What Is the Polypill?

Individually, aspirin, statins, ß-blockers, and blockers of the renin-angiotensin system (ACE inhibitors and angiotensin receptor blockers [ARBs]) can reduce heart disease risk. There is no debate about this and they are widely used. Millions of patients take more than one. Why not combine the drugs into one pill?

Public health figures have proposed a "polypill" as an inexpensive and effective way of mitigating factors that contribute to heart disease. The polypill is therefore a "cardioprotective bundle," that can be made and shipped to people at low cost.

Promoters say the bang-for-the-buck will be high, and point to advantages:

1) Improved delivery of care
2) Improved adherence
3) Reduced cost

Whether there will actually be improved adherence is not proven, but seems plausible. Patients who already have high blood pressure and dyslipidemia are at particular risk if they don’t take all their prescriptions every day which is another reason to combine medications.

Further, the polypill may be scalable for large-scale use around the world. The people who write heart disease prevention guidelines assume a pattern of what has become normal in the United States: doctors choose certain people for primary prevention, prescribe one drug at a time, and follow up regularly. That might not be do-able when you are trying to address a global epidemic. There is also data that shows average cholesterol levels have declined in the wealthier countries in recent years while they have increased in less well-off countries.

The appeal of the polypill is most evident for primary prevention, but even patients who have already had heart attacks may benefit. There are plenty of people in this category who don’t get adequate medical care, either because of cost or because a trip to the doctor’s office is inconvenient. Note that two trends in medicine are in the opposite direction: personalized treatment advocates finding a unique treatment plan for each patient, based on detailed information about the patient, including genetic information if possible. The polypill is a move toward homogeneous treatment where millions of people take the same medicine. That’s one way to look at it. Another way is that the polypill will be taken as a primary prevention by people who have no obvious signs of disease yet, and will not substitute for more customized treatment plans.

What Medicines do Cardiovascular Polypills Typically Contain?

Different polypills have different formulations. Constituents could include:

• a statin to lower blood cholesterol levels
• aspirin to help prevent blood from clotting within arteries
• an ACE inhibitor to treat hypertension and let blood flow more smoothly
• a beta-blocker to manage cardiac arrhythmias
• a diuretic to help reduce blood pressure
• folic acid to improve artery and vein health

The results of a small UK study released in July 2012 showed a four-in-one pill was effective in lowering blood pressure and cholesterol levels in people past age 50, even if those people were healthy. The common side effect of muscle weakness was reported by some participants. This polypill formulation included the ACE-inhibitor amlodipine, the antihypertensive diuretic hydrochlorothiazide, the angiotensin blood pressure medicine losartan and the statin simvastatin.

How Much Will It Cost?

Because there aren't yet any cardiovascular disease polypills available for general use at the drug store, we don't know how much they'll sell for. However, one of the main ideas behind the polypill is that it consists of low-cost ingredients, making it a potentially affordable drug for treating people all over the world, even in third-world countries. In India, 80% of health care costs are paid out of pocket, and some heart disease medications are not affordable to the majority of the people there. If the polypill proves effective, it will be produced to be affordable to people all around the world, so it is likely that it will be inexpensive.

"Red Heart Pill" Clinical Trials

One trial was for the Red Heart Pill, which contains aspirin, statins, and two blood pressure lowering medications, underwent a well-publicized two-year trial in the UK, the Netherlands, and India. A similar polypill began trials in Australia and New Zealand earlier in 2010, and trials are pending in China, Brazil, South Africa and Canada. Known as UMPIRE (Use of Multidrug Pill In Reducing cardiovascular Events). Researchers are also testing the theory that that people will be more likely to take preventive measures against heart disease if all the necessary medications are contained in a single pill.

This will be the first time the polypill has been tested on a large human population. Each element of the polypill has been tested separately, however, and proven to reduce incidence of heart disease.

Other Diseases Treated by Polypills

HIV, tuberculosis, and diabetes have all been treated with varying degrees of success with the theory that a combination of low-cost drugs can be more effective than a single, expensive wonder drug. A polypill for cardiovascular diseases could be the most important one of all, just because of the size of the problem. There is research showing lovastatin can help reduce brain inflammation and prevent neurological damage in mice with cerebral malaria. Some have proposed adding lovastatin to malaria treatment regimens but this is not done routinely yet.

Availability in the United States

Even though a hypothetical polypill would include only long-established medicines, for one to hit the market would require approval of the Food and Drug Administration. In 2014 that agency’s Cardiovascular and Renal Drugs Advisory Committee did not stomp on the idea, but did not approve full-blown development.

Doubts

A 2011 meeting of the European Society of Cardiology in Paris brought criticism that polypill use would be a great waste of money, and it was suggested that CT scans for high risk people would be a better management strategy. Other experts continue to say that polypills are the best hope against an epidemic in common aging diseases.

The concern is not related to statins so much as hypertension drugs. There are many ways to control blood pressure, but the best regimen varies considerably from patient to patient. Unlike cholesterol medications, which most people will respond to, there is a wide rsnge of treatments for blood pressure problems. Which is why some thinkers want to not approve the polypill, as they feel it would keep patients from seeking more nuanced treatment for them.

Ongoing studies:
Iran https://clinicaltrials.gov/show/NCT01271985
Canada https://clinicaltrials.gov/ct2/show/NCT00468923?term=HOPE-3&rank=1
https://clinicaltrials.gov/ct2/show/NCT01646437?term=TIPS-3&rank=1

 

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