Angiotensin Converting Enzyme, Angiotensin Receptor Blockers, Cardiopulmonary Bypass, Coronary Artery Disease, Fibrinolysis, Inflammation
Conditions
Keywords
Angiotensin Converting Enzyme, Angiotensin Receptor Blockers, Cardiopulmonary Bypass, Fibrinolysis, Inflammation
Brief summary
Each year over a million patients worldwide undergo cardiac surgery requiring cardiopulmonary bypass (CPB).1 CPB is associated with significant morbidity including hemodynamic instability, the transfusion of allogenic blood products, and inflammation. Blood product transfusion increases mortality after cardiac surgery. Enhanced fibrinolysis contributes to increased blood product transfusion requirements in the perioperative period. CPB activates the kallikrein-kinin system (KKS), leading to increased bradykinin concentrations. Bradykinin, acting through its B2 receptor, stimulates the release of nitric oxide, inflammatory cytokines and tissue-type plasminogen activator (t-PA). Based on data indicating that angiotensin-converting enzyme (ACE) inhibitors reduce mortality in patients with coronary artery disease, many patients undergoing CPB are taking ACE inhibitors. While interruption of the renin-angiotensin system (RAS) reduces inflammation in response to CPB, ACE inhibitors also potentiate the effects of bradykinin and may augment B2-mediated change in fibrinolytic balance and inflammation. In contrast, angiotensin II type 1 receptor antagonism does not potentiate bradykinin and does not inhibit bradykinin metabolism. Studies in animals suggest that bradykinin receptor antagonism inhibits reperfusion-induced increases in vascular permeability and neutrophil recruitment.A randomized, placebo controlled clinical trial of a bradykinin B2 receptor antagonist demonstrated some effect on survival in patients with systemic inflammatory response syndrome and gram-negative sepsis. In addition, we and others have shown bradykinin B2 receptor antagonism reduces vascular t-PA release during ACE inhibition. The current proposal derives from data from our laboratory and others elucidating the role of the KKS in the inflammatory, hypotensive and fibrinolytic response to CPB. Specifically, we have found that CPB activates the KKS and that ACE inhibition and smoking further increases bradykinin concentrations. During CPB, bradykinin concentrations correlate inversely with mean arterial pressure and directly with t-PA. Moreover, we have found that bradykinin receptor antagonism attenuates protamine-related hypotension following CPB. The current proposal tests the central hypothesis that the fibrinolytic and inflammatory response to cardiopulmonary bypass differ during angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor antagonism.
Interventions
DRUGPlacebo
Placebo
DRUGRamipril
Ramipril 2.5mg day 1 and 2 and then 5mg/d thereafter
DRUGCandesartan
Candesartan 16mg/d
Sponsors
Vanderbilt University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Inclusion Criteria 1. Subjects, 18 to 80 years of age, scheduled for elective cardiac surgery requiring CPB 2. For female subjects, the following conditions must be met: postmenopausal for at least 1 year, or status-post surgical sterilization, or if of childbearing potential, utilizing adequate birth control and willing to undergo urine beta-hcg testing prior to drug treatment and on every study day
Exclusion criteria
1. Left ventricle ejection fraction less than 30% 2. History of ACE inhibitor-induced angioedema 3. Hypotension (systolic blood pressure \<100 mmHg and evidence of hypoperfusion) 4. Hyperkalemia (baseline potassium \>5.0 mEq/L) 5. Inability to discontinue current ACE inhibitor or AT1 receptor antagonist. 6. Emergency surgery 7. Impaired renal function (serum creatinine \>1.6 mg/dl) 8. Pregnancy 9. Breast-feeding 10. Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult 11. History of alcohol or drug abuse 12. Treatment with any investigational drug in the 1 month preceding the study 13. Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study 14. Inability to comply with the protocol, e.g. uncooperative attitude and unlikelihood of completing the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tissue-type Plasminogen Activator (t-PA) Antigen Response | From the start of surgery until postoperative day 2 | To compare the effects of angiotensin II type I (AT1) receptor antagonism or angiotensin-converting enzyme (ACE) inhibition versus placebo on the fibrinolytic responses to cardiopulmonary bypass (CPB) as measured by t-PA antigen response |
| Plasminogen Activator Inhibitor-1 (PAI-1) Response | From the start of surgery until postoperative day 2 | To compare the effects of AT1 receptor antagonism or ACE inhibition versus placebo on the fibrinolytic responses to CPB as measured by PAI-1 response |
| Interleukin-6 (IL-6) Response | From the start of surgery until postoperative day 2 | To compare the effects of AT1 receptor antagonism or ACE inhibition versus placebo on the inflammatory response to CPB as measured by IL-6 |
| Interleukin-8 (IL-8) Response | From the start of surgery until postoperative day 2 | To compare the effects of AT1 receptor antagonism or ACE inhibition versus placebo on the inflammatory response to CPB as measured by IL-8 |
| Interleukin-10 (IL-10) Response | From the start of surgery until postoperative day 2 | To compare the effects of AT1 receptor antagonism or ACE inhibition versus placebo on the inflammatory response to CPB as measured by the IL-10 response |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acute Kidney Injury | From the start of surgery until postoperative day 3 | Acute kidney injury (AKI) was defined according to Acute Kidney Injury Network (AKIN) criteria,specifically any increase in subject serum creatinine concentration of 50% or 0.3 mg/dL (26.5 umol/L) within 72 hours of surgery. |
| Blood Loss | First 24 hours after arrival in the intensive care unit | Blood loss over 24 hours as measured by chest tube output |
| Length of Hospital Stay | From the start of surgery until discharge from hospital | — |
| Stroke | From arrival in intensive care unit until discharge from hospital | New onset neurological deficit with a duration of longer than 24 hours |
| Re-exploration for Bleeding | From arrival in intensive care unit until discharge from hospital | The percentage of patients that were taken back to the operating room for re-exploration because of bleeding |
| Blood Product Transfusion Requirement | From the start of surgery until discharge from hospital | Percentage of patients that received blood product transfusion |
| Vasopressor Drug Use | From the end of cardiopulmonary bypass until arrival in intensive care unit | — |
| New Onset Atrial Fibrillation | From arrival in intensive care unit until discharge from hospital | New onset atrial fibrillation based on electrocardiogram (ECG) rhythm strips with a duration longer than 10 seconds |
Countries
United States
Participant flow
Recruitment details
Adult patients scheduled for elective cardiac surgery requiring cardiopulmonary bypass were recruited from the Vanderbilt surgery clinic between 2006 and 2011.
Pre-assignment details
Patients were excluded after enrollment if they met exclusion criteria, if surgery was canceled or if the patient changed his mind.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Patients are randomized to placebo prior to surgery | 28 |
| Ramipril (ACEI) Ramipril 2.5mg day 1 and 2 and then 5mg/d thereafter | 24 |
| Candesartan (ARB) Patients are randomized to Candesartan 16mg/d (ARB) prior to surgery. | 22 |
| Total | 74 |
Baseline characteristics
| Characteristic | Ramipril (ACEI) | Candesartan (ARB) | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 13 Participants | 14 Participants | 15 Participants | 42 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 8 Participants | 13 Participants | 32 Participants |
| Age Continuous | 64.38 years STANDARD_DEVIATION 10.35 | 67.05 years STANDARD_DEVIATION 8.14 | 66.14 years STANDARD_DEVIATION 11.24 | 65.84 years STANDARD_DEVIATION 10.03 |
| Region of Enrollment United States | 24 participants | 22 participants | 28 participants | 74 participants |
| Sex: Female, Male Female | 12 Participants | 12 Participants | 19 Participants | 43 Participants |
| Sex: Female, Male Male | 12 Participants | 10 Participants | 9 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 28 | 10 / 24 | 12 / 22 |
| serious Total, serious adverse events | 2 / 28 | 1 / 24 | 2 / 22 |
Outcome results
Primary
Interleukin-10 (IL-10) Response
To compare the effects of AT1 receptor antagonism or ACE inhibition versus placebo on the inflammatory response to CPB as measured by the IL-10 response
Time frame: From the start of surgery until postoperative day 2
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Interleukin-10 (IL-10) Response | Pre CPB | 4.45 pg/mL | Standard Error 0.47 |
| Placebo | Interleukin-10 (IL-10) Response | Post surgery | 461.90 pg/mL | Standard Error 84.64 |
| Placebo | Interleukin-10 (IL-10) Response | Postoperative day 1 | 30.70 pg/mL | Standard Error 6.91 |
| Placebo | Interleukin-10 (IL-10) Response | Postoperative day 2 | 16.74 pg/mL | Standard Error 3.09 |
| Ramipril (ACEI) | Interleukin-10 (IL-10) Response | Postoperative day 2 | 14.59 pg/mL | Standard Error 3.16 |
| Ramipril (ACEI) | Interleukin-10 (IL-10) Response | Pre CPB | 5.36 pg/mL | Standard Error 0.8 |
| Ramipril (ACEI) | Interleukin-10 (IL-10) Response | Postoperative day 1 | 26.89 pg/mL | Standard Error 4.64 |
| Ramipril (ACEI) | Interleukin-10 (IL-10) Response | Post surgery | 815.74 pg/mL | Standard Error 273.29 |
| Candesartan (ARB) | Interleukin-10 (IL-10) Response | Postoperative day 2 | 14.26 pg/mL | Standard Error 2.13 |
| Candesartan (ARB) | Interleukin-10 (IL-10) Response | Post surgery | 749.56 pg/mL | Standard Error 199.31 |
| Candesartan (ARB) | Interleukin-10 (IL-10) Response | Postoperative day 1 | 22.55 pg/mL | Standard Error 3.04 |
| Candesartan (ARB) | Interleukin-10 (IL-10) Response | Pre CPB | 4.21 pg/mL | Standard Error 0.61 |
p-value: 0.46Mixed Models Analysis
Primary
Interleukin-6 (IL-6) Response
To compare the effects of AT1 receptor antagonism or ACE inhibition versus placebo on the inflammatory response to CPB as measured by IL-6
Time frame: From the start of surgery until postoperative day 2
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Interleukin-6 (IL-6) Response | Pre CPB | 6.29 pg/mL | Standard Error 1.25 |
| Placebo | Interleukin-6 (IL-6) Response | Post surgery | 116.04 pg/mL | Standard Error 28.19 |
| Placebo | Interleukin-6 (IL-6) Response | Postoperative day 1 | 224.96 pg/mL | Standard Error 63.26 |
| Placebo | Interleukin-6 (IL-6) Response | Postoperative day 2 | 166.96 pg/mL | Standard Error 28.79 |
| Ramipril (ACEI) | Interleukin-6 (IL-6) Response | Postoperative day 2 | 144.67 pg/mL | Standard Error 46.41 |
| Ramipril (ACEI) | Interleukin-6 (IL-6) Response | Pre CPB | 9.33 pg/mL | Standard Error 3.25 |
| Ramipril (ACEI) | Interleukin-6 (IL-6) Response | Postoperative day 1 | 172.65 pg/mL | Standard Error 68.93 |
| Ramipril (ACEI) | Interleukin-6 (IL-6) Response | Post surgery | 167.51 pg/mL | Standard Error 35.64 |
| Candesartan (ARB) | Interleukin-6 (IL-6) Response | Postoperative day 2 | 243.72 pg/mL | Standard Error 117.65 |
| Candesartan (ARB) | Interleukin-6 (IL-6) Response | Post surgery | 144.76 pg/mL | Standard Error 29.52 |
| Candesartan (ARB) | Interleukin-6 (IL-6) Response | Postoperative day 1 | 218.16 pg/mL | Standard Error 68.47 |
| Candesartan (ARB) | Interleukin-6 (IL-6) Response | Pre CPB | 6.44 pg/mL | Standard Error 1.2 |
p-value: 0.69Mixed Models Analysis
Primary
Interleukin-8 (IL-8) Response
To compare the effects of AT1 receptor antagonism or ACE inhibition versus placebo on the inflammatory response to CPB as measured by IL-8
Time frame: From the start of surgery until postoperative day 2
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Interleukin-8 (IL-8) Response | Pre CPB | 16.18 pg/mL | Standard Error 3.77 |
| Placebo | Interleukin-8 (IL-8) Response | Post surgery | 66.44 pg/mL | Standard Error 15.06 |
| Placebo | Interleukin-8 (IL-8) Response | Postoperative day 1 | 46.18 pg/mL | Standard Error 8.9 |
| Placebo | Interleukin-8 (IL-8) Response | Postoperative day 2 | 34.39 pg/mL | Standard Error 5.55 |
| Ramipril (ACEI) | Interleukin-8 (IL-8) Response | Postoperative day 2 | 28.06 pg/mL | Standard Error 5.28 |
| Ramipril (ACEI) | Interleukin-8 (IL-8) Response | Pre CPB | 11.86 pg/mL | Standard Error 1.42 |
| Ramipril (ACEI) | Interleukin-8 (IL-8) Response | Postoperative day 1 | 37.39 pg/mL | Standard Error 6.04 |
| Ramipril (ACEI) | Interleukin-8 (IL-8) Response | Post surgery | 80.07 pg/mL | Standard Error 20.28 |
| Candesartan (ARB) | Interleukin-8 (IL-8) Response | Postoperative day 2 | 37.77 pg/mL | Standard Error 5.43 |
| Candesartan (ARB) | Interleukin-8 (IL-8) Response | Post surgery | 76.76 pg/mL | Standard Error 18.9 |
| Candesartan (ARB) | Interleukin-8 (IL-8) Response | Postoperative day 1 | 37.11 pg/mL | Standard Error 4.44 |
| Candesartan (ARB) | Interleukin-8 (IL-8) Response | Pre CPB | 13.38 pg/mL | Standard Error 2.19 |
p-value: 0.97Mixed Models Analysis
Primary
Plasminogen Activator Inhibitor-1 (PAI-1) Response
To compare the effects of AT1 receptor antagonism or ACE inhibition versus placebo on the fibrinolytic responses to CPB as measured by PAI-1 response
Time frame: From the start of surgery until postoperative day 2
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasminogen Activator Inhibitor-1 (PAI-1) Response | Postoperative day 1 | 31.83 ng/mL | Standard Error 4.47 |
| Placebo | Plasminogen Activator Inhibitor-1 (PAI-1) Response | Post surgery | 39.69 ng/mL | Standard Error 3.78 |
| Placebo | Plasminogen Activator Inhibitor-1 (PAI-1) Response | Pre CPB | 15.14 ng/mL | Standard Error 1.42 |
| Placebo | Plasminogen Activator Inhibitor-1 (PAI-1) Response | 60min of CPB | 20.43 ng/mL | Standard Error 1.63 |
| Placebo | Plasminogen Activator Inhibitor-1 (PAI-1) Response | Postoperative day 2 | 21.59 ng/mL | Standard Error 3.77 |
| Ramipril (ACEI) | Plasminogen Activator Inhibitor-1 (PAI-1) Response | Post surgery | 41.62 ng/mL | Standard Error 5.89 |
| Ramipril (ACEI) | Plasminogen Activator Inhibitor-1 (PAI-1) Response | Pre CPB | 16.25 ng/mL | Standard Error 2.7 |
| Ramipril (ACEI) | Plasminogen Activator Inhibitor-1 (PAI-1) Response | 60min of CPB | 19.41 ng/mL | Standard Error 1.98 |
| Ramipril (ACEI) | Plasminogen Activator Inhibitor-1 (PAI-1) Response | Postoperative day 1 | 26.27 ng/mL | Standard Error 4.5 |
| Ramipril (ACEI) | Plasminogen Activator Inhibitor-1 (PAI-1) Response | Postoperative day 2 | 17.33 ng/mL | Standard Error 3.77 |
| Candesartan (ARB) | Plasminogen Activator Inhibitor-1 (PAI-1) Response | Postoperative day 2 | 13.4 ng/mL | Standard Error 1.55 |
| Candesartan (ARB) | Plasminogen Activator Inhibitor-1 (PAI-1) Response | Postoperative day 1 | 21.70 ng/mL | Standard Error 2.75 |
| Candesartan (ARB) | Plasminogen Activator Inhibitor-1 (PAI-1) Response | Pre CPB | 18.28 ng/mL | Standard Error 2.91 |
| Candesartan (ARB) | Plasminogen Activator Inhibitor-1 (PAI-1) Response | Post surgery | 49.10 ng/mL | Standard Error 7.32 |
| Candesartan (ARB) | Plasminogen Activator Inhibitor-1 (PAI-1) Response | 60min of CPB | 24.19 ng/mL | Standard Error 3.84 |
p-value: 0.84Mixed Models Analysis
Primary
Tissue-type Plasminogen Activator (t-PA) Antigen Response
To compare the effects of angiotensin II type I (AT1) receptor antagonism or angiotensin-converting enzyme (ACE) inhibition versus placebo on the fibrinolytic responses to cardiopulmonary bypass (CPB) as measured by t-PA antigen response
Time frame: From the start of surgery until postoperative day 2
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Tissue-type Plasminogen Activator (t-PA) Antigen Response | Postoperative day 1 | 20.25 ng/mL | Standard Error 2.03 |
| Placebo | Tissue-type Plasminogen Activator (t-PA) Antigen Response | Post surgery | 34.56 ng/mL | Standard Error 3.35 |
| Placebo | Tissue-type Plasminogen Activator (t-PA) Antigen Response | Pre CPB | 14.36 ng/mL | Standard Error 1.45 |
| Placebo | Tissue-type Plasminogen Activator (t-PA) Antigen Response | 60min of CPB | 27.65 ng/mL | Standard Error 3.39 |
| Placebo | Tissue-type Plasminogen Activator (t-PA) Antigen Response | Postoperative day 2 | 16.56 ng/mL | Standard Error 1.87 |
| Ramipril (ACEI) | Tissue-type Plasminogen Activator (t-PA) Antigen Response | Post surgery | 41.11 ng/mL | Standard Error 3.37 |
| Ramipril (ACEI) | Tissue-type Plasminogen Activator (t-PA) Antigen Response | Pre CPB | 14.05 ng/mL | Standard Error 1.86 |
| Ramipril (ACEI) | Tissue-type Plasminogen Activator (t-PA) Antigen Response | 60min of CPB | 36.67 ng/mL | Standard Error 7.26 |
| Ramipril (ACEI) | Tissue-type Plasminogen Activator (t-PA) Antigen Response | Postoperative day 1 | 17.10 ng/mL | Standard Error 1.38 |
| Ramipril (ACEI) | Tissue-type Plasminogen Activator (t-PA) Antigen Response | Postoperative day 2 | 12.49 ng/mL | Standard Error 0.93 |
| Candesartan (ARB) | Tissue-type Plasminogen Activator (t-PA) Antigen Response | Postoperative day 2 | 12.89 ng/mL | Standard Error 1.01 |
| Candesartan (ARB) | Tissue-type Plasminogen Activator (t-PA) Antigen Response | Postoperative day 1 | 15.75 ng/mL | Standard Error 1.32 |
| Candesartan (ARB) | Tissue-type Plasminogen Activator (t-PA) Antigen Response | Pre CPB | 11.97 ng/mL | Standard Error 1.03 |
| Candesartan (ARB) | Tissue-type Plasminogen Activator (t-PA) Antigen Response | Post surgery | 31.47 ng/mL | Standard Error 2.61 |
| Candesartan (ARB) | Tissue-type Plasminogen Activator (t-PA) Antigen Response | 60min of CPB | 24.89 ng/mL | Standard Error 2.96 |
p-value: 0.28Mixed Models Analysis
Secondary
Acute Kidney Injury
Acute kidney injury (AKI) was defined according to Acute Kidney Injury Network (AKIN) criteria,specifically any increase in subject serum creatinine concentration of 50% or 0.3 mg/dL (26.5 umol/L) within 72 hours of surgery.
Time frame: From the start of surgery until postoperative day 3
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Acute Kidney Injury | 28.6 percentage of patients |
| Ramipril (ACEI) | Acute Kidney Injury | 23.8 percentage of patients |
| Candesartan (ARB) | Acute Kidney Injury | 36.4 percentage of patients |
p-value: 0.51Chi-squared
Secondary
Blood Loss
Blood loss over 24 hours as measured by chest tube output
Time frame: First 24 hours after arrival in the intensive care unit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Blood Loss | 437 mL | Standard Error 35 |
| Ramipril (ACEI) | Blood Loss | 470 mL | Standard Error 59 |
| Candesartan (ARB) | Blood Loss | 511 mL | Standard Error 119 |
p-value: 0.67Kruskal-Wallis
Secondary
Blood Product Transfusion Requirement
Percentage of patients that received blood product transfusion
Time frame: From the start of surgery until discharge from hospital
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Blood Product Transfusion Requirement | Cryoprecipitate | 7.1 percentage of patients |
| Placebo | Blood Product Transfusion Requirement | Packed red blood cells | 67.9 percentage of patients |
| Placebo | Blood Product Transfusion Requirement | Plasma | 60.7 percentage of patients |
| Placebo | Blood Product Transfusion Requirement | Platelets | 46.4 percentage of patients |
| Ramipril (ACEI) | Blood Product Transfusion Requirement | Platelets | 29.2 percentage of patients |
| Ramipril (ACEI) | Blood Product Transfusion Requirement | Cryoprecipitate | 4.2 percentage of patients |
| Ramipril (ACEI) | Blood Product Transfusion Requirement | Plasma | 29.2 percentage of patients |
| Ramipril (ACEI) | Blood Product Transfusion Requirement | Packed red blood cells | 62.5 percentage of patients |
| Candesartan (ARB) | Blood Product Transfusion Requirement | Platelets | 22.7 percentage of patients |
| Candesartan (ARB) | Blood Product Transfusion Requirement | Packed red blood cells | 2.7 percentage of patients |
| Candesartan (ARB) | Blood Product Transfusion Requirement | Plasma | 31.8 percentage of patients |
| Candesartan (ARB) | Blood Product Transfusion Requirement | Cryoprecipitate | 4.5 percentage of patients |
p-value: 0.04Chi-squared
Secondary
Length of Hospital Stay
Time frame: From the start of surgery until discharge from hospital
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Length of Hospital Stay | 7.7 days | Standard Error 0.5 |
| Ramipril (ACEI) | Length of Hospital Stay | 6.3 days | Standard Error 0.6 |
| Candesartan (ARB) | Length of Hospital Stay | 8.1 days | Standard Error 1 |
p-value: 0.04Kruskal-Wallis
Secondary
New Onset Atrial Fibrillation
New onset atrial fibrillation based on electrocardiogram (ECG) rhythm strips with a duration longer than 10 seconds
Time frame: From arrival in intensive care unit until discharge from hospital
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | New Onset Atrial Fibrillation | 17.9 percentage of patients |
| Ramipril (ACEI) | New Onset Atrial Fibrillation | 16.7 percentage of patients |
| Candesartan (ARB) | New Onset Atrial Fibrillation | 27.3 percentage of patients |
p-value: 0.62Chi-squared
Secondary
Re-exploration for Bleeding
The percentage of patients that were taken back to the operating room for re-exploration because of bleeding
Time frame: From arrival in intensive care unit until discharge from hospital
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Re-exploration for Bleeding | 3.6 percentage of patients |
| Ramipril (ACEI) | Re-exploration for Bleeding | 8.3 percentage of patients |
| Candesartan (ARB) | Re-exploration for Bleeding | 4.5 percentage of patients |
p-value: 0.73Chi-squared
Secondary
Stroke
New onset neurological deficit with a duration of longer than 24 hours
Time frame: From arrival in intensive care unit until discharge from hospital
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Stroke | 7.1 percentage of patients |
| Ramipril (ACEI) | Stroke | 4.2 percentage of patients |
| Candesartan (ARB) | Stroke | 4.5 percentage of patients |
p-value: 0.87Chi-squared
Secondary
Vasopressor Drug Use
Time frame: From the end of cardiopulmonary bypass until arrival in intensive care unit
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Vasopressor Drug Use | Dobutamine | 35.7 percentage of patients |
| Placebo | Vasopressor Drug Use | Mlrinone | 25.0 percentage of patients |
| Placebo | Vasopressor Drug Use | Norepinephrine | 85.7 percentage of patients |
| Placebo | Vasopressor Drug Use | Epinephrine | 7.1 percentage of patients |
| Ramipril (ACEI) | Vasopressor Drug Use | Epinephrine | 4.3 percentage of patients |
| Ramipril (ACEI) | Vasopressor Drug Use | Dobutamine | 29.2 percentage of patients |
| Ramipril (ACEI) | Vasopressor Drug Use | Norepinephrine | 79.2 percentage of patients |
| Ramipril (ACEI) | Vasopressor Drug Use | Mlrinone | 25.0 percentage of patients |
| Candesartan (ARB) | Vasopressor Drug Use | Epinephrine | 13.6 percentage of patients |
| Candesartan (ARB) | Vasopressor Drug Use | Mlrinone | 22.7 percentage of patients |
| Candesartan (ARB) | Vasopressor Drug Use | Norepinephrine | 95.5 percentage of patients |
| Candesartan (ARB) | Vasopressor Drug Use | Dobutamine | 27.3 percentage of patients |
p-value: 0.27Chi-squared