Saturday, September 3, 2022

People, patients, polypills, primary care and POEMs: Making your health better in the real world

A recent article in the New England Journal of Medicine, Polypill Strategy in Secondary Cardiovascular Prevention”, also covered by the New York Times, demonstrated that people who had previous cardiovascular events, (ie., myocardial infarction -- MI, heart attack, stroke or urgent need for bypass for impending MI), had fewer recurrent heart attacks, including fatal ones, strokes, and urgent needs for bypass if they were treated with one pill a day (“polypill”) that combined their recommended medications than they did if they took multiple pills multiple times a day. The conclusion (from the Abstract) summarizes it as:

Treatment with a polypill containing aspirin, ramipril, and atorvastatin within 6 months after myocardial infarction resulted in a significantly lower risk of major adverse cardiovascular events than usual care.

This is good news, if not entirely surprising. The effectiveness of medications in preventing recurrent disease is a combination of both how effective the medication is if “taken as directed” and how difficult it is for a person (or, from a doctor-centered perspective, how “compliant” a “patient” is) to take the medication as directed. For an example of what this means, consider birth control, where “theoretical effectiveness” (how effective a method of pregnancy prevention would be if "used as directed" 100% of the time) is contrasted to “use effectiveness” (how likely a person who is ostensibly using a particular method of birth control is to get pregnant). Obviously, what matters to a person who does not want to get pregnant is the latter, and this is greatly impacted by how easy it is to not use it. Condoms and diaphragms have to be used every time and oral contraceptives have to be taken every day, which can contribute to a lower use effectiveness than forms of contraception that do not require this, such as IUDs and implants, known as LARC, long-acting reversible contraception.

So back to prevention of heart attack: Who is surprised that taking one pill a day results in better compliance than taking more pills more often? Hands? No one? Maybe cardiologists, since the alternative was “usual care”, which must have been “multiple pills multiple times a day”. Any sentient person would know, without needing to be a doctor, scientist, statistician, or epidemiologist, that taking one pill a day is not only easier but much more likely to happen than taking multiple pills, and especially taking pills multiple times. Remember, the medication only works if you take it, and the harder you make it to take, the less likely people will and the less likely it is to work. Even drug companies know this; you probably have noticed that when a drug is about to lose its patent one of the first “new drugs” that the company comes out with is a long-acting version of it that you have to take only once a day! I cannot prove that they would have been able to release this in the first place but instead held it in reserve just for this reason, but I would not be surprised. One pill once a day is also likely to be cheaper (except while under patent) and this is a big issue for people who have difficulty affording their medications (ie., most of us, but especially those with lower incomes. In the US, of course).

Though it seems obvious that one pill a day is more likely to be taken, this research study is not without importance. For starters, it showed that it worked to take one pill combining 3 drugs once a day. After all, if it didn’t help prevent disease, it wouldn’t be desirable. That it worked better than “usual care” is almost certainly related to it being one pill once a day, and how difficult it is to remember to take pills more often. [Even those of you who do not have chronic disease: have you ever been given antibiotics to take 4 times a day for 10 days? How often have you actually taken all 40 within the 10 days, even after you’ve started feeling better sooner?] We may presume that taking the multiple pills multiple times a day would have worked as well if people had done it, but because they don’t, it didn’t work as well. The contribution of the study is to show that the one pill once a day works, and because it is one pill once a day, works better.

Another important thing that the study did  is to look at meaningful outcomes: death, repeat heart attack or stroke, need for bypass. This also seems like a “duh”, if you are a regular person, but it has been common in the literature to not measure these but often “intervening variables” such as changes in cholesterol level (or blood sugar, or whatever you are studying) because this is easier to do and requires less follow-up. But having lower cholesterol, for example, only matters to the extent that you are less likely to have a heart attack or stroke!

When this study first came out, I commented on FB and Twitter that

Family physicians and other primary care clinicians know this better than subspecialists, since they are focused on "what works best for the disease?" and we on "what is going to work for this person?"!’

Of course, this is, probably, not completely true for all family physicians and all subspecialists, but it is certainly true that it is more likely for primary care clinicians to think about and be aware of how a treatment affects the whole person. Subspecialists are usually concerned with treating one condition, “their” disease”, and at how the treatment they prescribe ameliorates that, while primary care clinicians are looking at how it affects the person’s life. One simple example is drug interactions and “side effects” (which are actually just effects, but not the effects we want). Primary care clinicians care for a person with all the conditions that they have and have to not only see how, for example, their heart disease medicine works for the heart disease but if it is bad for another disease they have, or if its side effects (or difficult regimen, multiple pills multiple times a day) means that they don’t take it.

In research, family physicians and other primary care clinicians have looked for Patient-Oriented Evidence (POE) as opposed to Disease-Oriented Evidence (DOE). DOE looks at whether a treatment, usually in an experimental setting (which often has many differences from real life, such as free medicine and people to remind you to take it!) makes a disease better, while POE looks at whether it makes the person’s life, as a whole, better. This is important, especially if you are a person. (Or probably if you are an animal!) Indeed, family physicians have taken this a step farther to Patient-Oriented Evidence that Matters (POEMs), with sections reviewing recent research that does featured in several family medicine journals. POEMs is, in addition to being a cute acronym, has meaning; not all evidence, disease or patient oriented, actually matters. For example, the study cited above: showing that using a polypill decreases your risk of cardiovascular events and improves your life matters, while simply showing a change in a lab value might well not.

It is really good that there are treatments for diseases, whether common (like heart disease) or rare (like, ironically, I just discovered a rare blood condition also called POEMS!) that can make you better. It is also really good that there are subspecialists who know about them and can make recommendations for treatment (especially for the rarer ones) and who keep up on the literature. But it is also important that there is someone keeping an eye on the person, the patient, with all their diseases and medicines and treatment regimens and side effects, and, oh yeah, the stressors of their everyday life with money, and family, and work (or not having work) and how in heck, in this country, they are going to pay for their treatment. These are the real components of real life, sometimes called the “social determinants of health”, that are poorly addressed by US healthcare.

Polypills are good, as are POEMs. And so are primary care clinicians, especially when their employers allow them sufficient time and encouragement to actually provide comprehensive care for their patients.

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