Statins for the Primary Prevention of Heart Failure in Patients Receiving Anthracycline Pilot Study

Inclusion Criteria:

1. Patients with one of the following malignancies requiring anthracycline based chemotherapy with a curative intent: breast cancer; aggressive lymphomas; leukemia (acute myelogenous leukemia, acute lymphoblastic leukemia, mixed phenotype acute leukemia) or; sarcoma
2. Patients with high cardiovascular risk defined as:

   I. ≥60 years and at least one of the following:

   i. Compromised cardiac function based on baseline LVEF \<55% measured by echocardiography or MUGA or moderate left sided valvular heart disease (moderate mitral or aortic regurgitation or stenosis) ii. Planned cumulative doxorubicin dose equivalent 200mg/m² or more iii. Prior anthracycline therapy at any cumulative dose or prior chest/mediastinal radiation therapy iv. Any one of hypertension, smoking, obesity (BMI≥30), history of cardiomyopathy or heart failure but with recovered LVEF to ≥ 50%

   OR

   II. Age \<60 years with one of the following:

   i. and at least 2 of the risk factors listed above (I i-iv) ii. type 2 diabetes with age \<40 iii. type 1 diabetes duration \<15 years

   OR

   III. High anthracycline dose defined as ≥250mg/m² of doxorubicin, ≥600mg/m² epirubicin, or other isoequivalent dose
3. Living within geographic area conducive to repeated clinical and imaging follow-up

Exclusion Criteria:

1. Participating in another clinical research study where randomization would be unacceptable
2. Previous history of statin intolerance
3. Already on statin therapy or known statin indicated condition:

   I. atherosclerosis i. myocardial infarction ii. acute coronary syndrome iii. stable angina iv. documented coronary disease by angiography (\>10% stenosis) v. stroke vi. TIA vii. documented carotid disease viii. peripheral arterial disease ix. claudication and/or ABI \<0.9

   II. abdominal aortic aneurysm (\>3.0cm or previous aneurysm surgery)

   III. chronic kidney disease (\>3 months duration and ACR \>3.0mg/mmol or eGFR \<60mL/min/1.73m²)
4. CK level \>3x upper limit of normal
5. Evidence of hepatic dysfunction (ALT level \>2x upper limit of normal)
6. On a drug that is a strong inhibitor of cytochrome P450 3A4 or may require such treatment during the treatment period (because atorvastatin is metabolized by this pathway)
7. Significant valvular heart disease defined as severe stenotic or regurgitant lesions of any of the cardiac valves
8. Life expectancy less than 12 months
9. Contraindication to cardiac MRI (e.g. implanted pacemakers, ICDs, other implanted ferromagnetic objects unsafe for cardiac MRI or will result in significant artifact, eGFR \<30)
10. Creatinine \>177umol/L
11. Known history of uncontrolled hypothyroidism (TSH level \>1.5x upper limit of normal)