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 the
past five years

- High risk for the occurrence of a new cardiovascular disease event, defined as having
any 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 subclinical
cardiovascular disease [CVD])

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

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

2. Peripheral artery disease (PAD) with revascularization;

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

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

3. Subclinical CVD, confirmed in available medical records:

1. At least a 50% diameter stenosis of a coronary, carotid, or lower extremity
artery;

2. Coronary artery calcium score ≥400 Agatston units;

3. Ankle brachial index (ABI) ≤0.90;

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

5. 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 on
questions 7, 8, and 10

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

- AHA Class III-IV heart failure

- History of alcohol or substance abuse (medical record confirmed or self-reported
history)

- 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 liver
tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT] and
gamma-glutamyl transpeptidase [GGT]) >2 times the upper limit of the normal range
using 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 tissue
or chemotherapy

- Mother or sister ever diagnosed with breast cancer that required either surgery or
removal of breast tissue or chemotherapy

- Estimated glomerular filtration rate (eGFR) <30 ml/min /1.73m2 or end-stage renal
disease (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 CVD
outcomes. Note: Participant must wait until the completion of his/her activities or
the completion of the other trial before being screened for MACH15. Local restrictions
for entry by participants can be more conservative if mandated.

- Not willing or able to provide a name and contact information for at least one
additional contact person other than self

- Investigator discretion regarding appropriateness of participation or concern about
intervention 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.