ORLANDO — The multiplicity of reactions to a new drug-treatment concept has helped put “poly” in the polypill.
The idea of broadly administering a single, daily capsule containing five drugs proven to cut cardiovascular risk finally had its first field test on more than 2,000 people at 50 centers throughout India. The results proved the principle that three different antihypertensive drugs, a statin, and aspirin could safely and effectively coexist in a single pill, although the treatment effects were modest.
The study also triggered an outpouring of opinions on exactly what principles are involved. What is the potential role for a polypill, and who are the people who should take it?
According to the study's leader, Dr. Salim Yusuf, the underlying premise is that average risk-factor levels are abnormal in all individuals in most urban settings around the world, and so a polypill that reduces cardiovascular disease (CVD) risk could potentially be targeted to most or even all people older than 50 in countries spanning the globe.
The Indian Polycap Study (TIPS) enrolled people aged 45-80 years with a single CVD risk factor: type 2 diabetes, moderately elevated blood pressure (more than 140/90 mm Hg but less than 160/100 mm Hg), smoking within the prior 5 years, serum LDL cholesterol of more than 3.1 mmol/L (121 mg/dL), an HDL cholesterol of less than 1.04 mmol/L (40 mg/dL), or an elevated waist/hip ratio.
“The big question is whether you treat the whole world at large at a certain age. That's been proposed, and it's a possibility. I really don't know the answer right now,” Dr. Yusuf said during a press briefing before he reported his findings at the annual meeting of the American College of Cardiology. Accumulating evidence suggests that the threshold for diagnosing a level of blood pressure or serum LDL that poses a CVD risk should move lower than it is today, said Dr. Yusuf, professor of medicine and director of the Population Health Research Institute at McMaster University, Hamilton, Ont.
Others saw the polypill as a way to simplify treatment and boost compliance in the more conventional drug-treatment setting of secondary prevention.
“I would use it to treat people with some elevations of both blood pressure and lipids,” said Dr. Steven E. Nissen, chairman of the department of cardiovascular medicine at the Cleveland Clinic. “I wouldn't use a one-size-fits-all pill for many people who are not at a whole lot of risk. I would use it for people with [a few] risk factors and make it easy for them by giving a single pill once a day.”
Others saw as too global and facile the development of a single pill aimed at quickly and easily damping down blood pressure and serum lipids.
“It takes effort to educate the public about hypertension and obesity. If something like [the polypill] becomes prevalent, it takes away from that focus,” said Dr. Clyde Yancy, medical director of the Baylor Heart Institute in Dallas. “There is nothing more effective than modifying lifestyle, but people may tend to dismiss that concept if they believe a pill is lowering their risk of heart disease.”
Dr. Yusuf himself stressed that no matter where the polypill may lead, “lifestyle modification is the crux of CVD prevention.”
The 2,053 people participating in TIPS were recruited during March 2007-August 2008. Their average age was 54, their average blood pressure was 134/85 mm Hg, their average LDL level was 117 mg/dL, and 13% were recent smokers. Of them, 412 were randomized to receive the once-daily polypill, a capsule cocktail with three half-doses of blood pressure-lowering medications (5 mg ramipril, 50 mg atenolol, and 12.5 mg hydrochlorothiazide), 100 mg aspirin, and 20 mg simvastatin. Eight additional groups of about 200 people each were randomized into various treatment arms that received one, two, three, or four of these drugs in different combinations. Treatment was delivered for 12 weeks.
The study was sponsored by Cadila Pharmaceuticals, an Indian company that makes the polypill (Polycap). Dr. Yusuf reported receiving lecture fees and research grants from Cadila.
The polypill lowered blood pressure by an average of 7.4/5.6 mm Hg; LDL levels fell by an average of about 23%. These reductions tracked what was seen in the comparator groups. About 18% of participants discontinued the polypill arm of the study, and similar proportions dropped out of each of the other arms.
Concurrent with Dr. Yusuf's report at the meeting, the results were released in a paper published online (Lancet 2009 March 30 [doi:10.1016/S0140-6736(09)60611-5
Based on the risk factor reductions seen, polypill treatment was estimated to cut the average risk for coronary heart disease by 62%, and for stroke by 48%, Dr. Yusuf said.