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Nicholas Wald’s flash of insight came about Such patients with histories of 15 years ago. While recovering from a are perfect candidates serious illness at his wife’s family’s house in for the polypill, says Simon Thom, a New York, he watched as his father-in-law cardiologist at Imperial College London who swallowed multiple pills each day to treat led the UMPIRE study. “They’re the low- his cardiovascular disease. “I thought, my hanging fruit of the prevention populace.” goodness, the combined effect of these pills Similar results were previously observed in is very large, but the problem is they should Indian people between the ages of 45 and 80 ensoy / Alamy

have started giving them 30 years ago as a without established heart disease but with Ş preventative treatment,” recalls Wald, an a correlated risk factor such as

epidemiologist at the Wolfson Institute (Lancet 373, 1341–1351, 2009). Mehmet of Preventive Medicine at Barts and The What’s still unproven is whether the London School of Medicine and Dentistry improved adherence seen in people taking a Take to heart: One pill for prevention? in the UK. polypill translates to fewer heart attacks and In 2003, a few years after his Eureka in the long run. “I think most people, moment, Wald and his Wolfson colleague myself included, would like to see the data on multiple often simply stop Malcolm Law published a statistical analysis that it’s likely to lead to a better [clinical] taking them. “At the end of the day, taking suggesting that rolling a , an , outcome,” says Robert Bonow, a cardiologist something is better than taking nothing.” a B vitamin and three blood pressure– at the Northwestern University Feinberg The original populists of the polypill lowering drugs into a single so-called School of Medicine in Chicago who has not concept, for their part, have steadily moved polypill would slash the number of heart been involved in any polypill studies. forward. In June, Wald, Law and others attacks and strokes by more than 80% if A five-year trial of 8,000 people in ten low- began selling their pill directly to consumers given to everyone over 55 years of age (BMJ and middle-income countries, launched last through a company they cofounded called 326, 1419–1424, 2003). The study caused a year by Salim Yusuf, of McMaster University Polypill Ltd. After an online consultation stir: detractors said it strongly overstated in Hamilton, Canada, and his colleagues, with doctors at the website polypill.com, © 2013 Nature America, Inc. All rights reserved. America, Inc. © 2013 Nature the treatment’s benefits and bemoaned the will be the first to address this question. In people in the UK over 50 years of age can medicalization of society, while supporters such populations, where the drugs are often received a prescription to buy the polypill insisted that the population at large was less available or unaffordable and where under the brand name PolyTor for £1.05 npg indeed sufficiently at risk to justify such high-risk individuals often aren’t getting ($1.68) per tablet. This pill contains four wide uptake. any medicine at all, such a pill can be highly ingredients: to lower cholesterol That debate has raged on ever since, effective, Bonow predicts. “That’s where the and low doses of , with little clinical data involving people polypill has its sweet spot,” he says. But in losartan and amlodipine to reduce blood with established heart disease to inform wealthier populations, a one-size-fits-all pressure. Since all the components are the discussion. However, last month an approach falls short. It’s much better for widely used medicines to treat heart international consortium published the patients to see a clinician who can titrate the disease, physicians can prescribe the results from the first polypill trial involving best dose of each drug, he contends. pill off label for preventative use, with a high-risk individuals. The UMPIRE trial— compounding pharmacy making the four- short for use of a multidrug pill in reducing Better than nothing in-one formulation. However, Wald says cardiovascular events—enrolled around Views like that will be a major hurdle to he would like to eventually receive market 2,000 people in India and Europe who had a polypill’s acceptance by the medical authorization so he and other doctors can already experienced heart attacks or strokes. establishment, expects Anthony Rodgers, a offer the polypill more broadly. It found that 86% of study participants global health researcher at the University of For now, Wald concedes the most likely given a four-in-one polypill stayed on Sydney who was a co-author of the UMPIRE buyers are “the educated well,” but he hopes their , compared to only 65% trial and has run several other polypill to partner with public programs to make it of those who received standard care, which studies worldwide. “Specialists say, ‘This more widely and more cheaply available. His includes taking multiple pills separately is really bad medicine. I want people to be philosophy is simple: “If one can prevent a (JAMA 310, 918–929, 2013). The study also on the highest dose of the best statin and first cardiovascular event,” he says, “there demonstrated that people taking the polypill the best blood pressure medicine,’” he says. won’t be a second one to prevent. So primary experienced slightly greater improvements But, as Rodgers points out, adherence is a prevention should be the priority.” in blood pressure and lipid profiles. huge issue in wealthy countries, too. Patients Alla Katsnelson

1192 VOLUME 19 | NUMBER 10 | OCTOBER 2013 NATURE MEDICINE