Commentary by David Hatcher, MSIII (reviewed by Neil Shapiro, MD Editor-In-Chief, Clinical Correlations)
C.M. is a 68 year-old retired Caucasian male with a past medical history significant for coronary artery disease, hyperlipidemia, HTN, and a 30 pack year history of smoking. His drug regimen consists of a beta-blocker, an ace inhibitor, a statin, and aspirin.
Patients like C.M. are now more common than ever before. He has already had one heart attack, and he has multiple risk factors for another, many of them preventable. In the United States alone, heart disease and stroke are the first and third leading causes of death. For those like C.M., this means a lifetime on multiple medications; unfortunately, however, not everyone has access to the same resources or is as compliant. Despite the availability of medications proven to be effective for primary and secondary prevention of cardiovascular disease, they often are not used optimally, even in developed countries. A gap currently exists between our knowledge of prevention and its actual practice. Poor drug adherence to multidrug regimens and costly medications are common barriers to treatment, especially in middle and lower income areas.
In their paper, “A strategy to reduce cardiovascular disease by more than 80%” (published in the British Medical Journal on June 28, 2003), Professor Nicholas Wald of the Wolfson Institute of Preventative Medicine in London and Malcolm Law of the University of Auckland in New Zealand proposed the idea of a “Polypill”, a medication which contains a combination of active ingredients, to be given once daily for the prevention of cardiovascular disease. They argue such a pill would address the issues of cost and noncompliance while providing optimal treatment.
Using published data from meta-analyses and cohort studies, Wald and Law set out to find a combination of drugs and vitamins that would have a large effect on preventing cardiovascular disease with few side effects. To be included in their Polypill, a drug or vitamin must lower one of four cardiovascular risk factors (low density lipoprotein cholesterol, blood pressure, platelet function, and serum homocysteine), regardless of pretreatment levels. The formulation they devised consisted of a statin, a diuretic, a beta-blocker, an angiotensin converting enzyme inhibitor, folic acid, and aspirin. Most of these are available in generic form.
Wald and Law concluded that the combination could reduce ischemic heart disease by 88% and stroke by 80%. About one in three people taking the pill would benefit, gaining on average about 11 years of life without a heart attack or stroke. Adverse effects would only affect 8-15% of people, depending on the precise formulation, and those patients found to be intolerant could be prescribed an alternative formulation.
The paper recommends that the Polypill be given to everyone with existing cardiovascular disease and everyone aged 55 and older, regardless of risk factors. This is in direct contrast to the practice of measuring and treating individual risk factors. “Instead it should be recognized that in Western society the risk factors are high in us all, so everyone is at risk.” Wald and Law acknowledge that their position is extreme, but they are confident of its potential implications. “No other preventive method would have so great an impact on public health in the Western world.”
The Polypill proposal has raised numerous questions and criticisms since its publication. Different drug combinations have been contended. For example, a recent trial recommends inclusion of a calcium-channel blocker for primary prevention of cardiovascular disease. In addition, the authors themselves acknowledge that lowering serum homocysteine has not been proven to reduce the risk of cardiovascular disease. Another reservation about the Polypill is that tailoring treatments will be difficult. Pharmacokinetic and pharmacodynamic studies will need to be done on all combinations to address the issues of dosing and scheduling.
Perhaps the biggest obstacle the Polypill now faces is gaining the approval of clinicians and the public. In a 2003 reply to the correspondents of the BMJ, Wald stated, “The Polypill is not an alternative to adopting a healthy lifestyle, such as not smoking or not becoming overweight: it is a complementary means of prevention.” In 2004, a paper was published in the British Medical Journal suggesting the “Polymeal” as a natural (and tastier) alternative to the Polypill. Using methods similar to the Polypill study, its authors identified the foods that reduce the risk of cardiovascular disease and estimated the potential benefits of a diet comprised of those foods.
Despite the practical issues that have to be dealt with, the Polypill concept holds enormous potential. Its simplicity will address the key issue of long-term adherence. Tailoring treatments will become less time consuming, freeing up physicians to focus on other important prevention topics, such as exercise and smoking cessation. And perhaps most importantly, it will mainly consist of off-patent ingredients, costing mere dollars a month. In the meantime, we will just have to wait for results from clinical trials.
In 2003, Wald and Law filed a patent application on the formula of a combined pill to reduce four cardiovascular risk factors, in addition to a trademark application for the name Polypill.
Wald, NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ. 2003;326:1419-1423.
Franco OH, Bonneux L, de Laet C, Peeters A, Steyerberg EW, Mackenbach JP. The Polymeal: a more natural, safer, and probably tastier (than the Polypill) strategy to reduce cardiovascular disease by more than 75%. BMJ 2004;329:1447-1450.
Wald, NJ. “Polypill” to fight cardiovascular disease – Authors’ reply. BMJ 2003;327:809-810.