The NNT

I am one of the few medical students that actually enjoyed learning Biostatistics. This is the field of math doctors and scientists use to evaluate studies and make decision on how best to improve healthcare outcomes.

I love biostatistics because the math allows the implications of the research to blossom like a flower. You can see both how powerful some interventions are as well as catching inaccurate conclusions that are not supported by the data. In short, knowing your biostats helps me be a fully informed consumer of health research information.

One of the common measures used in this field is the "Number Needed to Treat" also referred to as the NNT. The NNT the average number of patients who need to be treated with a specific intervention to prevent one additional outcome.

Two examples using statins:

• The NNT for statins preventing heart attacks in patients with no known history of heart disease over a 5 year period is 104.

  • This means that you need to treat 104 patients with no known history of heart disease (what we call in the field 'primary prevention') with a statin for 5 years to prevent the occurrence of one heart attack compared to the same population not taking statins.

    
    

• The NNT for statins preventing strokes in patients with no known history of heart disease over a 5 year period is 154.

  • This means that you need to treat 154 patients with no known history of heart disease (what we call in the field 'primary prevention') with a statin for 5 years to prevent the occurrence of one stroke compared to the same population not taking statins.

In these examples we are using the NNT to see how many patients need to be treated to prevent a negative event from happening. However, the NNT can also be used to predict how many people will come to harm.

Two examples also using statins:

• The NNT for statins inducing diabetes in patients with no known history of heart disease over a 5 year period is 50.

  • This means that if you treat 50 patients with no known history of heart disease (what we call in the field 'primary prevention') with a statin for 5 years you can expect 1 additional patient to develop diabetes compared to the same population not taking statins.

    
    

• The NNT for statins inducing muscle damage in patients with no known history of heart disease over a 5 year period is 10.

  • This means that you need to treat 10 patients with no known history of heart disease (what we call in the field 'primary prevention') with a statin for 5 years you can expect 1 additional patient to develop signs of muscle damage compared to the same population not taking statins.

One limitation of the NNT is that it is based on a study that has a time limit. Most studies are 3-5 years long (the one we reference above is 5 years), with 7 years being on the longer end. That means the NNT needs to be take into context of time.

Let's dive into this 'time context' a bit deeper.

Bear in mind, as I will repeat ad nauseam, in the longevity medicine field, we are looking at interventions that affect the course of disease processes that take decades. You start developing the damage of cardiovascular disease in the form of fatty streaks in your arteries in late childhood/early adolescence (and in utero for families with hereditary lipid disorders). The process continues over multiple decades and only becomes clinically apparent starting in people's 50s and 60s.

So when taking an NNT from a 5 year study looking at people with no history of heart disease, preventing a heart attack in 1 out of 104 people over a course of 5 years is actually pretty impressive. If one were to extend the study over 10, 15, 30 additional years, it is reasonable to assume with what we know about the pathophysiology of the disease that the NNT would drop precipitously, and you would see a much smaller number needed to treat to prevent a heart attack compared to a similar group not taking a statin. Same holds true for stoke risk. Unfortunately, because of the cost and logistical hardship of running a multi-decade RCT, it is unlikely to ever happen.

But what about the diabetes?!

Yes, the NNT is much lower when it comes to bad outcomes like diabetes and muscle breakdown. But here is the rub. Both of those negative outcomes happen early, soon after starting the statin. They can be monitored easily with blood tests. AND they go away when you stop the drug. Awesome. We have way to monitor and mitigate.

In short, the desired outcomes take decades to manifest, where as the undesired outcomes happen fast and can be reversed by stopping the medication.

So, while the NNT may look underwhelming at first, in the context of the disease process we are fighting, it means that statins remain a potent drug in our arsenal when it comes to fighting cardiovascular disease.

As new medications are developed and come to market (e.g. Muvalaplin see below), and as current medications come off patent and fall precipitously in price (e.g. bempedoic acid) we will be able to improve these trade offs in NNT benefits vs side effects while keeping costs low.

By understanding NNT and applying it in the context of the disease state you are trying to mitigate, it becomes a powerful measure to translating clinical studies into clinical practice.

To see more about NNT and look up the NNT on different medications, I encourage you to visit the website https://thennt.com/