AA-2-1

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  • 06-JUL-00 2:30PM
  • 06-JUL-00 2:30PM
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  • 30-JUN-00 3:30 PM
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  • AA-2-1

    1. 1. Jerome D. Cohen, MD, FACC, FACP Professor of Internal Medicine / Cardiology Director, Preventive Cardiology Programs St. Louis University Health Sciences Center 7asdf
    2. 2. Background and Rationale for OTC Pravachol
    3. 3. Risk is Graded and Continuous Over Broad Range MRFIT (n=361,662) Neaton, et al. Intern. Med. 1992; 152; 1490-500 16 14 12 10 8 6 4 2 100 150 200 250 300 CHD Mortality Rate per 1,000 Plasma Cholesterol (mg/dl) 4.0 3.0 2.0 1.0 100 150 200 250 300 Risk Ratio Plasma Cholesterol (mg/dl) (0.7) (1.0) (2.0) (4.0)
    4. 4. Significant Proportion of Coronary Events Occur in Individuals with TC 200-240 mg/dl (MRFIT) Coronary Death as Fraction Plasma Cholesterol (mg/dl) Distribution of Cholesterol Levels Adapted from Martin, et al., Lancet, 1994;2:933-936. 150 200 250 300
    5. 5. NCEP Guidelines  CHD Risk Factors Other Than LDL-C <ul><ul><li>Positive risk factors </li></ul></ul><ul><ul><ul><li>Age </li></ul></ul></ul><ul><ul><ul><ul><li>Male  45 </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Female  55 or premature menopause without estrogen replacement therapy </li></ul></ul></ul></ul><ul><ul><ul><li>Family history of premature CHD </li></ul></ul></ul><ul><ul><ul><li>Current cigarette smoking </li></ul></ul></ul><ul><ul><ul><li>Hypertension </li></ul></ul></ul><ul><ul><ul><li>Diabetes mellitus </li></ul></ul></ul><ul><ul><ul><li>Low HDL-C (  35 mg/dl) </li></ul></ul></ul><ul><ul><li>Negative risk factor </li></ul></ul><ul><ul><ul><li>High HDL-C (  60 mg/dl) </li></ul></ul></ul>JAMA. 1993;269:3015-3023.
    6. 6. Rationale for OTC Therapy <ul><ul><li>National policies in place </li></ul></ul><ul><ul><ul><li>NCEP defines optimal levels for primary prevention: TC < 200 mg/dl, LDL-C < 130 mg/dl </li></ul></ul></ul><ul><ul><ul><li>Healthy People 2010 goal: Mean TC for US population = 199 mg/dl (Current : 206 mg/dl) </li></ul></ul></ul><ul><ul><li>Elevated cholesterol is significantly undertreated despite growing awareness. A therapeutic gap remains: </li></ul></ul><ul><ul><ul><li>< 4% of those eligible for 1° prevention are on therapy </li></ul></ul></ul><ul><ul><ul><li>> 50% of adults have TC > 200 mg/dl </li></ul></ul></ul>
    7. 7. <ul><ul><li>Increasing interest in self-care </li></ul></ul><ul><ul><ul><li>Supplements used extensively to lower cholesterol </li></ul></ul></ul><ul><ul><ul><ul><li>$400 million annually </li></ul></ul></ul></ul><ul><ul><ul><ul><li>safety not well characterized </li></ul></ul></ul></ul><ul><ul><ul><ul><li>many without proven benefit </li></ul></ul></ul></ul><ul><ul><ul><li>Prescription medicines: </li></ul></ul></ul><ul><ul><ul><ul><li>seen as “last resort” for people who consider themselves ill </li></ul></ul></ul></ul><ul><ul><li>OTC approach can complement current efforts: </li></ul></ul><ul><ul><ul><li>Narrow the therapeutic gap </li></ul></ul></ul><ul><ul><ul><li>Promote interaction with healthcare provider </li></ul></ul></ul><ul><ul><ul><li>Increase access </li></ul></ul></ul><ul><ul><li>Data support lowering cholesterol across a broad spectrum of cholesterol levels and CV risk </li></ul></ul>Rationale for OTC Therapy
    8. 8. Major Pravastatin Clinical Outcome Trials Study WOSCOPS Shepherd et al. NEJM 1995;333:1301-7. Sacks et al. NEJM 1996;335:1001-9. LIPID Study Group. NEJM 1998;339:1349-57. Study Drug Pravastatin 40 mg/day # of Patients 6,595 (men) Duration 5 Years Primary Endpoint NFMI / CHD Death 31% Reduction (P  0.001) Primary Prevention CARE Pravastatin 40 mg/day 4,159 (3,583 men, 576 women) 5 Years Nonfatal (NF) MI / CHD Death 24% Reduction (P=0.003) Secondary Prevention LIPID Pravastatin 40 mg/day 9,014 (7,498 men, 1,516 women) 6 Years CHD Death 24% Reduction (P  0.001)
    9. 9. WOSCOPS: Baseline Lipids and Outcome <ul><li>Baseline HDL-Cholesterol </li></ul>5-Year Event Rate (per 100) Quintile of HDL-C (mg/dl)
    10. 10. CARE AND LIPID Baseline Lipids and Events* <ul><li>HDL-Cholesterol </li></ul>*CAD death, nonfatal MI, CABG, PTCA B/L HDL-Cholesterol Quintile Event Rate (%) Placebo Pravastatin Interaction, p=0.98
    11. 11. Indications for Pravachol <ul><li>Approved Rx indications (1991 - 2000) </li></ul><ul><ul><li>Cholesterol lowering </li></ul></ul><ul><ul><li>Primary prevention of coronary events </li></ul></ul><ul><ul><li>Secondary prevention </li></ul></ul><ul><ul><ul><li>Total mortality by reducing coronary death </li></ul></ul></ul><ul><ul><ul><li>Myocardial infarction / Stroke </li></ul></ul></ul><ul><ul><ul><li>Slow progression of atherosclerosis </li></ul></ul></ul><ul><li>Proposed OTC indication (2000) </li></ul><ul><ul><li>Cholesterol lowering </li></ul></ul>
    12. 12. Rationale for Pravachol OTC: Safety <ul><ul><li>> 100,000 patient years experience in placebo controlled long-term trials </li></ul></ul><ul><ul><ul><li>Lack of significant drug interactions (differs from other statins) </li></ul></ul></ul><ul><ul><ul><li>Serious musculoskeletal events similar to placebo </li></ul></ul></ul><ul><ul><ul><li>Hepatobiliary profile comparable to placebo </li></ul></ul></ul><ul><ul><ul><li>Safety of 16x OTC dose has been demonstrated </li></ul></ul></ul><ul><ul><ul><li>No evidence of reproductive risk if taken inadvertently </li></ul></ul></ul><ul><ul><li>OTC Pravachol 10 provides a well-characterized, safe option for individual choice </li></ul></ul>“ Primum non nocere”
    13. 13. Rationale for Pravachol OTC: Summary <ul><ul><li>Pravachol 10 mg decreases LDL-C by 18% </li></ul></ul><ul><ul><li>CHD risk is significantly decreased by cholesterol reduction </li></ul></ul><ul><ul><li>Consumers are interested in non-prescription options </li></ul></ul><ul><ul><li>Provides an additional option to narrow the therapeutic gap </li></ul></ul><ul><ul><li>Major advantages of Pravachol 10 m g: </li></ul></ul><ul><ul><ul><li>Safety </li></ul></ul></ul><ul><ul><ul><li>Efficacy </li></ul></ul></ul><ul><ul><ul><li>Benefit / risk ratio highly favorable </li></ul></ul></ul>

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