ORLANDO, Fla. — A systolic BP target of less than 120 mm Hg was associated with lower rates of death and CV events compared with a target of less than 140 mm Hg, according to results from the SPRINT trial.
Top-line results of the large NIH-funded trial were made public in September. Researchers presented full results at the American Heart Association Scientific Sessions and the data were published in The New England Journal of Medicine.
Appropriate BP targets for reduction of CVD and mortality have been a controversial topic in recent years, with multiple guidelines coming to different conclusions.
Paul K. Whelton
Paul K. Whelton, MB, MD, MSc, from the department of epidemiology at Tulane University School of Public Health and Tropical Medicine, said investigators for the SPRINT trial randomly assigned 9,361 people with systolic BP ≥ 130 mm Hg and high CV risk but no diabetes to an intensive treatment regimen with target systolic BP < 120 mm Hg or a standard treatment regimen with target systolic BP < 140 mm Hg.
The primary outcome was a composite of MI, other ACS, stroke, HF and death from CV causes. Another outcome of interest was all-cause mortality.
“SPRINT was designed to examine the effect of more intensive [BP] reduction than we currently are recommended to use in patients on antihypertensive therapy,” Whelton said during a press conference. “Overall, we deem that the benefits are outweighing the potential for risk.”
Effect on BP
At 1 year, mean systolic BP was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the standard-treatment group, Whelton said. During the study period, the intensive-treatment group was prescribed an average of 2.8 hypertensive medications compared with 1.8 for the standard-treatment group. All prescribed medications were guideline-directed therapies commonly used for BP reduction, he said.
According to Whelton, SPRINT was stopped after a median follow-up of 3.26 years because the researchers observed a much lower rate of the primary outcome in the intensive-treatment group: 1.65% per year vs. 2.19% per year; HR = 0.75; 95% CI, 0.64-0.89. The curves began to separate at 1 year and widened over time, Whelton said.
In addition, he said, all-cause mortality was lower in the intensive-treatment group than in the standard-treatment group (HR = 0.73; 95% CI, 0.6-0.9). According to the researchers, the curves for mortality separated at 2 years, and death from CV causes was 43% lower in the intensive-treatment group (HR = 0.57; 95% CI, 0.38-0.85).
The number needed to treat to prevent one primary outcome event was 61. The number needed to treat to prevent one death was 90 and to prevent one CV death was 172, according to results presented.
The results were consistent across all subgroups. Treating death as a competing risk in a Fine-Gray model did not change the results for the primary outcome (HR = 0.76; 95% CI, 0.64-0.9).
HF impacted greatly
Among components of the primary outcome, the one that favored the intensive-treatment group the most was HF (HR = 0.62; 95% CI, 0.45-0.84), according to the researchers. MI and stroke favored the intensive-treatment group to a lesser extent (HR for MI = 0.83; 95% CI, 0.64-1.09; HR for stroke = 0.89; 95% CI, 0.63-1.25), and there was no difference in ACS (HR = 1; 95% CI, 0.64-1.55). Patients with prior stroke were excluded from SPRINT, so that might explain why the stroke results were not as dramatically different as those for HF, Whelton said.
“There was a very powerful effect on those with HF,” Whelton said. “HF itself was very carefully specified. It’s not just edema; almost all were hospitalized and seriously sick with HF.”
The overall rate of serious adverse events was similar in both groups (intensive-treatment group, 38.3%; standard-treatment group, 37.1%; HR = 1.04; P = .25).
However, Whelton said, serious adverse events related to hypotension, syncope, electrolyte abnormalities and acute kidney injury or failure were higher in the intensive-treatment group compared with the standard-treatment group.
There was no difference between the groups in rate of injurious falls, a common adverse event in people with hypotension. Nor was there a difference in bradycardia.
The intensive-treatment group was more likely to have a serious adverse event definitively related to the intervention (4.7% vs. 2.5%; HR = 1.88; P < .001).
Adverse event pattern and magnitude was similar for those aged 75 years or older and the overall cohort, Whelton and colleagues found.
In patients with chronic kidney disease at baseline, there was no difference between the groups in a decrease ≥ 50% in estimated glomerular filtration rate or onset of end-stage renal disease, according to the researchers. Among those without CKD at baseline, the intensive-treatment group was more likely to have a decrease in eGFR by at least 30% to < 60 ml/min/1.73m2 (1.21% per year vs. 0.35% per year; HR = 3.49; 95% CI, 2.44-5.1).
“In the group without kidney disease, we set a lower threshold and did see a signal,” Whelton said. “It was a little more common to see slight reductions [in eGFR]. We don’t exactly know what that means. It’s something we need to follow up on.”˗ by Erik Swain
Whelton PK, et al. Late-Breaking Clinical Trials 5. Presented at: American Heart Association Scientific Sessions; Nov. 7-11, 2015; Orlando, Fla.
The SPRINT Research Group. N Engl J Med. 2015;doi:10.1056/NEJMoa1511939.
Disclosure: The study was funded by the NIH. Whelton reports receiving nonfinancial support from Arbor Pharmaceuticals and Takeda Pharmaceuticals. See the full study for a list of the other researchers’ relevant financial disclosures.