Aortic Valve Replacement, Severe Aortic Stenosis, Transcatheter Aortic Valve Replacement
Conditions
Keywords
Transcatheter aortic valve replacement, Aortic valve replacement, Severe aortic stenosis
Brief summary
The objective of this study is to assess the safety and efficacy of using bivalirudin instead of unfractionated heparin (UFH) in transcatheter aortic valve replacements (TAVR). The primary hypothesis of BRAVO 3 was that bivalirudin would reduce major bleeding compared with heparin in TAVR procedures. Results for all participants enrolled into the randomized trial (BRAVO 3) are presented.
Interventions
DRUGBivalirudin
Bivalirudin is an anticoagulant that binds directly to thrombin in a bivalent and reversible fashion.
DRUGUnfractionated Heparin
Unfractionated heparin is an anticoagulant.
Sponsors
The Medicines Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males and females, ≥18 years of age * High risk (Euroscore ≥18, or considered inoperable) for surgical aortic valve replacement * Undergoing TAVR via transfemoral arterial access * Provide written informed consent before initiation of any study related procedures
Exclusion criteria
* Any known contra-indication to the use of bivalirudin (except presence of severe renal impairment \[glomerular filtration rate (GFR) \<30 milliliters (mL)/minute\] since these participants will be included in the trial or UFH * Refusal to receive blood transfusion * Mechanical valve (any location) or mitral bioprosthetic valve * Extensive calcification of the common femoral artery, or minimal luminal diameter \<6.5 millimeters (mm) * Use of elective surgical cut-down for transfemoral access * Concurrent performance of percutaneous coronary intervention with TAVR * International normalized ratio (INR) ≥2 on the day of TAVR procedure or known history of bleeding diathesis * History of hemorrhagic stroke, intracranial hemorrhage, intracerebral mass or aneurysm, or arteriovenous malformation * Severe left ventricular dysfunction (left ventricular ejection fraction \<15%) * Severe aortic regurgitation or mitral regurgitation (4+) * Hemodynamic instability (for example, requiring inotropic or intra-aortic balloon pump support) within 2 hours of the procedure * Dialysis dependent * Administration of thrombolytics, glycoprotein IIb/IIIa inhibitors, or warfarin in the 3 days prior to the procedure * Acute myocardial infarction, major surgery, or any therapeutic cardiac procedure (other than balloon aortic valvuloplasty) within 30 days * Percutaneous coronary intervention within 30 days * Upper gastrointestinal or genitourinary bleed within 30 days * Stroke or transient ischemic attack within 30 days * Any surgery or biopsy within 2 weeks * Administration of: * UFH within 30 minutes of the procedure * Enoxaparin within 8 hours of the procedure * Fondaparinux or other low-molecular-weight heparins (LMWHs) within 24 hours of the procedure * Dabigatran, rivaroxaban, or other oral anti-Xa or antithrombin agent within 48 hours of the procedure * Thrombolytics, glycoprotein IIb/IIIa inhibitor, or warfarin within 72 hours of the procedure * Absolute contraindications or allergy that cannot be pre-medicated to iodinated contrast * Contraindications or allergy to aspirin or clopidogrel * Known or suspected pregnant women or nursing mothers. Women of child-bearing potential will be asked if they are pregnant and will be tested for pregnancy * Previous enrollment in this study * Treatment with other investigational drugs or devices within the 30 days preceding enrollment or planned use of other investigational drugs or devices before the primary endpoint of this study has been reached
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Bleeding (BARC ≥3b) at 48 Hours or Before Hospital Discharge | at 48 hours or discharge, whichever occurs first | Major bleeding (Bleeding Academic Research Consortium \[BARC\] type ≥3b) was defined as follows: * Bleeds that were evident clinically, or by laboratory or imaging results, which resulted in surgical intervention or administration of IV vasoactive drugs; overt bleeds with a hemoglobin drop of at least 5 grams per deciliter (g/dL); and bleeding that caused cardiac tamponade. * BARC 3c includes intracranial or intraocular bleeds that compromised vision. * BARC type 4 (Coronary Artery Bypass Grafting \[CABG\]-related bleeding) includes perioperative intracranial bleeding within 48 hours, bleeds that result in reoperation following closure of sternotomy for the purpose of controlling bleeding, bleeds that result in treatment with transfusion of ≥5 units of whole blood or packed red blood cells within a 48 hour period; and chest tube output ≥2 liters (L) within a 24-hour period. * BARC type 5, fatal bleeding, describes bleeds that directly result in death with no other cause. |
| Net Adverse Clinical Events (NACE) at up to 30 Days | up to 30 days after procedure | The net adverse cardiac events (NACE) at 30 days is the composite of major adverse cardiovascular events (MACE) + major bleeding (BARC type ≥3b). The composite of MACE is defined as all-cause mortality, myocardial infarction (MI), and stroke. A participant was defined to have a composite event if the participant experienced at least 1 of the components. If the participant did not have any of the components, then he or she did not have the composite endpoint. If a participant had more than 1 of the components, he or she was only counted once in the determination of the total number of participants experiencing the composite endpoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| NACE at 48 Hours or Before Hospital Discharge | at 48 hours or before hospital discharge, whichever occurred earlier | NACE at 48 hours or before hospital discharge is the composite of major adverse cardiovascular events (MACE) + major bleeding (BARC type ≥3b). The composite of MACE is defined as all-cause mortality, MI, and stroke. A participant was defined to have a composite event if the participant experienced at least 1 of the components. If the participant did not have any of the components, then he or she did not have the composite endpoint. If a participant had more than 1 of the components, he or she was only counted once in the determination of the total number of participants experiencing the composite endpoint. |
| Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke | at 48 hours or before hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days) | The percentage of participants reporting a MACE overall and the individual components of MACE (including death, non-fatal MI, and stroke) are presented. |
| Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS) | at 48 hours or hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days) follow-up | Percentage of participants with major bleeding according to the following scales: * Valve Academic Research Consortium (VARC)=life threatening, disabling bleeding, or major bleeding * Thrombolysis in Myocardial Infarction (TIMI)=major bleeding * Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO)=severe or moderate * Acute Catheterization and Urgent Intervention Triage StrategY (ACUITY)/Harmonizing Outcomes with RevasculariZatiON and Stents (HORIZONS)=major bleeding |
| Transient Ischemic Attack | at 48 hours or before hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days) | The percentage of participants reporting transient ischemic attack is presented. |
| Major Vascular Complications | at 48 hours or before hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days) | The percentage of participants reporting a major vascular complications as defined by VARC is presented. |
| New Onset Atrial Fibrillation/Flutter | at 48 hours or before hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days) | The percentage of participants reporting new onset atrial fibrillation/flutter is presented. |
| Timing Effect on Bleeding Event Rate up to 48 Hours or Hospital Discharge | Up to 48 hours after procedure or at hospital discharge (but also includes any subsequent hospitalizations) | The effect of timing on bleeding event rates (the percentage of participants with an incidence of major bleeding) is presented. |
| Bleeding BARC 3a, BARC Types 1 or 2, and TIMI Minor | at 48 hours or hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days) follow-up | The percentage of participants with moderate bleeding as defined by BARC 3a and minor bleeding as defined as BARC type 1 and 2 and TIMI minor is presented. |
| Acute Kidney Injury | at 48 hours or hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days) follow-up | The percentage of participants reporting acute kidney injury is presented. |
| Acquired Thrombocytopenia | at 48 hours or before hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days) | The percentage of participants reporting acquired thrombocytopenia is presented. |
Countries
Canada, France, Germany, Italy, Netherlands, Switzerland, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bivalirudin Bivalirudin administered as a bolus and intravenous (IV) infusion during TAVR. It was recommended that the bolus (0.75 milligrams per kilogram \[mg/kg\]) be directly administered through the valve delivery sheath immediately following its successful delivery via percutaneous femoral access. Systemic IV administration of the bolus dose was also acceptable. The bivalirudin IV infusion was initiated immediately after the bolus administration. All wires, catheters, and sheaths were to be flushed with heparinized saline. | 404 |
| Unfractionated Heparin (UFH) The dose of UFH adhered to the standard institutional practice. An ACT target ≥250 seconds was recommended. All wires, catheters, and sheaths were to be flushed with heparinized saline. | 398 |
| Total | 802 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Inclusion/Exclusion Criteria Not Met | 3 | 0 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Physician decision: Day 30 visit <23 day | 1 | 5 |
| Overall Study | Physician decision: No 30-day visit | 2 | 1 |
| Overall Study | Reason Not Specified: No 30-day visit | 2 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Bivalirudin | Unfractionated Heparin (UFH) | Total |
|---|---|---|---|
| Age, Continuous | 82.3 years STANDARD_DEVIATION 6.5 | 82.3 years STANDARD_DEVIATION 6.5 | 82.3 years STANDARD_DEVIATION 6.5 |
| Region of Enrollment Canada | 36 participants | 38 participants | 74 participants |
| Region of Enrollment France | 108 participants | 106 participants | 214 participants |
| Region of Enrollment Germany | 180 participants | 173 participants | 353 participants |
| Region of Enrollment Italy | 37 participants | 39 participants | 76 participants |
| Region of Enrollment Netherlands | 10 participants | 10 participants | 20 participants |
| Region of Enrollment Switzerland | 25 participants | 22 participants | 47 participants |
| Region of Enrollment United Kingdom | 8 participants | 10 participants | 18 participants |
| Sex: Female, Male Female | 195 Participants | 196 Participants | 391 Participants |
| Sex: Female, Male Male | 209 Participants | 202 Participants | 411 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 73 / 393 | 70 / 394 |
| serious Total, serious adverse events | 112 / 393 | 116 / 394 |
Outcome results
Primary
Major Bleeding (BARC ≥3b) at 48 Hours or Before Hospital Discharge
Major bleeding (Bleeding Academic Research Consortium \[BARC\] type ≥3b) was defined as follows: * Bleeds that were evident clinically, or by laboratory or imaging results, which resulted in surgical intervention or administration of IV vasoactive drugs; overt bleeds with a hemoglobin drop of at least 5 grams per deciliter (g/dL); and bleeding that caused cardiac tamponade. * BARC 3c includes intracranial or intraocular bleeds that compromised vision. * BARC type 4 (Coronary Artery Bypass Grafting \[CABG\]-related bleeding) includes perioperative intracranial bleeding within 48 hours, bleeds that result in reoperation following closure of sternotomy for the purpose of controlling bleeding, bleeds that result in treatment with transfusion of ≥5 units of whole blood or packed red blood cells within a 48 hour period; and chest tube output ≥2 liters (L) within a 24-hour period. * BARC type 5, fatal bleeding, describes bleeds that directly result in death with no other cause.
Time frame: at 48 hours or discharge, whichever occurs first
Population: Participants in the ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bivalirudin | Major Bleeding (BARC ≥3b) at 48 Hours or Before Hospital Discharge | 6.9 percentage of participants |
| Unfractionated Heparin (UFH) | Major Bleeding (BARC ≥3b) at 48 Hours or Before Hospital Discharge | 9 percentage of participants |
p-value: 0.269295% CI: [0.48, 1.23]Chi-squared
Primary
Net Adverse Clinical Events (NACE) at up to 30 Days
The net adverse cardiac events (NACE) at 30 days is the composite of major adverse cardiovascular events (MACE) + major bleeding (BARC type ≥3b). The composite of MACE is defined as all-cause mortality, myocardial infarction (MI), and stroke. A participant was defined to have a composite event if the participant experienced at least 1 of the components. If the participant did not have any of the components, then he or she did not have the composite endpoint. If a participant had more than 1 of the components, he or she was only counted once in the determination of the total number of participants experiencing the composite endpoint.
Time frame: up to 30 days after procedure
Population: Participants in the ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bivalirudin | Net Adverse Clinical Events (NACE) at up to 30 Days | 14.4 percentage of participants |
| Unfractionated Heparin (UFH) | Net Adverse Clinical Events (NACE) at up to 30 Days | 16.1 percentage of participants |
p-value: 0.496795% CI: [0.64, 1.24]Chi-squared
Secondary
Acquired Thrombocytopenia
The percentage of participants reporting acquired thrombocytopenia is presented.
Time frame: at 48 hours or before hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days)
Population: Participants in the ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bivalirudin | Acquired Thrombocytopenia | at 48 hours or before hospital discharge | 16.6 percentage of participants |
| Bivalirudin | Acquired Thrombocytopenia | at up to 30 days (±7 days) | 24 percentage of participants |
| Unfractionated Heparin (UFH) | Acquired Thrombocytopenia | at 48 hours or before hospital discharge | 17.3 percentage of participants |
| Unfractionated Heparin (UFH) | Acquired Thrombocytopenia | at up to 30 days (±7 days) | 23.1 percentage of participants |
Secondary
Acute Kidney Injury
The percentage of participants reporting acute kidney injury is presented.
Time frame: at 48 hours or hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days) follow-up
Population: Participants in the ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bivalirudin | Acute Kidney Injury | at 48 hours or before hospital discharge | 10.9 percentage of participants |
| Bivalirudin | Acute Kidney Injury | at up to 30 days (±7 days) follow-up | 18.8 percentage of participants |
| Unfractionated Heparin (UFH) | Acute Kidney Injury | at 48 hours or before hospital discharge | 6.5 percentage of participants |
| Unfractionated Heparin (UFH) | Acute Kidney Injury | at up to 30 days (±7 days) follow-up | 13.8 percentage of participants |
Secondary
Bleeding BARC 3a, BARC Types 1 or 2, and TIMI Minor
The percentage of participants with moderate bleeding as defined by BARC 3a and minor bleeding as defined as BARC type 1 and 2 and TIMI minor is presented.
Time frame: at 48 hours or hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days) follow-up
Population: Participants in the ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bivalirudin | Bleeding BARC 3a, BARC Types 1 or 2, and TIMI Minor | BARC 3a at 48 hours or hospital discharge | 15.6 percentage of participants |
| Bivalirudin | Bleeding BARC 3a, BARC Types 1 or 2, and TIMI Minor | BARC types 1 and 2 at 48 hours or discharge | 20.8 percentage of participants |
| Bivalirudin | Bleeding BARC 3a, BARC Types 1 or 2, and TIMI Minor | TIMI minor at 48 hours or hospital discharge | 16.6 percentage of participants |
| Bivalirudin | Bleeding BARC 3a, BARC Types 1 or 2, and TIMI Minor | BARC 3a at 30 days | 18.8 percentage of participants |
| Bivalirudin | Bleeding BARC 3a, BARC Types 1 or 2, and TIMI Minor | BARC types 1 and 2 at 30 days | 27.7 percentage of participants |
| Bivalirudin | Bleeding BARC 3a, BARC Types 1 or 2, and TIMI Minor | TIMI minor at 30 days | 21.3 percentage of participants |
| Unfractionated Heparin (UFH) | Bleeding BARC 3a, BARC Types 1 or 2, and TIMI Minor | BARC types 1 and 2 at 30 days | 25.6 percentage of participants |
| Unfractionated Heparin (UFH) | Bleeding BARC 3a, BARC Types 1 or 2, and TIMI Minor | BARC 3a at 48 hours or hospital discharge | 13.3 percentage of participants |
| Unfractionated Heparin (UFH) | Bleeding BARC 3a, BARC Types 1 or 2, and TIMI Minor | BARC 3a at 30 days | 17.3 percentage of participants |
| Unfractionated Heparin (UFH) | Bleeding BARC 3a, BARC Types 1 or 2, and TIMI Minor | BARC types 1 and 2 at 48 hours or discharge | 21.1 percentage of participants |
| Unfractionated Heparin (UFH) | Bleeding BARC 3a, BARC Types 1 or 2, and TIMI Minor | TIMI minor at 30 days | 19.3 percentage of participants |
| Unfractionated Heparin (UFH) | Bleeding BARC 3a, BARC Types 1 or 2, and TIMI Minor | TIMI minor at 48 hours or hospital discharge | 14.3 percentage of participants |
Secondary
Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke
The percentage of participants reporting a MACE overall and the individual components of MACE (including death, non-fatal MI, and stroke) are presented.
Time frame: at 48 hours or before hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days)
Population: Participants in the ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bivalirudin | Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke | MI at 48 hours or before hospital discharge | 0 percentage of participants |
| Bivalirudin | Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke | MACE at 48 hours or before hospital discharge | 3.5 percentage of participants |
| Bivalirudin | Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke | Death at 48 hours or before hospital discharge | 1.5 percentage of participants |
| Bivalirudin | Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke | Stroke at 48 hours or before hospital discharge | 2 percentage of participants |
| Bivalirudin | Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke | MACE at up to 30 days | 7.7 percentage of participants |
| Bivalirudin | Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke | Death at up to 30 days | 4.7 percentage of participants |
| Bivalirudin | Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke | MI at up to 30 days | 0.5 percentage of participants |
| Bivalirudin | Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke | Stroke at up to 30 days | 3.5 percentage of participants |
| Unfractionated Heparin (UFH) | Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke | Stroke at up to 30 days | 2.8 percentage of participants |
| Unfractionated Heparin (UFH) | Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke | MACE at up to 30 days | 8 percentage of participants |
| Unfractionated Heparin (UFH) | Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke | MACE at 48 hours or before hospital discharge | 4.8 percentage of participants |
| Unfractionated Heparin (UFH) | Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke | MI at up to 30 days | 1.8 percentage of participants |
| Unfractionated Heparin (UFH) | Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke | Death at 48 hours or before hospital discharge | 1.8 percentage of participants |
| Unfractionated Heparin (UFH) | Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke | MI at 48 hours or before hospital discharge | 1.3 percentage of participants |
| Unfractionated Heparin (UFH) | Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke | Death at up to 30 days | 4.8 percentage of participants |
| Unfractionated Heparin (UFH) | Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke | Stroke at 48 hours or before hospital discharge | 2 percentage of participants |
Secondary
Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS)
Percentage of participants with major bleeding according to the following scales: * Valve Academic Research Consortium (VARC)=life threatening, disabling bleeding, or major bleeding * Thrombolysis in Myocardial Infarction (TIMI)=major bleeding * Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO)=severe or moderate * Acute Catheterization and Urgent Intervention Triage StrategY (ACUITY)/Harmonizing Outcomes with RevasculariZatiON and Stents (HORIZONS)=major bleeding
Time frame: at 48 hours or hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days) follow-up
Population: Participants in the ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bivalirudin | Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS) | VARC at 48 hours or before hospital | 21.8 percentage of participants |
| Bivalirudin | Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS) | TIMI at 48 hours or before hospital | 4 percentage of participants |
| Bivalirudin | Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS) | GUSTO at 48 hours or hospital discharge | 13.9 percentage of participants |
| Bivalirudin | Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS) | ACUITY/HORIZONS at 48 hours or hospital discharge | 26 percentage of participants |
| Bivalirudin | Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS) | VARC at 30 days | 26.5 percentage of participants |
| Bivalirudin | Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS) | TIMI at 30 days | 5.7 percentage of participants |
| Bivalirudin | Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS) | GUSTO at 30 days | 16.3 percentage of participants |
| Bivalirudin | Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS) | ACUITY/HORIZONS at 30 days | 33.4 percentage of participants |
| Unfractionated Heparin (UFH) | Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS) | ACUITY/HORIZONS at 30 days | 29.6 percentage of participants |
| Unfractionated Heparin (UFH) | Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS) | VARC at 48 hours or before hospital | 19.6 percentage of participants |
| Unfractionated Heparin (UFH) | Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS) | VARC at 30 days | 24.6 percentage of participants |
| Unfractionated Heparin (UFH) | Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS) | TIMI at 48 hours or before hospital | 6.5 percentage of participants |
| Unfractionated Heparin (UFH) | Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS) | GUSTO at 30 days | 14.6 percentage of participants |
| Unfractionated Heparin (UFH) | Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS) | GUSTO at 48 hours or hospital discharge | 11.6 percentage of participants |
| Unfractionated Heparin (UFH) | Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS) | TIMI at 30 days | 7.3 percentage of participants |
| Unfractionated Heparin (UFH) | Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS) | ACUITY/HORIZONS at 48 hours or hospital discharge | 24.4 percentage of participants |
Secondary
Major Vascular Complications
The percentage of participants reporting a major vascular complications as defined by VARC is presented.
Time frame: at 48 hours or before hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days)
Population: Participants in the ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bivalirudin | Major Vascular Complications | at 48 hours or before hospital discharge | 8.7 percentage of participants |
| Bivalirudin | Major Vascular Complications | at up to 30 days (±7 days) follow-up | 9.2 percentage of participants |
| Unfractionated Heparin (UFH) | Major Vascular Complications | at 48 hours or before hospital discharge | 9 percentage of participants |
| Unfractionated Heparin (UFH) | Major Vascular Complications | at up to 30 days (±7 days) follow-up | 9.5 percentage of participants |
Secondary
NACE at 48 Hours or Before Hospital Discharge
NACE at 48 hours or before hospital discharge is the composite of major adverse cardiovascular events (MACE) + major bleeding (BARC type ≥3b). The composite of MACE is defined as all-cause mortality, MI, and stroke. A participant was defined to have a composite event if the participant experienced at least 1 of the components. If the participant did not have any of the components, then he or she did not have the composite endpoint. If a participant had more than 1 of the components, he or she was only counted once in the determination of the total number of participants experiencing the composite endpoint.
Time frame: at 48 hours or before hospital discharge, whichever occurred earlier
Population: Participants in the ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bivalirudin | NACE at 48 Hours or Before Hospital Discharge | 8.9 percentage of participants |
| Unfractionated Heparin (UFH) | NACE at 48 Hours or Before Hospital Discharge | 12.6 percentage of participants |
Secondary
New Onset Atrial Fibrillation/Flutter
The percentage of participants reporting new onset atrial fibrillation/flutter is presented.
Time frame: at 48 hours or before hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days)
Population: Participants in the ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bivalirudin | New Onset Atrial Fibrillation/Flutter | at 48 hours or before hospital discharge | 3.2 percentage of participants |
| Bivalirudin | New Onset Atrial Fibrillation/Flutter | at up to 30 days (±7 days) follow-up | 5.4 percentage of participants |
| Unfractionated Heparin (UFH) | New Onset Atrial Fibrillation/Flutter | at 48 hours or before hospital discharge | 2.5 percentage of participants |
| Unfractionated Heparin (UFH) | New Onset Atrial Fibrillation/Flutter | at up to 30 days (±7 days) follow-up | 4 percentage of participants |
Secondary
Timing Effect on Bleeding Event Rate up to 48 Hours or Hospital Discharge
The effect of timing on bleeding event rates (the percentage of participants with an incidence of major bleeding) is presented.
Time frame: Up to 48 hours after procedure or at hospital discharge (but also includes any subsequent hospitalizations)
Population: Participants in the ITT population with an incidence of major bleeding. Participants were categorized as First half of study site's enrolled participants (Bivalirudin, N=173; UFH, N=173) and Second half of study site's enrolled participants (Bivalirudin, N=171; UFH, N=165). Only sites with \>20 participants are included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bivalirudin | Timing Effect on Bleeding Event Rate up to 48 Hours or Hospital Discharge | 6.4 percentage of participants |
| Unfractionated Heparin (UFH) | Timing Effect on Bleeding Event Rate up to 48 Hours or Hospital Discharge | 6.4 percentage of participants |
| UFH: First Half of Study Site's Enrolled Participants | Timing Effect on Bleeding Event Rate up to 48 Hours or Hospital Discharge | 11.6 percentage of participants |
| UFH: Second Half of Study Site's Enrolled Participants | Timing Effect on Bleeding Event Rate up to 48 Hours or Hospital Discharge | 8.5 percentage of participants |
Secondary
Transient Ischemic Attack
The percentage of participants reporting transient ischemic attack is presented.
Time frame: at 48 hours or before hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days)
Population: Participants in the ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bivalirudin | Transient Ischemic Attack | at 48 hours or before hospital discharge | 0 percentage of participants |
| Bivalirudin | Transient Ischemic Attack | at up to 30 days (±7 days) follow-up | 0 percentage of participants |
| Unfractionated Heparin (UFH) | Transient Ischemic Attack | at 48 hours or before hospital discharge | 0 percentage of participants |
| Unfractionated Heparin (UFH) | Transient Ischemic Attack | at up to 30 days (±7 days) follow-up | 0 percentage of participants |