More aggressive blood pressure (BP) lowering modestly reduces all-cause mortality in patients with chronic kidney disease (CKD) compared with less aggressive treatment, a systemic review and meta-analysis indicates.
Results of an analysis of 18 different studies suggest that a median difference of 8 mm Hg in systolic BP (SBP) between more intensive and less intensive antihypertensive regimens reduces mortality by 14% in patients with CKD during a median follow-up of 3.6 years.
“[O]ur objective was to conduct a systematic review and meta-analysis of
RCTs [randomized clinical trials] 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,” Joachim Ix, MD, University of California, San Diego, and colleagues observe. “These findings add to the body of evidence that may inform public health policy, clinical guideline development, and individual patient care in patients with CKD,” they add.
The study was published online September 5 in JAMA Internal Medicine.
The meta-analysis involved 15,924 individuals with hypertension and an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2. Patients were assigned to a more intensive treatment group or a less intensive treatment group. Before randomization, the mean baseline SBP was 148 mm Hg in both groups. At study endpoint, mean SBP had decreased by 16 mm Hg to a mean of 132 mm Hg in patients assigned to the more intensive treatment group.
This compared to an 8–mm Hg drop in SBP seen in the less intensive treatment group, in which the mean BP was 140 mm Hg at study endpoint. “The median difference in SBP achieved across arms was 10 mm Hg (IQR [interquartile range], 4-12 mm Hg), with a median of 130 mmHg (IQR, 125-141 mm Hg) in the more intensive arms vs 138 mm Hg (IQR, 134-146 mm Hg) in the less intensive arms,” the authors report.
There was also a trend toward greater mortality benefit with greater reductions in SBP, they add. Across the 18 trials analyzed, the all-cause mortality rate was 7.8% among participants randomly assigned to the more intensive BP-lowering group compared with 8.4% for participants receiving less intensive treatment, for an odds ratio for all-cause mortality of 0.86 in favor of the more intensive treatment group (95% confidence interval, 0.76 – 0.97; P = .01).
This mortality advantage in favor of a more intensive treatment strategy was preserved across a wide variety of subgroups, including diabetic vs nondiabetic patients, severe and less severe CKD, baseline SBP, and median duration of follow-up. As the researchers point out, the KDIGO Blood Pressure Work Group is about to review existing evidence regarding the effect that intensive vs less intensive BP lowering has on patients with CKD and may change their current guidelines based on findings from their review.
“The present meta-analysis may provide useful data for the upcoming
guideline review,” investigators suggest, and the “results may also offer additional information for patients and health care professionals and may
be useful to guide shared decision making about the relative risks and benefits of BP lowering among those with CKD,” they add.
“Valuable Addition”
In an accompanying editorial, Csaba Kovesdy, MD, University of Tennessee Health Science Center, Memphis, suggests the study represents a “valuable addition” to the community’s understanding about the impact hypertension can have in patients with CKD but he still calls for caution in interpreting the findings. “First, the question of whether a normal BP target (as most would define intensive BP control) is beneficial in patients with CKD remains unanswered,” he observes. As he points out, the mean SBP at 132 mm Hg in patients assigned to more intensive treatment was still within the range currently recommended by most guidelines.
“One could therefore interpret the results of this meta-analysis as solidifying
existing evidence about the benefits of lowering BP to a range of 130 to 140 mm Hg but not as proof that truly intensive BP lowering (ie, to a target <120 mm Hg) is beneficial,” Dr Kovesdy argues. He also notes that all-cause mortality rates reported among patients with CKD enrolled in the RCTs analyzed by study investigators were considerably lower than those usually reported in the general CKD population and that lowering BP may not affect many causes behind higher mortality rates.
Dr Kovesdy also expresses concerns about lumping patients with an eGFR less than 60 mL/min/1.73 m2 into a single group because this tactic could miss subgroups of patients with CKD who respond to BP-lowering strategies differently than others. Indeed, for patients with more advanced CKD, “[i]t is possible that intensive BP lowering may have a diminishing benefit along with an increase in the incidence of adverse outcomes such as acute kidney injury,” he suggests.
Finally, he reminds readers that the greatest risk for hypertension-related adverse events occurs among patients with extremely elevated BPs, while patients with relatively normal BP are at much less risk for the same adverse events. Thus, the subsequent benefits of lowering BP in those with less extreme BPs could be expected to be much less dramatic. “These diminishing absolute benefits have to be weighed against the increased likelihood of adverse effects and the higher costs associated with more intensive BP lowering,” Dr Kovesdy concludes.
One study coauthor reports serving as a consultant for Boehringer Ingelheim, being a contributor to UpToDate, and receiving funding from the National Institutes of Health for the conduct of the Systolic Blood Pressure Intervention Trial (SPRINT). The remaining coauthors and Dr Kovesdy have disclosed no relevant financial relationships.
JAMA Intern Med. Published online September 5, 2017. Abstract, Editorial
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