A cardiac pill that combines three drugs into one

Patients with heart disease often take two or more drugs. So, could one pill that combines several commonly-used medications make it easier to control their condition?

A new study published in The New England Journal of Medicine offers hope that a strategy of using a polypill with more than one medication can help save lives.

The polypill combines three of the most commonly-prescribed medications for heart disease: a blood pressure medication, a cholesterol-lowering drug and aspirin, which prevents blood clots.

The study followed 2,499 patients who had suffered a heart attack in the previous six months. Half of the participants received the polypill and the other half received the usual guideline-directed medical care. The study showed that after three years, the patients who took the polypill cut their risk of cardiovascular events 25 percent more than those following the usual regimen.

That is a significant reduction, said Cardiologist Lawrence McAuliffe, MD, at Cape Cod Healthcare Cardiovascular Center in Hyannis. He also pointed out that the study’s conclusion for why the polypill was so successful made perfect sense. It was because the patients taking the polypill had better compliance. A lot of people just don’t like to take pills. Dr. McAuliffe said most of his patients ask about taking fewer pills or lower doses at almost every visit.

“My answer always is I’m going to give you as little as possible but as much as necessary – necessary defined either by guidelines or by response for whatever issue I’m treating, whether it’s blood pressure or cholesterol,” he said.

Heart disease is the number one cause of death in the United States, according to the federal Centers for Disease Control and Prevention (CDC). Every 34 seconds someone in this country dies from it.

Many of Dr. McAuliffe’s patients take a double-digit number of medications. Ten to 15 medications a day is not uncommon and some medications have to be taken more than once a day. It’s also not uncommon for patients to either forget to take their medications or just not take them at all because they don’t want to take that many pills or because they experience negative side effects.

The polypill study proved that to be true. At six months, 70.6 percent of the polypill group were sticking to the medication regimen compared to 62.7 percent of the group taking the usual assortment. At 24 months, almost three-quarters of the polypill group were still taking it compared to 63.2 of the usual medication group.

That is similar to what other studies have shown, Dr. McAuliffe said. Studies show that after a significant event like a heart attack, people are scared by the fact they just spent time in the hospital and had a major procedure like a bypass or a stent. When they first get out of the hospital, they resolve to take their medications, stop smoking, eat well and exercise. Unfortunately, as time passes compliance usually drops.

“At the end of three years, compliance with all medications, which would otherwise be indicated, is low,” Dr. McAuliffe said. “So, if you can somehow make inroads towards that non-compliance and you can get somebody to take one pill a day as opposed to three or four or five, sometimes a couple of times a day, then your compliance will be much better and that’s what all the studies show. When compliance is better, outcomes are better.”

That said, Dr. McAuliffe pointed out that the particular drugs chosen for hypertension and cholesterol might not be his first choice of medications to prescribe. To control hypertension, the study chose Ramipril, which is an ACE inhibitor. It’s not the ACE inhibitor that Dr. McAuliffe prescribes and he actually prefers a class of drugs called ARBs to control high blood pressure.

“None of these may be my first choice, but if that’s the only option I had for a polypill, we know it works, so I might concede my personal preferences to a medicine that I know is going to work,” he said. “It muddies the issue in terms of choice, which is not so important if you can get them to take something. It’s better than taking nothing or not enough of something.”

One of the positives is that the polypill isn’t just a one-size-fits-all pill. There are actually six different pills with different doses of both the anti-hypertensive and lipid-lowering medicines. That allows doctors to customize what they give to any individual patient.

The polypill isn’t available in the United States yet, but Dr. McAuliffe doesn’t think it will face difficulty getting FDA approval because there are already other polypills for diseases like HIV and Hepatitis C currently available. A bigger issue might be getting the pharmaceutical industry onboard, because patients taking fewer pills means less profit for them, he said.

Not a New Idea

The authors of the polypill study have been proposing a similar polypill for 20 years, only with a different emphasis.

“When these authors first came out over 20 years ago, they proposed the same polypill for everyone over the age of 55. Everyone,” said Dr. McAuliffe. “And with that they estimated they would cut down cardiovascular mortality in that population by 80 percent.”

That plan failed for several reasons. First it would have treated hundreds of thousands of people who don’t necessarily need it, causing them possible side effects and unnecessary expenses. Another point of contention was that it’s a downward slide into a polypharmacy society where you just take a pill for everything, he said. That in turn could lead people to not worry about leading a heart-healthy lifestyle. Popping one pill is easier than quitting smoking, exercising and eating healthy – all things that are more effective in the long run than taking a pill.

This new study is different because it was only used for secondary prevention, Dr. McAuliffe said. Those patients had already had an event and were going to be prescribed those same medicines at any rate, so why not combine them? But in the future, he does see a possibility of using it as primary prevention with a certain population of high-risk patients that already take the same combination of medicines.

“Maybe you could apply it to a cohort of patients who is hypertensive, hyperlipidemic, diabetic, overweight and smoking,” he said. “You’re still going to give them all of those medications to treat their individual conditions in order to prevent that first heart attack or stroke so why not a polypill?”