Mortality Outcomes With Intensive Blood Pressure Targets in Chronic Kidney Disease Patients

Abstract

Hypertension is highly prevalent and morbid in the chronic kidney disease population, and blood pressure (BP) targets for this population are unclear. We aimed to compare all-cause mortality outcomes with intensively targeting systolic BP to <130 mm Hg versus a standard of <140 mm Hg. Individual patient data from 4983 chronic kidney disease patients with hypertension were pooled from 4 multicenter randomized control trials—AASK (African American Study of Kidney Disease and Hypertension), ACCORD (Action to Control Cardiovascular Risk in Diabetes), MDRD (Modification of Diet in Renal Disease), and the SPRINT (Systolic Blood Pressure Intervention Trial). Patients were assigned their trial-assigned randomized intervention group—standard (n=2474) versus intensive (n=2509) BP targets. Additional analyses included excluding patients with a glomerular filtration rate ≥60 mL/min per 1.73 m 2 along with those undergoing intensive glycemic control. The primary outcome was all-cause mortality. Average achieved BP was 125.0 mm Hg in the intensive group and 136.9 mm Hg in the standard group. In the primary analysis, the all-cause mortality rate trended towards improved outcomes with intensive treatment but was not statistically significant (hazard ratio: 0.87 [0.69–1.08]; P =0.21). One hundred seventy-three of 2474 patients (1.95% per year) in the standard group and 153 of 2509 patients (1.71% per year) in the intensive group died. After excluding patients with higher glomerular filtration rate values and those undergoing intensive glycemic control, there was a statistically significant decrease in all-cause mortality rate (hazard ratio: 0.79 [0.63–1.00]; P =0.048). An intensive BP target of <130 mm Hg decreases all-cause mortality when compared with a standard target of <140 mm Hg in patients with chronic kidney disease stage 3 or greater who are not undergoing intensive glycemic therapy.

Some methods for heterogeneous treatment effect estimation in high dimensions

“…Both of these methods found in the SPRINT data a relationship between kidney health and the treatment effect that has also been identified by other researchers. 32 An important next step is confidence interval construction. We have developed causal MARS so that it would be conducive to confidence interval construction, but we leave this task to future work.…”

“…They found that intensive blood pressure management does not improve primary outcomes for patients with CKD. 32 Something that the authors do not address is why they chose to analyze patients with CKD. Presumably, they used some combination of prior medical knowledge and manual hypothesis selection.…”

Blood pressure target for hypertension in chronic kidney disease: One size does not fit all

“…The evidence on the BP target in CKD patients is derived from four main sources: (a) ad hoc analyses of randomized clinical trials (RCTs) designed for renal outcomes, (b) observational follow‐up of these RCTs, (c) post hoc analyses of other RCTs, (d) meta‐analyses of individual or aggregate data from RCTs 4‐12 . Table 1 presents such key studies comparing intensive vs standard BP lowering arms 4‐12 . There is considerable heterogeneity among these studies in sample size, patients’ characteristics, BP measurement methodology, duration of follow‐up, examined end points (renal, cardiovascular, mortality and composite end points).…”

“…In a meta‐analysis of individual data from 4983 CKD hypertensive patients pooled from four RCT, including the AASK, ACCORD (Action to Control Cardiovascular Risk in Diabetes), MDRD, and SPRINT, the all‐cause mortality rate trended toward improved outcomes with intensive antihypertensive treatment, yet this difference did not reach statistical significance 12 . However, after excluding patients with GFR ≥60 mL/min/1.73 m 2 and those on intensive glycemic control, there was a statistically significant decrease in all‐cause mortality rate 12 .…”

“…In a meta‐analysis of individual data from 4983 CKD hypertensive patients pooled from four RCT, including the AASK, ACCORD (Action to Control Cardiovascular Risk in Diabetes), MDRD, and SPRINT, the all‐cause mortality rate trended toward improved outcomes with intensive antihypertensive treatment, yet this difference did not reach statistical significance 12 . However, after excluding patients with GFR ≥60 mL/min/1.73 m 2 and those on intensive glycemic control, there was a statistically significant decrease in all‐cause mortality rate 12 . A meta‐analysis by Malhotra et al of aggregate data from 18 trials without considerable heterogeneity, demonstrated that a more intensive vs less intensive BP control resulted in 14% lower risk of all‐cause mortality, which was consistent across multiple subgroups 10 .…”