Impact of Renal Impairment on Intensive Blood-Pressure-Lowering Therapy and Outcomes in Intracerebral Hemorrhage: Results From ATACH-2

Abstract

Background and objective: The clinical effect of renal impairment on intracerebral hemorrhage (ICH) is unknown. This study sought to assess whether estimated glomerular filtration rate (eGFR) affects clinical outcomes or modifies the efficacy of intensive systolic blood pressure (BP) control (target, 110-139 mm Hg) against the standard (target, 140-179 mm Hg) among patients with ICH.

Methods: We conducted post hoc analyses of ATACH-2, a randomized, 2-group, open-label trial. The baseline eGFR of each eligible patient was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. The outcome of interest was death or disability at 90 days. Multivariate logistic regression models were used for analysis.

Results: Among the 1,000 patients randomized, 974 were analyzed. The median baseline eGFR was 88 (interquartile range, 68, 99) mL/min/1.73 m2; 451 (46.3%), 363 (37.3%), and 160 (16.4%) patients had baseline eGFR values of ≥90, 60-89, and <60 mL/min/1.73 m2, respectively. Compared with normal eGFR (≥90 mL/min/1.73 m2), higher odds of death or disability were noted among those with eGFR values of <60 mL/min/1.73 m2 (adjusted odds ratio [OR], 2.02; 95% confidence interval [CI], 1.25-3.26) but not among those with eGFR values of 60-89 mL/min/1.73 m2 (OR, 1.01; 95% CI, 0.70-1.46). The odds of death or disability were significantly higher in the intensive arm among patients with decreased eGFR; the ORs were 0.89 (95% CI, 0.55-1.44), 1.13 (0.68-1.89), and 3.60 (1.47-8.80) in patients with eGFR values of ≥90, 60-89, and <60 mL/min/1.73 m2, respectively (p for interaction = 0.02).

Discussion: Decreased eGFR is associated with unfavorable outcomes following ICH. The statistically significant interaction between the eGFR group and treatment assignment raised safety concerns for the intensive BP-lowering therapy among patients with renal impairment.

Trial registration information: Clinicaltrials.gov identifier: NCT01176565.

Classification of evidence: This study provides Class II evidence that in spontaneous ICH, decreased eGFR identifies patients at risk of death or disability following intensive BP control.

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Figures

Figure 1. CONSORT (Consolidated Standards of Reporting Trials) Flow Diagram

eGFR = estimated glomerular filtration rate; SBP = systolic blood pressure.

Figure 2. Mean Minimum Systolic Blood Pressure (SBP) Profile Grouped by Treatment and Estimated Glomerular Filtration Rate (eGFR) Category

Figure 3. Risk of Death or Disability Across the Baseline Estimated Glomerular Filtration Rate (eGFR)

A restricted cubic splines curve with 3 knots illustrating the association of the baseline eGFR with odds ratios (solid line) and 95% confidence intervals (gray area). The model is adjusted for age, baseline Glasgow Coma Scale score, intraventricular hemorrhage, sex, initial hematoma volume, treatment allocation, and hematoma expansion. Reference value of eGFR: 60 mL/min/1.73 m2.

Figure 4. Efficacy of Intensive Blood Pressure (BP)–Lowering According to Baseline Estimated Glomerular Filtration Rate (eGFR) (mL/min/1.73 m2) Categories

Adjusted odds ratios of death or disability (modified Rankin Scale score 4–6) and death among eGFR categories. Model 1: adjusted for age, baseline Glasgow Coma Scale (GCS) score, and intraventricular hemorrhage (IVH). Model 2: adjusted for age, baseline GCS score, IVH, sex, and initial hematoma volume. pint Represents p values for interaction. CI = confidence interval.

Figure 5. Death or Disability Comparing Intensive Versus Standard Blood Pressure (BP)–Lowering by Baseline Estimated Glomerular Filtration Rate (eGFR) (mL/min/1.73 m2)

The multivariable fractional polynomial interaction plot shows the adjusted odds ratios (solid line) of death or disability (modified Rankin Scale score 4–6), comparing intensive vs standard BP-lowering therapies across the range of continuous values of baseline eGFR. The gray area shows 95% confidence intervals. Models were adjusted for age, baseline Glasgow Coma Scale score, intraventricular hemorrhage, sex, and initial hematoma volume. The p value is for interaction between baseline eGFR and treatment effect.