Impact of Anticoagulant and Anti-platelet Therapy on ICD Implant-Related Bleeding and Thromboembolic Events in Patients Enrolled in the NCDR ® ICD Registry TM Impact of Anticoagulant and Anti-platelet Therapy on ICD Implant-Related Bleeding and Thromboembolic Events in Patients Enrolled in the NCDR ® ICD Registry TM Alena Goldman, MD*, Jeptha P. Curtis, MD, Yongfei Wang, MS, William H. Maisel, MD, MPH*. Alena Goldman, MD*, Jeptha P. Curtis, MD †, Yongfei Wang, MS †, William H. Maisel, MD, MPH*. * Beth Israel Deaconess Medical Center, Boston, MA Yale-New Haven Hospital, New Haven, CT † Yale-New Haven Hospital, New Haven, CT

Disclosures Alena Goldman, Jeptha P. Curtis, Yongfei Wang, William H. Maisel: Alena Goldman, Jeptha P. Curtis, Yongfei Wang, William H. Maisel: No Industry Relationships to Disclose

Background >400K pacemaker and ICD implants a year in North America 1. >400K pacemaker and ICD implants a year in North America 1. Perioperative management of anticoagulation in patients undergoing device implant is not firmly established. Perioperative management of anticoagulation in patients undergoing device implant is not firmly established. Uninterrupted DAP mandated for millions of stent patients 2. Uninterrupted DAP mandated for millions of stent patients 2. Impact on ICD implant complications has not been evaluated. Impact on ICD implant complications has not been evaluated. 1 AHA Heart Disease and Stroke Statistics Maisel WH. N Engl J Med. 2007; 356(10):981-4

Clinical Implications of Pocket Hematoma Interruption of anticoagulation Interruption of anticoagulation Blood product transfusion Blood product transfusion Longer hospital stay Longer hospital stay Hematoma evacuation Hematoma evacuation Increased risk of infection Increased risk of infection Risk of thromboembolism if anticoagulation is interrupted Risk of thromboembolism if anticoagulation is interrupted Background

NCDR ICD Registry Database Developed by ACC/HRS in October of 2005 Developed by ACC/HRS in October of 2005 Collects information from 1,500 hospitals in US Collects information from 1,500 hospitals in US Required for all Medicare primary prevention ICD implants Required for all Medicare primary prevention ICD implants 76% of hospitals submit all implants 76% of hospitals submit all implants 88% of all ICD implants in US included 88% of all ICD implants in US included Good representation of “real-world” performance Good representation of “real-world” performance Goals: Goals: Track outcomes Track outcomes Determine if findings from major RCTs apply to general population 1 Determine if findings from major RCTs apply to general population 1 1. S. Hammill, et. al. Heart Rhythm 2008;6: Methods

> 130 data elements collected at the time of the initial ICD implant, device upgrade, and device replacement > 130 data elements collected at the time of the initial ICD implant, device upgrade, and device replacement Discharge medications recorded – No record of medications at time of implant Discharge medications recorded – No record of medications at time of implant Complications at the time of device implantation and prior to hospital discharge are collected Complications at the time of device implantation and prior to hospital discharge are collected Used data from 4/06-12/08 Used data from 4/06-12/08 Methods NCDR ICD Registry Database

HEMATOMA Resulting in re-operation or transfusion Resulting in re-operation or transfusion NON-HEMATOMA BLEEDING Cardiac Perforation Cardiac Perforation Cardiac Tamponade Cardiac Tamponade Hemothorax Hemothorax Study Endpoints (Based on NCDR Complication Definitions) THROMBOEMBOLISM MI MI TIA/CVA TIA/CVA DVT DVT Peripheral embolus Peripheral embolus

Patient Characteristics CharacteristicsNumberPercent Patients260, ICD Implants263, Mean Age68.0- Female AF HTN DM CHF Prior CVA

CharacteristicsNumberPercent 1 o Prevention o Prevention Non-ischemic dilated CM Ischemic heart disease Prior MI Prior CABG Prior PCI Patient Characteristics

Percent of Patients Baseline Antiplatelet/Anticoagulation Treatment None ASA T/C DAP Warfarin Warfarin Warfarin Warfarin + ASA + T/C + DAP 263,412 ICD Implants

% None ASA T/C DAP Warfarin Warfarin Warfarin Warfarin Overall + ASA + T/C + DAP Effect of AC and AP Therapy on Hematoma Rate P for trend for < ,412 ICD Implants – 2404 Hematomas P for trend <0.0001

% P for trend =0.004 Effect of AC and AP Therapy on Non-Hematoma Bleeding Rate 263,412 ICD Implants – 483 events None ASA T/C DAP Warfarin Warfarin Warfarin Warfarin Overall + ASA + T/C + DAP

P for trend for <0.001 Effect of AC and AP Therapy on Clotting Rate 263,412 ICD Implants events % None ASA T/C DAP Warfarin Warfarin Warfarin Warfarin Overall + ASA + T/C + DAP P for trend <0.0001

Impact of Heart Failure on Complication Rates Hematoma * * P<0.02 compared to NYHA Class I Non Hematoma Bleeding NYHA Class I II II III III IV IV Clotting * NYHA Class %^ I14 II35.8 III45.9 IV4.3 ^ Percent of total implants I II II III III IV IV I II II III III IV IV * * * * % %

Impact of Device Type on Complication Rates Hematoma Non Hematoma Bleeding Device Type SDB Clotting ^ Percent of total implants * * * % % SDB SDB % * P<0.001 Device Type %^ (S) Single 22.6 (D) Dual 39.9 (B) Bi-V 37.7

Impact of Procedure Type on Complication Rates Hematoma Non Hematoma Bleeding Procedure Type Clotting ^ Percent of total implants * * * % % ∆ * P<0.01 compared to Gen ∆ Device Type %^ ∆ Gen ∆16.2 New Implant 75.2 Device Upgrade 5.6 Gen. ∆ NewUpgrade NewUpgrade NewUpgrade * * *

Hospital Volume (Implants/yr) Low (<59/yr) Middle (60-213/yr) High (>214/yr) P for trend <0.001 Impact of Hospital Implant Volume on Hematoma Rate 263,412 ICD Implants Hematoma (%) Hospital Volume %* Low3.8 Middle20.7 High75.5 * Percent of total implants

Limitations Discharge medications recorded – not necessarily medications at time of procedure Discharge medications recorded – not necessarily medications at time of procedure Medication choices not randomized Medication choices not randomized Potential underreporting of complications Potential underreporting of complications

Conclusions Although anticoagulation and antiplatelet therapy are associated with increased ICD implant hematoma rates, overall rates are low. Although anticoagulation and antiplatelet therapy are associated with increased ICD implant hematoma rates, overall rates are low. DAP, warfarin, and triple therapy are associated with progressively higher bleeding rates. DAP, warfarin, and triple therapy are associated with progressively higher bleeding rates.

Conclusions Worsening NYHA class, increasing ICD device complexity, procedure type, and lower hospital implant volume are independently associated with increased rates of hematoma, non- hematoma bleeding, and thromboembolic events. Worsening NYHA class, increasing ICD device complexity, procedure type, and lower hospital implant volume are independently associated with increased rates of hematoma, non- hematoma bleeding, and thromboembolic events. These data should be considered when selecting patients for ICD implant. These data should be considered when selecting patients for ICD implant.