Heart disease kills more people than any other condition, but despite advances in treatment and prevention, patients often do not stick to their medication regimens. Now researchers may have found a solution: a so-called polypill that combines three drugs needed to prevent cardiovascular trouble.
In what is apparently the largest and longest randomized controlled trial of this approach, patients who were prescribed a polypill within six months of a heart attack were more likely to keep taking their drugs and had significantly fewer cardiovascular events, compared with those receiving the usual assortment of pills.
The participants also experienced one-third fewer cardiovascular deaths, although their overall risk of death from all causes was not significantly changed.
The study of more than two thousand heart patients, who were followed for three years, was published Friday morning in The New England Journal of Medicine, as the findings were presented at the European Society of Cardiology Congress in Barcelona.
The study is the culmination of 15 years of work by researchers led by Dr. Valentin Fuster, director of Mount Sinai Heart at Mount Sinai Hospital in New York City, and general director of the National Center for Cardiovascular Research in Spain.
“Combination pills are easier for the physician and for the patient, and the data are pretty clear — it translates into a benefit,” said Dr. Thomas J. Wang, chair of the department of internal medicine at UT Southwestern Medical Center, who was not involved in the research but wrote an editorial accompanying the study.
“It’s easier to take one pill versus multiple pills, and it’s easier to take them once a day than multiple times a day.”
The availability of a polypill also appears to nudge physicians to write prescriptions more in line with practice guidelines, Dr. Wang added: “Under ordinary circumstances, physicians often under-prescribe medications that should be given.”
The polypill combines a blood-pressure medication, a cholesterol-lowering drug and aspirin, which helps prevent blood clots. The idea was first floated two decades ago in a more radical form: Advocates proposed giving a daily polypill to everyone once they turned 55, saying it would slash cardiovascular events globally by 80 percent.
That notion was roundly criticized and quickly laid to rest. But the benefits of a polypill for patients at risk of heart problems have been tested in numerous studies since. Polypills are already available to treat other medical conditions, such as H.I.V. and hepatitis C, Dr. Wang noted.
The polypill used in the study has not been approved by the Food and Drug Administration and is not available to patients in the United States right now. Dr. Fuster said the results of the new trial would be submitted to the agency shortly in an effort to obtain approval.
He called the results of the new study “striking,” and said the benefit of the polypill for prevention rivaled that of low-dose aspirin, which is now routinely prescribed to people who have already had a heart attack or other cardiovascular event.
And since participants became even more likely to keep taking the polypill over time, he said, “The potential results could be even better with more follow-up.” Several studies have shown that only about half of patients, or even less, take all their medications as instructed.
The new study, a randomized controlled clinical trial, enrolled just under 2,500 patients at 113 sites in Spain, Italy, France, Germany, Poland, the Czech Republic and Hungary.
All enrollees had survived a heart attack within the previous six months. They were either older than 75, or at least 65 with other health conditions like diabetes or kidney disease. Overall, about 80 percent had high blood pressure, nearly 60 percent had diabetes, and over half had a history of smoking.
Almost all of the patients were white, and fewer than one-third were women. A vast majority were not high school graduates.
Half of the trial participants received the polypill, while the other half received usual care. There were several types of polypills, and treatment was tailored to individual patients.
All of the polypills contained 100 milligrams of aspirin, but doctors could choose between three doses of ramipril, a blood pressure drug, and between two doses of atorvastatin, a cholesterol-lowering medication.
Adherence to medication was higher among the polypill users, and increased over time, the researchers found. At six months, 70.6 percent of the polypill group were sticking to their regimens, compared with 62.7 percent of those taking usual assortment of pills.
At 24 months, about three-quarters of the patients were still taking a polypill, compared with 63.2 percent of the patients taking the usual pills.
Over three years, 12.7 percent of the patients taking an assortment of pills experienced another heart attack or stroke, or died of a cardiac event or needed urgent treatment to open a blocked artery, compared with 9.5 percent of patients taking a polypill, for a relative reduction in risk of 24 percent.
There was no difference between the two groups in overall mortality, however, as the reduction in cardiovascular deaths in the polypill group was offset by deaths from other causes.
Asked why the polypill was effective, and why adherence to medication was so poor, Dr. Fuster said, “People forget when there are a number of pills to be taken, they don’t take all of them or they take none.”
Although most patients stick to treatment in the immediate aftermath of a heart attack, adherence drops off after the first few months, he said.
The polypill may be less expensive to produce and distribute than a series of different pills. The findings may help make cardiovascular prevention therapy more accessible, especially to individuals in low-income and middle-income countries.
Although the patient cohort in the European study was very homogeneous, other studies have looked at polypill use in minority and underserved populations.
Dr. Wang led a study of a polypill prescribed for primary prevention of cardiovascular disease in a low-income, mostly Black group of adults in Alabama. Adherence was very high, and the participants saw greater decreases in cholesterol and blood pressure than those receiving medications in their usual form.
A review of eight studies that included over 25,000 patients, also led by Dr. Wang, found significantly improved adherence to drug regimens with a polypill and significant reductions in cardiovascular risk factors.
Overall mortality declined among patients assigned to take polypills, as did serious cardiac events, particularly among those who were at low risk to begin with and had no previous heart disease.