ACE Inhibitors and Beta Blockers for the Protection of the Heart among Patients Receiving Intensive Chemotherapy for Acute Myeloid Leukemia

Inclusion Criteria

• Signed informed consent obtained prior to conducting any study-specific screening procedures.
• Willing and able to understand the nature of this study and to comply with both the study as well as follow-up procedures for the duration of the study.
• Age >= 18 years old with newly-diagnosed acute myeloid leukemia (AML).
• Eastern Cooperative Oncology Group (ECOG) performance status must be =< 2.
• Planning to receive initial induction therapy containing an anthracycline for AML. Participants may have started initial induction therapy if anthracycline has not yet been administered
• Total bilirubin =< 1.5 x upper limit of normal (ULN) or < 3 x ULN for patients with Gilbert’s Syndrome
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
• Creatinine clearance > 60 mL/min
• Ability to take oral medication and a willingness to adhere to the beta blocker and lisinopril regimen.
• Echocardiogram demonstrating an ejection fraction ≥ 50% prior to the initiation of induction chemotherapy. Note: if a range, rather than a single percentage, is given as the result, the midpoint of the range should be used.
• For females of reproductive potential and males: Agree to abstain from sexual activity or use reliable contraception while undergoing treatment with chemotherapy and/or angiotensin-converting-enzyme (ACE) inhibitors due to the risk of teratogenicity to the fetus

Exclusion Criteria

• Ongoing use of any beta blocker, ACEi, or angiotensin II receptor agonist (ARB) at the time of pre-enrollment screening.
• Uncontrolled, intercurrent illnesses including but not limited to symptomatic unstable angina pectoris, cardiac arrhythmias not well controlled with medications, myocardial infarction in the 6 months preceding registration or psychiatric illness/social situations that would limit compliance with study requirements as determined by the study personnel, all at the discretion of the treating oncologist.
• Patient receiving concurrent investigational agents, or those who have received an investigational agent within one week of registration. * Exception – Participants may receive concurrent investigational agents, or have done so within one week of registration if: ** The side effects of the drug are well studied and well known AND ** The drug is not known to be cardioprotective or cardiotoxic
• Females who are pregnant or lactating.
• Life-threatening illnesses other than AML, uncontrolled medical conditions or organ system dysfunction that, in the investigator’s opinion, could compromise the patient’s safety or study outcomes.
• Active, untreated and/or severe infections as determined by the treating oncologist.
• History of hematopoietic stem cell transplant (HSCT) with active graft vs host disease, immunosuppression other than low-dose prednisone (=< 5 mg) or calcineurin inhibitors within the four weeks preceding registration.
• Moderate or severe mitral or aortic valve disease, as determined by echocardiography.
• Congestive heart failure as clinically diagnosed by treating oncologist at the time of presentation for induction chemotherapy, or documented diagnosed by a previous physician.
• History of (repaired or unrepaired) congenital heart disease that precludes recommendation for or administration of additional anthracyclines
• Significant liver disease, including cirrhosis or history of transplant or hepatorenal syndrome).
• Bradycardia (defined as baseline resting heart rate =< 60 beats per minute) or third degree atrioventricular heart block at presentation for induction chemotherapy.
• Baseline resting systolic blood pressure < 95mmHg at presentation for induction chemotherapy.
• Documented allergy to beta blockers or ACE inhibitors.