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Original Investigation
October 2017

Association Between More Intensive vs Less Intensive Blood Pressure Lowering and Risk of Mortality in Chronic Kidney Disease Stages 3 to 5A Systematic Review and Meta-analysis

Author Affiliations
  • 1Division of Nephrology and Hypertension, Department of Medicine, University of California, San Diego, La Jolla
  • 2Imperial Valley Family Care Medical Group, El Centro, California
  • 3Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, Canada
  • 4Department of Biostatistics and Bioinformatics, MedStar Health Research Institute, Hyattsville, Maryland
  • 5Georgetown-Howard Universities Center for Clinical and Translational Research, Hyattsville, Maryland
  • 6Department of Public Health and Primary Care, University of Cambridge, Cambridge, England
  • 7School of Biological and Population Health Sciences, Oregon State University, Corvallis
  • 8Division of Nephrology, Department of Medicine, University of California, San Francisco
  • 9Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah, Salt Lake City
  • 10Medical Service, Veterans Affairs Salt Lake City Healthcare System, Salt Lake City, Utah
  • 11Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
  • 12Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Oxford, England
  • 13Istituto Auxologico Italiano, Center of Clinical Physiology and Hypertension, Università Degli Studi di Milano, Milan, Italy
  • 14School of Public Health, Imperial College London, London, England
  • 15Care of the Elderly, Imperial College London, London, England
  • 16Research Unit Hypertension and Cardiovascular Epidemiology, Katholieke Universiteit Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium
  • 17Research and Development Group VitaK, Maastricht University, Maastricht, the Netherlands
  • 18Division of Preventive Medicine, Department of Family Medicine and Public Health, University of California, San Diego, La Jolla
  • 19Nephrology Section, Veterans Affairs San Diego Healthcare System, La Jolla, California
JAMA Intern Med. 2017;177(10):1498-1505. doi:10.1001/jamainternmed.2017.4377
Key Points

Question  Does intensive blood pressure lowering decrease the risk of mortality in patients with chronic kidney disease?

Findings  In this meta-analysis of 18 randomized clinical trials comprising 15 924 patients with chronic kidney disease, more intensive blood pressure lowering was associated with significantly lower risk of mortality compared with less intensive blood pressure control.

Meaning  Targeting more intensive blood pressure lowering may provide a mortality benefit in persons with chronic kidney disease.


Importance  Trials in patients with hypertension have demonstrated that intensive blood pressure (BP) lowering reduces the risk of cardiovascular disease and all-cause mortality but may increase the risk of chronic kidney disease (CKD) incidence and progression. Whether intensive BP lowering is associated with a mortality benefit in patients with prevalent CKD remains unknown.

Objectives  To conduct a systematic review and meta-analysis of randomized clinical trials (RCTs) to investigate if more intensive compared with less intensive BP control is associated with reduced mortality risk in persons with CKD stages 3 to 5.

Data Sources  Ovid MEDLINE, Cochrane Library, EMBASE, PubMed, Science Citation Index, Google Scholar, and clinicaltrials.gov electronic databases.

Study Selection  All RCTs were included that compared 2 defined BP targets (either active BP treatment vs placebo or no treatment, or intensive vs less intensive BP control) and enrolled adults (≥18 years) with CKD stages 3 to 5 (estimated glomerular filtration rate <60 mL/min/1.73 m2) exclusively or that included a CKD subgroup between January 1, 1950, and June 1, 2016.

Data Extraction and Synthesis  Two of us independently evaluated study quality and extracted characteristics and mortality events among persons with CKD within the intervention phase for each trial. When outcomes within the CKD group had not previously been published, trial investigators were contacted to request data within the CKD subset of their original trials.

Main Outcome and Measure  All-cause mortality during the active treatment phase of each trial.

Results  This study identified 30 RCTs that potentially met the inclusion criteria. The CKD subset mortality data were extracted in 18 trials, among which there were 1293 deaths in 15 924 participants with CKD. The mean (SD) baseline systolic BP (SBP) was 148 (16) mm Hg in both the more intensive and less intensive arms. The mean SBP dropped by 16 mm Hg to 132 mm Hg in the more intensive arm and by 8 mm Hg to 140 mm Hg in the less intensive arm. More intensive vs less intensive BP control resulted in 14.0% lower risk of all-cause mortality (odds ratio, 0.86; 95% CI, 0.76-0.97; P = .01), a finding that was without significant heterogeneity and appeared consistent across multiple subgroups.

Conclusions and Relevance  Randomization to more intensive BP control is associated with lower mortality risk among trial participants with hypertension and CKD. Further studies are required to define absolute BP targets for maximal benefit and minimal harm.