Intensive Blood Pressure Lowering and Renal Function in Ischemic Stroke Patients: Secondary Analysis of the ENCHANTED Trial

Introduction: Renal failure is a major safety concern of intensive systolic blood pressure (SBP) lowering. We aimed to determine the effect of this treatment on early change in renal function in participants of the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Methods: Post hoc analysis of the ENCHANTED BP-arm in which thrombolyzed patients with acute ischemic stroke (AIS) were randomized to intensive (target 130-140 mm Hg within 1 h) or guideline-recommended (target <180 mm Hg) management within 6 h of symptom onset. Primary outcome is the early change in renal function, defined by a difference in estimated glomerular filtration rate (triangle eGFR = 24 h - baseline eGFR), analyzed using linear regression with adjustment for clinical variables. Key SBP parameters were attained (mean), variability (standard deviation), and magnitude of reduction within 24 h. Results: Of 2,151 participants (mean age 66.9 years; 38% female) included with the available baseline eGFR, there were significant differences in attained 144.3 +/- 10.2 versus 149.8 +/- 12.0 [Delta 5.5 mm Hg]; p < 0.0001), variation (15.1 +/- 5.4 vs. 14.0 +/- 5.6 mm Hg; p < 0.0001), and magnitude of reduction (44.6 +/- 16.2 vs. 38.7 +/- 17.6 mm Hg; p < 0.0001) in SBP within 24 h. 1,718 (79.9%) participants with complete follow-up eGFR were included in the primary analysis, and there was no significant difference in triangle eGFR (adjusted mean difference -1.10, 95% confidence interval [CI] -3.14 to -0.94; p = 0.29) between the intensive and guideline groups, respectively. The neutral effect on triangle eGFR was consistent in patients with different baseline eGFR stages and in sensitivity analysis after multiple imputations for missing follow-up eGFR. SBP variability was significantly associated with decreasing triangle eGFR (per 5 mm Hg increase by category: adjusted mean difference -1.35, 95% CI: -2.43 to -0.28; p for trend = 0.01). Conclusion: Intensive SBP lowering with a target of 130-140 mm Hg had no impact on early renal function in thrombolyzed AIS patients. Wide SBP variability was associated with a larger decline in eGFR.