Blood Pressure Lowering and Risk of Mortality in Chronic Kidney Disease: A Meta2 Analysis of Randomized Controlled Trials

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Malhotra, R 
Nguyen, Hoang Anh 
Benavente, O 
Mete, M 
Howard, BV 

Importance: Trials in hypertensive patients demonstrate that intensive blood pressure (BP) lowering reduces risk of cardiovascular disease (CVD) and all-cause mortality, but may increase 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.

Objective: We conducted a meta-analysis of Randomized controlled trials (RCTs) to determine if more intensive, compared with a less intensive, BP control is associated with reduced mortality risk in persons with CKD stages 3-5.

Data Sources: Ovid Medline, Cochrane Library, Embase, Pubmed, Science Citation Index, Google Scholar, and electronic databases.

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

Data extraction and synthesis: Two reviewers 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, we contacted trial investigators and requested data within the CKD subset of their original trials.

Main outcomes and measures: All-cause mortality during the active treatment phase of each trial.

Results: We identified 30 RCTs that potentially met inclusion criteria, among which we were able to extract the CKD subset mortality data in 18 trials. Among these, there were 1293 deaths among 15,924 participants with CKD. The mean baseline systolic blood pressure (SBP) was 148±16 mm hg in both intensive and less-intensive arms. The mean SBP dropped by 16 mm Hg to 132 mm Hg in the intensive arm and by 8 mm Hg to 140 mm Hg in the less-intensive arm. More vs. less-intensive BP control resulted in 14% lower risk of all-cause mortality (Odds Ratio (OR) 0.86; 95% CI 0.76 to 0.97, p = 0.01); a finding that was without significant heterogeneity and appeared consistent across multiple subgroups including type of treatment in the comparator arm (placebo vs. less intensive BP target), length of follow-up, presence of diabetes, CKD severity, baseline systolic blood pressure (SBP), achieved SBP during the trial and degree of SBP differences across the treatment arms.

Conclusion 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.

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JAMA Internal Medicine
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