SPRINT Challenges Current Standard of Care for Patients Without Diabetes

On September 11, 2015, the SPRINT trial (Systolic Blood Pressure Intervention Trial) came to an appropriately swift conclusion, stopping years ahead of schedule at the request of the data and safety monitoring board, after early results revealed a significantly improved survival rate with intensive blood pressure treatment compared with standard treatment.^1,2

In the trial, investigators tested a systolic blood pressure target of less than 120 mm Hg (intensive treatment) vs a target of less than 140 mm Hg (standard treatment) in 9361 patients with a systolic blood pressure of at least 130 mm Hg and an increased cardiovascular risk. Patients did not have diabetes.

One-year results, which were reported at the American Heart Association Scientific Sessions 2015 and published in the New England Journal of Medicine, demonstrated that patients in the intensive arm (mean systolic blood pressure, 121.4 mm Hg) compared with the standard care arm (mean systolic blood pressure, 136.2 mm Hg) had a significantly lower risk for the primary composite end point of myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes (hazard ratio [HR]=0.75; 95% 0.64-0.89; P<.001), as well as a lower risk for all-cause mortality (HR=0.73; 95% CI, 0.60-0.90; P=.003).³

In light of these potentially transformative findings, experts interviewed by Endocrinology Advisor shared several key factors clinicians should keep in mind as they interpret these results and decide on how best to apply them in their practice.

Clinical Considerations

Hertzel C. Gerstein, MD, MSc, professor and director of the division of endocrinology and metabolism at McMaster University at Hamilton Health Sciences in Ontario, Canada, said one of the key drivers for the difference in the primary composite end point was the reduction of heart failure in the intensive arm.

“There was a 38% reduction in heart failure [P=.002], whereas the reductions in myocardial infarction [P=.19] and stroke [P=.5] with intensive therapy were much more modest,” Dr Gerstein said in an interview.

SPRINT researchers also found that rates of hypotension (P=.001), syncope (P=.05), electrolyte abnormalities (P=.02), and acute kidney injury or renal failure (P<.001), but not of injurious falls (P=.71), were increased in the intensive arm. ³

“Targeting a very tight blood pressure level is not without adverse consequences,” said Dr Gerstein. “So you are paying that cost for a reduction in death and heart failure.”

George L. Bakris, MD, professor of medicine and director of the Comprehensive Hypertension Center at the University of Chicago Medicine, noted that blood pressure is just one of the variables physicians should consider when assessing their patients.

“It is shortsighted to think you are done when you fix [blood pressure],” Dr Bakris told Endocrinology Advisor. “You have to look at cholesterol, glucose, comorbidities, and competing risks for death.”

Dr Bakris added that SPRINT investigators recruited patients who were relatively healthy in terms of their arterial status — those who typically do not come in with stiff vessels and blood pressures of 180/70 mm Hg.

“It’s not that [the trialists] excluded them, but those kinds of patients didn’t get into SPRINT, which is a concern because if you try to get those patients down to even 130 mm Hg, they experience a lot of side effects,” he said.

Reaching an ACCORD

In 2010, investigators for ACCORD (Action to Control Cardiovascular Risk in Diabetes), a trial with a similar protocol to SPRINT, tested an intensive therapy targeting a systolic blood pressure of less than 120 mm Hg vs standard therapy targeting a systolic blood pressure of less than 140 mm Hg in patients with type 2 diabetes, and found no significant effect on outcomes with the intensive approach.⁴

Dr Gerstein, who was an ACCORD investigator, highlighted differences between the 2 trials that may have contributed to the findings.

“In the ACCORD trial, the primary outcome was the composite of myocardial infarction, stroke, and death from a cardiovascular cause; in SPRINT, the composite was larger, as it included myocardial infarction, acute coronary syndrome, stroke, heart failure, or death from cardiovascular causes,” he explained. “In addition, people with diabetes have many more comorbidities than people without diabetes … and are more prone to falls and fractures.”

However, according to an analysis in an editorial accompanying the SPRINT trial, also published in the New England Journal of Medicine, the differences in outcomes between SPRINT and ACCORD may be less than they appear. Authors Vlado Perkovic, MB, BS, PhD, and Anthony Rodgers, MB, ChB, PhD, both from the University of Sydney in Australia, noted that their findings indicated that the effects on individual outcomes in both trials were generally consistent.⁵

“The main differences were that the ACCORD trial had less statistical power than SPRINT, and its primary outcome included a higher proportion of events that are less sensitive to blood-pressure reduction,” wrote Drs Perkovic and Rodgers.

After looking at the analysis, Dr Bakris agreed that there is equipoise between the 2 studies. “If you take all the end points together, there is a benefit seen in ACCORD,” he said.

Impact on Guidelines

One of the changes Dr Bakris expects as a result of the SPRINT findings is with current clinical guidelines.

“The international kidney guidelines — Kidney Disease: Improving Global Outcomes — are going to be modified, but not by much,” he noted. “The general [hypertension] guidelines from the American Heart Association and American College of Cardiology (the group that replaced the Joint National Committee) are definitely going to change.”

While the exact modifications have yet to be determined, Dr Bakris explained that a range for blood pressure would be a more reasonable target than a specific number.

“You don’t need to be below 125 [mm Hg] and you really shouldn’t be above 130 [mm Hg], and that sits beautifully with the SPRINT data because that is where things were. Some of the SPRINT senior investigators and I have talked, and they agree with this notion of a range,” he said.

“This is not physics; it’s biology,” Dr Bakris continued. “There is variability much greater than what you would expect and there was variability in the trial, so it is unreasonable to pick a number and go from that. It’s a guidepost.”

The new hypertension guidelines are slated for publication in 2016.⁶

Crossing the Finish Line

For Dr Gerstein, the data from SPRINT will help inform how he treats patients going forward, but what remains foremost in his patient care is treating patients as individuals.

“You have to individualize your care for the patient by doing a good history and physical examination, the right blood test, and deciding what their risks are for having an event,” he said. “With SPRINT, we now have another piece of evidence to incorporate into our decision-making. However, the evidence shouldn’t dictate how we manage patients, but rather it should inform how we manage them.”

Disclosures: Drs Bakris and Gerstein report no relevant financial disclosures.

References

1. Drazen JM, Morrissey S, Campion EW, Jarcho JA. A SPRINT to the finish. N Engl J Med. 2015;373:2174-2175. doi:10.1056/NEJMe1513991.
2. Landmark NIH study shows intensive blood pressure management may save lives [news release]. Bethesda, MD: National Heart, Lung, and Blood Institute; September 11, 2015. https://www.nhlbi.nih.gov/news/press-releases/2015/landmark-nih-study-shows-intensive-blood-pressure-management-may-save-lives. Accessed December 21, 2015.
3. The SPRINT Research Group. A randomized trial of intensive versus standard blood-pressure Control. N Engl J Med. 2015;373:2103-2116. doi:10.1056/NEJMoa1511939.
4. The ACCORD Study Group. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362:1575-1585. doi:10.1056/NEJMoa1001286.
5. Perkovic V, Rodgers A. Redefining blood-pressure targets — SPRINT starts the marathon. N Engl J Med. 2015;373:2175-2178. doi:10.1056/NEJMe1513301.
6. Hypertension guideline writing process underway [news release]. Dallas, TX: American Heart Association; February 17, 2015. http://newsroom.heart.org/news/hypertension-guideline-writing-process-underway. Accessed December 22, 2015.