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Association Between More Intensive vs Less Intensive Blood Pressure Lowering and Risk of Mortality in Chronic Kidney
Rakesh Malhotra1,2, Hoang Anh Nguyen1, Oscar Benavente3
1Division of Nephrology and Hypertension, Department of Medicine, University of California, San Diego, La Jolla.
Insights
Intensive blood pressure control in patients with chronic kidney disease (CKD) significantly lowers the risk of death. This meta-analysis of randomized trials shows a 14% reduction in all-cause mortality for those with CKD stages 3-5.
Area of Science:
- Nephrology
- Cardiology
- Clinical Trials
Background:
- Intensive blood pressure (BP) lowering in hypertension reduces cardiovascular disease and mortality.
- However, intensive BP control may increase the risk of chronic kidney disease (CKD) incidence and progression.
- The mortality benefit of intensive BP lowering in patients with prevalent CKD is not well-established.
Purpose of the Study:
- 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.
- This systematic review and meta-analysis included randomized clinical trials (RCTs).
Main Methods:
- Searched multiple electronic databases including Ovid MEDLINE, Cochrane Library, EMBASE, PubMed, Science Citation Index, Google Scholar, and clinicaltrials.gov.
- Included RCTs comparing two defined BP targets in adults (≥18 years) with CKD stages 3-5 (eGFR <60 mL/min/1.73 m2) or a CKD subgroup.
- Extracted mortality events and characteristics from 18 RCTs involving 15,924 participants with CKD.
Main Results:
- Identified 30 RCTs meeting inclusion criteria, with CKD subset mortality data extracted from 18 trials (1293 deaths).
- Mean baseline systolic BP was 148 mm Hg in both intensive and less intensive arms.
- More intensive BP control (mean SBP 132 mm Hg) versus less intensive control (mean SBP 140 mm Hg) resulted in a 14.0% lower risk of all-cause mortality (OR, 0.86; 95% CI, 0.76-0.97; P=.01).
Conclusions:
- More intensive BP control is associated with a lower mortality risk in patients with hypertension and CKD.
- Findings were consistent across subgroups and showed no significant heterogeneity.
- Further research is needed to determine optimal BP targets for maximizing benefits and minimizing harm in CKD patients.
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.