Circulation: Arrhythmia and Electrophysiology from Ref. 23)
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9. Empirical approaches to reduce the perioperative bleeding complications We previously reported that chronic kidney disease was an independent risk factor for pocket hematoma after CIED implantation, probably due to a higher bleeding tendency in these patients [32]. A recent report from a prospective, multicenter registry confirmed that HAS-BLED score predicted bleedings during bridging of chronic oral anticoagulation [33]. Such data are not available in patients on continuous warfarin therapy undergoing CIED surgery. There is hope that improvement in patient co-morbidities, by aggressively treating the underlying diseases, will lead to a lower risk of postoperative bleeding complications. It is important to coordinate the timing of elective PCI and device surgery. Elective PCI should be postponed if possible after device surgery to avoid DAPT in the immediate postoperative period. Target vein venography could be used more frequently if the patient has preserved renal function. Contrast subclavian and auxillary venogram provides a clear anatomical picture and facilitates direct venopuncture [34]. We propose the use of a micropuncture technique to reduce the severity of bleeding in case of inadvertent arterial punctures [35]. A generator pocket formed between the deep fascia and the pectoral muscle probably has less bleeding risk than an intramuscular pocket, however, there are no comparative data to draw clear conclusions. Although the fibrous capsule surrounding the CIED generator often has ample vascular supply and may prone to bleed than new implantation, there is no controlled study available for comparison. In a multicenter prospective study of complications related to CIED generator replacement, Pooles et al. reported the rates of hematoma requiring surgical evacuation were 0.7% in patients had generator change only and significantly higher at 1.5% in those with upgrade and transvenous lead additions [36]. Careful intraoperative hemostasis is crucial, especially if the patient is on the continued warfarin therapy. We usually avoid the practice of temporary placement of gauzes into the pocket during the operation to decrease the risk of delayed bleeding and hematoma formation after pocket closure. Application of sterile pressure dressings on the wound is a common practice although its duration and effectiveness have not been studied. Finally, the practice of sealants injected into the pocket before incision closure remains to be controversial [21,37].
10. Practical management of perioperative anticoagulation and antiplatelet therapy in CIED surgery By integrating the current literature and the experience from our own practice, we developed a practical algorithm recently to guide the perioperative management of anticoagulation and antiplatelet therapy in patients on warfarin therapy undergoing CIED surgery (Fig.2). Because patients may have coexisting risk factors for bleeding such as liver disease, renal dysfunction or bleeding tendencies, the actual situation may be more complex. A decision should be made based on baseline risk and the individual patient factors. Different protocols have been proposed by the others [14,38]. Update is needed when the results of the ongoing and future multicenter, randomized controlled clinical trials become available [39]. At this time, there are no data with the newer generation of anticoagulants such as dabigatran, rivaroxaban, and apixaban in the settings of CIED surgery. For most patients with a low risk for thromboembolism, such as atrial fibrillation with CHADS2r1 or remote deep venous thrombosis (DVT), warfarin could be withheld for 2–3 days before surgery and then resumed in the same day after surgery. One exception to this strategy is in patients with atrial fibrillation undergoing ICD surgery involving defibrillation threshold testing. Since defibrillation
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Fig. 2. Practical algorithm for the perioperative management of anticoagulation and antiplatelet therapy in surgery of cardiac implantable electronic devices. ASA, Aspirin; BMS, Bare Metal Stent; CRT Cardiac Resynchronization Therapy; DAPT, Dual Antiplatelet Therapy; DES, Drug Eluting Stent; ICD, Internal Cardioverter Defibrillator; PPM Permanent Pacemaker; TE, Thromboembolism.
testing may restore sinus rhythm, such patients should be kept on uninterrupted warfarin therapy with therapeutic INR. For patients with moderate to high risks for thromboembolism, such as mechanical valves, atrial fibrillation with mitral stenosis or CHADS2Z2, or recent deep venous thrombosis, CIED surgery including LV lead placement appears to be safe and cost effective with the strategy of continuing warfarin therapy with therapeutic INR as compared to bridging therapy or temporarily withholding anticoagulation. Increasing evidence suggests that perioperative bridging therapy, with intravenous heparin or IMWH, significantly increases the risk of pocket hematoma after CIED surgery. This practice is also associated with higher costs, complexity of procedure scheduling and a longer hospital stay. Therefore, we believe that this strategy should not be recommended to most patients undergoing CIED surgery. DAPT could increase the risk of intraoperative bleeding and pocket hematoma. On the other hand, DAPT prevents stent thrombosis which is a devastating complication with a high morbidity and mortality. In patients who require urgent device surgery within 6 weeks of placement of a bare-mental stent or within 6–12 months of placement of a drug-eluting stent, we suggest to continue DAPT around the time of device surgery while applying hemostasis measures carefully and observing these patients closely. For CIED surgery beyond that critical period in patients with stent(s), aspirin therapy should be continued while clopidogrel may be withhold 7 days prior to the surgery to reduce the risk of bleeding especially if the patient is also on concurrent warfarin therapy. Aspirin monotherapy does not seem to have a significant impact on bleeding complications and can be continued safely during the surgery. Concurrent aspirin use with warfarin has been associated with significantly higher bleeding risk than warfarin alone. On the other hand, clopidogrel monotherapy seems be predictive of pocket hematoma, and may be held temporarily. If the purpose of aspirin or clopidogrel use is for primary prevention of cardiovascular disease, it may be reasonable to temporarily withhold these agents if concurrent warfarin therapy is continued during the perioperative period.
Conflict of interest The authors have no conflict of interest to declare.
Acknowledgement The authors wish to express their appreciation to Chad M House, BS, RDCS for his assistance in the preparation and submission of this manuscript.
References [1] Douketis JD, Berger PB, Dunn AS, et al. The perioperative management of antithrombotic therapy. Chest 2008;133:299S–399S. [2] Douketis JD, Spyropoulos AC, Spencer FA., et al. Perioperative management of antithrombotic therapy: antithrombotic therapy and prevention of thrombosis, 9th ed. American College of hest physicians evidence-based clinical practice guidelines. Chest 2012;141:e326S-e3250. [3] Krahn AD, Healey JS, Simpson CS, et al. Anticoagulation of patients on chronic warfarin undergoing arrhythmia device surgery: wide variability of perioperative bridging in Canada. Heart Rhythm 2009;6:1276–9. [4] DeBono J, Nazir S, Ruparelia N, et al. Perioperative management of anticoagulation during device implantation—the UK perspective. Pacing Clin Electrophysiol 2010;33:389–93. [5] Dunn AS, Turpie AG. Perioperative management of patients receiving oral anticoagulants: a systemic review. Arch Intern Med 2003;163:521–34. [6] Garcia DA, Regan S, Henault LE, et al. Risk of thromboembolism with shortterm interruption of warfarin therapy. Arch Intern Med 2008;168:63–9. [7] Ahmed I, Gertner E, Nelson WB, et al. Continuing warfarin therapy is superior to interrupting warfarin with or without bridging anticoagulation therapy in patients undergoing pacemaker and defibrillator implantation. Heart Rhythm 2010;7:745–9. [8] Wiegand UK, LeJeune D, Boguschewski F, et al. Pocket hematoma after pacemaker or implantable cardioverter defibrillator surgery: influence of patient morbidity, operation strategy, and perioperative antiplatelet/anticoagulation therapy. Chest 2004;126:1177–86. [9] Michaud GF, Pelosi Jr F, Noble MD, et al. A randomized trial comparing heparin initiation 6 h or 24 h after pacemaker or defibrillator implantation. J Am Coll Cardiol 2000;35:1915–8. [10] Marquie C, DeGeeter G, Klug D, et al. Post-operative use of heparin increases morbidity of pacemaker implantation. Europace 2006;8:283–7. [11] Tompkins C, Cheng A, Dalal D, et al. Dual antiplatelet therapy and heparin ‘‘bridging’’ significantly increase the risk of bleeding complications afterpacemaker or implantable cardioverter-defibrillator device implantation. J Am Coll Cardiol 2010;55:2376–82. [12] Robinson M, Healey JS, Eikelboom J, et al. Postoperative low-molecularweight heparin bridging is associated with an increase in wound hematoma following surgery for pacemakers and implantable defibrillators. Pacing Clin Electrophysiol 2009;32:378–82. [13] Li HK, Chen FC, Rea RF, et al. No increased bleeding events with continuation of oral anticoagulation therapy for patients undergoing cardiac device procedure. Pacing Clin Electrophysiol 2011;34:868–74. [14] Cano O, Munoz B, Tejada D, et al. Evaluation of a new standardized protocol for the perioperative management of chronically anticoagulated patients receiving implantable cardiac arrhythmia devices. Heart Rhythm 2012;9:361–7. [15] Zhu DWX. Management of pacemaker and defibrillator complications. In: LU F, Benditt DG, editors. Cardiac pacing and defibrillator: principle and practice. Beijing, China: People’s Medical Publishing House; 2008. p. 521–34. [16] Goldstein DJ, Losquadro W, Spotnitz HM. Outpatient pacemaker surgery in orally anticoagulated patients. Pacing Clin Electrophysiol 1998;21:1730–4. [17] Al-Khadra AS. Implantation of pacemakers and implantable cardioverter defibrillators in orally anticoagulated patients. Pacing Clin Electrophysiol 2003;26:511–4. [18] Giudici MC, Barold SS, Paul DL, et al. Pacemaker and implantable cardioverter defibrillator implantation without reversal of warfarin therapy. Pacing Clin Electrophysiol 2004;27:358–60. [19] Cheng A, Nazarian S, Brinker JA, et al. Continuation of warfarin during pacemaker or implantable cardioverter-defibrillator implantation: a randomized clinical trial. Heart Rhythm 2011;8:536–40. [20] Tischenko A, Gula LJ, Yee R, et al. Implantation of cardiac rhythm devices without interruption of oral anticoagulation compared with perioperative bridging with low-molecular weight heparin. Am Heart J 2009;158:252–6. [21] Milic DJ, Perisic ZD, Zivic SS, et al. Prevention of pocket related fibrin sealant in patients undergoing pacemaker implantation who are receiving anticoagulant treatment. Europace 2005;7:374–9. [22] Tolosana JM, Berne P, Mont L, et al. Preparation for pacemaker or implantable cardiac defibrillator implants in patients with high risk of
D.W. Zhu, I. Ahmed / Journal of Arrhythmia 29 (2013) 162–167
[23]
[24]
[25]
[26]
[27]
[28]
[29]
[30]
thrombo-embolic events: oral anticoagulation or bridging with intravenous heparin? A prospective randomized trial Eur Heart J 2009;30:1880–4. Bernard ML, Shotwell M, Nietert PJ, et al. Meta-analysis of bleeding complications associated with cardiac rhythm device implantation. Circ Arrhythm Electrophysiol 2012;5:468–74. Ghanbari H, Phard WS, Al-Ameri H, et al. Meta-analysis of safety and efficacy of uninterrupted warfarin compared to heparin-based bridging therapy during implantation of cardiac rhythm devices. Am J Cardiol 2012;110:1482–8. Gras D, Bocker D, Lunati M, et al. CARE-HF Study Steering Committee and Investigators. Implantation of cardiac resynchronization therapy systems in the CARE-HF trials: procedure success rate and safety. Europace 2007;9: 516–22. Ahmed I, Nelson WB, Dahiya R, et al. Safety of cardiac resynchronization therapy device implantation in patients with uninterrupted chronic warfarin therapy. Circulation 2009;120(18):S823 abstract. Ghanbari H, Feldman D, Schmidt M, et al. Cardiac resynchronization therapy device implantation in patients with therapeutic international normalized ratios. Pacing Clin Electrophysiol 2010;33:400–6. Daubert JC, Saxon L, Adamson PB, et al. 2012 EHRA/HRA expert consensus statement on cardiac resynchronization therapy in heart failure: implant and follow-up recommendations and management. Heart Rhythm 2012;9: 1524–76. Dreger H, Grohmann A, Bondke H, et al. Is antiarrhythmia device implantation safe under dual antiplatelet therapy? Pacing Clin Electrophysiol 2010;33:394–9. Thal S, Goldman S. The relationship between warfarin, aspirin, and clopidogrel continuation in the peri-procedural period and the incidence of hematoma formation after device implantation. Pacing Clin Electrophysiol 2010;33:385–8.
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[31] Kutinsky IB, Jarandilla R, Jewett M, Haines DE. Risk of hematoma complications after device implant in the clopidogrel era. Circ Arrhythm Electrophysiol 2010;3:312–8. [32] Ahmed I, Gertner E, Nelson WB, et al. Chronic kidney disease is an independent predictor of pocket hematoma after pacemaker and defibrillator implantation. J Interv Card Electrophysiol 2010;29:203–7. [33] Omran H, Bauersachs R, Rubenacker S, et al. The HAS-BLED score predicts bleedings during bridging of chronic oral anticoagulation. Results from the national multicentre BNK Online bRiDging REgistRy (BORDER). Thromb Haemost 2012;102:65–73. [34] Spencer WH, Zhu DWX, Kirkpatrick C, et al. Subclavian venogram as a guide to lead implantation. Pacing Clin Electrophysiol 1998;21:499–502. [35] Schneider PA. Endovascular skills: guidewire and catheter skills for endovascular surgery. 3rd ed. Jersey, Switzerland: Informa HealthCare; 2009 26. [36] Poole JE, Gleva MJ, Mela T, et al. Complication rates associated with pacemaker or implantable cardioverter-defibrillator generator replacements and upgrade procedures: results from the REPLACE registry. Circulation 2010;122:1553–61. [37] Ohlow MA, Lauer B, Buchter B, et al. Pocket related complications in 163 patients receiving anticoagulation or dual antiplatelet therapy: D-Stat Hemostat versus standard of care. Int J Cardiol 2012;159:177–80. [38] Korantzopoulos P, Letsas KP, Liu T, et al. Anticoagulation and antiplatelet therapy in implantation of electrophysiological devices. Europace 2011;13: 1669–80. [39] Birnie D, Healey JS, Krahn, et al. Bridge or continue Coumadin for device surgery: a randomized controlled trial rationale and design. Curr Opin Cardiol 2008;24:82–7.
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Journal of Arrhythmia journal homepage: www.elsevier.com/locate/joa
Review
Perioperative management of anticoagulation in patients on warfarin therapy undergoing surgery for cardiac implantable electronic devices Dennis Weixi Zhu MD, FACC, FHRSn, Imdad Ahmed MD Regions Hospital and HealthPartners Medical Group, University of Minnesota, Saint Paul, MN, United States
a r t i c l e i n f o
a b s t r a c t
Article history: Received 6 December 2012 Received in revised form 8 January 2013 Accepted 9 January 2013 Available online 17 March 2013
Many patients on chronic warfarin therapy are undergoing surgery for permanent pacemakers and implantable defibrillators, collectively known as cardiac implantable electronic device (CIED). The perioperative management of anticoagulation in these patients is a challenging clinical situation that requires balance between the risk of acute thrombosis and perioperative hemorrhage. This issue however, is inadequately addressed in the guidelines published by professional organizations. Increasing evidence suggests that temporarily interrupting anticoagulation is associated with a small but real thromboembolic risk, whereas cessation of warfarin with heparin bridging anticoagulation frequently leads to a higher incidence of pocket hematoma. Continuing warfarin with a therapeutic international normalized ratio appears to be a safe and cost-effective approach for CIED surgery in most patients with moderate to high thromboembolic risk. An algorithm is proposed for the practical management of anticoagulation and antiplatelet therapy in these patients during the perioperative period. & 2013 Japanese Heart Rhythm Society. Published by Elsevier B.V. All rights reserved.
Keywords: Anticoagulation Warfarin Pocket hematoma Pacemaker/defibrillator Thromboembolism
Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2. Perioperative risk assessment of thromboembolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3. Current management options . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4. Risk of thromboembolism with short-term interruption of warfarin therapy. . . . . . . . . . . . . . . . . . 5. Risk of pocket hematoma on bridging therapy with heparin or LMWH . . . . . . . . . . . . . . . . . . . . . . 6. Safety of continuation of warfarin during the perioperative period of pacemaker and defibrillator 7. Safety of cardiac resynchronization therapy device implantation with continuation of warfarin . . 8. Risk of bleeding complications with dual antiplatelet agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9. Empirical approaches to reduce the perioperative bleeding complications. . . . . . . . . . . . . . . . . . . . 10. Practical management of perioperative anticoagulation and antiplatelet therapy in CIED surgery . Conflict of interest. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Introduction The optimal management of perioperative anticoagulation in patients on warfarin therapy undergoing cardiac implantable electronic device (CIED) surgery is not yet established.
n Correspondence to: Cardiology 11102H, HealthPartners Medical Group, Regions Hospital, University of Minnesota, 640 Jackson Street, Saint Paul, MN 55101. Tel.: þ1 651254 0829; fax: þ1 651254 4129. E-mail address: [email protected] (D.W. Zhu MD, FACC, FHRS).
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Neither the recent American Heart Association/American College of Cardiology nor European Society of Cardiology guidelines mentioned device surgery in patients on chronic anticoagulation therapy. The 2008 guidelines from the American College of Chest Physicians (ACCP) have recommended the use of bridging anticoagulation with therapeutic dose of subcutaneous low-molecularweight heparin (LMWH) or intravenous heparin in patients with mechanical heart valves, atrial fibrillation, or venous thromboembolism who are at moderate or high risk for thromboembolic events [1]. This recommendation, however, was largely based on
1880-4276/$ - see front matter & 2013 Japanese Heart Rhythm Society. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.joa.2013.01.010
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Table 1 Risk stratification for perioperative thromboembolism. Risk group Mechanical heart valve High
Moderate
Low
Atrial fibrillation
VTE
CHADS2 score of 5 or 6 VTE r3months Stroke or TIAr 3 months Severe thrombophilia (deficiency of protein C, protein S or antithrombin; antiphospholipid Stroke or TIAr 6 months Rheumatic valvular heart disease Aortic valve prosthesis CHADS2 score of 2 to 4 VTE within3–12 months Nonsevere thrombophilia (e.g., heterozygous factor Leiden) Recurrent VTE Active cancer CHADS2 score of 0 to 1 VTE 412 months and no other risk factors
Mitral valve prosthesis
CHADS2¼ congestive heart failure, hypertension, ageZ 75 years, diabetes mellitus, and stroke or transient ischemic attack. TIA¼ transient ischemic attack, VTE ¼ venous thromboemolic event.
expert opinion. The new ACCP 2012 guidelines considered CIED surgery to be a procedure associated with an increased bleeding risk during perioperative antithrombotic administration [2]. CIED implantation in which separation of infraclavicular fascial layers and lack of suturing of unopposed tissues within device pocket may predispose to hematoma development. However, the updated guidelines did not provide specific recommendations on the management of this patient population. Recent surveys in Canada and United Kingdom revealed a lack of consensus among the CIED implanting physicians on whether to withhold anticoagulation and whether to use bridging therapy [3,4]. As increasing data are emerging during the last decade, we are here to provide an updated literature review and to offer our suggestions on the practical management of this important clinical issue.
In the second strategy, bridging therapy with intravenous heparin or subcutaneous LMWH is used to minimize the time before and after the procedure during which INR is subtherapeutic in patients with moderate to high risk of thromboembolic events. Bridging therapy, however, has been associated with an increased incidence of pocket hematoma and other bleeding complications, higher costs, and complexity of procedure scheduling. In the third strategy, CIED surgery is performed without cessation or reduction of oral anticoagulation to keep the INR in the therapeutic range during the perioperative period. In the past, continuing anticoagulation throughout the perioperative period was perceived to increase the risk of bleeding complications. Recent studies, however, have challenged this concern and suggested that there was no greater risk of bleeding by maintaining therapeutic warfarin than simply withholding warfarin during the implantation period.
2. Perioperative risk assessment of thromboembolism The current thromboembolic risk stratification is largely based on indirect evidence from studies outside of the perioperative setting involving patients with a mechanical heart valve, chronic atrial fibrillation or venous thromboembolism who either did not receive anticoagulation ( i.e., placebo-treated group in atrial fibrillation trials) or received less-effective treatment (e.g., aspirin-treated group in mechanical heart valve trials) [2]. Table 1 is a simplified risk stratification scheme for perioperative thromboembolism. Patients are classified as high risk (annual risk410%), moderate risk (annual risk 5% to 10%), and low risk (annual risko5%) for thromboembolism. An estimate of individual patient risk for perioperative thromboembolism is subjective but should consider both the baseline risk and the individual patient factors. For patients who are already on chronic warfarin therapy, most of them should have been considered by their physicians as moderate to high risk for thromboembolism.
3. Current management options Three strategies in the management of anticoagulation during the perioperative period of CIED surgery are frequently used in the current clinical practice. In the first strategy, device implantation in patients on warfarin therapy is often postponed until the International Normalized Ratio (INR) has decreased to a nontherapeutic or ‘‘safe’’ level by withholding warfarin, with or without administration of coagulation factors (fresh frozen plasma) or vitamin K. Several days may be needed to reestablish therapeutic anticoagulation after the procedure. Although the period of subtherapeutic anticoagulation is short, exposing patients to potential thromboembolic complications is a concern, especially in those deemed to be moderate or high risk.
4. Risk of thromboembolism with short-term interruption of warfarin therapy A systematic review of perioperative anticoagulation suggested that risk of stroke for patients in whom warfarin was withheld might be substantially higher than would be predicted based on annual thromboembolic rates of patients with atrial fibrillation or a mechanical heart valve [5]. In a prospective, observational cohort study, 1293 episodes of warfarin therapy interruption in 1024 patients for an outpatient invasive procedure were included [6]. Warfarin therapy was withheld for r5 days in 83.8% of the episodes. Seven patients (0.7%) experienced postprocedural thromboembolic events. All those patients with arterial events were in atrial fibrillation with CHADS2 score of Z2. In our study, 114 patients on chronic warfarin therapy had anticoagulation temporarily interrupted for CIED surgery without bridging therapy. Among them, 4 patients with atrial fibrillation and CHADS score Z3 experienced a transient ischemic attack (TIA) even though these patients continued to receive aspirin [7]. Although it is generally safe for low risk patients, a short period of interruption of warfarin therapy during the periprocedural period in patients with moderate to high risk factors could potentially expose them to a small, but real thromboembolic threat.
5. Risk of pocket hematoma on bridging therapy with heparin or LMWH A substantial risk of pocket hematoma related to bridging therapy with therapeutic dose of heparin or LMWH has been consistently observed in patients undergoing device surgery. In a retrospective cohort study, Wiegand et al. reported that patients who received bridging therapy, with a therapeutic dose of heparin,
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had a higher incidence of pocket hematoma as compared to the group who did not receive such treatment (10.7% vs. 2.9%; po0.001) [8]. In a randomized trial, Michaud et al. demonstrated up to 10-fold greater risk of pocket hematoma after device implantation in patients who received intravenous heparin than in patients who did not receive such therapy [9]. The risk was similar whether heparin therapy was initiated 6 h or 24 h after surgery. Marquie et al. confirmed that the postoperative use of heparin of any type conferred a 14-fold increased risk for pocket hematoma [10]. Similar findings were reported by us and other authors [7,11]. Robinson et al. showed that omission of LMWH the night before procedure did not reduce hematoma rates, but omission of postoperative LMWH dramatically reduced the occurrence of hematoma [12]. Several studies also demonstrated that bridging therapy is associated with a longer hospital stay after the procedure [7,13,14]. This finding is expected, as a patient on bridging therapy with intravenous heparin must be kept in the hospital until their INR reaches the therapeutic range. Although subcutaneous LMWH could be self-administered, many of these patients were unable to do so and required transfer to a transitional facility. In addition, patients who developed a pocket hematoma stayed in the hospital longer for observation, transfusion, or surgical evacuation [15]. More importantly. the development of pocket hematoma often lead to withhold anticoagulation therapy for a prolonged time and thus potentially increase the risk for thromboembolism in these patients.
6. Safety of continuation of warfarin during the perioperative period of pacemaker and defibrillator surgery An increasing body of literature has suggested that pacemaker and defibrillator implantation without cessation of oral anticoagulation is safe and feasible. Goldstein et al. were among the first to report their experience implanting devices in 37 patients continued on warfarin with a mean INR of 2.5 at the time of device surgery and compared to 113 patients who did not receive warfarin. The incidence of pocket hematoma in warfarin continuation group was not significantly different from the controls [16]. Al-Khadra reported similar findings in 47 patients with a mean INR 2.3 at device implantation [17]. Only 1 patient in his study had a small hematoma, which resolved spontaneously. The largest observational study was provided by Giudici et al. who assessed the risk of major bleeding complications in 1025 patients undergoing pacemaker or ICD implantation, 470 of whom were continued on warfarin therapy (mean INR 2.5, range 1.5 to 7.5) [18]. They found similar complication rates between patients continued on warfarin therapy and patients who had a normal INR while warfarin was
Table 2 Postoperative hemorrhagic and thromboembolic complications in 459 patients on chronic warfarin therapy managed by three perioperative strategies Outcome
Continued warfarin (n ¼222)
Bridging (n¼123)
Anticoagulation withheld (n¼ 114)
Hematoma
1 (0.45%)
Transient ischemic attack
0
7 (5.7%) p¼ .004 1 (0.8%)
2 (1.75%) p ¼ .26 4 (3.5%)
p¼ .35 1.33 70.20 1.1–1.7
p ¼ .01 1.35 7 0.32 1.0–1.6
Mean INR ( 7SD) 2.577 0.49 INR range 1.5–4.7
INR ¼ International normal ratio. Source: Table reproduced with permission from Heart Rhythm Society.
withheld. Cheng et al. randomized 100 patients undergoing pacemaker and defibrillator implantation into a warfarin continued group and a warfarin interrupted group [19]. Of warfarin interrupted group, 7 patients received bridging with heparin and 43 patients received no bridging therapy. Two patients developed pocket hematoma in bridging group and one patient had TIA in no bridging group. No events were noted in warfarin continued group. Li et al. retrospectively studied 766 patients on chronic warfarin therapy who underwent device-related procedures [13]. Patients were divided into three groups: discontinued warfarin, continued warfarin, and discontinued warfarin with heparin bridging. Bleeding events occurred more often in the heparin bridging group (7.0%) than the discontinued warfarin group (2.1%) or continued warfarin group (3.7%, p¼0.029). Concurrent aspirin use with warfarin significantly increased bleeding risk than warfarin alone (5.6% vs. 1.4%, p¼0.02). We performed a retrospective analysis of 459 consecutive patients on chronic warfarin therapy who underwent CIED surgery [7]. Warfarin was continued in 222 patients, discontinued with heparin or LMWH bridging in 123 patients, and temporarily discontinued without bridging therapy in 114 patients. The perioperative pocket hematoma and thromboembolic complications in these patients are shown in Table 2. Patients who continued warfarin had a lower incidence of pocket hematoma than did patients in the bridging group. Holding warfarin without bridging was associated with a higher incidence of transient ischemic attacks than those on continued warfarin. Similar findings were observed by other authors [20]. Only two small studies failed to show a negative impact of bridging therapy [21,22]. Two recent articles used a meta-analysis to compare various strategies in the perioperative management of anticoagulation therapy in patients undergoing CIED surgery. Bernard et al. analyzed bleeding complications of 5978 patients from 11 studies and found that the estimated odds of bleeding increased by 8.3 times in patients with heparin bridging, 5 times for dual antiplatelet therapy (DAPT) compared to 1.6 times for continued oral anticoagulation [23]. The authors concluded that continuation of oral anticoagulation did not increase bleeding events compared to no anticoagulation therapy. The meta-analysis by Ghanbari et el evaluated 2321 patients undergoing implantation of CIED from 8 studies and found that continuation of therapeutic warfarin therapy was associated with lower risk of bleeding compared to heparin-based bridging therapy without increasing risk for thromboembolic events [24].
7. Safety of cardiac resynchronization therapy device implantation with continuation of warfarin Many patients requiring cardiac resynchronization therapy (CRT) are on chronic warfarin therapy. Although previous studies have suggested that placement of pacemaker or implantable defibrillator in patients with continuation of oral anticoagulation is safe, the safety of this approach in patients for CRT device surgery has not been well established. A specific concern is the potential serious bleeding consequence if coronary sinus (CS) dissection or perforation occurred during placement of a left ventricular (LV) lead. Fortunately, coronary venous perforation during the procedure is rare [25]. We retrospectively analyzed 90 consecutive patients on chronic warfarin therapy who underwent CRT device implantation at our institution [26]. Warfarin therapy was continued in 65 patients, interrupted with bridging in 10 patients and without bridging in 15 patients. A LV lead was successfully implanted in 92% of patients. Pre-procedural mean INR was 2.5 70.38 in patients with continued warfarin. CS dissection occurred in four patients: 3 in patients with continued warfarin and 1 with warfarin discontinued without bridging. CS
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dissection during the procedure did not interfere with LV lead placement nor did it lead to pericardial effusion or tamponade even when INR were in the therapeutic range. Clinically significant pocket hematoma occurred in two patients: one was on heparin bridging and one without bridging but was on DAPT. One patient with discontinued warfarin had a TIA. None of the 65 patients on continued warfarin therapy had bleeding or thromboembolic events. Ghanbari et al. reported the incidence of pocket hematoma in patients undergoing CRT device implantation was 5% in the 20 patients with uninterrupted warfarin as compared to 20.7% in the 29 patients who received bridging therapy (p¼0.03) [27]. No patient had pericardial effusion. Although published data are limited, CRT device implantation with continuation of warfarin appears to be safe, with a low risk of bleeding complications [28].
8. Risk of bleeding complications with dual antiplatelet agents Dual antiplatelet therapy (DAPT) with combined aspirin and clopidogrel has become a standard treatment after percutaneous coronary intervention (PCI). Recent studies have examined the impact of such therapy on the incidence of bleeding complications after CIED surgery. Dreger et al. did not notice an increased risk of clinically relevant hematoma when a drainage system was applied [29]. However, several other studies have demonstrated a consistently higher risk of bleeding complications in these patients. Wiegand et al. reported that the use of DAPT was highly predictive for intraoperative bleeding and pocket hematoma in patients who have undergone pacemaker and defibrillator implantation, while aspirin monotherapy did not appear to have a significant impact on bleeding complications [8]. Tompkins et al. demonstrated that patients on DAPT had a significantly increased bleeding risk as compared with controls (7.2% vs. 1.6%; p¼0.004), while bleeding risk was only marginally higher in patients taking aspirin alone (3.9% vs. 1.6%, p¼0.078) [11]. Thal et al. noted that more patients with hematoma were on DAPT than warfarin therapy alone, and those with the highest incidence of hematoma (40%) were on DAPT combined with warfarin [30]. Kutinsky et al. reported the incidence of pocket hematoma after CIED surgery: aspirin 4.2%, warfarin 6.9%, warfarinþaspirin 10.3%, clopidogrel11.1%, DAPT 24.2%, and warfarinþDAPT 9.5% [31]. Clopidogrel use was one of the predictors of pocket hematoma, while aspirin monotherapy did not seem to have a significant impact on bleeding complications. In the meta-analysis by Bernard et al., bleeding event rates were 2.2% for no therapy, 2.5% for warfarin held, 2.8% for warfarin continued, 3.9% for single antiplatelet therapy, 9.4% for DAPT and 14.6% for heparin bridging strategy (Fig. 1) [23].
Fig. 1. Meta-analysis of unadjusted, pooled rates of bleeding complications associated with CIED implantation. AC = anticoagulant; SAPT = single antiplatelet therapy; DAPT = dual antiplatelet therapy; HBS = heparin bridging strategy (Reproduced with permission of Circulation: Arrhythmia and Electrophysiology from Ref. 23)
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9. Empirical approaches to reduce the perioperative bleeding complications We previously reported that chronic kidney disease was an independent risk factor for pocket hematoma after CIED implantation, probably due to a higher bleeding tendency in these patients [32]. A recent report from a prospective, multicenter registry confirmed that HAS-BLED score predicted bleedings during bridging of chronic oral anticoagulation [33]. Such data are not available in patients on continuous warfarin therapy undergoing CIED surgery. There is hope that improvement in patient co-morbidities, by aggressively treating the underlying diseases, will lead to a lower risk of postoperative bleeding complications. It is important to coordinate the timing of elective PCI and device surgery. Elective PCI should be postponed if possible after device surgery to avoid DAPT in the immediate postoperative period. Target vein venography could be used more frequently if the patient has preserved renal function. Contrast subclavian and auxillary venogram provides a clear anatomical picture and facilitates direct venopuncture [34]. We propose the use of a micropuncture technique to reduce the severity of bleeding in case of inadvertent arterial punctures [35]. A generator pocket formed between the deep fascia and the pectoral muscle probably has less bleeding risk than an intramuscular pocket, however, there are no comparative data to draw clear conclusions. Although the fibrous capsule surrounding the CIED generator often has ample vascular supply and may prone to bleed than new implantation, there is no controlled study available for comparison. In a multicenter prospective study of complications related to CIED generator replacement, Pooles et al. reported the rates of hematoma requiring surgical evacuation were 0.7% in patients had generator change only and significantly higher at 1.5% in those with upgrade and transvenous lead additions [36]. Careful intraoperative hemostasis is crucial, especially if the patient is on the continued warfarin therapy. We usually avoid the practice of temporary placement of gauzes into the pocket during the operation to decrease the risk of delayed bleeding and hematoma formation after pocket closure. Application of sterile pressure dressings on the wound is a common practice although its duration and effectiveness have not been studied. Finally, the practice of sealants injected into the pocket before incision closure remains to be controversial [21,37].
10. Practical management of perioperative anticoagulation and antiplatelet therapy in CIED surgery By integrating the current literature and the experience from our own practice, we developed a practical algorithm recently to guide the perioperative management of anticoagulation and antiplatelet therapy in patients on warfarin therapy undergoing CIED surgery (Fig.2). Because patients may have coexisting risk factors for bleeding such as liver disease, renal dysfunction or bleeding tendencies, the actual situation may be more complex. A decision should be made based on baseline risk and the individual patient factors. Different protocols have been proposed by the others [14,38]. Update is needed when the results of the ongoing and future multicenter, randomized controlled clinical trials become available [39]. At this time, there are no data with the newer generation of anticoagulants such as dabigatran, rivaroxaban, and apixaban in the settings of CIED surgery. For most patients with a low risk for thromboembolism, such as atrial fibrillation with CHADS2r1 or remote deep venous thrombosis (DVT), warfarin could be withheld for 2–3 days before surgery and then resumed in the same day after surgery. One exception to this strategy is in patients with atrial fibrillation undergoing ICD surgery involving defibrillation threshold testing. Since defibrillation
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Fig. 2. Practical algorithm for the perioperative management of anticoagulation and antiplatelet therapy in surgery of cardiac implantable electronic devices. ASA, Aspirin; BMS, Bare Metal Stent; CRT Cardiac Resynchronization Therapy; DAPT, Dual Antiplatelet Therapy; DES, Drug Eluting Stent; ICD, Internal Cardioverter Defibrillator; PPM Permanent Pacemaker; TE, Thromboembolism.
testing may restore sinus rhythm, such patients should be kept on uninterrupted warfarin therapy with therapeutic INR. For patients with moderate to high risks for thromboembolism, such as mechanical valves, atrial fibrillation with mitral stenosis or CHADS2Z2, or recent deep venous thrombosis, CIED surgery including LV lead placement appears to be safe and cost effective with the strategy of continuing warfarin therapy with therapeutic INR as compared to bridging therapy or temporarily withholding anticoagulation. Increasing evidence suggests that perioperative bridging therapy, with intravenous heparin or IMWH, significantly increases the risk of pocket hematoma after CIED surgery. This practice is also associated with higher costs, complexity of procedure scheduling and a longer hospital stay. Therefore, we believe that this strategy should not be recommended to most patients undergoing CIED surgery. DAPT could increase the risk of intraoperative bleeding and pocket hematoma. On the other hand, DAPT prevents stent thrombosis which is a devastating complication with a high morbidity and mortality. In patients who require urgent device surgery within 6 weeks of placement of a bare-mental stent or within 6–12 months of placement of a drug-eluting stent, we suggest to continue DAPT around the time of device surgery while applying hemostasis measures carefully and observing these patients closely. For CIED surgery beyond that critical period in patients with stent(s), aspirin therapy should be continued while clopidogrel may be withhold 7 days prior to the surgery to reduce the risk of bleeding especially if the patient is also on concurrent warfarin therapy. Aspirin monotherapy does not seem to have a significant impact on bleeding complications and can be continued safely during the surgery. Concurrent aspirin use with warfarin has been associated with significantly higher bleeding risk than warfarin alone. On the other hand, clopidogrel monotherapy seems be predictive of pocket hematoma, and may be held temporarily. If the purpose of aspirin or clopidogrel use is for primary prevention of cardiovascular disease, it may be reasonable to temporarily withhold these agents if concurrent warfarin therapy is continued during the perioperative period.
Conflict of interest The authors have no conflict of interest to declare.
Acknowledgement The authors wish to express their appreciation to Chad M House, BS, RDCS for his assistance in the preparation and submission of this manuscript.
References [1] Douketis JD, Berger PB, Dunn AS, et al. The perioperative management of antithrombotic therapy. Chest 2008;133:299S–399S. [2] Douketis JD, Spyropoulos AC, Spencer FA., et al. Perioperative management of antithrombotic therapy: antithrombotic therapy and prevention of thrombosis, 9th ed. American College of hest physicians evidence-based clinical practice guidelines. Chest 2012;141:e326S-e3250. [3] Krahn AD, Healey JS, Simpson CS, et al. Anticoagulation of patients on chronic warfarin undergoing arrhythmia device surgery: wide variability of perioperative bridging in Canada. Heart Rhythm 2009;6:1276–9. [4] DeBono J, Nazir S, Ruparelia N, et al. Perioperative management of anticoagulation during device implantation—the UK perspective. Pacing Clin Electrophysiol 2010;33:389–93. [5] Dunn AS, Turpie AG. Perioperative management of patients receiving oral anticoagulants: a systemic review. Arch Intern Med 2003;163:521–34. [6] Garcia DA, Regan S, Henault LE, et al. Risk of thromboembolism with shortterm interruption of warfarin therapy. Arch Intern Med 2008;168:63–9. [7] Ahmed I, Gertner E, Nelson WB, et al. Continuing warfarin therapy is superior to interrupting warfarin with or without bridging anticoagulation therapy in patients undergoing pacemaker and defibrillator implantation. Heart Rhythm 2010;7:745–9. [8] Wiegand UK, LeJeune D, Boguschewski F, et al. Pocket hematoma after pacemaker or implantable cardioverter defibrillator surgery: influence of patient morbidity, operation strategy, and perioperative antiplatelet/anticoagulation therapy. Chest 2004;126:1177–86. [9] Michaud GF, Pelosi Jr F, Noble MD, et al. A randomized trial comparing heparin initiation 6 h or 24 h after pacemaker or defibrillator implantation. J Am Coll Cardiol 2000;35:1915–8. [10] Marquie C, DeGeeter G, Klug D, et al. Post-operative use of heparin increases morbidity of pacemaker implantation. Europace 2006;8:283–7. [11] Tompkins C, Cheng A, Dalal D, et al. Dual antiplatelet therapy and heparin ‘‘bridging’’ significantly increase the risk of bleeding complications afterpacemaker or implantable cardioverter-defibrillator device implantation. J Am Coll Cardiol 2010;55:2376–82. [12] Robinson M, Healey JS, Eikelboom J, et al. Postoperative low-molecularweight heparin bridging is associated with an increase in wound hematoma following surgery for pacemakers and implantable defibrillators. Pacing Clin Electrophysiol 2009;32:378–82. [13] Li HK, Chen FC, Rea RF, et al. No increased bleeding events with continuation of oral anticoagulation therapy for patients undergoing cardiac device procedure. Pacing Clin Electrophysiol 2011;34:868–74. [14] Cano O, Munoz B, Tejada D, et al. Evaluation of a new standardized protocol for the perioperative management of chronically anticoagulated patients receiving implantable cardiac arrhythmia devices. Heart Rhythm 2012;9:361–7. [15] Zhu DWX. Management of pacemaker and defibrillator complications. In: LU F, Benditt DG, editors. Cardiac pacing and defibrillator: principle and practice. Beijing, China: People’s Medical Publishing House; 2008. p. 521–34. [16] Goldstein DJ, Losquadro W, Spotnitz HM. Outpatient pacemaker surgery in orally anticoagulated patients. Pacing Clin Electrophysiol 1998;21:1730–4. [17] Al-Khadra AS. Implantation of pacemakers and implantable cardioverter defibrillators in orally anticoagulated patients. Pacing Clin Electrophysiol 2003;26:511–4. [18] Giudici MC, Barold SS, Paul DL, et al. Pacemaker and implantable cardioverter defibrillator implantation without reversal of warfarin therapy. Pacing Clin Electrophysiol 2004;27:358–60. [19] Cheng A, Nazarian S, Brinker JA, et al. Continuation of warfarin during pacemaker or implantable cardioverter-defibrillator implantation: a randomized clinical trial. Heart Rhythm 2011;8:536–40. [20] Tischenko A, Gula LJ, Yee R, et al. Implantation of cardiac rhythm devices without interruption of oral anticoagulation compared with perioperative bridging with low-molecular weight heparin. Am Heart J 2009;158:252–6. [21] Milic DJ, Perisic ZD, Zivic SS, et al. Prevention of pocket related fibrin sealant in patients undergoing pacemaker implantation who are receiving anticoagulant treatment. Europace 2005;7:374–9. [22] Tolosana JM, Berne P, Mont L, et al. Preparation for pacemaker or implantable cardiac defibrillator implants in patients with high risk of
D.W. Zhu, I. Ahmed / Journal of Arrhythmia 29 (2013) 162–167
[23]
[24]
[25]
[26]
[27]
[28]
[29]
[30]
thrombo-embolic events: oral anticoagulation or bridging with intravenous heparin? A prospective randomized trial Eur Heart J 2009;30:1880–4. Bernard ML, Shotwell M, Nietert PJ, et al. Meta-analysis of bleeding complications associated with cardiac rhythm device implantation. Circ Arrhythm Electrophysiol 2012;5:468–74. Ghanbari H, Phard WS, Al-Ameri H, et al. Meta-analysis of safety and efficacy of uninterrupted warfarin compared to heparin-based bridging therapy during implantation of cardiac rhythm devices. Am J Cardiol 2012;110:1482–8. Gras D, Bocker D, Lunati M, et al. CARE-HF Study Steering Committee and Investigators. Implantation of cardiac resynchronization therapy systems in the CARE-HF trials: procedure success rate and safety. Europace 2007;9: 516–22. Ahmed I, Nelson WB, Dahiya R, et al. Safety of cardiac resynchronization therapy device implantation in patients with uninterrupted chronic warfarin therapy. Circulation 2009;120(18):S823 abstract. Ghanbari H, Feldman D, Schmidt M, et al. Cardiac resynchronization therapy device implantation in patients with therapeutic international normalized ratios. Pacing Clin Electrophysiol 2010;33:400–6. Daubert JC, Saxon L, Adamson PB, et al. 2012 EHRA/HRA expert consensus statement on cardiac resynchronization therapy in heart failure: implant and follow-up recommendations and management. Heart Rhythm 2012;9: 1524–76. Dreger H, Grohmann A, Bondke H, et al. Is antiarrhythmia device implantation safe under dual antiplatelet therapy? Pacing Clin Electrophysiol 2010;33:394–9. Thal S, Goldman S. The relationship between warfarin, aspirin, and clopidogrel continuation in the peri-procedural period and the incidence of hematoma formation after device implantation. Pacing Clin Electrophysiol 2010;33:385–8.
167
[31] Kutinsky IB, Jarandilla R, Jewett M, Haines DE. Risk of hematoma complications after device implant in the clopidogrel era. Circ Arrhythm Electrophysiol 2010;3:312–8. [32] Ahmed I, Gertner E, Nelson WB, et al. Chronic kidney disease is an independent predictor of pocket hematoma after pacemaker and defibrillator implantation. J Interv Card Electrophysiol 2010;29:203–7. [33] Omran H, Bauersachs R, Rubenacker S, et al. The HAS-BLED score predicts bleedings during bridging of chronic oral anticoagulation. Results from the national multicentre BNK Online bRiDging REgistRy (BORDER). Thromb Haemost 2012;102:65–73. [34] Spencer WH, Zhu DWX, Kirkpatrick C, et al. Subclavian venogram as a guide to lead implantation. Pacing Clin Electrophysiol 1998;21:499–502. [35] Schneider PA. Endovascular skills: guidewire and catheter skills for endovascular surgery. 3rd ed. Jersey, Switzerland: Informa HealthCare; 2009 26. [36] Poole JE, Gleva MJ, Mela T, et al. Complication rates associated with pacemaker or implantable cardioverter-defibrillator generator replacements and upgrade procedures: results from the REPLACE registry. Circulation 2010;122:1553–61. [37] Ohlow MA, Lauer B, Buchter B, et al. Pocket related complications in 163 patients receiving anticoagulation or dual antiplatelet therapy: D-Stat Hemostat versus standard of care. Int J Cardiol 2012;159:177–80. [38] Korantzopoulos P, Letsas KP, Liu T, et al. Anticoagulation and antiplatelet therapy in implantation of electrophysiological devices. Europace 2011;13: 1669–80. [39] Birnie D, Healey JS, Krahn, et al. Bridge or continue Coumadin for device surgery: a randomized controlled trial rationale and design. Curr Opin Cardiol 2008;24:82–7.