Anticoagulation and Antiplatelet Therapy in Implantation of Electrophysiological Devices

Panagiotis Korantzopoulos; Konstantinos P. Letsas; Tong Liu; Nikolaos Fragakis; Michael Efremidis; John A. Goudevenos

Europace. 2011;13(12):1669-1680.

Abstract and Introduction

Abstract

The growing implantations of electrophysiological devices in the context of increasing rates of chronic antithrombotic therapy in cardiovascular disease patients underscore the importance of an effective periprocedural prophylactic strategy for prevention of bleeding complications. In this review, we provide a concise overview of the data regarding anticoagulation and antiplatelet therapy in arrhythmia device surgery. Also, we critically discuss risk factors and procedural parameters that are potentially associated with haemorrhagic untoward events in this setting. Of note, current evidence suggests that heparin bridging therapy in patients on chronic anticoagulation and dual-antiplatelet therapy are associated with increased risk of pocket haematoma formation. Continuation of oral anticoagulation and short-term interruption of clopidogrel with aspirin maintenance in eligible patients, respectively, represent promising strategies with an acceptable safety profile. Besides the perioperative management of antithrombotic therapy, some extra supportive measures may also reduce the incidence of haematomas. High-risk cases should be better treated by experienced operators in high-volume centres. More randomized studies are needed to elucidate the exact role of particular antithrombotic therapy protocols. Finally, the recently accumulated data on this subject should be incorporated into the professional guidelines regarding arrhythmia device therapy.

Introduction

More than 50 years after the first permanent pacemaker (PPM) implantation, we witness the continuous development and growing clinical application of implantable devices in a wide range of heart rhythm disorders.^[1–3] Apart from the conventional use of PPMs for the management of bradycardia, more sophisticated devices are increasingly used for cardiac resynchronization therapy (CRT) in heart failure while the implantable cardioverter–defibrillator (ICD) has become established as the most effective therapy against malignant arrhythmias and sudden cardiac death.^[2,3]

Data on temporal trends of implantation rates are sparse, but there have clearly been considerable increases over past decades.^[4,5] Potential factors that possibly contribute to the increase in implantation rates of electrophysiological devices (EPDs) include an ageing population, advances in device technology, and the growing number of evidence-based indications.^[4,5] Also, there is an increase in other related operations such as upgrade procedures, device/lead revisions, and lead extractions. The complexity of the modern advanced devices requiring longer and more sophisticated procedures for implantation as well as the comorbidities and medications of the patients may increase the risk of complications.

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Europace. 2011;13(12):1669-1680. © 2011 Oxford University Press
Copyright 2007 European Heart Rhythm Association of the European Society of Cardiology (ESC). Published by Oxford University Press. All rights reserved.

Table 1. Studies examining the role of anticoagulation therapy on the incidence of bleeding complications in electrophysiological device implantation
Author; year (reference no.)	Study design	Study population and protocol	Reason for antithrombotic therapy	EPD type—procedure type	Vein access	Implantation techniques	Bleeding complications	Other outcomes	Nil	Mortality
Goldstein et al.; 1998¹⁷	Retrospective observational	150 pts, outpatient pacemaker procedures, 37 of 150 pts on warfarin (mean INR 2.5)	N.R.	Pacemaker implantation/pacemaker generator replacement/lead revision	Cephalic vein cut down (>70%)	Electrocautery, pre-pectoral pocket	No significant pocket haematoma in both groups	No cardiac perforation	F/U visit 7–10 days postoperatively	Nil
Michaud et al.; 2000⁴⁴	Prospective randomized trial	192 pts, 77 of 192 pts on chronic anticoagulation, 52% of all pts on aspirin, 49 of 192 pts on i.v. heparin bridging (initiation 6 h postoperatively —26 pts; 24 h postoperatively—23 pts), 28 of 192 continuation of warfarin	Anticoagulation due to chronic AF, MV, and DVT	Pacemaker or ICD first implantation	N.R.	Pre-pectoral pocket	Incidence of pocket haematoma: 23% i.v. heparin – 6 h postoperatively 17% i.v. heparin—24 h postoperatively 4% warfarin continuation 2% no anticoagulation mean time to haematoma formation 5.1 days	Longer hospital stay in heparin groups (3.6 vs. 2.3 days in warfarin group vs. 2.5 days in no anticoagulation)	Until hospital discharge—physician contact thereafter	1 death (no anticoagulation group) due to pulmonary edema
Al-Khadra; 2003⁴⁶	Case series	47 pts on warfarin (mean INR 2.3)	AF, valve disease, MV, DVT, stroke, and MI	Pacemaker or ICD implantation, Generator replacement (7 of 47)	Axillary vein	Pre-pectoral pocket, active fixation leads electrocautery, pressure dressing for 24 h	One case of pocket haematoma	N.R.	6 weeks	Nil
Giudici et al.; 2004⁴⁷	Prospective observational	1025 pts, 470 of 1025 pts on OAC (mean INR 2.6), the rest: control group	N.R.	Pacemaker or ICD implantation, lead revisions, generator replacement alone (53 of 1025)	Subclavian vein (89%), Subclavian venogram, Micropuncture technique	Active fixation leads	Nine in-hospital haematomas and three late haematomas in each of the two groups	N.R.	2 weeks	N.R.
Milic et al.; 2005⁴⁸	Randomized controlled trial	81 pts, 41 pts control (20 heparin bridging, 21 OAC continuation), 40 pts application of fibrin sealant, all pts were on aspirin	AF, MV, and DVT	First pacemaker implantation	93.8% cephalic vein cut down	Pre-pectoral pocket, application of fibrin sealant before wound closure in the treatment group, pressure dressing for 24 h	10 haematomas in the control group (five in heparin bridging subgroup, five in OAC continuation subgroup), no haematoma in fibrin sealant group, mean time for haematoma formation 4.4 days	Mean time of hospital stay 4.3 days in heparin subgroup vs. 2.6 days in OAC group, mean time of hospital stay in haematoma pts was 5.6 days vs. 2.9 days in non-haematoma pts, one stroke in an OAC patient	1 week and then every 2 months	N.R.
Marquie et al.; 2006¹⁸	Retrospective case–control	76 pts with AF—76 controls, 38 pts with mechanical valve—38 controls, heparin bridging in all MV pts, heparin bridging in 67% of AF pts	AF and MV	Pacemaker implantation/Generator replacement with lead insertion	Cephalic vein/Subclavian vein	Electrocautery, Wound drainage (31/38 pts with mechanical valve; 9/76 AF pts)	MV group: 11 haematomas vs. 1 in controls, AF group: 8 with haemorrhagic complications^a vs. 1 in controls	Mean hospital stay 14 days in bridging group and 7.3 days in controls, no thrombotic or embolic event	30 days	1 fatal event in a patient with aortic valve prosthesis who had a pocket haematoma (surgery—shock)
Tischenko et al.; 2009²⁸	Prospective observational	3 groups: 117 pts on warfarin (mean INR 2.2), 117 matched controls, 38 bridging with LMWH	High-risk AF pts/MVpatients/recent DVT	Pacemaker/ICD implantation including CRT devices, replacements/revisions	Subclavian or axillary vein	Pre-pectoral pocket, active fix. leads, electrocautery, pressure dressings for 24 h	Incidence of haematomas: 23.7% bridging group, 7.7% warfarin group, 4.3% control, In warfarin group: number of leads implanted the only independent risk factor	No thromboembolic events, tamponade, haemothorax	1 month	Nil
Robinson et al.; 2009³²	Retrospective observational	148 pts underwent bridging with LMWH, different protocols: pre-/post-operative LMWH administration or not, aspirin not stopped	AF (73%), LV dysfunction (12%), MV (10%), and DVT	Pacemaker/ICD implantation generator replacements, ILR implantations (1%)	Cephalic or subclavian vein	Pre-pectoral pocket, electrocautery	Haematoma rates: pre/post 22%, no pre/post 29%, pre/no post 8%, no pre/no post 9%, no further risk in pts taking aspirin, independent predictors of haematoma: postoperative LMWH, high INR, male sex	No stroke	4 weeks	Nil
Cheng et al.; 2009⁴⁹	Prospective observational	109 pts on anticoagulation, 51 pts: warfarin suspended 3 days before surgery, 58 pts: warfarin continuation	MV with or without AF	First pacemaker implantation	Subclavian vein	Pre-pectoral pocket, pressure dressings for 24 h	Pocket haematoma: 3.4 % in warfarin cessation, 5.9% in warfarin continuation, excessive bleeding during operation in warfarin continuation (31.4 vs. 8.6%)	No difference in embolic events, (1 embolic event in warfarin continuation group)	3 months	Nil
Tolosana et al.; 2009²²	Prospective randomized trial	101 high-risk pts on OAC, 51 pts heparin bridging, 50 pts on OAC (mean INR: 2)	High-risk AF, MV, DVT, and intracavitary thrombi	Pacemaker/ICD implantation including CRT devices, generator replacements	Subclavian vein under fluoroscopic guidance	Pre-pectoral pocket, passive fixation leads, pressure dressings for 6 h	Incidence of pocket haematoma: 7.8% heparin group, 8% OAC group	No thromboembolic events, median hospital stay: 5 days in heparin group, 2 days in OAC group	45 days	1 patient from each group had a fatal endocarditis of the prosthetic valve
Ahmed et al.; 2010⁵⁰	Retrospective observational	459 pts on chronic OAC, 222 pts continuing OAC (mean INR 2.6), 123 pts heparin bridging, 114 OAC stop without bridging, concomitant aspirin use in 58, 77, and 68 of pts, respectively	AF, MV, DVT, and LV thrombus	Pacemaker/ICD implantation including CRT devices, replacements/revisions	Subclavian vein, venogram and micropuncture technique	Pre-pectoral pocket, pressure dressings	Incidence of pocket haematoma: continued OAC group 0.45%, bridging group 5.7%, OAC withheld group 1.75%, all pts with haematoma were on antiplatelet therapy, no other bleeding complications	Transient ischemic attacks: Continued OAC group 0%, bridging group 0.8%, OAC withheld group 3.5%, mean hospital stay (days): continued OAC group: 1.2, bridging group 2.3, OAC withheld group 1.2	N.R.	N.R.
Ghanbari et al.; 2010²⁴	Retrospective observational	Chronic OAC pts, 49 pts high thromboembolic risk: 20 OAC continuation (mean INR: 2.4), 29 Heparin bridging, 74 pts of low risk—OAC cessation	AF, MV, and DVT	Implantation of CRT-D devices including upgrade procedures	Axillary vein (puncture under fluoroscopy)	Pre-pectoral pocket, pocket prior to lead implantation, electrocautery	Incidence of pocket haematoma: Continued OAC group 5%, bridging group 20.7%, OAC cessation group 4%	Mean hospital stay (days): Continued OAC group: 2.9, bridging group 3.7, OAC cessation group 1.6, longer hospital stay in haematoma pts vs. no haematoma (4.3 vs. 2.1 days)	30 days	N.R.
Chow et al.; 2010²⁹	Retrospective observational	518 pts, perioperative anticoagulation 15.4% (OAC or bridging), perioperative antiplatelets (23.7%)	N.R.	First pacemaker implantation	Cephalic vein	Implantation by cardiothoracic surgeons	Incidence of haematoma 4.9%, in anticoagulation group all haematomas associated with bridging therapy, no haematomas in warfarin pts, multivariate predictors: peri-operative anticoagulation, acute procedure	Median hospital stay in haematoma pts 8 days vs. 1 day in no complication pts	6 weeks	N.R.
Cheng et al.; 2011⁵¹	Randomized clinical trial	100 pts on chronic OAC, 83 'moderate' risk pts randomized to OAC continuation or OAC discontinuation without heparin bridging, 17 'high' risk pts randomized to OAC continuation or OAC discontinuation with heparin bridging, mean INR in OAC continuation group 2.2, 43 pts were on either aspirin or clopidogrel	AF, MV, prior stroke, depressed EF, and pre-existing thrombus	Implantation of pacemakers and ICDs, generator changes, lead revisions/upgrades	No cephalic vein cut down, Upper extremity venogram, micropuncture technique	Pre-pectoral pocket, electrocautery	Only 2 cases of pocket haematoma, both in pts of the heparin bridging group	1 transient ischemic attack in a non-heparin patient, 1 patient suffered heparin-induced thrombocytopenia	4–6 weeks	N.R.

AF, atrial fibrillation; EPD, electrophysiological device; CRT, cardiac resynchronization therapy; DVT, deep venous thrombosis; F/U, follow-up; ICD, implantable cardioverter–defibrillator; N.R., not reported; ILR, implantable loop recorder; INR, international normalized ratio; LMWH, low-molecular weight heparin; MI, myocardial infarction; MV, mechanical valve; OAC, oral anticoagulation; pts, patients; i.v., intravenously.
^aIncluding pocket haematoma, blood transfusion, haemopericardium, intramediastinal bleeding.

Table 2. Studies examining the role of anticoagulation and/or dual-antiplatelet therapy on the incidence of bleeding complications in electrophysiological device implantation
Author; year (reference no.)	Study design	Study patients and protocol	Reason for antithrombotic therapy	EPD type—procedure type	Vein access	Implantation techniques	Bleeding complications	Other outcomes	F/U	Mortality
Wiegand et al.; 2004⁶	Prospective observational	3165 pts, prospective evaluation of predictors of haematoma occurrence, 42% of pts on antiplatelet therapy, 0.7% of pts on DAP, 33.6% of pts on OAC	CAD, AF, MV, LV thrombus, LA thrombus	First implantation of pacemakers and ICDs, generator replacements and lead revisions	Mainly cephalic vein cut down	Pacemakers placed in pre-pectoral pockets, ICDs in subpectoral pockets, drainage system in excessive intra-operative bleeding	Incidence of pocket haematoma: ASA only 3.1%, Ticlopidine/clopidogrel only 6.7%, DAP 21.7%, OAC continuation 7.6%, high-dose heparinization bridging 12.2%, independent predictors of haematoma: DAP, high-dose heparinization, operator experience	No other major bleeding event within 1 month of F/U, 5 ischemic strokes, No embolism	3 months	3-month all-cause mortality 0.16%
Tompkins et al.; 2010⁸	Retrospective observational	Overall 1388 pts, controls 255 pts, DAP 139 pts, aspirin alone 536 pts, heparin bridging 154 pts, OAC withheld 258 pts, OAC continuation 146 pts	N.R.	Primary ICD (including CRT-D) or pacemaker implantation	Axillary vein, Rarely, cephalic cut down	N.R.	Incidence of bleeding complications: controls 1.6%, DAP 7.2%, aspirin alone 3.9%, heparin bridging 14.3%, OAC withheld 4.3%, OAC continuation 6.5%, the addition of aspirin to OAC did not increase risk, multivariate predictors: male gender, african American race, weight, procedure time, DAP, heparin bridging	3 strokes, 11 DVT, 6 pericardial tamponades, (no significant differences beween groups)	N.R.	N.R.
Kutinsky et al.; 2010²⁰	Prospective observational study	935 pts in total, 126 pts on DAP, 305 pts on OAC, 122pts received heparin, predictors of pocket haematoma, OAC and/or antiplatelet therapy in some pts	CAD, coronary stent placement, PVD, cerebrovascular disease, AF, MV	New implantation of pacemakers and ICDs (including CRT-Ds), Generator replacements/lead revisions/device upgrades	Subclavian vein in 87% of cases, axillary vein 6%, Cephalic vein 7%	Pre-pectoral pockets	Pocket haematoma in 89/935 pts (9.5%), incidence of haematoma: clopidogrel only 11.1%, aspirin only 4.2%, DAP 24.2%, DAP+OAC 9.5%, OAC 6.9%, OAC+aspirin 10.3%, multivariate predictors: primary prevention of SCD, heparin use, clopidogrel use	Hospital stay was longer in haematoma pts (median 4 vs. 2 days). 2 of 89 haematoma pts developed infection	N.R.	N.R.
Thal et al.; 2010⁴⁵	Retrospective observational	200 pts in total, pts on OAC and/or antiplatelets were maintained on this therapy, 58 pts on OAC (mean INR 1.9), 15 pts on DAP, 5 pts (2.5%) on DAP and OAC	N.R.	New implantation of pacemakers and ICDs (including CRT-D), generator replacements	Extrathoracic portion of subclavian vein under fluoroscopy	N.R.	Seven haematomas (3.5%), three in DAP group (20%), two in triple therapy group (40%), one in aspirin only group, one in warfarin only group	N.R.	6 weeks	N.R.
Przybylski et al.; 2010¹⁹	Prospective observational	247 pts receiving aspirin (n= 194) or DAP (n= 53) in the perioperative period	CAD, previous acute coronary syndromes, previous PCI	Primary implantations of pacemakers and ICDs (including CRT-Ds)	Subclavian vein (55%), Cephalic vein cut down (29%), Both (16%)	Electrocautery in only six cases	Bleeding complications (major + minor): 13.9% in aspirin group vs. 24.5% in DAP group, major bleeding complications: 3.6% in aspirin group (1 cardiac perforation, 2 pericardial effusions, 4 pocket haematomas) vs. 3.8% in DAP group (1 pericardial effusion, 1 pocket haematoma)	N.R.	7–10 days after the operation and every 3 months thereafter	N.R.
Dreger et al.; 2010³⁰	Observational with prospective and retrospective arm	Control group (318 pts): aspirin or nothing, DAP group (109 pts)	CAD and PCI	New implantation of pacemakers and ICDs, generator replacements	Subclavian vein	Pre-pectoral pocket in most cases, electrocautery in all pts, vacuum drainage systems in all pts	Pocket haematomas: 3 in the control group (0.9%), 1 in the DAP group (0.9%)	Procedure times of pacemaker implantations were longer in the DAP group, Fluid drained postoperatively higher in DAP group, 2 lead perforations in the control group	N.R.	N.R.
Cano et al.; 2011³⁵	Prospective observational	849 pts in total, Single antiplatelet group (220 pts), DAP group (60 pts), OAC+enoxaparin, bridging+antiplatelet therapy (40 pts), no antiplatelets or OAC (375 pts), OAC+enoxaparin bridging (154 pts)	CAD, Stroke, AF, and MV	New implantation of pacemakers and ICDs, generator replacements/upgrade procedures	Subclavian vein under fluoroscopy	Active fixation leads, pre-pectoral pockets, electrocautery, pressure dressings for 24 h	53 pocket haematomas (6.2%), incidence: 3.2% in single antiplatelet group, 13.3% in DAP group, 15% in OAC+enoxaparin, bridging+antiplatelet therapy group, 2.4% in no antiplatelets or OAC group, 14.9% in OAC+enoxaparin bridging group, mean time for haematoma formation 3.5 days, multivariate predictors: obesity (negative), renal insufficiency, DAP, enoxaparin bridging	Mean hospital stay longer in haematoma pts (7.9 vs. 2.6 days), 1 stroke event (in the group of no antiplatelets or OAC), 2 haemothoraces (in the group of no antiplatelets or OAC), 2 pericardial effusions requiring paracentesis (group 1, group 4)	7 days, Further weekly F/U in haematoma cases until total recovery	N.R.

AF, atrial fibrillation; DAP, dual-antiplatelet therapy; EPD, electrophysiological device; CRT, cardiac resynchronization therapy; DVT, deep venous thrombosis; F/U, follow-up; ICD, implantable cardioverter defibrillator; ILR, implantable loop recorder; INR, international normalized ratio; LA, left atrial; LMWH, low-molecular weight heparin; LV, left ventricular; MI, myocardial infarction; MV, mechanical valve; N.R, not reported; OAC, oral anticoagulation; PCI, percutaneous coronary intervention; pts, patients; PVD, peripheral vascular disease; SCD, sudden cardiac death.