Therapies Not Indicated Andrew P. DeFilippis, Ty J. Gluckman, James Mudd, Catherine Campbell, Gregg Fonarow & Roger

1. Therapies Not Indicated Andrew P. DeFilippis, Ty J. Gluckman, James Mudd, Catherine Campbell, Gregg Fonarow & Roger S. Blumenthal

2. Vitamin E: Secondary Prevention Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico (GISSI)-Prevenzione Trial 11,324 patients with a recent MI randomized to Vitamin E (300 mg) or placebo for 3.5 years Vitamin E provides no CV benefit following a MI Primary End Point (%)* RR 0.95, P=0.293 Months *Includes freedom from death, nonfatal MI, and stroke MI=Myocardial infarction GISSI-Prevenzione Investigators. Lancet 1999;354:447-55

3. HRT: Secondary Prevention Heart and Estrogen/progestin Replacement Study (HERS) 2,763 postmenopausal women with known CAD randomized to conjugated equine estrogen (0.625 mg) and medroxyprogesterone acetate (2.5 mg) or placebo for 4.1 years HRT provides no CV benefit in women with known CAD 60 Placebo Year RR HRT 50 1 2 3 4+5 1.52 1.00 0.87 0.67 Number of CV Events* ** 40 30 Year 1 Year 2 Year 3 Year 4 + 5 *Includes coronary revascularization, unstable angina, congestive heart failure, resuscitated cardiac arrest, transient ischemic attack or stroke, peripheral arterial disease, and all-cause mortality **P=0.009 for trend-time analysis CAD=Coronary artery disease, CV=Cardiovascular, HRT=Hormone replacement therapy Hulley S et al. JAMA 1998;280:605-613

4. Folic Acid and B-Vitamins: Secondary Prevention Heart Outcomes Prevention Evaluation (HOPE)-2 Study 5,522 patients with vascular disease or DM randomized to folic acid (2.5 mg), vitamin B6 (50 mg), and vitamin B12 (1 mg) or placebo for 5 years Folic acid and B-vitamin supplementation provides no benefit DM=Diabetes mellitus HOPE 2 Investigators. NEJM 2006;354:1567-1577

5. Folic Acid and B-Vitamins: Secondary Prevention 3,749 patients with a recent myocardial infarction randomized in a 2 x 2 factorial design to B-vitamins + folic acid or placebo for 40 months Folic acid and B-vitamin supplementation provides no benefit * Treatment Arms • Vitamin B6 (40 mg), Vitamin B12 (0.4 mg), and Folic acid (0.8 mg)† • Vitamin B12 (0.4 mg) and Folic acid (0.8 mg)‡ • Vitamin B6 (40 mg)^ • Placebo *Includes recurrent myocardial infarction, stroke, and sudden death attributed to coronary artery disease †HR=1.22, P=0.05 compared to placebo ‡HR=1.08, P=0.31 compared to placebo ^HR=1.14, P=0.09 compared to placebo Bonna KH et al. NEJM 2006;354:1578-1588

6. Folic Acid and B-Vitamins: Secondary Prevention Vitamin Intervention for Stroke Prevention (VISP) Trial 3,680 patients with previous stroke randomized to high-dose vitamins or low-dose vitamins for 2 years* There is no cardiovascular benefit from combination vitamin therapy to lower homocysteine levels Coronary Events Treatment Arms • High-dose vitamins • 25 mg pyridoxine, 0.4 mg cobalamin, 2.5 mg of folic acid • Low-dose vitamins • 0.2 mg pyridoxine, 0.006 mg cobalamin, and 0.02 mg folic acid *Primary endpoint is a composite of cerebral infarction **Secondary endpoint includes coronary heart disease events Toole JF et al. JAMA. 2004;291:565-575

7. Prevention Guidelines Conclusions • Aggressive comprehensive risk factor management reduces CV events, the need for interventional procedures, and improves quality of life. • Every effort should be made to ensure that patients are treated with evidence-based, guideline recommended, life-prolonging therapies in the absence of contraindications or intolerance.