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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 2  |  Issue : 2  |  Page : 68-72

Safety of continuing warfarin therapy in patients undergoing cardiac resynchronization therapy device implantation


1 Department of Cardiology, Regions Hospital, St. Paul, Minnesota; Health Partners Medical Group, Minneapolis, USA
2 University of Minnesota Medical School, Minneapolis, Minnesota, USA
3 Department of Cardiology, Regions Hospital, St. Paul, Minnesota; Health Partners Medical Group, Minneapolis; University of Minnesota Medical School, Minneapolis, Minnesota, USA

Date of Web Publication31-Jan-2018

Correspondence Address:
Dr. Dennis W.X. Zhu
Mail Stop 11102M, 640 Jackson Street, St. Paul, MN 55101
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJHR.IJHR_5_17

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  Abstract 


Background: Continuing warfarin therapy is considered safe for patient undergoing pacemaker or implantable cardioverter defibrillator procedures, but less evidence exists for patients undergoing cardiac resynchronization therapy (CRT) device implantation. Subjects and Methods: We retrospectively evaluated 136 consecutive patients who received a CRT device. Three periprocedural anticoagulation strategies were utilized: Group 1, continuation of therapeutic warfarin; Group 2, cessation of warfarin with heparin bridging; and Group 3, cessation of anticoagulation temporarily. Groups were compared on the incidence of complications. Results: Of the 136 patients, 87 (64%) were in Group 1, 18 (13%) were in Group 2, and 31 (23%) were in Group 3. Group 1 patients had an international normalized ratio of 2.3 ± 0.5, which was significantly higher than the other two groups. Coronary sinus dissection occurred in four patients: Three in Group 1 and one in Group 2, but no patient experienced pericardial effusion or tamponade. Group 2 experienced a higher incidence of pocket hematoma (P = 0.0065) and a longer length of hospital stay (P = 0.0069) than Group 1. Transient ischemic attack occurred in one patient in Group 3. Conclusion: Continuing warfarin with therapeutic international normalized ratio seems to be safe in individuals undergoing CRT device implantation.

Keywords: Anticoagulation, cardiac resynchronization therapy, heparin bridging, warfarin


How to cite this article:
House CM, Gao R, Ahmed I, Nelson WB, Zhu DW. Safety of continuing warfarin therapy in patients undergoing cardiac resynchronization therapy device implantation. Int J Heart Rhythm 2017;2:68-72

How to cite this URL:
House CM, Gao R, Ahmed I, Nelson WB, Zhu DW. Safety of continuing warfarin therapy in patients undergoing cardiac resynchronization therapy device implantation. Int J Heart Rhythm [serial online] 2017 [cited 2018 Aug 20];2:68-72. Available from: http://www.ijhronline.org/text.asp?2017/2/2/68/224357




  Introduction Top


About a quarter of patients who receive defibrillator or pacemaker are on chronic warfarin therapy.[1] A growing body of literature has demonstrated that continuing warfarin periprocedurally is a reasonably safe approach.[1],[2],[3],[4],[5],[6] Withholding warfarin and using a bridging anticoagulant such as heparin or enoxaparin before and after device implantation has been associated with an increased incidence of pocket hematoma and a longer hospital stay.[1],[2],[3],[4],[5],[6] Moreover, compared to patients who have anticoagulation withheld, patients who continue warfarin might exhibit a lower incidence of thromboembolic events.[2] There is, however, scanty evidence regarding a safe approach for patients undergoing implantation of cardiac resynchronization therapy (CRT) devices.[7],[8] Compared to conventional pacemaker or defibrillator implantation, CRT device surgery is associated with additional safety concerns for patients on chronic warfarin therapy. Implantation requires cannulation of the thin wall coronary sinus and placement of a lead into one of the lateral branches. Although rare, this process might lead to dissection or perforation of the coronary sinus or its branch (es). In a fully anticoagulated patient, there is the concern of potential risk of pericardial effusion or even pericardial tamponade.

Here, we retrospectively compared the safety of three perioperative anticoagulation regimens – continuation of warfarin, cessation of warfarin with bridging therapy, and cessation of anticoagulation temporarily – in patients undergoing CRT device implantation at our institution.


  Subjects and Methods Top


Study cohort

Between February 2005 and June 2012, a retrospective data collection on 136 consecutive patients on chronic warfarin therapy undergoing CRT-D (defibrillator) or CRT-P (pacemaker) implantation at Regions Hospital, a major teaching affiliate of the University of Minnesota Medical School, was conducted. Based on the attending physician's discretion, one of three perioperative anticoagulation regimens was employed:

  • Group 1, continuing warfarin – Warfarin was continued throughout the perioperative period. The patients' international normalized ratio (INR) was maintained in the therapeutic range (2.0–3.5) throughout the perioperative period.
  • Group 2, bridging anticoagulation – Warfarin was discontinued 2–5 days before surgery and patients received a bridging anticoagulant with heparin or low-molecular-weight heparin. Intravenous heparin was discontinued 4–6 h before the procedure and restarted 12 h after the procedure. Heparin or low-molecular-weight heparin was withheld 12–18 h before the procedure and restarted 24 h after the procedure. Warfarin was restarted the evening of the day of surgery, and bridging therapy was discontinued when INR reached the therapeutic range.
  • Group 3, anticoagulation withheld – Warfarin was discontinued 2–5 days before surgery and patients received no bridging therapy. Warfarin was restarted the evening of the day of surgery.


In patients with current antiplatelet therapy, the drug(s) were continued throughout the perioperative period.

For patients in all three groups, data were collected on the prevalence of complications and the length of postprocedural hospital stay.

The Institutional Review Board approved this study, with waiver of consent.

Implantation

An ipsilateral subclavian venogram was performed. The initial subclavian venous puncture was made using a micropuncture introducer set with a 21-gauge needle; with the intention of reducing the severity of bleeding in case of inadvertent arterial puncture. A generator pocket was formed between the deep fascia and the pectoral muscles. After the coronary sinus sheath was in place, an occlusive venogram was performed to identify the target branch for left ventricular lead implantation. If coronary sinus dissection occurred during the procedure, efforts to place the left ventricular lead would be continued as long as the patient was stable hemodynamically. Transthoracic echocardiography was performed after the procedure in patients who had coronary sinus dissection and in patients whose procedure was challenging or prolonged.

The device procedures were performed by three staff electrophysiologists. Outpatients were released within 24 h of the procedure unless complications occurred or assigned to bridging therapy. All patients were followed up in the device clinic 1 and 8 weeks postimplantation.

Definition of complications

Coronary sinus dissection was defined by occlusive venography as the local contrast staining and extravasation. If free flow of contrast into the pericardial space was detected, then coronary sinus perforation was present.

A pocket hematoma was defined as a palpable tense swelling causing pain that required prolonged hospitalization and/or discontinuation of anticoagulation and/or surgical evacuation and/or transfusion.

Other direct procedure-related bleeding events, including hemothorax, pericardial effusion, and tamponade, were documented by chest X-ray films and or echocardiography as indicated.

Thromboembolic events were defined as transient ischemic attack (TIA) and stroke diagnosed by a neurologist.

Statistical analysis

Comparison of continuous variables was performed using analysis of variance, while categorical variables were compared using a contingency table. Fisher's exact test was used to determine the association between perioperative anticoagulation regimen and incidence of complications. This association was tested between Group 1 versus Group 2 and Group 1 versus Group 3. Unpaired t-tests were used to compare the mean days of postprocedural hospitalization between the same groups. For all tests, a two-tailed alpha of 0.05 was set as the threshold of significance.


  Results Top


Study patients

Data were collected on 136 patients on chronic warfarin therapy who underwent CRT-D or CRT-P implantation. The majority of the patients (119) underwent initial device implantation, with the remaining patients (17) undergoing CRT upgrade. Of the patients, 87 continued warfarin periprocedurally, 18 received bridging therapy, and 31 withheld anticoagulation temporarily. The baseline characteristics of these patients are summarized in [Table 1]. As expected, the preoperative mean INR level was lower in patients who received bridging (P< 0.0001) and in patients who withheld anticoagulation (P< 0.0001) than patients who continued warfarin. Preoperative anticoagulation regimen did not differ significantly among the three groups. Indications for anticoagulation are shown in [Table 2]. The anticoagulation withheld group more commonly had atrial fibrillation/atrial flutter as the indication for anticoagulation therapy than either of the other two groups (P = 0.01).
Table 1: Baseline characteristics

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Table 2: Indications for anticoagulation

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Adverse events

The prevalence of coronary sinus dissection, pocket hematoma, and thromboembolism is shown in [Figure 1]. Coronary sinus dissection was reported in 4 patients. Of these, 3 (3%) occurred in patients on continued warfarin, and 1 (3%) occurred in a patient whose anticoagulation was withheld. The prevalence did not differ significantly among the three groups. The presence of coronary sinus dissection did not prevent left ventricular lead implantation in these individuals. No patient experienced pericardial effusion or tamponade, other major bleeding, or death.
Figure 1: Prevalence of complications related to procedure by anticoagulation strategy. CS = Coronary sinus, statistically significant differences are reported on the graph, with the remaining differences not statistically significant

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Postoperative pocket hematoma was observed in 4 patients. Of these, 3 (17%) occurred in the bridging group (P = 0.0002) and 1 (3%) occurred in the anticoagulation withheld group (P = 0.26). No patients who continued warfarin developed pocket hematoma.

Four patients in the cohort were on concurrent antiplatelet therapy: three in the continued warfarin group and one in the anticoagulation withheld group. The latter patient developed a pocket hematoma.

Postoperative thromboembolism developed in one patient who withheld anticoagulation. This patient had transient hemianopsia postoperatively. No patients on continued warfarin or bridging therapy experienced thromboembolism following the procedure.

Length of postprocedural hospital stay

The length of hospital stay after the procedure for each of the patient groups is shown in [Figure 2]. Patients who received bridging therapy had a significantly longer hospital stay than patients who continued warfarin (P = 0.0069) or patients who had anticoagulation withheld temporarily (P = 0.003).
Figure 2: Length of hospital stay by anticoagulation strategy. One-way ANOVA (P = 0.005).

Click here to view



  Discussion Top


Key findings

Our study compared three different strategies for the management of perioperative anticoagulation in patients undergoing CRT device implantation. Continuing warfarin therapy targeting a therapeutic INR of 2.0–3.5 during device implantation appears to be safe and seems to be superior to holding warfarin with or without a bridging therapy. Bridging therapy was associated with a higher incidence of pocket hematoma and longer hospital stay. Continuing warfarin therapy did not increase the risk of coronary sinus dissection. When it occurred, coronary sinus dissection did not lead to pericardial tamponade, nor did it prevent the placement of a left ventricular lead. No patient experienced hemothorax, pericardial effusion or tamponade, or death.

Previous studies

While guidelines from the American College of Chest Physicians still recommend the use of bridging anticoagulation with intravenous heparin or subcutaneous low-molecular-weight heparin in patients at moderate or high risk for thromboembolism events undergoing cardiac rhythm devices implantation, the recent updates from the American College of Cardiology, American Heart Association, and Heart Rhythm Society have addressed the safety of implantation while continuing warfarin therapy, and suggested such approach as a viable consideration.[9],[10] In the past decade, several retrospective and prospective studies in patients receiving conventional pacemakers or defibrillators have demonstrated that continuing warfarin perioperatively was associated with a low incidence of pocket hematoma, a shorter hospital stay, and greater overall patient satisfaction compared to using bridging therapy. However, when it comes to the safety of uninterrupted warfarin therapy in patients undergoing implantation of CRT devices; there is a paucity of supporting literature. Within the BRUISE CONTROL study cohort, it was noted that 12%–13% of the patients in each study arm received a CRT device.[1] These patients contributed to the conclusion that continuing warfarin resulted in fewer clinically significant pocket hematomas compared to heparin bridging. In addition, the BRUISE CONTROL study found no difference in death, TIA, hemothorax, and notably no difference in cardiac tamponade.

While evaluating the safety of cardiac rhythm device implantation with continuing warfarin therapy perioperatively, Tolosana et al. included 14 patients who received a CRT device.[8] The overall findings of that study suggested uninterrupted warfarin therapy did not increase the risk of pocket hematoma, but no subanalysis was performed on the incidence of hematoma, thromboembolic event, or coronary sinus dissection in the CRT cohort. Ghanbari et al.[7] studied CRT implantation with continuing warfarin therapy in 20 patients. They found continuing warfarin to be safe, with a lower incidence of pocket hematoma and shorter length of stay compared to bridging. Our study confirms similar findings in a larger population receiving a CRT device. In addition, we evaluated the incidence of coronary sinus dissection in patients with therapeutic INR. None of these patients developed pericardial effusion or tamponade. The findings of our study support the practice of continuing warfarin therapy in patients undergoing implantation of CRT devices.

Limitations and future studies

Patient data collection was retrospective and nonrandomized from a single medical center. It is possible that differences in implanting techniques among operators might influence the complication rate. Patient selection bias could have also skewed results. These limitations should be considered when interpreting the findings of this study. Our study did not address the safety issue of perioperative administration of newer anticoagulant agents, which are increasingly used in the patient population with nonvalvular atrial fibrillation or deep vein thrombosis/pulmonary embolism


  Conclusion Top


Continuing warfarin therapy, with therapeutic INR in patients receiving CRT devices, appears to be safe and cost-effective compared to withholding warfarin with or without bridging therapy. Future prospective, randomized, and controlled trials may be needed to confirm our findings.

Financial support and sponsorship

This study was self-funded by the Regions Hospital, Cardiology Department.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Birnie DH, Healey JS, Wells GA, Verma A, Tang AS, Krahn AD, et al. Pacemaker or defibrillator surgery without interruption of anticoagulation. N Engl J Med 2013;368:2084-93.  Back to cited text no. 1
[PUBMED]    
2.
Ahmed I, Gertner E, Nelson WB, House CM, Dahiya R, Anderson CP, 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.  Back to cited text no. 2
[PUBMED]    
3.
Ghanbari H, Phard WS, Al-Ameri H, Latchamsetty R, Jongnarngsin K, Crawford T, et al. Meta-analysis of safety and efficacy of interrupted warfarin compared to heparin-based bridging therapy during implantation of cardiac rhythm devices. Am J Cardiol 2012;110:1482-88.  Back to cited text no. 3
[PUBMED]    
4.
Airaksinen KE, Korkeila P, Lund J, Ylitalo A, Karjalainen P, Virtanen V, et al. Safety of pacemaker and implantable cardioverter-defibrillator implantation during uninterrupted warfarin treatment – The FinPAC study. Int J Cardiol 2013;168:3679-82.  Back to cited text no. 4
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5.
Cheng A, Nazarian S, Brinker JA, Tompkins C, Spragg DD, Leng CT, et al. Continuation of warfarin during pacemaker or implantable cardioverter-defibrillator implantation: A randomized clinical trial. Heart Rhythm 2011;8:536-40.  Back to cited text no. 5
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6.
Zhu DW, Ahmed I. Perioperative management of anticoagulation in patients on warfarin therapy undergoing surgery for cardiac implantable electronic devices. J Arrhythm 2013;29:162-7.  Back to cited text no. 6
    
7.
Ghanbari H, Feldman D, Schmidt M, Ottino J, Machado C, Akoum N, et al. Cardiac resynchronization therapy device implantation in patients with therapeutic international normalized ratios. Pacing Clin Electrophysiol 2010;33:400-6.  Back to cited text no. 7
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8.
Tolosana JM, Berne P, Mont L, Heras M, Berruezo A, Monteagudo J, et al. Preparation for pacemaker or implantable cardiac defibrillator implants in patients with high risk of thrombo-embolic events: Oral anticoagulation or bridging with intravenous heparin? A prospective randomized trial. Eur Heart J 2009;30:1880-4.  Back to cited text no. 8
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9.
Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ, American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis Panel. Executive summary: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:7S-47S.  Back to cited text no. 9
    
10.
January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr., et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2014;64:e1-76.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2]


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