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.
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