Amy Pollak, MD: Greetings. I'm Dr Amy Pollak, an assistant professor of medicine and cardiologist at Mayo Clinic Florida, and today during Mayo Clinic Talks Podcast, we'll be discussing the SPRINT trial.
I'm thrilled to be joined by my colleague, Dr William Haley, a professor of medicine who specializes in nephrology and hypertension here at Mayo. Welcome, Bill.
William Haley MD: Thanks, Amy. Great to be here with you.
Dr Pollak: I'd like to start with having you tell us a little bit about the SPRINT trial. There's been a lot of press about this—a very exciting trial—and I'd like to learn a little more about what the SPRINT trial really looked at. What was your involvement in the SPRINT trial?
Dr Haley: SPRINT is a National Institutes of Health (NIH)-sponsored, multicenter, randomized, controlled trial that has what I like to call a lot of moving parts. It included nondiabetics (which is important) but otherwise a diverse population of patients with hypertension along with other major risks, such as known cardiovascular disease or known excess risk for cardiovascular disease, chronic kidney disease, and also advanced age. What SPRINT aimed to do was determine whether or not a blood pressure goal that is lower than what's currently recommended would result in a reduction in risk for cardiovascular disease, chronic kidney disease, dementia, and cognitive decline. So that was a big agenda.
SPRINT at Mayo
Dr Pollak: Absolutely, and it's an incredibly important study that's focusing on a really critical area: What blood pressure goal should we be focusing on for these higher-risk patients?
Tell me a little bit about our involvement here at Mayo Clinic Florida.
Dr Haley: We were fortunate to recruit almost 300 participants here in Florida. This turned out to be the most in our coordinating network, which is made up of about 20 centers. And right up to the last minute, we were also leading the entire SPRINT trial in terms of recruitment, so we were proud of that. I'd also like to make note of the fact that Drs Joseph Blackshear, Brian Shapiro, and Peter Fitzpatrick here at Mayo Clinic Florida were coinvestigators and a big help, as were Dr Michael Phillips in Internal Medicine and Dr Richard Presutti in Family Medicine.
In addition, I'd like to point out that we're involved in two major ancillary studies in SPRINT. One is called SPRINT Ambulatory Blood Pressure Monitoring; and, of course, 24-hour blood pressure monitoring can be very important in the interpretation of these results. The other is called SPRINT-FAST, which has to do with peripheral vascular disease and atherosclerosis—again, very important mechanistic topics.
Dr Pollak: Absolutely. When we look at this study, which is, as you pointed out, really higher-risk individuals, so their Framingham risk over the next 10 years on average, is about 20%, and as you also noted, the blood pressure goals were much more strict than we typically do in our day-to-day practice. Interestingly, about a third of the patients had an initial blood pressure <132 mm Hg, a third fell into the systolic blood pressure of 132-145 mm Hg, and then a third had a blood pressure >145 mm Hg. So this really is an important population of patients to be trying to determine: What is the goal blood pressure?
Stopping the Trial Prematurely
Dr Pollak: SPRINT was designed to have a median follow-up of 5 years but, instead, was stopped early at just 3.25 years. I'm interested to know your thoughts in terms of why there was this important decision to stop the trial prematurely.
Dr Haley: The NIH has a Data Safety Management Board that oversees trials such as this, and that board gets to see the results as we go along periodically, whereas the rest of us are blinded. We were expecting to run between 4 and 6 years on all the participants—which, by the way, was right at 9400 equally divided into the intensive arm group, which was the group that was targeted to <120 mm Hg systolic, and the standard group, which was targeted to a systolic <140 mm Hg.
The Data Safety Management Board found, at its August meeting, that they were going to recommend to the National Heart, Lung, and Blood Institute (NHLBI) that the blood pressure intervention management part of this trial be halted. The reason for that was that the benefit for the intensive arm compared with the standard arm for the primary outcome and for total mortality was significant. In fact, there was a 30% reduction in the composite endpoint that was made up of nonfatal myocardial infarction, acute coronary syndrome, nonfatal stroke, heart failure, and cardiovascular death. And there was also a 25% reduction in the risk for mortality.
In addition to all of that, it was said that the benefits of the lower blood pressure were outweighing the risk. So the NHLBI accepted that recommendation and agreed that these findings needed to be shared with the participants and with their primary care doctors at that point. And so we began to transition blood pressure management as of September of this year.
What's Next for SPRINT?
Dr Pollak: These are really pretty dramatic results, with this number needed to treat of 61 patients to have an impact on that primary outcome that you mentioned.
Is the SPRINT trial finished now? It stopped early. We have really impressive results. What are the next steps for the SPRINT trial?
Dr Haley: The SPRINT trial is not finished. This is very important. We had other agenda items, as you recall, so even though it was decided that we cannot continue the blood pressure goal part of this study, recall that we're also examining kidney disease, cognitive function, and dementia. Those results are still being analyzed, and data are being collected on those areas. Close-out visits will begin in a month or two.
Reconciling SPRINT and ACCORD
Dr Pollak: When we look at the results of the SPRINT trial, which, as you pointed out, was done in patients who are nondiabetics, and we try to then reconcile the impressive results we have compared with the ACCORD trial, which looked at similar blood pressure goals, although in a diabetic population, how do you reconcile the differences in the results we have for the outcomes based on the more intensive blood pressure lowering?
Dr Haley: The ACCORD trial is a good example of good intentions gone wrong, in a way. There's a real temptation with trials such as this to try to do too much; to think in terms of, well, it would be interesting to look at this and this while we've got this group of patients who are going to be under study. And that's what happened in ACCORD. They had a standard and intensive blood pressure arm, together with a standard and intensive glycemic arm, together with a standard and intensive lipid treatment group. In addition, their event rate was only about 50% of what was expected; and, to boot, they only had about 4700 patients, which is about half as many as in SPRINT.
The bottom line for all of that is that ACCORD was suffering from less statistical power than it really needed; and, in addition to all of that, its primary outcome included a higher proportion of events that turned out to be less sensitive to blood pressure reduction. In addition, SPRINT recruited an older cohort, with an average age of 68 years, rather than 62, and almost a third of our patients in SPRINT were 75 years old or older. And, in addition, SPRINT included a high-risk group of patients with chronic kidney disease, which was not included in ACCORD. So there are a lot of differences.
But the bottom line is that the wide confidence interval that was achieved in ACCORD did not exclude the possibility of a 25% to 27% benefit for the primary outcome, and that would be entirely consistent with SPRINT.
Applying the Results of SPRINT: Which Patients?
Dr Pollak: So when we look to the patients for whom we should be applying the results of this trial—this is really the fundamental question that, as practitioners, we're faced with in our day-to-day practice—when we try to determine which patients are going to be most likely to benefit from that more intensive goal of a systolic blood pressure of <120 mm Hg, who are the patients that you are focusing on for that more intensive goal based on the results of the SPRINT trial?
Dr Haley: This is a very important question and one that practitioners struggle with, especially given the fact that the JNC8 recommendations just a year or so ago suggested that, for patients over 60 years, perhaps 150/90 mm Hg was okay. It's important to recognize that that recommendation was based on available evidence at that time, and that report actually looked towards SPRINT to help get the answer. So we expect that those recommendations will be forthcoming in terms of changes.
In the meantime, the short answer is "stay tuned" because subgroup analysis is going to be important here. Those analyses are ongoing, and we expect there to be—in fact, I know there will be scores of publications coming out of SPRINT—at least 10 or 12 in the next several months that will help with this determination.
In the meantime, Dr Lawrence Fine, the NHLBI's Clinical Applications and Prevention branch chief, said it well, and I'd like to quote that, if I can. He said, "Our results provide important evidence that treating blood pressure to a lower goal in older or high-risk patients can be beneficial and yield better health results overall, but patients should talk to their doctor to determine whether this lower goal is best for their individual case."
Dr Haley: What I think needs to happen now is that individual patients should be talking to their doctors—their primary care doctors, their cardiologists, their kidney doctors, whoever it is that's responsible for their care—about this study, about the potential benefits and potential ill effects, of which were there were a number. There were what's called serious adverse events, including hypotension, syncope, and kidney and electrolyte abnormalities, in the lower blood pressure target group. However, that said, the risks of treating to the lower blood pressure target are really felt to be small relative to the potential gains in terms of cardiovascular outcomes. So it's an individualization situation, and we expect to get some help from more publications that are going to be coming out, addressing not only the subgroups but addressing these areas of concern such as development of acute kidney injury.
Dr Pollak: Dr Haley, I agree completely. I think that while we're waiting for that subgroup analysis, just as you outlined so nicely, we really need to individualize the results of the trial to the patient that we're seeing at that moment and have a discussion about the risks and the benefits of the more aggressive blood pressure lowering, I think, in general, because the SPRINT trial looked at nondiabetic patients at higher cardiovascular risk. These are the patients that I'm focusing on in my practice and having that discussion with and trying to decide: Do we need to achieve that lower blood pressure goal? The reduction in cardiovascular events and cardiovascular mortality is striking. The chances of having one of these adverse events—low blood pressure, syncope, electrolyte abnormalities, or kidney dysfunction—they're pretty small. They were there, for certain, but fairly small, and as you're looking at that risk-benefit ratio, that's where that discussion with the individual patient is so important.
Thank you so much for these very important insights into the SPRINT trial. I've learned a lot, and I think that, as you pointed out, there is more to come with how to really translate this pivotal trial into clinical practice and which patients are likely going to benefit the most.
Thanks to our listeners for tuning in to Mayo Clinic Talks at theheart.org on Medscape.
Cite this: William Haley, Amy Pollak. SPRINT: What Does It Mean for Blood Pressure Management? - Medscape - Jan 15, 2016.