Intensive Blood Pressure Targets Could Benefit Clinical CKD Populations, Study Finds

New research is highlighting the transportability of outcomes observed in the Systolic Blood Pressure Intervention Trial (SPRINT) to patients with chronic kidney disease (CKD) in clinical practice, suggesting the potential population-level benefits of implementing intensive blood pressure targets in CKD populations.1

Leveraging data from the Veterans Health Administration (VHA) and Kaiser Permanente of Southern California (KPSC) for SPRINT-eligible adults with CKD, the comparative effectiveness study found trial results were transportable to the clinical populations and corresponded with similar or more favorable benefits on the absolute scale.1

An open-label nonblinded randomized clinical trial, SPRINT enrolled adults without diabetes and with hypertension and elevated cardiovascular risk, indicated by the presence of CKD or other cardiovascular risk factors. In the study, 9361 participants were randomly assigned to a treatment target of systolic BP < 120 mm Hg versus < 140 mm Hg and followed from randomization until dropout, death, or trial termination.2

SPRINT results showed targeting a systolic BP of < 120 mm Hg resulted in lower rates of fatal and nonfatal major cardiovascular events and death from any cause than targeting < 140 mm Hg, but significantly increased rates of some adverse events were observed in the intensive-treatment group.2

“One of the main points of controversy concerning the KDIGO BP target is the uncertain generalizability of SPRINT to adults with CKD in clinical practice,” Manjula Kurella Tamura, MD, MPH, a professor of Medicine at Stanford University and director of the Palo Alto Veterans Affairs Geriatric Research and Education Clinical Center, and colleagues wrote.1

To assess whether the beneficial and adverse effects of intensive versus standard BP control observed in SPRINT are transportable to a target population of adults with CKD in clinical practice, investigators conducted a comparative effectiveness study using 2 populations with CKD who met the eligibility criteria for SPRINT between January 1 and December 31, 2019, in the VHA and KPSC. Patients were required to meet the following inclusion criteria from SPRINT:

• ≥ 50 years of age
• Systolic blood pressure of 130 to 180 mm Hg
• Increased risk of cardiovascular events, defined by ≥ 1 of the following: clinical or subclinical cardiovascular disease other than stroke; CKD, excluding polycystic kidney disease, with an estimated glomerular filtration rate (eGFR) of 20 to less than 60 ml per minute per 1.73 m2 of body-surface area, calculated with the use of the four-variable Modification of Diet in Renal Disease equation; a 10-year risk of cardiovascular disease of ≥ 15% on the basis of the Framingham risk score; or age of ≥ 75 years.

The outcomes used in the present analysis are those defined in SPRINT: the primary outcome was a composite of myocardial infarction; acute coronary syndrome; stroke; heart failure; or death from cardiovascular causes, based on adjudication. The secondary outcomes included all-cause mortality; individual major adverse cardiovascular events; adjudicated dementia and mild cognitive impairment; CKD progression; and individual components of the CKD outcome.1

​​A total of 85,938 patients from the VHA and 13,983 patients from KPSC were included in the analysis. In the VHA cohort, the mean age was 75.7 years and 95.0% of patients were male. In the KPSC cohort, the mean age was 77.4 years and 38.4% of patients were male.1

Using SPRINT data for 9361 participants with a mean age of 67.9 years and were predominantly (64.4%) male, investigators replicated the sample mean treatment effect in the trial population for the primary and secondary cardiovascular, cognitive, and kidney outcomes and adverse events. They then assessed treatment associations in the primary target populations, SPRINT-eligible adults with CKD in the VHA and KPSC.1

Results showed the associations of intensive versus standard BP control with major cardiovascular events, all-cause death, and adverse events were transportable from the trial to the VHA and KPSC populations. However, investigators noted treatment effects on the primary cognitive outcome of dementia were not transportable in both the VHA and KPSC populations, and while the effects of intensive BP treatment on CKD progression were transportable to the KPSC population, the same did not apply to the VHA population.1

Further analysis revealed intensive versus standard BP treatment was associated with lower absolute risks for major cardiovascular events at 4 years by 5.1% (95% CI, −9.8% to 3.2%) in the VHA population and 3.0% (95% CI, −6.3% to 0.3%) in the KPSC population and higher risks for adverse events by 1.3% (95% CI, −5.5% to 7.7%) in the VHA population and 3.1% (95% CI, −1.5% to 8.3%) in the KPSC population.1

Investigators acknowledged multiple limitations to these findings, some of which included the potentially biased assumptions of transportability analyses; the use of estimate agreement rather than requirement agreement; transportability analyses’ inability to overcome limited power for infrequent outcomes; the use of BP measurements in routine practice to define trial eligibility; and the inability to independently validate the estimates produced by transportability analyses.1

“This example highlights the potential for transportability methods to provide insights that can bridge evidence gaps and inform the application of novel therapies to patients with CKD who are treated in everyday practice,” investigators concluded.1

References

1. Tamura MK, Huang M, An J, et al. SPRINT Treatment Among Adults With Chronic Kidney Disease From 2 Large Health Care Systems. JAMA Network Open. 2025;8(1):e2453458. doi:10.1001/jamanetworkopen.2024.53458
2. The SPRINT Research Group. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Eng J Med. doi:10.1056/NEJMoa1511939