Effect of Intensive Versus Usual Blood Pressure Control on Kidney Function Among Individuals With Prior Lacunar Stroke A Post Hoc Analysis of the Secondary Prevention of Small Subcortical Strokes (SPS3) Randomized Trial

; 95% CI, −0.97 to −3.2), whereas rates of eGFR decline did not differ after year 1 (−0.095; 95% CI, −0.47 to 0.23). A total of 313 patients (24%) in the lower BP group had rapid kidney function decline compared with 247 (19%) in the higher BP group (odds ratio, 1.4; 95% CI, 1.1–1.6). Differences in rapid decline by treatment arm were apparent in the first year (odds ratio, 1.4; 95% CI, 1.1–1.8) but were not significant after year 1 (odds ratio, 1.0; 95% CI, 0.73–1.4). Rapid decline was associated with higher risk for stroke, major vascular events, and composite after full adjustment among individuals randomized to the higher BP target (stroke hazard ratio, 1.93; 95% CI, 1.15–3.21) but not the lower BP arm (stroke hazard ratio, 0.93; 95% CI, 0.50–1.75; all P for interaction <0.06). Conclusions —In patients with prior lacunar stroke and relatively preserved kidney function, intensive BP lowering was associated with a greater likelihood of rapid kidney function decline. Differences were observed primarily during the first year of antihypertensive treatment. Rapid kidney function decline was not associated with increased risk for clinical events among those undergoing intensive BP lowering. Clinical blocker, -blocker) lower study arms the compared annualized eGFR decline in the higher and lower BP groups using linear mixed models with random intercepts. splines to pictori-ally eGFR decline over the study period by treatment arm. We compared differences up to 5 years of follow-up. We stratified our results by study period (baseline to year 1 versus year to the end of proportion of patients with rapid decline by study arm. We compared odds of rapid decline by usual versus intensive BP treatment using logistic regression. In these analyses, we present comparisons for the entire study and by study period as above. These analyses followed intention-to-treat principles. Next, we were interested in understanding the clinical relevance of rapid decline. Thus, we first evaluated whether kidney function loss could explain the trial null findings. Specifically, on the basis of the intention-to-treat principles, we used Cox regression models to compare time to event for the clinical outcomes by treatment arm. We then adjusted for eGFR slope or rapid decline in year 1 separately and determined the importance on the treatment effect. In a second step, we used an observational design. We estimated the association of baseline characteristics and achieved SBP (defined as mean SBP at 6 and 9 months) with rapid kidney function decline using multi- variable logistic regression. Our final objective was to compare the associations of rapid kidney function decline in the first year with the clinical outcomes of stroke, MVE, and the composite outcome (death, MVE, myocardial infarction, or stroke). We used Cox propor- tional hazards regression models adjusted for treatment arm and then additionally adjusted for age, sex, ethnicity, smoking, diabetes mel- litus, hypertension, use of an ACEI/ARB, baseline SBP, and baseline eGFR. We included tests of the interaction between rapid decline and treatment arm to determine whether the effects of kidney decline on the clinical outcomes differed by intensive versus usual BP treatment, and we repeated the analyses stratified by treatment arm. All analyses were performed unclear. Both SPRINT and have rates of function decline with intensification of antihypertensive therapy. In the setting of established CKD, randomized trials show a benefit from lower BP levels only among individuals with proteinuria, 5–7,9 and SPRINT did not show a difference in CKD progression to ESRD by study arm. Our study suggests that among individuals with cerebrovascular disease relatively preserved eGFR, intensive sharper eGFR Our individuals undergoing usual treatment to established goals. In the intensive treatment group, rapid kidney function decline was not associated with a higher risk for stroke, death, or major vascular events. In contrast, among individuals undergoing usual antihypertensive treatment, rapid decline was associated with a higher risk for all outcomes, as has been observed in many prior observational studies. Taken together, our findings could guide clinicians to understand that decline in kidney function is common and expected among patients undergoing intensive blood pressure lowering. In this specific setting, kidney function decline does not appear to pose significant clinical risk for adverse cardiovascular outcomes. Further studies are needed to understand whether rapid kidney function decline in the setting of intensive BP lowering is associated with end-stage renal disease in longer follow-up.