Combination Pharmacotherapy and Public Health Research Working Group*
Note: Lawrence Green, DrPH; William S. Weintraub, MD; K.M. Venkat Narayan, MD, MPH, MBA; David F. Williamson, PhD; Michael Engelgau, MD, MS; and Andrew Friede, MD, MPH, were responsible for the preparation of this manuscript. A full list of the members of the Combination Pharmacotherapy and Public Health Research Working Group is provided in the Appendix.
Potential Financial Conflicts of Interest: None disclosed.
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Cardiovascular disease (CVD) is the major cause of death in developed countries and is rapidly becoming the major cause of death in the developing world. The increasing rates of obesity and type 2 diabetes, however, may slow the current favorable trends for deaths attributable to CVD in many developed countries. To improve control of risk factors for CVD, Wald and Law proposed a “polypill,” containing a statin, a diuretic, a β-blocker, an angiotensin-converting enzyme inhibitor, aspirin, and folic acid. This combination pharmacotherapy (CP) could be made widely available without treating specific risk factors or individuals. A workshop sponsored by the Centers for Disease Control and Prevention reviewed the concept of CP for both primary and secondary prevention. Combination pharmacotherapy may prove to be efficacious but may also have side effects and poor adherence, which may be greater than or less than that of other preventive approaches. Randomized trials are needed to study these issues, although the design for such trials is uncertain. The ability of CP to prevent CVD in a cost-effective manner must be demonstrated. Minority groups and people with low socioeconomic status in the United States have an increased risk for CVD, and the effectiveness of such pharmacotherapy must be considered for these populations. Combination pharmacotherapy may prove especially effective in the developing world, where studies of CP may precede those done in wealthier countries. Combination pharmacotherapy may have tremendous potential, but additional study and detailed evaluation are necessary.
*For the members of the Combination Pharmacotherapy and Public Health Research Working Group, see the Appendix.
Estimated direct and indirect costs (in billions of dollars) of cardiovascular disease (CVD) and stroke, United States, 2004.
Action framework for a comprehensive public health strategy to prevent heart disease and stroke.
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Mark R Goldstein
November 13, 2005
Problems With the Polypill
The widespread use of a "polypill" (a combination of a statin, a diuretic, a beta-blocker, an angiotensin-converting enzyme inhibitor, aspirin and folic acid)proposed for the prevention of cardiovascular disease will be problematic (1). It will de-emphasize prevention by lifestyle change, homogenize treatment for heterogeneous populations and violate the "first do no harm" dictum. The assumption is that a majority of people will benefit from a given combination of medications despite their individual problems. That assumption is dangerous.
What about individuals who require surgery and must stop aspirin one week prior to the proceedure? Abruptly stopping a beta-blocker may lead to myocardial ischemia. What about individuals with renal insufficiency who use a salt substitute containing potassium chloride and become hyperkalemic because of the angiotensin-converting enzyme inhibitor? Presently, there is controversy as to whether folic acid supplementation may increase cancer(2).
The best measures for cardiovascular disease prevention are a diet rich in fruits, vegetables, whole grains and low-fat dairy, and regular exercise, started in childhood and maintained throughout life(3). Perhaps, the Public Health Research Working Group could have better utilized the approximately 700,000 pages of the Annals (100,000 issues in circulation,7 page article) by discussing ways to better implement lifestyle change in our population of rapidly expanding waistlines(4).
1) Combination Pharmacotherapy and Public Research Working Group. Combination pharmacotherapy for cardiovascular disease. Ann Intern Med. 2005; 143: 593-599.
2) Bonaa KH (for the NORVIT Study Group). NORVIT: Randomised trial of homocysteine-lowering with B vitamins for secondary prevention of cardiovascular disease after acute myocardial infarction. European Society of Cardiology, September 3-7, 2005, Abstract 1334.
3)McGill HC, McMahan CA. Starting earlier to prevent heart disease. JAMA. 2003; 290: 2320-2322.
4)Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the Third National Health and Nutrition Examination Survey. JAMA. 2002; 287: 356-359.
Combination Pharmacotherapy and Public Health Research Working Group*. Combination Pharmacotherapy for Cardiovascular Disease. Ann Intern Med. ;143:593–599. doi: 10.7326/0003-4819-143-8-200510180-00010
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Published: Ann Intern Med. 2005;143(8):593-599.
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