Effect of Baseline Kidney Function on the Risk of Recurrent Stroke and on Effects of Intensive Blood Pressure Control in Patients With Previous Lacunar Stroke: A Post Hoc Analysis of the SPS3 Trial (Secondary Prevention of Small Subcortical Strokes)

Abstract

Background We conducted a post hoc analysis of the SPS3 (Secondary Prevention of Small Subcortical Strokes) Trial to examine the association of chronic kidney disease (CKD) with recurrent stroke, and to assess whether baseline renal function modifies the effects of intensive systolic blood pressure control in patients with previous stroke. Methods and Results A total of 3020 patients with recent magnetic resonance imaging-defined symptomatic lacunar infarctions were randomized to a systolic blood pressure target of <130 mm Hg versus 130 to 149 mm Hg. Predefined primary outcomes were (all-recurrent) stroke and a composite of stroke, acute myocardial infarction, or all-cause death; secondary outcomes were acute myocardial infarction, all-cause death, and intracerebral hemorrhage individually. Among 3017 patients with baseline estimated glomerular filtration rate measurements, we evaluated, using Cox proportional hazards models, the association of CKD with recurrent stroke and effects of the blood pressure targets on outcomes using baseline estimated glomerular filtration rate both as a categorical and linear variable. Regardless of the randomized treatment, CKD at baseline was significantly associated with an increased risk of the primary cardiovascular composite outcome (hazard ratio, 1.7; 95% CI, 1.4-2.1), and all-recurrent stroke (1.5; 1.1-2.0). However, the effects of the lower systolic blood pressure intervention on the primary outcome were not influenced by baseline CKD status (P for interaction=0.62). Conclusions CKD increases the risk of recurrent stroke by 50% in patients with previous lacunar stroke. We found no definitive evidence that renal dysfunction modifies the effects of systolic blood pressure control in patients with previous stroke. Conclusive evidence for this will require adequately powered studies with moderate-to-advanced CKD. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306.

Keywords: high blood pressure; hypertension; lacunar stroke; renal function.

Figure 1

Achieved blood pressures by randomized SBP intervention and 2 baseline eGFR subgroups. Boxplots display the median, 25th, and 75th percentiles of the patients’ follow‐up values at 1 year for systolic blood pressure (SBP; A) and diastolic blood pressure (DBP; B) by randomized SBP intervention and two baseline eGFR groups. One hundred twenty‐three of 3017 subjects (4.1%; 68 in the higher‐target group and 55 in the lower‐target group) had missing blood pressure measurements at 1 year and were not included. eGFR indicates estimated glomerular filtration rate.

Figure 2

Cumulative incidence of the composite outcome and all recurrent stroke for those with and without CKD. A, Composite outcome. B, All recurrent stroke. CKD indicates chronic kidney disease; eGFR, estimated glomerular filtration rate HR, hazard ratio.

Figure 3

Forest plots with hazard ratios for the effect of SBP intervention on the events of primary and secondary outcomes by 2 baseline eGFR subgroups. *The interaction test for each outcome compared HRs below and above eGFR value of 60 mL/min/1.73 m². Composite CV indicates composite cardiovascular outcome; HR, hazard ratio; IC hemorrhage, intracerebral hemorrhage; MI, myocardial infarction; SBP, systolic blood pressure.