Angiotensin receptor blockers are associated with lower mortality than ACE inhibitors in predialytic stage 5 chronic kidney disease: A nationwide study of therapy with renin-angiotensin system blockade

Dual renin angiotensin system (RAS) blockade using angiotensin-receptor blockers (ARBs) in combination with angiotensin converting enzyme inhibitors (ACEIs) is reported to improve proteinuria in both diabetic and non-diabetic patients. However, its renoprotective effect and safety remain uncertain in patients with advanced chronic kidney disease (CKD). From January 1, 2000 through June 30, 2009, we enrolled 14,117 pre-dialytic stage 5 CKD patients with serum creatinine >6mg/dL and hematocrit <28% under the treatment with erythropoiesis stimulating agents and RAS blockade. We used Cox proportional hazards regression models to estimate the hazard ratios (HRs) against the commencement of long-term dialysis and all-cause mortality for ACEI/ARB users. Over a median follow-up of 7 months, 9,867 patients (69.9%) required long-term dialysis and 2,805 (19.9%) died before progression to end-stage renal disease requiring dialysis. In comparison with the ARB-only users, dual blockade with ACEIs and ARBs was associated with a significantly higher risk of (1) death in all CKD patients (HR = 1.49, [95%CI, 1.30-1.71]; P = 0.02) and in diabetic subgroup (HR = 1.58, [95%CI, 1.34-1.86]; P = 0.02); (2) composite endpoint of long-term dialysis or death in diabetic subgroup (HR = 1.10, [95%CI, 1.01-1.20]; P = 0.04); (3) hyperkalemia-associated hospitalization in non-diabetic subgroup (HR, 2.74, [95%CI, 1.05-7.15]; P = 0.04). However, ACEIs users were associated with higher mortality than ARBs users in all CKD patients (HR = 1.17, [95%CI, 1.07-1.27]; P = 0.03) and in diabetic subgroup (HR = 1.32, [95%CI, 1.18-1.48]; P = 0.03). Monotherapy of RAS blockade, especially ARB, is more effective and safer than dual RAS blockade in pre-dialytic stage 5 CKD patients.