Combination Pharmacotherapy and Public Health Research Working Group*
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.
All estimates prepared by Thomas Thom, National Heart, Lung, and Blood Institute.
The figure is split diagonally in halves, representing opportunity, not current spending, for the spectrum of preventive and therapeutic care. CHF = congestive heart failure; CVD = cardiovascular disease; DM = diabetes mellitus; HBP = high blood pressure; MI = myocardial infarction; TC = total cholesterol.
The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.
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. 2005;143:593-599. doi: 10.7326/0003-4819-143-8-200510180-00010
Download citation file:
Published: Ann Intern Med. 2005;143(8):593-599.
Results provided by:
Copyright © 2017 American College of Physicians. All Rights Reserved.
Print ISSN: 0003-4819 | Online ISSN: 1539-3704
Conditions of Use
This PDF is available to Subscribers Only