A single pill that combines three heart drugs has dramatically reduced heart and other deaths heart problems in people who have already had heart attacks, according to a new study published Friday in the New England Journal of Medicine.
The “polypill” results were so compelling — a 24% reduction in deaths from heart disease or other heart problems — that the researchers plan to submit the data to the Food and Drug Administration for approval, the agency said. The study’s lead author, Dr. Valentin Fuster, director of Mount Sinai Heart and chief medical officer of Mount Sinai Hospital in New York City.
“The results were, frankly, very exciting,” said Fuster, who presented the results Friday at a meeting of the European Society of Cardiology in Barcelona, Spain.
The idea of a polypill to treat heart disease is not new; researchers have toyed with the idea for two decades. A separate study published in 2020 found that a polypill combining four drugs reduced the risk of first heart attacks and strokes in people at risk for such problems.
Dr Salim Yusuf, lead author of the 2020 study, a cardiologist and professor of medicine at McMaster University in Ontario, said the new research confirms that a polypill would provide “substantial” benefits.
“The evidence is now overwhelming,” he said.
FDA committees have already met to discuss the potential risks and benefits of other versions of a polypill, but none have been approved in the United States. The pill in the new study – by Spanish drugmaker Ferrer – was approved for use in Europe in 2014.
In the United States, however, clinical trials of polypills were not large enough to prove the drug had any real-world benefit, wrote Dr. Thomas Wang, a cardiologist at UT Southwestern Medical Center in Dallas in a editorial that accompanied the new study.
Another challenge was determining the right combination of drugs in the right dosages for a pill that could be widely prescribed.
The apparent one-size-fits-all approach has been a sticking point for some doctors. Dr. Steven Nissen, a cardiologist at the Cleveland Clinic, said providers should be able to customize dosages of these drugs for each patient.
Still, Nissen, who was not involved in the research, said he was intrigued by the results. “The polypill shows promising results in this trial, although it would be useful to have a larger confirmatory trial,” he said.
Fuster said he and his team scoured 50 variations of such a pill to find the right recipe that would provide benefits.
They finally landed on three drugs: a statin to lower cholesterol, an ACE inhibitor to lower arterial pressure and aspirin, which makes blood less likely to clot. All three drugs are available in generic forms and should therefore keep costs low.
But it may not have been the combination of drugs in the polypill that ultimately led to improvements; it could just be that people were more likely to take their medication if they had just one pill instead of several.
People discharged from hospital after a heart attack are usually sent home with four to five prescriptions to prevent a second heart attack, said Dr. Donald Lloyd-Jones, a cardiologist who is the former president of the American Heart Association.
“It’s a lot to ask people to keep track of five medications,” he said, especially for older patients who may need extra support managing their prescriptions.
It’s not uncommon for people to initially take their prescribed heart medications after a heart attack, but become less diligent over time.
“It’s natural human instinct that as you move away from this event, you feel like they’re less at risk and they stop taking one or more of their medications,” said the Dr. Gregg Fonarow, acting chief of cardiology at UCLA Health in Los Angeles.
Combining the drugs in one pill reduces the likelihood that a person will miss potentially life-saving drugs. In fact, that was the main driver of the new study’s results: people who were prescribed the polypill were more likely to take it.
“Membership was the most important factor,” Fuster said. “That was actually the driver of the results.”
Fuster’s study included 2,499 patients over the age of 65 who had previously had heart attacks.
All patients were given the same three drugs, but half received them as a single pill, while the others were prescribed the drugs as usual, in separate pills.
Over the next three years, 12.7% of people in the usual care group had heart attacks or strokes or required interventions such as bypass surgery to restore blood flow to veins and blocked arteries, or died because of their heart disease, compared to 9.5% of those given the polypill.
Side effects were similar in both groups.
Fonarow, who was not involved in the new study, called the data “exceptional”.
The benefits of the polypill were clearly evident, he said: the single pill made people more likely to take the prescribed doses, leading to a reduced risk of future heart problems.