More intensive BP lowering cuts risk of death for patients with chronic kidney disease

Patients with hypertension and chronic kidney disease (CKD) who underwent more intensive blood pressure (BP) control experienced a 14 percent reduced risk of all-cause mortality than those with less intensive treatment, according to a meta-analysis published in JAMA Internal Medicine.

Researchers extracted mortality data from 18 randomized clinical trials comprising 15,924 adults with both hypertension and stage 3 to 5 CKD. Thirteen of the trials had two defined BP targets, while the other five compared BP treatment to either no treatment or a placebo. The median follow-up period was 3.6 years.

The mean baseline systolic blood pressure (SBP) for the entire population was 148. Patients receiving more aggressive therapy saw an average drop of 16 millimeters of mercury, while those receiving less intensive therapy saw an average drop of 8 mm Hg. The finding of reduced mortality for patients treated more intensively was consistent across multiple subgroups.

“The highest mortality benefit was observed in studies that achieved the greatest difference in SBP during the trial, a result that did not reach statistical significance (P = .06 for heterogeneity),” wrote lead researcher Rakesh Malhotra, MD, MPH, and colleagues. “These data will need to be re-evaluated when additional trials evaluating intensive BP control among those with CKD are completed. Nonetheless, this preliminary finding supports our overall conclusion that more intensive BP control may be beneficial for individuals with CKD.”

The researchers noted a previous meta-analysis demonstrated more intensive BP lowering for CKD patients resulted in fewer cardiovascular-related deaths. However, they felt all-cause mortality was a more appropriate endpoint.

“We evaluated all-cause mortality because it balances the competing risk of multiple clinical outcomes and because it is a ‘hard’ outcome assessed similarly across studies,” Malhotra et al. wrote. “For example, if more intensive BP lowering leads to higher risk of AKI (acute kidney injury) and CKD progression but lower risk of CVD events, these outcomes could offset one another, with no overall effect on all-cause mortality. This consideration is particularly important in persons who have CKD at baseline.”

The authors noted their research could inform upcoming guidelines from the Kidney Disease: Improving Global Outcomes expert panel. It may also help CKD patients and health care professionals discuss the relative risks of BP lowering, they said.

A notable limitation of the analysis was a lack of data on the severity of CKD within each study. Therefore, the researchers were unable to stratify the results based on disease class.

“Most individuals in the included trials had CKD stage 3, and we acknowledge that the risks and benefits of more intensive BP lowering may differ in persons with more advanced CKD,” the authors wrote.

In an invited commentary, a nephrologist pointed out additional caveats of the analysis.

“The mean overall intensive SBP of 132 mm Hg in the meta-analysis actually falls within the clinical target recommended by most current guidelines (i.e., less than 140 mm Hg) and is also within the range that has been associated with the best outcomes in large observational studies,” wrote Csaba P. Kovesdy, MD, with the division of nephrology at the University of Tennessee Health Science Center in Memphis. “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 (i.e., to a target less than 120 mm Hg) is beneficial.”

Kovesdy also noted 167 patients would need to be treated with the more intensive therapy in order to prevent one death. In addition, a different meta-analysis showed 250 patients would need to be treated to prevent one renal failure event.

“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,” Kovesdy wrote.