Dual blockade of the renin-angiotensin system versus maximal recommended dose of ACE inhibition in diabetic nephropathy.

Abstract

BACKGROUND:

Albuminuria and hypertension are predictors of poor renal and cardiovascular outcome in diabetic patients. We tested whether dual blockade of the renin-angiotensin system (RAS) with both an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II receptor blocker (ARB) is superior to maximal recommended dose of ACE inhibitor in type 1 diabetic patients with diabetic nephropathy (DN).

METHODS:

We performed a randomized, double-blind, crossover trial with 8 weeks treatment with placebo and irbesartan 300 mg (once daily), added on top of enalapril 40 mg (once daily). We included 24 type 1 patients with DN. At the end of each treatment period, albuminuria, 24-hour blood pressure, and glomerular filtration rate (GFR) were measured.

RESULTS:

Values on ACE inhibitors + placebo were: albuminuria [mean (95% CI)], 519 (342 to 789) mg/24 hours; blood pressure [mean (SEM)], 131 (3)/74 (1) mm Hg, and GFR [mean (SEM)], 65 (5) mL/min/1.73 m2. Dual blockade of the RAS induced a reduction in albuminuria [mean (95% CI)] of 25% (15, 34) (P < 0.001), a reduction in systolic blood pressure of 8 mm Hg (4, 12) (P = 0.002), and a reduction of 4 mm Hg (2, 7) (P = 0.003) in diastolic blood pressure. GFR and plasma potassium remained unchanged during both treatment regimes. Dual blockade was safe and well tolerated.

CONCLUSION:

Dual blockade of the RAS is superior to maximal recommended dose of ACE inhibitors with regard to lowering of albuminuria and blood pressure in type 1 patients with DN. Long-term trials are needed to further establish the role of dual blockade of the RAS in renal and cardiovascular protection.

• Authors: Peter Jacobsen, Steen Andersen, Kasper Rossing, Berit R Jensen, Hans-Henrik Parving
• Journal: Kidney international (Kidney Int) Vol. 63 Issue 5 Pg. 1874-80 (May 2003) ISSN: 0085-2538 [Print] United States
• PMID: 12675866 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Antihypertensive Agents
• Biphenyl Compounds
• Tetrazoles
• Enalapril
• Irbesartan

Topics

• Adult
• Albuminuria (drug therapy)
• Angiotensin-Converting Enzyme Inhibitors (administration & dosage, adverse effects)
• Antihypertensive Agents (administration & dosage, adverse effects)
• Biphenyl Compounds (administration & dosage, adverse effects)
• Blood Pressure (drug effects)
• Cross-Over Studies
• Diabetes Mellitus, Type 1 (complications)
• Diabetic Nephropathies (drug therapy)
• Double-Blind Method
• Drug Synergism
• Drug Therapy, Combination
• Enalapril (administration & dosage, adverse effects)
• Female
• Humans
• Irbesartan
• Male
• Middle Aged
• Renin-Angiotensin System (drug effects)
• Tetrazoles (administration & dosage, adverse effects)