If you take blood pressure medications you probably have some interest in following your own blood pressure. But what many people don’t know is what target blood pressure they should be aiming for. If your blood pressure after treatment is 140/85, say, is that good or bad?
The SPRINT trial (Systolic Blood Pressure Intervention Trial) set out to answer that question. It was funded by the NIH (National Institutes of Health) and the results were published in 2015.
SPRINT was a randomized controlled trial in which 9361 people with a systolic blood pressure between 130 and 180 were randomized to have their systolic blood pressure treated to a target of less than 120 (intensive treatment) or a target of 135 to 139 (usual treatment).
So far, so good. 9361 is a nice big number, and being funded by the NIH rather than some pharmaceutical company that’s looking to sell more of its drugs makes me more prone to trust the data.
In order to be accepted to the study it wasn’t enough to just have an elevated blood pressure. You also had to be over 50 years of age and have known heart disease or kidney disease, or be over 75 years of age, in which case you didn’t have to have any known diseases to qualify. For some reason people with diabetes or prior stroke weren’t allowed to take part in the trial.
Now this is problematic. Choosing to limit your study to people over 50 makes sense, because people under 50 are exceedingly unlikely to have any health problems as a result of their high blood pressure, so you would need an astronomically large number of participants to see any measureable effect over the five years or so of your average clinical trial. Hypertension takes decades to cause noticeable disease.
But only taking people with known heart and kidney disease is a problem, because it means the results can’t be generalized to people who are otherwise healthy and only have an elevated blood pressure. This is a big segment of the population, and because the trial chose to not include them, no conclusions can be drawn as far as that group is concerned. Additionally, people with diabetes and people who have had a stroke are also big segments of the population, and not including them just makes the results even less generalizeable, and therefore less worth listening to.
For practical reasons this trial was open-label, which means that both the patients and the treating physicians knew what drugs they were taking and whether they were in the intensive or standard treatment arm. This is understandable, because it would have been logistically much harder to do the study in such a way that it was completely blinded. But it is also problematic – there is much more scope for manipulation of the data in an unblinded study, and it doesn’t even have to happen for malign reasons. Pretty much everyone involved in doing a study wants it to be a success and lots of people acting in little ways to make the results look better can end up skewing the end result completely.
In the initial plan for the study, the patients were going to be followed for an average of five years. Unfortunately, the study was halted after just three years. This is a huge problem, and makes the study much less reliable. The reason for this is a statistical phenomenon known as “regression to the mean”. According to this phenomenon, the more data you collect of any type, the closer you will get to the mean value. The fewer data points you have, the more wild your results are likely to be, just due to chance. When you stop a study part of the way through, you are generally stopping it at the point when the results look most favourable (if the results had been less favourable, the study wouldn’t have been stopped at that point). So if you stop a five year study at the three year mark, the results will generally look more impressive than if you had followed through for the full five years. This is why pharmaceutical companies like to stop their studies early, at least if the results are good.
Anyway, we’ll look at the results, and then we can discuss how much merit they have. The intensive treatment group had an average of three blood pressure lowering medications and an average systolic blood pressure of 122, while the standard treatment group had an average of two blood pressure medications and an average systolic blood pressure of 135. In the intensive treatment group 3.3% were dead after three years, while 4.5% were dead in the standard treatment group. That is an absolute difference of 1.2 percent, and although it was small, it was statistically significant. Basically, for every 83 people who received intensive treatment, one less person died over the course of three years (100/1.2=83).
Now we get to the interesting part. If we ignore for a moment all the flaws in the study and assume that the 1.2 percent difference is real, then what we need to consider is what the negative effects of treatment were, since that is what determines if we think it is worth following a treatment that decreases our three year risk of dying by 1.2%
So what were the negative effects?
The most common problem I see in the emergency room from people who are treated with blood pressure lowering medication is feinting and falls. In the intensive treatment group 2.3% feinted, while in the standard treatment group 1.7% feinted, so an absolute difference of 0.6% Luckily, this increase in feinting didn’t seem to increase the frequency of injurious falls. 7.1% of patients experienced an injurious fall in both groups. No difference at all.
Another negative effect of increasing the intensity of treatment was an increased frequency of acute renal failure. In the intensive treatment group 4.4% suffered an episode of acute renal failure, compared with 2.6% in the standard treatment group. That is an absolute difference of 1.8% .
Additionally, there was in the intensive treatment group an increase in electrolyte abnormalities like hyponatremia (increased from 2.1% to 3.8%) and hypokalemia (increased from 1.6% to 2.4%).
One problem I have with the study is that no data was gathered on how people felt their quality of life was, so we simply don’t know. If lowering people’s blood pressure down to 120 makes them live a bit longer but makes them feel like crap, then the trade-off probably isn’t worth it.
One weird result of the study is that orthostatic hypotension (a drop in blood pressure when standing) was more common in the standard treatment group (18.3%) than in the intensive treatment group (16.6%). This makes absolutely no sense, and in itself makes me question the whole study. The more blood pressure medicines someone is on, the more likely they should be to be orthostatic, physiologically speaking, because blood pressure medicines have a negative effect on the body’s mechanisms for maintaining perfusion to the brain when you go from sitting to standing.
Now, do I think the 1.2% improvement in survival over three years is real? No, I don’t. Why not?
1. Because the study was stopped early, at a point when it most likely showed a bigger benefit than it would have done if followed through for five years.
2. Because the study was open-label, which created lots of opportunities for those carrying out the study to adjust the results in a more favourable direction.
3. Because orthostatic hypertension was more common in the standard treatment group, which makes no sense, and suggests that the results are not reliable.
Conclusion: A more aggressive blood pressure treatment aimed at lowering blood pressure to less than 120 may marginally improve life expectancy, but also increases the frequency of feinting, acute renal failure, and electrolyte abnormalities, and we don’t know anything about the effect on experienced quality of life. So you may, potentially, maybe, just might, live a little bit longer, but you’ll probably also be spending significantly more time in the hospital. Note that this only applies if you are over 50 years old and have heart disease or kidney disease. If you are younger than 50 or don’t have these underlying conditions, then the benefit to intensive blood pressure management is likely to be even less.
You might also be interested in my article detailing how much of an effect salt consumption has on your blood pressure or my article about how much longer you can expect to live if you take statins.