Combination of Angiotensin II Receptor Antagonist with Calcium Channel Blocker or Diuretic as Antihypertensive Therapy for Patients with Chronic Kidney Disease

Abstract

We compared treatment with an angiotensin II receptor antagonist (ARB) and a calcium channel blocker (CCB) combination and a fixed-dose ARB and thiazide diuretic in 18 chronic kidney disease (CKD) patients. A randomized crossover study was performed using a fixed-dose combination of losartan-hydrochlorothiazide or losartan combined with controlled-release nifedipine. Both systolic blood pressure (SBP) and diastolic blood pressures (DBPs) were lower during the nifedipine period than during the diuretic period. No significant difference was observed in urinary albumin excretion, but the estimated glomerular filtration rate was higher in the nifedipine than in the diuretic period. Serum uric acid and low-density lipoprotein cholesterol were higher in the diuretic than in the nifedipine period. A significantly low cardio-ankle vascular index, an index of arterial wall stiffness, was observed in the nifedipine period. A combination of ARB and a controlled-release nifedipine at 20-40 mg used showed a superior antihypertensive effect in CKD patients compared to a fixed-dose combination of losartan 50 mg-hydrochlorothiazide 12.5 mg in terms of blood control. The former combination is considered advantageous for maintaining renal function and artery wall elasticity without influencing uric acid or lipid metabolism.

Renoprotective effects of renin–angiotensin system inhibitor combined with calcium channel blocker or diuretic in hypertensive patients

“…1 ). One study was based on a cross-over RCT, [ 24 ] and 13 studies were based on parallel RCTs. The final 14 RCTs consisted of a total of 18,125 patients with hypertension.…”

“…The final 14 RCTs consisted of a total of 18,125 patients with hypertension. Among them, 8 RCTs recruited Asian subjects only, [ 13 – 15 , 18 , 20 , 21 , 23 , 24 ] while the other 6 RCTs were conducted in either mixed-race or unmentioned-race populations. Six RCTs compared the 2 combined treatments in 1001 patients with diabetes mellitus, [ 13 , 14 , 16 , 17 , 22 , 25 ] and 3 RCTs compared treatments in 1079 CKD patients.…”

“…Six RCTs compared the 2 combined treatments in 1001 patients with diabetes mellitus, [ 13 , 14 , 16 , 17 , 22 , 25 ] and 3 RCTs compared treatments in 1079 CKD patients. [ 19 , 23 , 24 ] Regarding the sample size, ACCOMPLISH (11,506 patients) and COLM (5141 patients) were the 2 largest RCTs. [ 19 , 20 ]…”

Comparison of efficacy and safety between benidipine and hydrochlorothiazide in fosinopril-treated hypertensive patients with chronic kidney disease: protocol for a randomised controlled trial

“…Regarding the change of eGFR level, the required sample size for detecting a five difference with SD=16 between the two treatment arms (type I error, one sided α=0.025, power 1−β=0.90) was about 217 for each arm (434 in total) according to Ishimitsu et al 's study 6. The formula isu α =1.96, u β =1.282, δ=5, σ=16.…”

“…Hayashi et al 5 found the addition of diuretics or CCB to ARB was equally effective for the control of HTN in CKD, while diuretics may be better than CCB in reducing proteinuria (PROTECT study). However, Ishimitsu et al 6 found losartan plus nifedipine showed a superior antihypertensive and renoprotective effect in CKD patients compared to losartan plus HCTZ, but nifedipine was not associated with lower urinary albumin excretion compared to HCTZ. The ACCOMPLISH study7 concluded that hypertensive patients treated with benazepril plus amlodipine had a lower risk of progression to CKD than those treated with benazepril plus HCTZ.…”