Atrial Fibrillation, Bradycardia, Tachycardia, Valvular Heart Disease
Conditions
Keywords
bleeding, anticoagulation, pacemaker, implantable cardioverter-defibrillator, patients undergoing implantation of a pacemaker or defibrillator (ICD)
Brief summary
Patients requiring long term anticoagulation often undergo transition of their warfarin to heparin in anticipation of invasive surgical procedures such as pacemaker or ICD implantation. This may require inpatient hospitalization several days prior to and after the procedure, potentially increasing medical costs and patient inconvenience. Patients undergoing such a process are initiated on heparin while their INRs drift to normal levels. Immediately prior to surgery, heparin is discontinued and restarted several hours after the procedure. Unfortunately, this process has resulted in a high incidence of surgical wound hematomas and other bleeding complications often requiring longer periods of discontinued anticoagulation or repeat surgical exploration. Previous investigators have tried to reduce the incidence of wound hematomas by prolonging the time from surgical wound closure to the reinitiation of heparin. A small randomized trial demonstrated that there was no significant difference in the incidence of wound hematomas whether heparin was started 6 hours or 24 hours after surgery (J Am Coll Cardiology 2000;35:1915-8). This has led many investigators to perform pacemaker and ICD implantation without reversal of warfarin therapy. A recent retrospective observational study demonstrated that the incidence of wound hematomas in patients with an INR of 2.6 was no different than patients with an INR of 1.5 (PACE 2004;27:358-60). Furthermore, a more recent, larger retrospective observational study reported in abstract form at the recent Heart Rhythm Society Annual 2007 Scientific Meeting demonstrated that not only is performing pacemaker and ICD implantations safe without reversing warfarin anticoagulation, but the incidence of wound hematomas is significantly smaller as compared to the strategy of reversing warfarin and initiating periprocedural heparin. Given these findings, the hypothesis of this randomized study is that pacemaker and ICD implantation while fully anticoagulated on warfarin therapy is safe. Findings from this study will have significant implications on the clinical practice of pacemaker or ICD implantation in this patient population given that no randomized study on this subject has been performed to date.
Interventions
DRUGHold warfarin
For moderate risk patients, warfarin will be held for 4-5 days prior to the procedure.
DRUGcontinue warfarin through the procedure
The usual dose of warfarin (resulting in a therapeutic INR) is taken throughout the peri-procedural period.
DRUGWarfarin held with heparin transition.
For high risk patients, warfarin is held for 4-5 days prior to the procedure and heparin is given to provide anticoagulation while the INR is subtherapeutic.
Sponsors
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* scheduled for clinically indicated permanent pacemaker or implantable cardioverter-defibrillator * currently on chronic warfarin therapy
Exclusion criteria
* unwilling to participate in trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bleeding Complication | 30 days | Significant bleeding was defined as extracardiac bleeding or pocket hematomas that required additional intervention and/or temporary discontinuation of anticoagulation therapy. |
| Thromboembolic Events | 30 days | — |
| Anticoagulant Related Complications | 30 days | Defined as warfarin induced skin necrosis or heparin-induced thrombocytopenia |
Countries
United States
Participant flow
Pre-assignment details
Two patients from each treatment arm were excluded from the analysis. Three of these patients withdrew after being told of the treatment assignment, and one patient's procedure was cancelled owing to need for a left ventricular assist device.
Participants by arm
| Arm | Count |
|---|---|
| Moderate Risk Continuing Warfarin Moderate risk patients (afib, mechanical aortic valve) randomized to continue coumadin at their usual dose through the procedure.
These patients continue warfarin through the procedure : The usual dose of warfarin (resulting in a therapeutic INR) is taken throughout the peri-procedural period. | 42 |
| Moderate Risk Holding Warfarin Moderate risk patients randomized to hold their coumadin for 4-5 days prior to the procedure (to allow the INR to normalize).
These patients hold warfarin : For moderate risk patients, warfarin will be held for 4-5 days prior to the procedure. | 42 |
| High Risk Continuing Warfarin High risk patients (mechanical mitral valve, prior stroke, current deep vein thrombosis, hypercoagulable syndrome) randomized to continue coumadin at the usual dose through the procedure.
These patients continue warfarin through the procedure : The usual dose of warfarin (resulting in a therapeutic INR) is taken throughout the peri-procedural period. | 8 |
| High Risk Holding Warfarin These high risk patients randomized to holding coumadin for 4-5 days and using a heparin transition for bridging. | 8 |
| Total | 100 |
Baseline characteristics
| Characteristic | Moderate Risk Holding Warfarin | High Risk Continuing Warfarin | Moderate Risk Continuing Warfarin | High Risk Holding Warfarin | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 21 Participants | 4 Participants | 21 Participants | 4 Participants | 50 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 4 Participants | 21 Participants | 4 Participants | 50 Participants |
| Age, Continuous | 68.8 years STANDARD_DEVIATION 11.7 | 72.9 years STANDARD_DEVIATION 11.4 | 72.9 years STANDARD_DEVIATION 11.4 | 68.8 years STANDARD_DEVIATION 11.7 | 71.5 years STANDARD_DEVIATION 11.6 |
| Region of Enrollment United States | 42 participants | 8 participants | 42 participants | 8 participants | 100 participants |
| Sex: Female, Male Female | 20 Participants | 2 Participants | 18 Participants | 2 Participants | 42 Participants |
| Sex: Female, Male Male | 22 Participants | 6 Participants | 24 Participants | 6 Participants | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 42 | 0 / 42 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 0 / 42 | 1 / 42 | 0 / 8 | 2 / 8 |
| serious Total, serious adverse events | 0 / 42 | 1 / 42 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Anticoagulant Related Complications
Defined as warfarin induced skin necrosis or heparin-induced thrombocytopenia
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Moderate Risk Continuing Warfarin | Anticoagulant Related Complications | 1 participants |
| Moderate Risk Holding Warfarin | Anticoagulant Related Complications | 0 participants |
| High Risk Continuing Warfarin | Anticoagulant Related Complications | 1 participants |
| High Risk Holding Warfarin | Anticoagulant Related Complications | 0 participants |
Primary
Bleeding Complication
Significant bleeding was defined as extracardiac bleeding or pocket hematomas that required additional intervention and/or temporary discontinuation of anticoagulation therapy.
Time frame: 30 days
Population: Baseline characteristics of both groups were well matched except that patients randomized to warfarin discontinuation were more obese (P = .024).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Moderate Risk Continuing Warfarin | Bleeding Complication | 0 participants |
| Moderate Risk Holding Warfarin | Bleeding Complication | 2 participants |
| High Risk Continuing Warfarin | Bleeding Complication | 0 participants |
| High Risk Holding Warfarin | Bleeding Complication | 2 participants |
Comparison: Continuous variables were expressed as mean ± standard deviation and analyzed using Student's t-test and Mann-Whitney U-test in cases of nonparametric distribution. Categorical variables were expressed as numbers or percentages and analyzed with two-tailed Fisher's exact test or χ2-test as appropriate. Data were analyzed on an intention-to-treat basis using STATA 10.1 (College Station, TX). A two-tailed alpha of 0.05 was considered statistically significant.
Primary
Thromboembolic Events
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Moderate Risk Continuing Warfarin | Thromboembolic Events | 0 participants |
| Moderate Risk Holding Warfarin | Thromboembolic Events | 1 participants |
| High Risk Continuing Warfarin | Thromboembolic Events | 0 participants |
| High Risk Holding Warfarin | Thromboembolic Events | 0 participants |