1

Therapies Not IndicatedTherapies Not Indicated

Andrew P. DeFilippis, Ty J. Gluckman, James Mudd, Catherine Campbell, Gregg Fonarow

& Roger S. Blumenthal

2

0 6 12 18 24 30 36 42 48

Months

70

75

80

85

90

95

100% Surviving (free of MI, stroke, death)

Vitamin E

Placebo

GISSI-Prevenzione Investigators. Lancet 1999;354:447-55

RR 0.95, P=0.293

Vitamin E: Secondary PreventionVitamin E: Secondary PreventionGruppo Italiano per lo Studio della Sopravvivenza nell’Infarto

miocardico (GISSI)-Prevenzione TrialP

rimar

y E

nd P

oint

(%

)*

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

30

40

50

60

Year 1 Year 2 Year 3 Year 4 + 5

Num

ber

of C

V E

vent

s*

PlaceboHRT

Year RR

123

4+5

1.521.000.870.67

**P=0.009 for trend-time analysis

Hulley S et al. JAMA 1998;280:605-613

HRT: Secondary PreventionHRT: 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

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

Folic Acid and B-Vitamins: Secondary PreventionFolic Acid and B-Vitamins: Secondary Prevention

Heart Outcomes Prevention Evaluation (HOPE)-2 Study5,522 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

5Bonna KH et al. NEJM 2006;354:1578-1588

Folic Acid and B-Vitamins: Secondary PreventionFolic 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

Folic Acid and B-Vitamins: Secondary PreventionFolic 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

• 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 ConclusionsPrevention Guidelines Conclusions