It’s always exciting to learn about the “next big thing” in medicine.
The scientific advancement in healthcare is pretty breathtaking - look no further than the incredible speed of the development of safe and effective COVID vaccines.
But as we’ve been learning with vaccinations, healthcare implementation is way harder than healthcare innovation. Innovation is much more exciting, but implementation is what makes the real difference in outcomes.
And so it’s not surprising that we would probably rather learn about the development of a vaccine to cure heart disease and genetically engineered T-cells that fight cancer than about the boring efforts to get more people to take their blood pressure medications.
But getting vaccine distribution right and helping people to adhere to taking their medications is much more important for the outcomes that we care about.
So I wanted to spend this newsletter discussing a an implementation innovation in cardiovascular disease that’s captured my fascination: the polypill.
What is a polypill?
It’s exactly what it sounds like.
A polypill is a pill that has multiple medications in it. Poly comes from the Greek word for “many” and pill is self explanatory.
A polypill for heart disease contains a number of different types of cardiac medications, not multiple medications of the same type. The medications come in fixed doses, so there’s no adjustment over time. The Polycap pill, which I’ll talk more about below, comes with 5 different medications in it, dosed below the maximum amount that we will prescribe.
Aspirin 100mg - a blood thinner to prevent blood clots causing heart attacks
Simvastatin 40mg - a statin cholesterol medication, generic for Zocor
Atenolol 50mg - a beta blocker, blood pressure medicine
Ramipril 5mg - an ACE inhibitor, another blood pressure medicine
Hydrochlorothiazide 12.5mg - a diuretic, another blood pressure medicine
But a polypill isn’t just exciting because it’s a single pill with a bunch of different medications. It’s exciting because of how it reduces the risk of heart problems.
A polypill reduces cardiovascular disease
The case for a polypill is pretty simple - taking a polypill reduces cardiovascular disease compared to a placebo in people at risk for cardiac events.
This has been tested in a couple of different clinical trials, most recently highlighted with the TIPS-3 trial published in the New England Journal of Medicine earlier this year, which looked at a specific polypill called Polycap in an international population across India, Canada, Columbia, and a number of other countries.
I always take a look at the outcome curves in any trial, and it’s interesting to review it for this polypill. The horizontal axis here is time and the vertical axis is cardiovascular disease. You’ll see that a polypill decreases cardiovascular disease over time:
The most interesting aspect of this chart is the shape of the curves - their slopes are different and diverging more as you go further along in time. At the conclusion of the trial, these curves are still separating, telling us that efficacy is increasing over time.
That means the longer you take the polypill, the more your risk of cardiovascular disease is reduced.
This makes sense with what we know about the biology of cardiovascular disease - it’s a long term process related to cumulative exposure to a variety of different risk factors. It’s area under the curve rather than single snapshot in time.
Almost all effective treatments for heart disease will have a similar shape to the curves, where by reducing an exposure over the long haul we see an ongoing increased benefit in terms of disease.
Why is this so exciting to you? It seems kind of boring
Well, I get that it feels boring to take a bunch of old medications (including ones that are certainly no longer considered the standard of care) and see a small reduction in heart disease risk.
I’m fascinated with this for a few reasons:
It’s really hard to reduce heart disease in a group of people that’s never had a heart attack or a stroke, and a polypill seems to do that. Most treatments tested in this way (preventing a first heart attack or stroke) are not successful.
Getting people to take multiple medications is really challenging in the real world, for a variety of different reasons, and a polypill can solve that issue for a really common medical problem. Ease of implementation matters.
These aren’t even close to the best medications in their class. It’s easy to imagine improving on this polypill to generate even better outcomes. I will sometimes joke with my residents that the only indication to put someone on atenolol or simvastatin is that you have a doctor who doesn’t keep up with the literature and know about better treatments.
So we have an easy to implement intervention that seems well tolerated and fairly straightforward to adhere to. Eliminating dose titration simplifies the treatment process even more.
Easing barriers to treatment adherence is one of the most important things that we can do
I take care of patients every day, so I’m always hearing stories about the difficulties of medical treatments: they’re expensive, some require frequent bloodwork to evaluate safety, prescriptions can run out, and it’s hard to take any medication that’s more than once a day.
These barriers to care are most difficult to navigate for our most vulnerable patients so they perpetuate medical inequality.
But just because you can navigate these barriers doesn’t mean that you want to navigate them. The US health care system is a tremendous annoyance even for many people who can afford their care.
A polypill exciting to me because it helps to solve a lot of the problems I see everyday.
If the contradiction between the rapid innovation of a COVID vaccine and the glacial pace of vaccinations has a lesson for us, it’s that ease of implementation is incredibly important. And while the vaccine provides the most recent and salient example, there are microversions of the implementation problem playing out in communities and doctors offices around the world everyday.
Maybe more polypills is a solution to consider moving forward.
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