Antiproteinuria effect of dual- versus single-class RAS blockadea
| Subjects | Design | Dual-Class > ARB? | Dual-Class > ACEI? |
|---|---|---|---|
| Mogensen et al. (1); n = 199; HTN, type 2 diabetes, microalbuminuria | Candesartan 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 study | Yesb; 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 nephropathy | Benazepril 20 mg/d versus valsartan 80 mg/d versus the combination; 8-wk randomized, double-blind, placebo-controlled, crossover trial | Yes; 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 qd | Enalapril 40 mg/d plus either placebo or irbesartan 300 mg/d; 8-wk randomized, double-blind, controlled, crossover trial | NA | Yes; 25% (95% CI 15 to 34%; P < 0.001) |
| Agarwal (4); n = 16; HTN, proteinuria, moderate CRF | Lisinopril 40 mg/d with and without losartan 50 mg/d or placebo; 1-mo randomized, controlled, crossover trial | NA | No (P = 0.89) |
| Campbell et al. (5); n = 24; HTN, CKD | Full-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 trial | Yes; −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/d | Full-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 trial | Noc; 5.1% (P = 0.70) | Noc; −0.80% (P = 0.17) |
| Doulton et al. (7); meta-analysis | Eight trials reporting effect of dual versus single RAS blockade on proteinuriad | Yes; 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.