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

Abstract

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.

Figure 1.. PRISMA Diagram of Selection of Studies for Meta-analysis

BP indicates blood pressure; CKD, chronic kidney disease; and PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Figure 2.. Effect of Intensive Blood Pressure (BP) Lowering on Risk of Mortality in Hypertensive Trial Participants With Chronic Kidney Disease

In the 18 included trials, there were 584 deaths among 7451 participants in the more intensive BP arm and 709 deaths among 8473 participants in the less intensive BP arm during the trial phase. The trial by Howard et al had no mortality outcomes in both BP arms (more intensive vs less intensive) and was dropped from the analysis.

Figure 3.. Studies Evaluating Intensive Blood Pressure Control Relative to Mortality Among Persons With Chronic Kidney Disease

A symmetrical inverted funnel implies no publication bias. Each open circle represents an individual published study.

Figure 4.. Effect of More Intensive Blood Pressure (BP) Lowering on Risk of Mortality in Patients With Chronic Kidney Disease Stratified by Subgroups

Shown are the results among adults with estimated glomerular filtration rate less than 60 mL/min/1.73 m². Among the 18 trials, only 12 included individuals with diabetes. BP indicates blood pressure; SBP, systolic blood pressure.