Moderate Alcohol and Cardiovascular Health Trial

Inclusion Criteria:

• Age ≥50 years at screening

• Postmenopausal, defined as 12 consecutive months without menstruation

• Not alcohol naïve, defined by having consumed at least one drink of alcohol in thepast five years

• High risk for the occurrence of a new cardiovascular disease event, defined as havingany one of the following:

1. American Heart Association (AHA)/American College of Cardiology (ACC) Risk Score ≥15% within the past 24 months (among those without clinical or subclinicalcardiovascular disease [CVD])

2. Clinical CVD (more than 6 months prior to randomization), defined by:

3. Previous myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), carotid endarterectomy (CE),carotid stenting;

4. Peripheral artery disease (PAD) with revascularization;

5. Acute coronary syndrome with or without resting electrocardiogram (ECG)change, ECG changes on a graded exercise test (GXT), or positive cardiacimaging study;

6. Prior stroke documented on brain imaging or with a persistent deficit.

7. Subclinical CVD, confirmed in available medical records:

8. At least a 50% diameter stenosis of a coronary, carotid, or lower extremityartery;

9. Coronary artery calcium score ≥400 Agatston units;

10. Ankle brachial index (ABI) ≤0.90;

11. Left ventricular hypertrophy (LVH) by ECG (based on computer reading),echocardiogram report, or other cardiac imaging procedure report;

12. Abdominal aortic aneurysm (AAA) ≥5 cm with or without repair.

Exclusion Criteria:

• High alcohol consumption, defined by any one of the following:

1. Alcohol Use Disorders Identification Test (AUDIT) score >5 at screening

2. Drinking, on average, >7 alcoholic beverages/week during the past 6 months

3. Drinking 6 or more alcoholic beverages on one occasion during the past 6 months

• Yale-Brown Obsessive Compulsive Scale-heavy drinking (Y-BOCS-hd) total score of ≥6 onquestions 7, 8, and 10

• Cardiovascular disease event (MI, revascularization procedure, or stroke) within the 6months prior to randomization

• AHA Class III-IV heart failure

• History of alcohol or substance abuse (medical record confirmed or self-reportedhistory)

• Other intolerance or allergy to alcohol

• Dual antiplatelet therapy

• History of gastric bypass surgery

• Any serious chronic liver disease (e.g., active hepatitis B and C infections) or livertests (aspartate aminotransferase [AST], alanine aminotransferase [ALT] andgamma-glutamyl transpeptidase [GGT]) >2 times the upper limit of the normal rangeusing local standards

• Personal history of any colon or liver cancer

• Any other cancer with a life expectancy of less than 3 years

• Diagnosed with breast cancer that required either surgery or removal of breast tissueor chemotherapy

• Mother or sister ever diagnosed with breast cancer that required either surgery orremoval of breast tissue or chemotherapy

• Estimated glomerular filtration rate (eGFR) <30 ml/min /1.73m2 or end-stage renaldisease (ESRD)

• Ongoing use of any medication for which alcohol consumption is contraindicated

• A Patient Health Questionnaire (PHQ-9) ≥15 at screening

• History of any organ transplant

• Unintentional weight loss >10% in last 6 months

• Currently participating in another clinical trial (intervention trial) with CVDoutcomes. Note: Participant must wait until the completion of his/her activities orthe completion of the other trial before being screened for MACH15. Local restrictionsfor entry by participants can be more conservative if mandated.

• Not willing or able to provide a name and contact information for at least oneadditional contact person other than self

• Investigator discretion regarding appropriateness of participation or concern aboutintervention adherence, including:

1. moderate - severe psychiatric illness

2. behavioral concerns regarding likelihood of low adherence to trial protocol

3. a medical condition likely to limit survival to less than 3 years

4. advanced chronic disease, such as dementia, that requires 24-hour care

• Not willing or able to provide a signed and dated informed consent form

• Not willing or able to comply with all trial procedures.