Clinical outcomes of renin angiotensin system inhibitor-based dual antihypertensive regimens in chronic kidney disease: a network meta-analysis

Abstract

This study comprehensively investigated clinical outcomes associated with renin angiotensin system inhibitor-based dual antihypertensive regimens in non-dialysis chronic kidney disease (CKD) patients. Keyword searches of databases were performed per PRISMA-NMA guidelines. Frequentist network meta-analysis were conducted with 16 head-to-head randomized controlled trials. The effect sizes of dichotomous and continuous variables were estimated with odds ratio (OR) and standard mean differences (SMD), respectively. The protocol is registered in PROSPERO (CRD42022365927). Dual antihypertensive regimens with combination of angiotensin receptor blockers (ARB) and calcium channel blockers (CCB) demonstrated substantially reduced odd of major cardiovascular disease (CVD) events over other regimens including angiotensin converting enzyme inhibitor (ACEI) monotherapy (OR 3.19) and ARB monotherapy (OR 2.64). Most significant reductions in systolic (SBP) and diastolic blood pressure (DBP) were observed with ARB-based CCB dual regimen over ACEI monotherapy (SMD 17.60 SBP and 9.40 for DBP), ACEI-based CCB regimen (SMD 12.90 for SBP and 9.90 for DBP), and ARB monotherapy (SMD 13.20 for SBP and 5.00 for DBP). However, insignificant differences were noticed for the odds of hyperkalemia, end stage renal disease progression, and all-cause mortality. ARB-based CCB regimen has the greatest benefits on BP reduction as well as major CVD risks in non-dialysis CKD patients.

Pharmacological Nephroprotection in Non-Diabetic Chronic Kidney Disease—Clinical Practice Position Statement of the Polish Society of Nephrology

“…The Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) trial, in which only a certain proportion of patients suffered from CKD (with mean eGFR 45 mL/min/1.73 m 2 ), compared the benefits of combining an ACEi + amlodipine versus ACEi + hydrochlorothiazide (HCTZ) in high-risk hypertensive patients and found a lower risk of CKD progression and reduced incidence of CV events when the ACEi was combined with amlodipine (as compared to ACEi + HCTZ) [ 47 , 48 ]. The recently published meta-analysis of 16 randomized controlled trials that included hypertensive patients with CKD treated with different BP-lowering regimens showed the most significant reduction of SBP and DBP with the ARB + CCB dual regimen over ACEi monotherapy (standardized mean difference (SMD) 17.60 for SBP and 9.40 for DBP), ACEi + CCB regimen (SMD 12.90 for SBP and 9.90 for DBP), and ARB monotherapy (SMD 13.20 for SBP and 5.00 for DBP) [ 49 ]. Consequently, combining CCB and a RASi is a good option as a first-line combination therapy for managing hypertension in CKD.…”