Cardioprotection in AML

Participants will know which group they are assigned to, and if someone in the group not receiving the preventive drugs needs these drugs for their clinical care, they will be able to receive them.

Participants in both groups will receive the standard clinical care medicines and lab tests for their AML. Everyone will have electrocardiograms (also called ECGs or EKGs) and echocardiograms before and at multiple timepoints during the study. They will also have a special blood test to see their levels of troponin, a protein that helps with muscle contractions in your heart. All participants will complete questionnaires at a few timepoints during the study to measure their quality of life. Participants in the preventive beta blocker and ACEi group will take these drugs when they're in the hospital and at home, keeping a diary of when they take it when they're at home.

The hypothesis of the study is that taking a beta blocker and ACEi during initial therapy for AML and through about 90 days after they last take an anthracycline will prevent the development of this heart problem.

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)
• 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.
• Adequate organ function as evidenced by the following laboratory findings:

• 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
• For females of reproductive potential and males: Agree to abstain from sexual activity or use reliable contraception while undergoing treatment with chemotherapy and/or 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 (≤ 5mg) or calcineurin inhibitors within the four weeks preceding registration

8 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.