SPRINT's Impact on BP Management: 'Groundbreaking' but Many Questions Remain

Deborah Brauser

November 18, 2015

ORLANDO, FL — "I think the number-one take-away from SPRINT is: in this group of somewhat older hypertensives, there seems to be very convincing evidence of dramatic benefit" with a systolic BP target of less than 120 mm Hg, trial investigator Dr Paul K Whelton (Tulane University, New Orleans, LA) told heartwire from Medscape.

Dr Paul Whelton

However, Whelton pointed out that this lower level was just a target to try to get patients to a lower BP rate. "This isn't the same as a performance indicator, and we're not saying 100% of people need to be less than 120," he said.

Dr Daniel Jones (University of Mississippi, Jackson) told heartwire that the trial was impressive. Although the lowered BP target will require more attention on the part of patients in partnership with healthcare providers, "it's obviously worthwhile."

Jones, who was not involved with SPRINT, is a former president of the AHA and a member of the writing committee for the upcoming AHA/American College of Cardiology (ACC) BP management guidelines. "I certainly encourage the guideline group to look at lowering the goal systolic blood pressure and to consider broad generalization of the findings," he said.

Dr Suzanne Oparil

"I think the guidelines will change, but that's just a guess," said SPRINT coinvestigator and cochair of the Eighth Joint National Committee (JNC8) Dr Suzanne Oparil (University of Alabama at Birmingham).

However, "hopefully future guidelines will be careful in how they're worded, with an emphasis on individualized patient care," added Dr Sripal Bangalore (New York University School of Medicine, NY).

Dr Sripal Bangalore

Chatter erupted among experts and thought leaders last week after full findings of the much-anticipated SPRINT trial were released at the American Heart Association (AHA) 2015 Scientific Sessions and simultaneously published in the New England Journal of Medicine[1]. Whether they thought it was practice changing or needed more work, all agreed that this was one of the biggest stories coming out of the meeting.

Some Concerns

Official late-breaking clinical-trial discussant Dr Clive Rosendorff (Mount Sinai School of Medicine, New York City) called SPRINT a "groundbreaking trial" and noted that he was impressed with the large percentage of patients who are often underrepresented in other trials, such as older and black individuals, those with kidney disease, and those with or at high risk of developing CVD.

Dr Clive Rosendorff

He noted that two important findings were that intensive BP lowering had a greater impact on the participants who were 75 years or older vs those who were younger, "which goes against the guidelines and so need a rethink," and that even those who had baseline systolic BP of less than 132 mm Hg benefited from the intensive lowering therapy.

That said, he pointed out that in patients without chronic kidney disease (CKD) at baseline, there was a decline of at least 30% in estimated GFR in 1.21% of the intensive-therapy group per year vs 0.35% of the standard-therapy group (P<0.0001). "This could be due to the well-known renal hemodynamic reactions of more ARBs or more ACE inhibitors at higher doses. But still, that seems rather a large number." Also, 4.1% vs 2.5% of each respective group had acute kidney injury (AKI). "We don't know why and really look forward to seeing a more detailed analysis of the renal outcomes," said Rosendorff.

Complementary With ACCORD

As reported by heartwire , the >9000-person SPRINT trial of hypertensive patients at increased CV risk showed that targeting systolic blood pressure of less than 120 mm Hg rather than the standard target of less than 140 mm Hg was associated with significantly lower risks of the primary composite end point (MI, ACS, stroke, acute decompensated HF, and CV death), as well as all-cause mortality and CV death.

However, there were also significantly higher rates of hypotension, syncope, and AKI in the intensive-therapy group, which received roughly three antihypertensive medications, vs the standard therapy group, which received an average of two antihypertensives.

Although the trial excluded patients with diabetes, Whelton suggested that the study is complementary with the ACCORD trial, which did assess diabetics—but did not show a significant benefit with a systolic BP goal of 120 vs 140 mm Hg for its primary end point of composite CV events.

However, "we had twice the sample size in SPRINT and hit all the parameters for statistical power to answer the questions," said Whelton, adding that ACCORD had a more complicated design and roughly half the event rates that they expected, making them "stuck with a negative result." However, "it shouldn't be interpreted as meaning the treatment didn't work. I'd say it's more likely that we don't know if it did or didn't give benefit," he said.

"I'd also say the only way to answer this once and for all is to do another trial in diabetics that is better powered. But the practice community will need to make decisions before such a trial can be conducted, based on the data we have."

Dr David Goff

Dr David Goff (University of Colorado, Aurora) was an investigator for both the ACCORD and SPRINT trials. He told heartwire that the original plan was that ACCORD would answer BP-control questions in those with diabetes, whereas SPRINT would focus on other groups, including those who were older and those who had CVD and/or kidney disease.

Interestingly, new long-term results from ACCORD, which were also presented at the scientific sessions, suggest that intensive BP lowering may actually lead to significant benefits for diabetic patients.

Informed Patients Needed

The JNC8's current, and controversial, guideline on adult hypertension recommends treating to a target of 150/90 mm Hg in patients who are at least 60 years of age and to a target of 140/90 in those who are younger.

When asked about this, Oparil noted that "there is a big difference between 150 and 120," as targeted in SPRINT. And although "the trial gives quite strong evidence that lowering the blood pressure to 120 gave improvement [in a specific population], I'm not sure if the guideline committee will take that as a recommendation. They might try some intermediate level, based on extrapolation of this evidence," she said.

"This is just one study, but if I had a patient with characteristics of SPRINT and they could tolerate the medication and were willing to go through more steps of titration, I'd want to try to get them to 120. That's not to guideline, but it's what I think."

Although Bangalore voiced concerns with the trial's early termination, he said that it really comes down to discussing risks and benefits. "We need informed patients. Tell them that we can try to get to 120, but they'll need to take more medications and they may have side effects. So they need to let us know if that happens. That's key," he stressed.

What Now?

Dr Daniel Jones

A moderator at an earlier press briefing and at a late-breaking clinical-trial session, Jones also made a presentation here that was simultaneously published as an editorial in Hypertension[2].

In his talk, he noted that although SPRINT showed "remarkable results," there are still a lot of questions, especially regarding generalizability. Also, how is the so-called "J-curve" relationship affected by elevated BP, age, CV and cerebrovascular disease, chronic kidney disease, and diabetes? "What is uncertain is where the inflection point is on the J curve and how it's affected. SPRINT answered some of these questions but not all," said Jones.

He noted that further study is also needed on goal BP in patients with preserved and with reduced ejection fraction HF. And: can goal systolic BP lead to meaningful ways to prevent and treat obesity?

Overall, Jones noted that the guideline committee should consider "whether treatment recommendations should be based on global cardiovascular risk rather than blood pressure alone," as well as what the implications are of classifying BP.

"Where do we go from here? We should continue to increase efforts in hypertension-related research, including obesity and precision medicine," he said "And we should continue efforts to better implement lifestyle therapy with a strong focus on prevention in early childhood—and on improving food and physical-activity environments."

Cognitive and Renal Outcomes

Dr David Reboussin

SPRINT investigator Dr David Reboussin (Wake Forest University School of Medicine, Winston-Salem, NC) reported that the researchers are now assessing cognitive outcomes in the participants and expect to release their findings by the end of 2016.

The main secondary outcome in that analysis will be incident dementia, with other outcomes including global and domain-specific rate of cognitive decline and incident mild cognitive impairment.

In addition, "there is interest in doing exploratory analysis of some of our targeted subgroups, especially seniors and participants with CKD at baseline," said Reboussin, adding that "we're working with a team of nephrologists" to especially focus on what's happening with the renal outcomes.

"There's more work to be done, a lot more probing of the data. We owe that to the study participants and to science to take maximum advantage of the information and try to get data sets out as quickly as possible," concluded Whelton.

SPRINT was funded by the National Institutes of Health (NIH). Whelton reports nonfinancial support from Arbor Pharmaceuticals and Takeda, as does Reboussin, who also reports grant support from the National Heart, Lung, and Blood Institute (NHLBI). Oparil reports grant support, personal fees, and nonfinancial support from Medtronic; grants and personal fees from AstraZeneca and Bayer; grants from Merck, NIH/NHLBI, Novartis, and Arbor; and personal fees from Forest Laboratories, Amgen, Boehringer Ingelheim, and GlaxoSmithKline. Goff reports grant support from the NIH during the conduct of the study. Disclosures for the coauthors are listed in the paper. Rosendorff reported grant and/or other support from Eisai Pharmaceuticals, GlaxoSmithKline, McNeil Pharmaceuticals, Medtronic, and Abbott. Jones and Bangalore report no relevant financial relationships.

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