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

2. 2 GISSI-Prevenzione Investigators. Lancet 1999;354:447-55 RR 0.95, P=0.293 Vitamin E: Secondary Prevention Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico (GISSI)-Prevenzione Trial Primary End Point (%)* Months 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 *Includes freedom from death, nonfatal MI, and stroke MI=Myocardial infarction

3. 3 30 40 50 60 Year 1Year 2Year 3Year 4 + 5 Number of CV Events* Placebo HRT YearRR 1 2 3 4+5 1.52 1.00 0.87 0.67 **P=0.009 for trend-time analysis Hulley S et al. JAMA 1998;280:605-613 HRT: Secondary Prevention ** Heart and Estrogen/progestin Replacement Study (HERS) *Includes coronary revascularization, unstable angina, congestive heart failure, resuscitated cardiac arrest, transient ischemic attack or stroke, peripheral arterial disease, and all-cause mortality 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 CAD=Coronary artery disease, CV=Cardiovascular, HRT=Hormone replacement therapy

4. 4 HOPE 2 Investigators. NEJM 2006;354:1567-1577 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

5. 5 Bonna KH et al. NEJM 2006;354:1578-1588 Folic Acid and B-Vitamins: Secondary Prevention 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 Treatment Arms *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 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

6. 6 Folic Acid and B-Vitamins: Secondary Prevention Toole JF et al. JAMA. 2004;291:565-575 Vitamin Intervention for Stroke Prevention (VISP) Trial 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 Treatment Arms *Primary endpoint is a composite of cerebral infarction **Secondary endpoint includes coronary heart disease events Coronary Events 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

7. 7 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. Prevention Guidelines Conclusions