Hypertension management after the SPRINT trial

Anna Mathew, James Douketis

Dr Anna Mathew, nephrologist and associate professor of medicine at McMaster University, joins Dr James Douketis to discuss the results of the SPRINT trial and their effect on hypertension management in clinical practice.

SPRINT Research Group; Lewis CE, Fine LJ, Beddhu S, et al. Final Report of a Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med. 2021 May 20;384(20):1921-1930. doi: 10.1056/NEJMoa1901281. PMID: 34010531.

For a Publications of the Week article discussing the results of the SPRINT trial, click here.

James Douketis, MD: Hello, everyone. My name is Jim Douketis. It’s my pleasure to welcome you back to the McMaster Textbook of [Internal] Medicine Paper of the Week, McMaster Perspective. I’m pleased to have with me today Dr Anna Mathew, who is an associate professor of medicine at McMaster University and a nephrologist. We will be talking about the SPRINT trial and its effect on hypertension management. I should also mention that Dr Mathew has an interest [in] and runs a specific clinic on hypertension management. Welcome, Anna.

Anna Mathew, MD: Thank you so much for inviting me. It’s a pleasure.

James Douketis: It’s our pleasure as well. So, let’s get started with the SPRINT trial. This is a major landmark trial that was initially published ~4 or 5 years ago and now has been published again in terms of the long-term follow-up as well as the posttrial follow-up. How do you think, overall, this trial changes [the] landscape in terms of how we approach patients with hypertension? And how much of a practice-changing trial do you think it is?

Anna Mathew: The SPRINT trial was a landmark trial and it was published 5 or >5 years ago now, as you stated, and, [as] with all trials, the practice changing always takes a few years after the evidence comes out. But in Canada this was definitely a practice-changing trial. The newest 2020 Hypertension Canada guidelines directly reflect the SPRINT trial results. So, for those high-risk SPRINT populations—specifically those with chronic kidney disease and an estimated glomerular filtration rate (eGFR) between 20 and 60, for those elderly patients aged ≥75, for those with known cardiovascular disease, and for those with [a] high Framingham Risk [Score] of ≥15%—now the target blood pressure in the latest Canadian hypertension guidelines is a systolic [blood pressure] <120 [mm Hg]. That’s a direct practice-changing effect of the SPRINT trial.

James Douketis: Right, so we’re targeting the blood pressure perhaps a lot lower than, in some cases, many clinicians’ comfort levels. In fact, one of the issues I wanted to raise with you is how feasible a goal is this in everyday practice to have this really low blood pressure target, relatively speaking, and at the same time mitigate against the risk of adverse effects from perhaps excessive use of antihypertensive[s]? In other words, how do we get to that sweet spot? Is it really attainable in everyday practice?

Anna Mathew: I see that in my practice as well what you’re alluding to. I definitely agree. There is a bit of a narrow therapeutic window there. And I think it’s very important not to apply these guidelines beyond the target population that [the] SPRINT [trial] looked at and also to measure the blood pressure in the same way that the SPRINT trial did. So, I’ll just go into that a little bit.

You know, the trial did... Even though it did find ~25% relative benefit in terms of reducing that cardiovascular endpoint and the mortality endpoint in these high-risk groups, there was also higher risk of side effects, just like you say, acute kidney injury, hypotension, electrolyte abnormalities such as hyperkalemia and hyponatremia. Those are all seen [with] ~2% or 3% absolute [risk], but higher risk [was reported] in the intensive arm compared to the standard arm. So, how do we work around that in practice? These feasibility issues... I think the first thing is not trying to apply these guidelines beyond the groups that were included in [the] SPRINT [trial]. So, younger people [aged] <50 [whom] this may not apply to necessarily. In my practice, specifically, people with GFR >60, people with >1 g of protein [in the urine], people with an ejection fraction <35%, people with diabetes—were excluded from [the] SPRINT [trial]. So, you need to be careful when extrapolating these guidelines beyond the population included in [the] SPRINT [trial].

The second thing I think is… It’s important to measure the blood pressure the same way as [it] was done in [the] SPRINT [trial]. So, [if] you have a patient sitting in front of you and you’re standing in front of them measuring their blood pressure once, you will likely get a higher reading, falsely higher reading than they would get at home. And if you diagnose hypertension that way, you’re likely to overtreat the patient and perhaps induce more complications and side effects. So, the way the blood pressure was measured in [the] SPRINT [trial] and the way that we measure it in our hypertension clinic here in the Nephrology Department is [as follows]: The patient sits at rest, unattended, in a room for 5 minutes. There’s an automated cuff that’s placed on them. Three blood pressures are taken and the average is taken of that. And that’s how we check the blood pressure—similarly to how [it] was done in [the] SPRINT [trial]. You’re less likely to overdiagnose hypertension that way.

It’s also important to counsel your patients, right? So whenever I try to attempt this aggressive target, I counsel patients as to the reasons why, you know, and I go over the results of the SPRINT trial and [explain] why they are in this high-risk population. I go over the possible risks and I always individualize and tailor my treatment based on patient preference. So, those are some of the ways to get around this feasibility issue that you mentioned, which is a real issue that we see in the clinic.

James Douketis: So, in other words, no pun intended, we’re not sort of sprinting towards that low blood pressure target [in our] work.

Anna Mathew: No. [Not] for everybody.

James Douketis: We’re trying to do it carefully and we want to be aware of the potential adverse effects.

Anna Mathew: Yeah.

James Douketis: I had some other questions, but you know what? You’ve answered them all—[questions] about your practical insights as to how to manage patients with hypertension. Any last clinical pearls for our audience about hypertension management and what you would... might want to convey to them about this important and sometimes challenging patient population?

Anna Mathew: Oh, thank you. I think that there are some residual questions that are still remaining. There are patients [who] we see all the time, [in whom] we’re still not sure what the blood pressure target should be, in my opinion. So, again, people with chronic kidney disease, with more than 1-g proteinuria, or [with] GFR of <20—[it's] specific to my patient population, but we have questions about that. Patients with diabetes: The ACCORD trial, which was also a very well-done study, didn’t show that same benefit when intensifying the blood pressure control to <120 [mm Hg]. And it’s difficult for me to understand biologically why people with diabetes should be different than people without diabetes. It would be nice to have a consolidated blood pressure target that we can just use for all of our high-risk patients, but based on the evidence that we have now and based on the Hypertension Canada latest guidelines, we cannot apply the same target in all patients. So, whether more research needs to be done or how [should] we individualize that target—that’s a big residual question.

Then the last question is the diastolic [pressure] target. [The] SPRINT [trial] only looked at the systolic [pressure] target. So, what is the appropriate diastolic [pressure] target in these high-risk patients? We don’t know the answer to that [question]. Some people propose that a very low diastolic [pressure] target may actually increase the risk of some cardiovascular events. There is some newer observational study that doesn’t indicate that there might not be a lower threshold for diastolic pressure. That’s another residual question. Still lots of work to be done.

James Douketis: Anna, thank you so much for these valuable perspectives. Once again, it was our pleasure to have Dr Anna Mathew, associate professor of Medicine, McMaster University, Division of Nephrology. Thank you again and I think we’re gonna be hearing from you again, given these unanswered questions.

Anna Mathew: OK, thank you.

James Douketis: Bye-bye now. Thank you.

Anna Mathew: Bye-bye.

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