Ajay K. Singh, MBBS, FRCP, MBA
Brigham and Women’s Hospital and Harvard Medical School
The target blood pressure in patients with chronic kidney disease (CKD), both with diabetic and non-diabetic CKD, remains controversial. In early September 2017, a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies conference will convene in Edinburgh, Scotland, to address blood pressure (BP) management in CKD patients, including questions related to the BP goal: What should the target BP be? How should elderly and frail CKD patients be treated compared with younger patients? Should the BP targets for diabetic and non-diabetic patients be the same? Should diastolic BP be taken into account when treating? An analysis by Cheung et al of CKD patients within the Systolic Blood Pressure Intervention Trial (SPRINT), recently published in the Journal of the American Society of Nephrology (JASN), will be grist to the mill for various opinion leaders in the KDIGO conference.
SPRINT recruited 9361 subjects with systolic BP of ≥130 mm Hg and an increased cardiovascular risk, but without diabetes, to a systolic BP target of <120 mm Hg (intensive treatment) or a target of <140 mm Hg (standard treatment). The primary composite outcome was myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes.
Among the 2646 CKD subjects enrolled in the SPRINT study, 1330 subjects with CKD were assigned to the intensive BP group (systolic BP target of <120 mm Hg) and 1316 CKD subjects were assigned to the standard group (systolic BP target of <140 mm Hg). The mean age of participants was approximately 72 years with 44% over the age of 75 years. Nearly two thirds of enrolled CKD patients were non-Hispanic whites, but other racial types were well represented. The mean systolic/diastolic BP at baseline was, on average, approximately 139/75 mmHg. Participants had a median follow-up of 3.3 years.
Among the subjects with CKD, the primary composite cardiovascular outcome occurred in 112 of the intensive group and in 131 of the standard group (hazard ratio [HR], 0.81; 95% confidence interval [95% CI], 0.63 to 1.05). The intensive BP group also had a lower rate of all-cause death (HR, 0.72; 95% CI, 0.53 to 0.99). This benefit was observed regardless of baseline CKD status. Additionally, there seemed, at least in the unadjusted analysis, a more pronounced benefit in intensive BP reduction for the primary cardiovascular composite end point among elderly (age>75 years) patients (P=.04 unadjusted for baseline factors).
The SPRINT CKD analysis also reported no significant benefit of the intensive BP target on the pre-specified main kidney outcome of the composite of ≥50% decrease in estimated glomerular filtration rate (eGFR) from baseline or end-stage renal disease (HR, 0.90; 95% CI, 0.44 to 1.83). Still, intensive systolic BP lowering did result in a slightly higher rate of eGFR decline. Intensive BP control was also associated with a significantly higher rate of hypokalemia, hyperkalemia, and acute kidney injury (HR, 1.87, HR, 1.36, and HR 1.46, respectively).
The number-needed-to-treat to prevent a primary composite outcome event, death from any cause, and death from cardiovascular causes in the CKD subgroup of SPRINT (at 4 years of follow-up) was 66, 28, and 61, respectively.
The SPRINT CKD subgroup analysis published by Cheung et al in JASN was a well conducted large study in a racially and age diverse group of patients. That said, SPRINT only enrolled non-diabetic CKD patients; conclusions should only impact practice in non-diabetic CKD patients, until, of course, further evidence emerges.
The bottom line: intensive treatment of CKD patients resulted in a substantial decrease in the primary CVD outcome and all-cause death regardless of baseline CKD stage. And, this benefit seemed more pronounced among elderly patients (age≥75 years). Furthermore, treatment was worth it when one balanced benefit and risk. Lastly, in order to effectively achieve blood pressure reduction in the intensive treatment arm, multiple BP medications are needed—60% of subjects were on three or more medications.
How should this analysis impact clinical practice? I will aim for a SBP of 120 mmHg or lower in non-diabetic CKD patients, regardless of CKD stage. However, I plan to remain cautious with aggressive BP control in elderly and frail patients, being careful to slowly calibrate down the BP and bailing out at a higher BP at the very whisper of side effects.
Cheung AK, Rahman M, Reboussin DM, et al. Effects of intensive blood pressure control in chronic kidney disease. Journal of the American Society of Nephrology. 2017;doi:10.1681/ASN. 2017020148