Prevention of heart failure events with intensive versus standard blood pressure lowering across the spectrum of kidney function and albuminuria: a SPRINT substudy

Aims: To determine whether a strategy of intensive blood pressure control reduces the risk of heart failure (HF) events consistently across the spectrum of kidney function and albuminuria.

Methods and results: SPRINT was a randomized clinical trial in which 9361 individuals ≥50 years, at high risk for or with cardiovascular disease, a systolic blood pressure of 130-180 mmHg, but without diabetes, were randomized to intensive (target <120 mmHg) vs. standard (target <140 mmHg) blood pressure control. We assessed whether estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) modified the effects of the blood pressure control strategy in reducing HF events (either hospitalization or emergency department visits) and the composite of HF events or cardiovascular death, using Cox proportional hazards regression and restricted cubic splines. Of the 9361 individuals included in SPRINT, eGFR and UACR were available for 9324 (99.6%) and 8913 (95.2%) subjects, respectively, including 2650 (28.4%) with eGFR <60 mL/min/1.73 m² and 248 (2.8%) with UACR >300 mg/g. During a median follow-up of 3.2 years (range 0-4.8 years), 160 (1.8%) participants had HF events and 233 (2.6%) had HF events or cardiovascular death. Risks of HF events or cardiovascular death increased from 0.42 (0.34-0.53) per 100 patient-years in patients with eGFR ≥60 mL/min/1.73 m² and UACR <30 mg/g to 4.55 (3.00-6.91) per 100 patient-years in patients with eGFR <60 mL/min/1.73 m² and UACR >300 mg/g. A similar gradient was observed for HF events alone. Both eGFR and UACR were independently, non-linearly associated with HF hospitalization and HF hospitalization or cardiovascular death (test for overall trend, P < 0.001). While the effects of intensive blood pressure control on HF event risk appeared to attenuate at lower eGFR and higher UACR, there was no significant interaction between eGFR or UACR and blood pressure control strategy (continuous and categorical interaction P > 0.05).

Conclusion: In SPRINT, eGFR and albuminuria were strong and additive determinants in forecasting HF risk. The effect of intensive blood pressure control in decreasing HF risk did not significantly vary across the spectrum of kidney function or albuminuria. Multidisciplinary pathways, incorporating blood pressure control, are needed for at-risk patients with chronic kidney disease to attenuate HF risk.

Trial registration: ClinicalTrials.gov Identifier NCT01206062.