Heart Failure
Conditions
Keywords
heart failure, ventricular assist device, LVAD, aspirin
Brief summary
Prospective, randomized, double-blinded, placebo-controlled clinical investigation of advanced heart failure patients treated with the HM3 with two different antithrombotic regimens: vitamin K antagonist with aspirin versus vitamin K antagonist with placebo
Detailed description
This clinical investigation is a prospective, randomized, double-blinded, placebo-controlled study of advanced heart failure patients treated with the HM3 with two different antithrombotic regimens: vitamin K antagonist with aspirin versus vitamin K antagonist with placebo.
Interventions
DEVICELVAD Implant
Subjects will undergo Heartmate 3 LVAD implant prior to randomization
DRUGAspirin 100mg
Subjects will be randomized to either Placebo or Aspirin post implant.
DRUGPlacebo oral tablet
Subjects will be randomized to either Placebo or Aspirin post implant
Sponsors
Abbott Medical Devices
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Investigator, site, patient, CEC, and core lab are blinded.
Intervention model description
Double-blinded, randomized 1:1, active arm versus placebo arm
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject will receive the HeartMate 3 per standard of care (SOC) in accordance with the approved indications for use in the country of implant. 2. Subject will receive the HeartMate 3 as their first durable VAD. 3. Subject must provide written informed consent prior to any clinical investigation related procedure. 4. In female patients of child bearing capability, subject will not be currently pregnant or breastfeeding and on appropriate contraception.
Exclusion criteria
1. Post-implant additional temporary or permanent mechanical circulatory support (MCS). 2. Investigator mandated antiplatelet therapy for other conditions (including mandated presence or absence of antiplatelet agent). 3. Patients who are nil per os (NPO) post-implant through day 7. 4. Subjects with a known allergy to acetylsalicylic acid (aspirin). 5. Participation in any other clinical investigation(s) involving an MCS device, or interventional investigation(s) likely to confound study results or affect study outcome. 6. Presence of other anatomic or comorbid conditions, or other medical, social, or psychological conditions that, in the investigator's opinion, could limit the subject's ability to participate in the clinical investigation or to comply with follow-up requirements, or impact the scientific soundness of the clinical investigation results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Powered Primary Endpoint of Survival Free of Non-surgical Major Hemocompatibility Related Adverse Events | 12 Months | The primary end point was a composite of survival free of non-surgical major hemocompatibility related adverse events (specifically stroke, pump thrombosis, major non-surgical bleeding, and arterial peripheral thromboembolism) at 1-year post implant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rates of Bleeding Events | Through Study Completion with a Median Follow up of 14 Months | The bleeding rate was calculated by dividing the number of bleeding events by the cumulative duration of study exposure (years of support). |
| Rates of Non-surgical Major Hemorrhagic Events | Through Study Completion with a Median Follow up of 14 Months | The rate of non-surgical hemorrhagic events were compared between the two arms of the study. Non-surgical Major Hemorrhagic events: Hemorrhagic event rate per patient year was calculated by dividing all non-surgical bleeding events and hemorrhagic stroke events by the cumulative years of study exposure. |
| Rates of Non-surgical Major Thrombotic Events | Through Study Completion with a Median Follow up of 14 Months | The rates of non-surgical major thrombotic events was compared between the two arms of the study. The thrombotic event rate per patient year was calculated by dividing the number of non-surgical ischemic strokes, pump thrombosis and arterial peripheral thromboembolic events by the cumulative years of study exposure |
| Rates of Stroke | Through Study Completion with a Median Follow up of 14 Months | The stroke rate was calculated based on the number of strokes experienced by subjects, 14 days or more after device implant, and while on their treatment assignment, divided by the cumulative duration of study exposure (years of support). |
| Survival Rates | 24 Months | The overall survival rate was analyzed using a Kaplan-Meier analysis and the treatment groups were compared using log-rank test. Survival was calculated starting at 14 days post implant. |
| Risk of Non-Surgical Bleeding Events | 24 Months | Risk of non-surgical bleeding events was analyzed using a Kaplan-Meier analysis. The treatment groups were compared using a log-rank test. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Economic Cost Implications - Average Cost Per Bleeding Event | 12 Months | These values were derived by dividing the total estimated cost for bleeding events by the number of events to determine the average cost per bleeding event. Consequently, a measure of dispersion is not available for these outcomes. |
| Economic Cost Implications - Average Cost Per Study Patient Over the First-year Post-implant | 12 Months | These values were derived by dividing the total estimated cost for bleeding events by the number of patients to obtain the average cost per study patient. Consequently, a measure of dispersion is not available for these outcomes. |
| Economic Cost Implications - Cost of Bleeding Hospitalization for 1000 LVAD Implants Over the First-year Post-implant | 12 Months | Cost of bleeding episodes was calculated based on a previously published economic model, adjusted for inflation using the US Bureau of Labor Statistics Medical Consumer Price Index. To ensure uniformity in care practices and relevance of the previously published model, only US subjects were included. |
| Economic Cost Implications - Total Estimated Cost for Bleeding Events (CMS Cost Basis) | 12 Months | Cost of bleeding episodes was calculated based on a previously published economic model, adjusted for inflation using the US Bureau of Labor Statistics Medical Consumer Price Index. To ensure uniformity in care practices and relevance of the previously published model, only US subjects were included. |
| Rate of Rehospitalization | Through Study Completion with a Median Follow up of 14 Months | This study assessed changes in the rehospitalization as a result of removal of antiplatelet therapy from the antithrombotic regimen. |
Countries
Australia, Austria, Canada, Czechia, France, Italy, Kazakhstan, United Kingdom, United States
Participant flow
Recruitment details
The study enrolled and randomized 628 subjects at 51 sites. Enrollment took place between July 2020 and September 2022, with the last subject follow up concluding in August 2023.
Pre-assignment details
The intent to treat (ITT) population consisted of all subjects randomized including follow up beyond transition to open label (n=314 in each arm).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Arm Patients randomized to the placebo arm were given placebo medication. | 296 |
| Aspirin Arm Patients randomized to the aspirin arm were given aspirin medication (100mg/day). | 293 |
| Total | 589 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Modified Intent-to-Treat (mITT) | Death | 1 | 2 |
| Modified Intent-to-Treat (mITT) | Transitioned to open label | 8 | 12 |
| Modified Intent-to-Treat (mITT) | Withdrawal by Subject | 9 | 7 |
| Principal Analysis | Withdrawn without primary end point event | 25 | 20 |
Baseline characteristics
| Characteristic | Placebo Arm | Aspirin Arm | Total |
|---|---|---|---|
| Age, Continuous | 57.6 years STANDARD_DEVIATION 12.8 | 56.5 years STANDARD_DEVIATION 14.4 | 57.1 years STANDARD_DEVIATION 13.6 |
| Heart Failure Etiology Dilated Cardiomyopathy | 86 Participants | 81 Participants | 167 Participants |
| Heart Failure Etiology Idiopathic Cardiomyopathy | 68 Participants | 63 Participants | 131 Participants |
| Heart Failure Etiology Ischemic Cardiomyopathy | 106 Participants | 101 Participants | 207 Participants |
| Heart Failure Etiology Other | 36 Participants | 48 Participants | 84 Participants |
| Intended Use Bridge to Candidacy for Transplantation | 46 Participants | 50 Participants | 96 Participants |
| Intended Use Bridge to Recovery | 14 Participants | 11 Participants | 25 Participants |
| Intended Use Bridge to Transplantation | 56 Participants | 58 Participants | 114 Participants |
| Intended Use Destination Therapy | 180 Participants | 174 Participants | 354 Participants |
| INTERMACS Profile 1 | 12 Participants | 18 Participants | 30 Participants |
| INTERMACS Profile 2 | 76 Participants | 75 Participants | 151 Participants |
| INTERMACS Profile 3 | 133 Participants | 133 Participants | 266 Participants |
| INTERMACS Profile 4 | 66 Participants | 54 Participants | 120 Participants |
| INTERMACS Profile 5 | 6 Participants | 8 Participants | 14 Participants |
| INTERMACS Profile 6 | 3 Participants | 5 Participants | 8 Participants |
| INTERMACS Profile 7 | 0 Participants | 0 Participants | 0 Participants |
| New York Heart Association (NYHA) Class Class II | 3 Participants | 2 Participants | 5 Participants |
| New York Heart Association (NYHA) Class Class IIIA | 27 Participants | 29 Participants | 56 Participants |
| New York Heart Association (NYHA) Class Class IIIB | 40 Participants | 38 Participants | 78 Participants |
| New York Heart Association (NYHA) Class Class IV | 226 Participants | 224 Participants | 450 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 13 Participants | 9 Participants | 22 Participants |
| Race (NIH/OMB) Black or African American | 93 Participants | 84 Participants | 177 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 13 Participants | 19 Participants |
| Race (NIH/OMB) White | 179 Participants | 181 Participants | 360 Participants |
| Region of Enrollment North America | 251 Participants | 248 Participants | 499 Participants |
| Region of Enrollment Other | 45 Participants | 45 Participants | 90 Participants |
| Sex: Female, Male Female | 72 Participants | 61 Participants | 133 Participants |
| Sex: Female, Male Male | 224 Participants | 232 Participants | 456 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 21 / 296 | 22 / 293 |
| other Total, other adverse events | 200 / 296 | 181 / 293 |
| serious Total, serious adverse events | 208 / 296 | 223 / 293 |
Outcome results
Primary
Powered Primary Endpoint of Survival Free of Non-surgical Major Hemocompatibility Related Adverse Events
The primary end point was a composite of survival free of non-surgical major hemocompatibility related adverse events (specifically stroke, pump thrombosis, major non-surgical bleeding, and arterial peripheral thromboembolism) at 1-year post implant.
Time frame: 12 Months
Population: The primary end point was analyzed in the principal analysis population, which excluded patients with events occurring within 14 days after LVAD implantation to avoid counting surgical complications not attributed to the treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo Arm (Principal Analysis Population) | Powered Primary Endpoint of Survival Free of Non-surgical Major Hemocompatibility Related Adverse Events | 201 Participants |
| Aspirin Arm (Principal Analysis Population) | Powered Primary Endpoint of Survival Free of Non-surgical Major Hemocompatibility Related Adverse Events | 186 Participants |
p-value: <0.0001Farrington-Manning risk difference
Secondary
Rates of Bleeding Events
The bleeding rate was calculated by dividing the number of bleeding events by the cumulative duration of study exposure (years of support).
Time frame: Through Study Completion with a Median Follow up of 14 Months
Population: Modified Intention to Treat Population (mITT)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Arm (Principal Analysis Population) | Rates of Bleeding Events | Moderate Bleeding | 8.46 Event Per 100 Patient-Year |
| Placebo Arm (Principal Analysis Population) | Rates of Bleeding Events | GI Bleeding | 13.10 Event Per 100 Patient-Year |
| Placebo Arm (Principal Analysis Population) | Rates of Bleeding Events | Severe Bleeding | 17.47 Event Per 100 Patient-Year |
| Placebo Arm (Principal Analysis Population) | Rates of Bleeding Events | Fatal Bleeding | 0.55 Event Per 100 Patient-Year |
| Placebo Arm (Principal Analysis Population) | Rates of Bleeding Events | All Bleeding Events | 25.92 Event Per 100 Patient-Year |
| Aspirin Arm (Principal Analysis Population) | Rates of Bleeding Events | Fatal Bleeding | 0.85 Event Per 100 Patient-Year |
| Aspirin Arm (Principal Analysis Population) | Rates of Bleeding Events | All Bleeding Events | 39.53 Event Per 100 Patient-Year |
| Aspirin Arm (Principal Analysis Population) | Rates of Bleeding Events | Moderate Bleeding | 13.65 Event Per 100 Patient-Year |
| Aspirin Arm (Principal Analysis Population) | Rates of Bleeding Events | Severe Bleeding | 25.88 Event Per 100 Patient-Year |
| Aspirin Arm (Principal Analysis Population) | Rates of Bleeding Events | GI Bleeding | 21.61 Event Per 100 Patient-Year |
Secondary
Rates of Non-surgical Major Hemorrhagic Events
The rate of non-surgical hemorrhagic events were compared between the two arms of the study. Non-surgical Major Hemorrhagic events: Hemorrhagic event rate per patient year was calculated by dividing all non-surgical bleeding events and hemorrhagic stroke events by the cumulative years of study exposure.
Time frame: Through Study Completion with a Median Follow up of 14 Months
Population: Modified Intention to Treat Population (mITT)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Arm (Principal Analysis Population) | Rates of Non-surgical Major Hemorrhagic Events | All Non-surgical Major Hemorrhagic events | 26.2 Event Per 100 Patient-Year |
| Placebo Arm (Principal Analysis Population) | Rates of Non-surgical Major Hemorrhagic Events | Bleeding | 25.93 Event Per 100 Patient-Year |
| Placebo Arm (Principal Analysis Population) | Rates of Non-surgical Major Hemorrhagic Events | Hemorrhagic Stroke | 0.27 Event Per 100 Patient-Year |
| Placebo Arm (Principal Analysis Population) | Rates of Non-surgical Major Hemorrhagic Events | Ischemic Stroke with Hemorrhagic Conversion | 0.00 Event Per 100 Patient-Year |
| Aspirin Arm (Principal Analysis Population) | Rates of Non-surgical Major Hemorrhagic Events | Ischemic Stroke with Hemorrhagic Conversion | 0.28 Event Per 100 Patient-Year |
| Aspirin Arm (Principal Analysis Population) | Rates of Non-surgical Major Hemorrhagic Events | All Non-surgical Major Hemorrhagic events | 40.7 Event Per 100 Patient-Year |
| Aspirin Arm (Principal Analysis Population) | Rates of Non-surgical Major Hemorrhagic Events | Hemorrhagic Stroke | 0.85 Event Per 100 Patient-Year |
| Aspirin Arm (Principal Analysis Population) | Rates of Non-surgical Major Hemorrhagic Events | Bleeding | 39.53 Event Per 100 Patient-Year |
Secondary
Rates of Non-surgical Major Thrombotic Events
The rates of non-surgical major thrombotic events was compared between the two arms of the study. The thrombotic event rate per patient year was calculated by dividing the number of non-surgical ischemic strokes, pump thrombosis and arterial peripheral thromboembolic events by the cumulative years of study exposure
Time frame: Through Study Completion with a Median Follow up of 14 Months
Population: Modified Intention to Treat Population (mITT)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Arm (Principal Analysis Population) | Rates of Non-surgical Major Thrombotic Events | All Major Thrombotic events | 1.64 Event Per 100 Patient-Year |
| Placebo Arm (Principal Analysis Population) | Rates of Non-surgical Major Thrombotic Events | Ischemic Stroke without Hemorrhagic Conversion | 1.64 Event Per 100 Patient-Year |
| Placebo Arm (Principal Analysis Population) | Rates of Non-surgical Major Thrombotic Events | Device Thrombosis | 0.00 Event Per 100 Patient-Year |
| Placebo Arm (Principal Analysis Population) | Rates of Non-surgical Major Thrombotic Events | Arterial Peripheral Thromboembolism | 0.00 Event Per 100 Patient-Year |
| Aspirin Arm (Principal Analysis Population) | Rates of Non-surgical Major Thrombotic Events | Arterial Peripheral Thromboembolism | 0.00 Event Per 100 Patient-Year |
| Aspirin Arm (Principal Analysis Population) | Rates of Non-surgical Major Thrombotic Events | All Major Thrombotic events | 2.84 Event Per 100 Patient-Year |
| Aspirin Arm (Principal Analysis Population) | Rates of Non-surgical Major Thrombotic Events | Device Thrombosis | 0.00 Event Per 100 Patient-Year |
| Aspirin Arm (Principal Analysis Population) | Rates of Non-surgical Major Thrombotic Events | Ischemic Stroke without Hemorrhagic Conversion | 2.56 Event Per 100 Patient-Year |
Secondary
Rates of Stroke
The stroke rate was calculated based on the number of strokes experienced by subjects, 14 days or more after device implant, and while on their treatment assignment, divided by the cumulative duration of study exposure (years of support).
Time frame: Through Study Completion with a Median Follow up of 14 Months
Population: Modified Intention to Treat Population (mITT)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Arm (Principal Analysis Population) | Rates of Stroke | All Stroke | 1.91 Event Per 100 Patient-Year |
| Placebo Arm (Principal Analysis Population) | Rates of Stroke | Debilitating Stroke (MRS>3) | 0.82 Event Per 100 Patient-Year |
| Placebo Arm (Principal Analysis Population) | Rates of Stroke | Non-Debilitating Stroke (MRS<=3) | 1.09 Event Per 100 Patient-Year |
| Aspirin Arm (Principal Analysis Population) | Rates of Stroke | Non-Debilitating Stroke (MRS<=3) | 3.13 Event Per 100 Patient-Year |
| Aspirin Arm (Principal Analysis Population) | Rates of Stroke | All Stroke | 3.70 Event Per 100 Patient-Year |
| Aspirin Arm (Principal Analysis Population) | Rates of Stroke | Debilitating Stroke (MRS>3) | 0.57 Event Per 100 Patient-Year |
Secondary
Risk of Non-Surgical Bleeding Events
Risk of non-surgical bleeding events was analyzed using a Kaplan-Meier analysis. The treatment groups were compared using a log-rank test.
Time frame: 24 Months
Population: Modified Intention to Treat Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Arm (Principal Analysis Population) | Risk of Non-Surgical Bleeding Events | 30.0 Percentage of Participants |
| Aspirin Arm (Principal Analysis Population) | Risk of Non-Surgical Bleeding Events | 42.4 Percentage of Participants |
Secondary
Survival Rates
The overall survival rate was analyzed using a Kaplan-Meier analysis and the treatment groups were compared using log-rank test. Survival was calculated starting at 14 days post implant.
Time frame: 24 Months
Population: Modified Intention to Treat Population (mITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Arm (Principal Analysis Population) | Survival Rates | 93 Percentage of Participants |
| Aspirin Arm (Principal Analysis Population) | Survival Rates | 89.7 Percentage of Participants |
Other Pre-specified
Economic Cost Implications - Average Cost Per Bleeding Event
These values were derived by dividing the total estimated cost for bleeding events by the number of events to determine the average cost per bleeding event. Consequently, a measure of dispersion is not available for these outcomes.
Time frame: 12 Months
Population: Only US subjects were included in this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Arm (Principal Analysis Population) | Economic Cost Implications - Average Cost Per Bleeding Event | 13,674 USD |
| Aspirin Arm (Principal Analysis Population) | Economic Cost Implications - Average Cost Per Bleeding Event | 13,836 USD |
Other Pre-specified
Economic Cost Implications - Average Cost Per Study Patient Over the First-year Post-implant
These values were derived by dividing the total estimated cost for bleeding events by the number of patients to obtain the average cost per study patient. Consequently, a measure of dispersion is not available for these outcomes.
Time frame: 12 Months
Population: Only US subjects were included in this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Arm (Principal Analysis Population) | Economic Cost Implications - Average Cost Per Study Patient Over the First-year Post-implant | 2,214 USD |
| Aspirin Arm (Principal Analysis Population) | Economic Cost Implications - Average Cost Per Study Patient Over the First-year Post-implant | 3,799 USD |
Other Pre-specified
Economic Cost Implications - Cost of Bleeding Hospitalization for 1000 LVAD Implants Over the First-year Post-implant
Cost of bleeding episodes was calculated based on a previously published economic model, adjusted for inflation using the US Bureau of Labor Statistics Medical Consumer Price Index. To ensure uniformity in care practices and relevance of the previously published model, only US subjects were included.
Time frame: 12 Months
Population: Only US subjects were included in this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Arm (Principal Analysis Population) | Economic Cost Implications - Cost of Bleeding Hospitalization for 1000 LVAD Implants Over the First-year Post-implant | 2,214,362 USD/1000 implants/1 year |
| Aspirin Arm (Principal Analysis Population) | Economic Cost Implications - Cost of Bleeding Hospitalization for 1000 LVAD Implants Over the First-year Post-implant | 3,799,344 USD/1000 implants/1 year |
Other Pre-specified
Economic Cost Implications - Total Estimated Cost for Bleeding Events (CMS Cost Basis)
Cost of bleeding episodes was calculated based on a previously published economic model, adjusted for inflation using the US Bureau of Labor Statistics Medical Consumer Price Index. To ensure uniformity in care practices and relevance of the previously published model, only US subjects were included.
Time frame: 12 Months
Population: Only US subjects were included in this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Arm (Principal Analysis Population) | Economic Cost Implications - Total Estimated Cost for Bleeding Events (CMS Cost Basis) | 546,947 USD |
| Aspirin Arm (Principal Analysis Population) | Economic Cost Implications - Total Estimated Cost for Bleeding Events (CMS Cost Basis) | 927,040 USD |
Other Pre-specified
Rate of Rehospitalization
This study assessed changes in the rehospitalization as a result of removal of antiplatelet therapy from the antithrombotic regimen.
Time frame: Through Study Completion with a Median Follow up of 14 Months
Population: Modified Intention to Treat Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Arm (Principal Analysis Population) | Rate of Rehospitalization | Other | 0.41 Event Per 100 Patient-Year |
| Placebo Arm (Principal Analysis Population) | Rate of Rehospitalization | Hemocompatibility Related | 0.15 Event Per 100 Patient-Year |
| Placebo Arm (Principal Analysis Population) | Rate of Rehospitalization | Major Infection | 0.34 Event Per 100 Patient-Year |
| Placebo Arm (Principal Analysis Population) | Rate of Rehospitalization | Hypertension | 0.03 Event Per 100 Patient-Year |
| Placebo Arm (Principal Analysis Population) | Rate of Rehospitalization | Cardiovascular Related | 0.33 Event Per 100 Patient-Year |
| Placebo Arm (Principal Analysis Population) | Rate of Rehospitalization | Non-cardiovascular organ dysfunction | 0.06 Event Per 100 Patient-Year |
| Placebo Arm (Principal Analysis Population) | Rate of Rehospitalization | Neurologic dysfunction (excluding stroke, TIA) | 0.01 Event Per 100 Patient-Year |
| Aspirin Arm (Principal Analysis Population) | Rate of Rehospitalization | Other | 0.42 Event Per 100 Patient-Year |
| Aspirin Arm (Principal Analysis Population) | Rate of Rehospitalization | Cardiovascular Related | 0.33 Event Per 100 Patient-Year |
| Aspirin Arm (Principal Analysis Population) | Rate of Rehospitalization | Hemocompatibility Related | 0.28 Event Per 100 Patient-Year |
| Aspirin Arm (Principal Analysis Population) | Rate of Rehospitalization | Neurologic dysfunction (excluding stroke, TIA) | 0.02 Event Per 100 Patient-Year |
| Aspirin Arm (Principal Analysis Population) | Rate of Rehospitalization | Major Infection | 0.36 Event Per 100 Patient-Year |
| Aspirin Arm (Principal Analysis Population) | Rate of Rehospitalization | Non-cardiovascular organ dysfunction | 0.05 Event Per 100 Patient-Year |
| Aspirin Arm (Principal Analysis Population) | Rate of Rehospitalization | Hypertension | 0.02 Event Per 100 Patient-Year |