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SCIENCE & TECHNOLOGY Polypill: A Means to Live Longer? By Max Sherman In a New York Times editorial several years ago, William Safire wrote an essay entitled, “Why Die?”1 According to the writer, nothing makes the weak strong or the fearful brave as much as the body’s innate drive to stay alive. His point was that the genetic clock is set to run no more than 120 years, although many people would like to live much longer. A government report summarized the will to survive, noting that the inevitability of aging and the specter of dying have always haunted human life, and the desire to overcome age has long been a human dream.2 There are, of course, a number of suggestions for living longer. Among them are eating a balanced diet, consuming less fat from meat and dairy, focusing on fruits and vegetables, exercising daily, reducing stress and having routine medical checkups. All of the suggestions are important. Whatever the regimen, it should be one that prevents the major causes of premature death: heart disease and stroke.3 Some experts believe such a regimen could include taking multiple drugs. It may even be more advantageous to combine all of the recommended drugs into a single pill, a magic bullet to extend life expectancy. Remarkably, there is a product that may meet this requirement. Unfortunately, it is not available in the US. It is, however, well known in the UK, where it is described as the “Polypill.” The combination drug was first proposed in 2003 by cardiologists Nicholas Wald and Malcolm Law of Queen Mary University of London.4 They summed up the preventive effects of a generic beta blocker, diuretic, aspirin, an ACE inhibitor, folic acid and a statin and concluded that combining the low doses of all six into a once-a-day pill would lower cholesterol and blood pressure. According to Wald and Law, the combination of drugs would decrease the incidence of cardiovascular disease in at-risk patients by up to 80%.5 Constituents and Early Results One of the drugs being studied, the Polycap, contains simvastatin (a statin), 20 mg; thiazide 38 December 2011 (a diuretic), 12.5 mg; atenolol (a beta blocker), 50 mg; ramipril (an ACE inhibitor), 5 mg; and aspirin, 100 mg. Statins are used to lower cholesterol. Thiazides are diuretics and stimulate the flow of urine. Beta blockers block the effects of sympathetic activation and help the heart to beat with less force. Angiotensin converting enzyme (ACE) inhibitors lower blood pressure and help keep blood vessels open. Aspirin is used for its effects on platelets to reduce blood clots. In a Phase II trial conducted in India, Polycap lowered blood pressure, reduced concentrations of low density lipoprotein (LDL) cholesterol, and impaired platelet activity to broadly the same extent as its components. The only unexpected result was that Polycap was not quite as good as simvastatin alone at lowering LDL cholesterol concentrations. The drug seemed to be well tolerated and no serious side effects emerged.6 In November 2011, the company will launch a five-year, Phase III study with 5,000 patients who are at low risk of cardiovascular disease. In another 12 week, placebo-controlled study conducted in the UK with 378 patients at high risk of CVD, the investigators estimated a 60% reduction in heart disease.7 The same investigators are currently following patients in several countries for longer periods. The Premise The rapidly increasing financial and socioeconomic global burdens of cardiovascular disease call for interventions that have a populationwide effect as well as ones that identify and protect individual patients who have a high risk of major adverse events. This is especially true in low- and middleincome countries, which can ill afford the huge losses in human and financial resources that will result from unchecked development of clinical disease.8 Despite their potential for saving lives, the drugs used in the Polypill have not been used optimally in developed countries. Poor adherence to multidrug regimens is a common barrier to effective therapy almost everywhere. Moreover, the availability of most of these drugs in generic form would reduce the cost of the Polypill. Economic analyses suggest that such multidrug regimens would be quite cost effective in reducing the burden of cardiovascular disease. The Pitfalls One of the drawbacks is patients’ complacency. In other words, patients rely on the pill rather than adhering to a healthy lifestyle. And, of course, it is imperative that the Polypill’s value be clearly demonstrated through long-term clinical studies rather than simply assuming that it works. There are also difficulties in conducting studies. In the UK, for example, cardiovascular screening requires participants in the placebo group with problems identified by baseline tests to get some treatment, making it harder to show the Polypill’s effects.9 The US Food and Drug Administration (FDA) requires evidence of efficacy in populations with low risk as well, perhaps as evidence that each component of the Polypill adds something important.10 There are also side effects to consider, i.e., aspirin-induced bleeding. In the study mentioned above, about one in six patients experienced a side effect in the short term. Most were mild, but about one in 20 patients overall stopped treatments due to side effects, indicating that treatment is best targeted to those at elevated risk of disease.11 Side effects may take five to seven years to emerge.12 Even though the drugs used are generic, there are doubts as to whether developing countries could afford to provide them broadly to everyone over 55 years of age. Cardiologists are critical of the one-size-fits-all treatment of patients who may not be at risk. Many physicians want to be involved in personalized care.13 At least one blogger notes that the Polypill may keep patients away from doctors and hospitals. According to the writer, not all patients are ready to assume self-care and autonomy and he is against medicalization. This is a term defined as the process by which health or behavior conditions come to be defined and treated as medical issues, and thus come within the purview of doctors and other healthcare professionals to engage with, study and treat.14 Final Thoughts According to Science News Daily, the Polypill will be available soon in India, then elsewhere within a few years, based on regulatory timelines within each individual country. That may not be true in the US, where it is more difficult to gain approval for combination drugs. However, there may be an alternative: the polymeal, a safer, non-pharmacological, natural and tastier choice. The polymeal combines seven food components in a healthy diet: chocolate, wine, fish, nuts, garlic, fruit and vegetables. All are known to have a positive effect on cardiovascular disease enjoyed by humankind for centuries. The combined meal could reduce heart disease by more than 75% based on the Framingham heart study and the Framingham offspring studies used to build life tables to model the benefits of the polymeal in the general population from age 50.15 References 1. Safire W. Why die? New York Times. January 1, 2000. 2. Beyond Therapy: Biotechnology and the Pursuit of Happiness. President’s Council on Bioethics. October, 2003. 3. Watts G. What happened to the Polypill? BMJ. 2008;337:786. 4. Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ. 2003;326:1419-24. 5. Reardon S. Experts debate Polypill: a single pill for global health. Science. 2011;333:181. 6. Indian Polycap Study: Effects of a Polypill (Polycap) on risk factors in middle-aged individuals without cardiovascular disease: a phase II, double blind randomized trial. Lancet. 2009; 373(9672):1341-51. 7. Op cit 5. 8. Reddy KS. The preventive Polypill—much promise, insufficient evidence. NEJM. 2007;356(3):212. 9. Op cit 3. 10. Smith R. Take forward the Polypill idea, concludes expert committee. BMJ. 2005; 330:8. 11. Polypill halves predicted heart disease and stroke risk, study suggests. Science Daily. May 25, 2011. 12. Op cit 5. 13.Ibid. 14. Smith R. The Polypill is about demedicalisation not medicalisation. BMJ Group Blogs. 1 May 2009. 15. Franco OH, et al. The Polymeal: a more natural, safer and probably tastier (than the Polypill) strategy to reduce cardiovascular disease by more than 75%. BMJ. 2004; 329:1447-50. Author Max Sherman is president of Sherman Consulting Services in Warsaw, IN. He can be reached by email at maxsherman@ kconline.com. 40 December 2011