DocTalk Podcast: Polypill with Dr. Kazi

While new therapies and drugs are often the subject of discussion among cardiologists in developed nations, use of polypill for cardiovascular disease is usually not one of them.

Polypill, which is a drug that combines multiple pharmaceutical agents into one pill, has been applied in other specialties but is seldom explored in populations in developed nations. In contrast, polypill has been studied and found to be effective in reducing cardiovascular events in nations such as Iran in the PolyIran study.

Another recent study examined the cost-effectiveness of polypill for secondary prevention of cardiovascular disease in Mexico as well as African and Asian countries. The lead investigator of that study, Dhruv Kazi, MD, associate director of the Smith Center at Beth Israel Deaconess Medical Center, recently took part in the DocTalk Podcast to share his insights on polypill and why we haven’t seen it gain the same traction in other countries.

MD Mag: Hello, everybody, and welcome to the DocTalk podcast. I'm Patrick Campbell, associate editor with MD Magazine, and I will be your host for this edition of DocTalk as we discuss polypill with Dr. Kazi. Welcome to the DocTalk. If you wouldn’t mind giving us a brief introduction and some background into your recent study that you led, then we can dive into our chat.

Kazi: So, I'm Dhruv Kazi. I'm a member of the faculty of medicine at Harvard Medical School. I'm the Associate Director of that of the Smith Center, which is a research center at Beth Israel Deaconess Medical Center in Boston and I also run the cardiac critical care unit here at the BIDMC.

I became interested in the polypill because there is a contradiction of sorts in the policy world. On the one hand, we believe polypills are really effective for conditions like HIV and malaria, and TB, where by putting the number of drugs that the patient needs to take into a single pill, we make it easier for the patients, patients more likely to take the medication, we're more likely to achieve the health goals we want to achieve. It seems like an approach that should work for cardiovascular disease, because people who have had heart attacks and strokes in the past need to be on 4, sometimes even more medications.

So, putting them in a single pill would reduce pill burden and this should be an effective approach. It's actually been described for cardiovascular disease now over two decades ago and there are some polypills available globally, but there hasn't been much uptake. So part of our question with this study was to try and understand why, why has that not become the standard of care? And if it were to become the standard of care, what benefits could be achieved?

So it turns out that the reason people don't physicians in particular don't like to prescribe the polypill in in some of these countries is because there is a concern that, well, what if patients have side effects to one of the drugs and we don't have the ability to monitor for side effects? Would would we end up hurting our patients? And there's the concern about costs, which is if you put all the drugs into a single pill, is it possible that the pill will be too expensive for the patient to afford? And what we've shown in this analysis, and we take it into the clear, it complements the poly around study, which was PolyIran was run in, as the name suggests, and multiple villages in Iran, where people will randomized to the polypill or usual care.

We on the other hand, we're building a mathematical simulation model of multiple countries, India, China, Nigeria, South Africa, and Mexico, large countries populace with very high burden of cardiovascular disease and asking the same question, which is, what happens if we were to use instead of the usual care, switch people over to the hypothetical polypill that contains the four pills, and we showed that, you know, the benefits clearly outweigh the side effects. So for every thousand patients 3 to 5 years, you'd avoid about 50 major cardiovascular events, and somewhere between 5 and 10 adverse events.

So, the clinical benefit was there and if the cost of the pill were, if we were just talking about purchase this pill so that it was available at an affordable price, then, in fact, what we call a public sector pricing. In fact, adopting the pills saves money, and there's almost no intervention in cardiovascular medicine today that both saves lives and has the potential to save money. There's very few of those. And so this is one of them where in the short term, intermediate term, we could end up saving money by putting people on the drugs that need because you avoid heart attacks and strokes. So, we were really encouraged by that finding. And the it because we're able to address effectiveness concerns, safety concerns, and cost concerns all in one study across multiple countries and those are the key barriers that currently exists to widespread adoption of the polypill.

MD Mag: All right, thank you for that. Now, what difference does this make from a patient — and also a physician perspective?

Kazi: Yeah, so it's very interesting is that that when we started this project, the governing idea about polypill was that rolling different medications into a single pill achieves most of its benefit because patients take the pills. I'm more likely to take one pill than I am to take 4 pills if i were a patient. What we found, interestingly, was that this increase in patient compliance or what we now call patient adherence is a very small part of the effectiveness of the polypill and low- and middle- income countries — the cardiovascular polypill.

What was happening is that, in most cases, patients weren't even being prescribed all before guideline directed medications. So the four medications that they needed, weren't even being prescribed. So, someone some patients are getting on the aspirin and some are getting aspirin and a statin. But very few patients were actually getting all 4 meds. So, when you introduce the polypill the major benefit is that said when you write when the doctor writes one prescription for a heart pill to get all for drugs. That is a major driver from a public health standpoint.

So, this is while we while this is great for patients, the real mechanism of action is because physicians are prescribing more medications, more life-saving medications for patients who need them. So it's kind of easier — from a physicians perspective, they don't have to track 4 separate prescriptions, refill 4 sets of prescriptions, etc. From the patient's perspective, instead of taking 4 pills, I will be taking 1 pill that helps me not just start the pill, but also stay on it long term. And it's the combination of these two effects, easier for physicians and easier for patients that results in this large population level benefit of avoiding heart attacks, avoiding strokes. And from a societal perspective, heart attacks and strokes, in low and middle income countries, often occur at ages 55 or 57, meaning these individuals are still working and actively contributing to the economy.

So the societal perspective is avoiding all of this early disability or death, and lost productivity, while at the same time avoiding costs related to heart attack and stroke. So it's clearly beneficial to patients, it's easier for physicians, and it has substantial clinical and economic benefits for society.

MD Mag: There has to be some societal changes in the way polypill is accepted and viewed, but what would it mean to a lot of these low- and middle- income countries that are stricken with incredible rates of atherosclerotic cardiovascular disease? What would it mean to them to have a cost effective option to treat this disease?

Kazi: Yeah, so thank you for asking. So, now we're talking about the economics of heart disease in low- and middle-income countries. We think of heart disease is a health condition for the wealthy. But we now know that it's not the case 80% of heart attacks and strokes happen among low and middle income countries, which where 80% of people live. So the rates are about the same as in high income countries. But they happen when patients are younger, in low and middle income countries.

So, we have our first heart attacks in the US, typically around the age of 62. In the US, in India, it's between 52 and 55. So almost a decade earlier in life. for low and middle income countries, the distinction between something that's cost saving and cost effective, is an important one. cost saving means that not only does the intervention pay for itself in the long term, in fact, you know, earn some money in return. So by switching to the polypill all the same things that you're making, from avoiding heart attacks, etc, over a five year period, if we are able to get the quality of the good price, these countries will actually save money.

So, certainly breakeven, the Maven save money, in contrast to the polypill were to be more expensive than that, there would still be a lot of lives saved, but there would be some money that has to be spent by the country in order to save those lives. So, it's a good value for money, but the countries still have to add that to the health care budget. And as you were alluding to, these budgets tend to be tight healthcare budgets are tight and low and middle income countries, they don't have the room to suddenly allow for a new expenditure, even if it's very cost effective.

So, what we're trying to say is that this is good value for money. The secondary prevention, polypill price correctly used correctly, is good value for money from a societal perspective. But it will require strategic thinking on a how to make the pill widely and reliably available in these countries where supply chains can be difficult. And at the same time, have physicians and other providers use this drug more widely. So we're providing the evidence days, but I think this is only getting us halfway down. We're going to need strategic global investments to reduce the cost of the polypill and to increase uptake of the polypill in these countries.

MD Mag: Okay, and then just lastly, why don't you think we'll ever see the implementation of polypill in the US or other "developed" nations?

Kazi: Yeah, so the so the poly pill in, in higher income countries, has also been a source of considerable controversy. And if you look at some of our leading cardiovascular providers talk with the polypill, it's like, well, I don't want a one size fit all fits all — I want to be able to customize my therapy for the individual patient. I think in reality, the challenges that patients don't want to take multiple pills, they'd love to have their pills, all rolled into a single pills, and they're taking 1 pill twice a day instead of 5 pills twice a day. And similarly, physicians would be only writing for one prescription. I think all of the advantages that we're talking about in low and middle income countries also exist in high income countries.

There are polypills available in Europe, there are, we're already using fixed dose combination pills for hypertension in the US. So slowly, but surely, we're seeing polypills being used more frequently in cardiovascular disease. But this particular quality bill that we're talking about the polypill for people who have already have heart disease, or have had a stroke in the past is not available in the US market. And we'd like to see that change. I think that with more and more data coming around, both from PolyIran, and from simulation modeling studies like ours, there is a new evidence base saying that this drug is effective and safe, is cost effective.

So, if the demand were to increase in the US, I'm optimistic that we see a poly bill available for our populations, I don't think that the political is a single pill in the US and in the US it might be 7 polypills with varying doses of various drugs. So you can still pick and choose what's the right combination of drugs for your patient. But what the patient sees is a single pill, which would be very good for them.

MD Mag: Right now, that was about it on my questions before I let you go with Is there anything else about politics that you want to share with our listeners that you think is important that I might not have asked you about?

Kazi: Yes, I think it's important to at this stage to make a distinction between a cardiovascular polypill for primary prevention, and a cardiovascular polypill for secondary prevention — meaning those who are at high risk for disease versus those who already have the disease. What we've studied in our analysis is exclusively patients who have preexisting disease, and so our conclusions cannot be extrapolated to people who are at high risk but don't currently have disease. In contrast, the PolyIran study included individuals both in primary prevention and secondary prevention categories, and showed the polypill works.

We, as clinicians, and cardiologists have to understand that, while there is value in precisely fine tuning, each other being the digital medications for our patients, sometimes what our patients want is a single pill, because it improves adherence. And what the health system might need is simply getting more people on the medications, so that we can have fewer heart attacks and strokes. This is a global problem, we're starting to see this cardiovascular disease on the rise again in the US as well. And so we're going to require we're going to have to think creatively about solutions to tackle this problem at scale.

At the same time, the polypill is not a silver bullet, it's not going to fix all our problems. And as we try and think of creative ways to tackle cardiovascular disease in low and middle income countries, we're going to know we're going to have to acknowledge that the polypill is one piece of the our armamentarium and we're going to have to invest in high quality primary care and ensuring reliable supply chains for medications and ensuring that patients who have a heart attack or stroke and get diagnosed correctly and started on effective lifesaving treatments quickly. And those strategic investments still need to happen. And given the scale of the problem, the time to act on them as now.

MD Mag: That's it for this edition of DocTalk. Thank you again Dr. Kazi for taking part. For the latest on polypill and in cardiovascular news, be sure to head to MDMagazine.com. Thank you for listening.