Once-a-day heart combo pill shows promise in study

[March 31, 2009]  ORLANDO, Fla. (AP) -- It's been a dream for a decade: a single daily pill combining aspirin, cholesterol medicine and blood pressure drugs -- everything people need to prevent heart attacks and strokes in a cheap, generic form. Skeptics said five medicines rolled into a single pill would mean five times more side effects. Some people would get drugs they don't need, while others would get too little. One-size-fits-all would turn out to fit very few, they warned. Now the first big test of the "polypill" has proved them wrong.

The experimental combo pill was as effective as nearly all of its components taken alone, with no greater side effects, a major study found. Taking it could cut a person's risk of heart disease and stroke roughly in half, the study concludes.

The approach needs far more testing -- as well as approval from the Food and Drug Administration, something that could take years -- but it could make heart disease prevention much more common and more effective, doctors say.

"Widely applied, this could have profound implications," said Dr. Robert Harrington, an American College of Cardiology spokesman and chief of Duke University's heart research institute. "President Obama is trying to offer the greatest care to the greatest number. This very much fits in with that."

The polypill also has big psychological advantages, said Dr. James Stein of the University of Wisconsin-Madison.

"If you take any medicines, you know that every pill you see in your hand makes you feel five years older. Patients really object to pill burden" and respond by skipping doses, he said.

No price for the polypill has been disclosed, but its generic components cost only a total of $17 a month now and doctors expect the combo would sell for far less.

The study was led by Dr. Salim Yusuf of McMaster University in Hamilton, Ontario, and Dr. Prem Pais of St. John's Medical College in Bangalore, India. The findings were presented Monday at the cardiology college's conference in Florida and published online by the British medical journal Lancet.

The study tested the Polycap, an experimental combo formulated by Cadila Pharmaceuticals of Ahmedabad, India. It contains low doses of three blood pressure medicines (atenolol, ramipril and the "water pill" thiazide), plus the generic version of the cholesterol-lowering statin drug Zocor, and a baby aspirin (100 milligrams).

Doctors have talked about such a possibility for years. As the patents on many heart medicines expired and the drugs became available as cheap generics, a few companies started trying to develop all-in-one pills.

Formulating a single pill of five drugs that work in five different ways is a complex task -- more complex than simply mixing the medicines. Pills have coatings and other ingredients that control the rate at which the medicine is released into the bloodstream. The polypill must be designed so that the five drugs work as intended.

The Polycap is the furthest along, and this is the largest study of one so far.

The study involved about 2,000 people at 50 centers across India, average age 54, with at least one risk factor for heart disease -- high blood pressure, high cholesterol, obesity, diabetes or smoking.

Four hundred were given the polypill. The rest were placed in eight groups of 200 and given individual components of the pill or various combinations. Treatment lasted 12 weeks.

Compared to groups given no blood pressure medicines, those who got the polypill lowered their systolic blood pressure (the top number) by more than 7 units and their diastolic (the bottom number) by about 6 -- comparable to levels for people who were given the three drugs without aspirin and the cholesterol drug.

These drops were modest, probably because doses were low and most participants had only moderately high blood pressure to start with, Yusuf said.

LDL, or bad cholesterol, dropped 23 percent on the polypill versus 28 percent in those taking the statin drug separately. Triglycerides dropped 10 percent on the combo pill versus 20 percent with individual statin use. Neither pill affected levels of HDL, or good cholesterol.

Anti-clotting effects seemed the same with the polypill as with aspirin alone.

Side effect rates were the same for the polypill as for the five medicines individually.

"That was a big surprise. I would have expected five times the number of people to have side effects," because of the possibility the drugs would interact and magnify any problems, said Dr. Christopher Cannon, a cardiologist at Harvard-affiliated Brigham and Women's Hospital in Boston who had no role in the study.

Collectively, the results show the polypill could cut the risk of heart disease by 62 percent and the risk of stroke by 48 percent, based on what previous studies show from lowering risk factors by these amounts, the study concludes.

Polycap's maker sponsored the study, and Yusuf has been a paid speaker for several makers of heart drugs.

A bigger study is now needed to see whether the polypill actually does cut heart attacks and strokes, he wrote in a commentary in the medical journal.

"It's a first step. I would caution against jumping to the conclusion this is the magic solution to our prevention problems," said Dr. Raymond Gibbons of the Mayo Clinic, a former American Heart Association president.

Studies show that healthy diets and exercise give better protection than pills, and too many people already think "that because they're on a statin, they can go to McDonald's," Gibbons said.

A big issue is who should get the polypill. The study tested it in people with risk factors that would already qualify them for treatment.

"Should high-risk people who do not yet have heart disease take it? My guess is, that's where the field will go to rapidly," Yusuf said.

Conversely, people with established heart disease may need more medicines than the modest amounts in this all-in-one pill.

"It won't be for everybody," Cannon said. Some people would be overtreated by getting medicines for conditions they don't yet have, such as high cholesterol. Others may be undertreated by too-low doses in the combo pill. Several polypills of different strengths may be needed, he said.

"We have to be cautious about assuming that one size fits all," Stein said. "Treating risk factors is a lot like cooking -- the ingredients count."

A polypill also would need FDA approval, even though all of its components have long been sold separately. And establishing the proper doses could become a regulatory nightmare, Cannon warned.

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On the Net:

Cardiology meeting: http://www.acc.org/

Medical journal: http://www.lancet.com/

[Associated Press; By MARILYNN MARCHIONE]

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