Table 1.

Antiproteinuria effect of dual- versus single-class RAS blockadea

SubjectsDesignDual-Class > ARB?Dual-Class > ACEI?
Mogensen et al. (1); n = 199; HTN, type 2 diabetes, microalbuminuriaCandesartan 16 mg/d versus lisinopril 20 mg/d versus the combination; 12-wk monotherapy, then 12-wk monotherapy or combination therapy; prospective, randomized, parallel-group, double-blind studyYesb; adjusted mean difference 34% (95% CI 3 to 55%; P = 0.04)Nob; adjusted mean difference 18% (95% CI −20 to 44%; P > 0.20)
Jacobsen et al. (2); n = 20; type 1 diabetes, diabetic nephropathyBenazepril 20 mg/d versus valsartan 80 mg/d versus the combination; 8-wk randomized, double-blind, placebo-controlled, crossover trialYes; 43% (95% CI 29 to 54%; P < 0.001)Yes; 43% (95% CI 29 to 54%; P < 0.001)
Jacobsen et al. (3); n = 24; type 1 diabetes, diabetic nephropathy, >3 mo enalapril 40 mg qdEnalapril 40 mg/d plus either placebo or irbesartan 300 mg/d; 8-wk randomized, double-blind, controlled, crossover trialNAYes; 25% (95% CI 15 to 34%; P < 0.001)
Agarwal (4); n = 16; HTN, proteinuria, moderate CRFLisinopril 40 mg/d with and without losartan 50 mg/d or placebo; 1-mo randomized, controlled, crossover trialNANo (P = 0.89)
Campbell et al. (5); n = 24; HTN, CKDFull-dosage monotherapy (benazepril 20 mg/d, valsartan 160 mg/d) versus half-dosage combination therapy (benazepril 10 mg/d, valsartan 80 mg/d); 8-wk randomized, prospective, open-label, crossover trialYes; −14.5% (P = 0.002)Yes; −10.1% (P = 0.024)
Esnault et al. (6); n = 18; proteinuric (>1 g/d), 6 mo ramipril 5 mg/dFull-dosage monotherapy (ramipril 10 mg/d, valsartan 160 mg/d) versus half-dosage combination therapy (ramipril 5 mg/d, valsartan 80 mg/d); 4-wk randomized, prospective, open-label, crossover trialNoc; 5.1% (P = 0.70)Noc; −0.80% (P = 0.17)
Doulton et al. (7); meta-analysisEight trials reporting effect of dual versus single RAS blockade on proteinuriadYes; 39% (95% CI 31 to 48%)Yes; 30% (95% CI 23 to 37%)
  • a Length of treatment in crossover studies refers to time on each therapy rather than total study length. ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CI, confidence interval; CKD, chronic kidney disease; CRF, chronic renal failure; HTN, hypertensive; RAS, renin-angiotensin system.

  • b Urinary albumin-to-creatinine ratio.

  • c Urinary protein-to-creatinine ratio.

  • d Proteinuria refers to albuminuria, proteinuria, or urinary albumin-to-creatinine ratio.