Details

Autor(en) / Beteiligte

• Ruggenenti, Piero
• Lauria, Giuseppe
• Iliev, Ilian Petrov
• Fassi, Anna
• Ilieva, Aneliya Parvanova
• Rota, Stefano
• Chiurchiu, Carlos
• Barlovic, Drazenka Pongrac
• Sghirlanzoni, Angelo
• Lombardi, Raffaella
• Penza, Paola
• Cavaletti, Guido
• Piatti, Maria Luisa
• Frigeni, Barbara
• Filipponi, Marco
• Rubis, Nadia
• Noris, Greta
• Motterlini, Nicola
• Ene-Iordache, Bogdan
• Gaspari, Flavio
• Perna, Annalisa
• Zaletel, Jelka
• Bossi, Antonio
• Dodesini, Alessandro Roberto
• Trevisan, Roberto
• Remuzzi, Giuseppe

Titel

Effects of Manidipine and Delapril in Hypertensive Patients With Type 2 Diabetes Mellitus: The Delapril and Manidipine for Nephroprotection in Diabetes (DEMAND) Randomized Clinical Trial

Ist Teil von

• Hypertension (Dallas, Tex. 1979), 2011-11, Vol.58 (5), p.776-783

Ort / Verlag

Hagerstown, MD: American Heart Association, Inc

Erscheinungsjahr

2011

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• To assess whether angiotensin-converting enzyme inhibitors and third-generation dihydropyridine calcium channel blockers ameliorate diabetic complications, we compared glomerular filtration rate (GFR; primary outcome), cardiovascular events, retinopathy, and neuropathy in 380 hypertensive type 2 diabetics with albuminuria <200 mg/min included in a multicenter, double-blind, placebo-controlled trial (DEMAND [Delapril and Manidipine for Nephroprotection in Diabetes]) and randomized to 3-year treatment with manidipine/delapril combination (10/30 mg/d; n=126), delapril (30 mg/d; n=127), or placebo (n=127). GFR was centrally measured by iohexol plasma clearance. Median monthly GFR decline (interquartile range [IQR]) was 0.32 mL/min per 1.73 m (IQR0.16–0.50 mL/min per 1.73 m) on combined therapy, 0.36 mL/min per 1.73 m (IQR0.18–0.53 mL/min per 1.73 m) on delapril, and 0.30 mL/min per 1.73 m (IQR0.12–0.50 mL/min per 1.73 m) on placebo (P=0.87 and P=0.53 versus combined therapy or delapril, respectively). Similar findings were observed when baseline GFR values were not considered for slope analyses. Albuminuria was stable in the 3 treatment groups. The hazard ratio (95% CI) for major cardiovascular events between combined therapy and placebo was 0.17 (0.04–0.78; P=0.023). Among 192 subjects without retinopathy at inclusion, the hazard ratio for developing retinopathy between combined therapy and placebo was 0.27 (0.07–0.99; P=0.048). Among 200 subjects with centralized neurological evaluation, the odds ratios for peripheral neuropathy at 3 years between combined therapy or delapril and placebo were 0.45 (0.24–0.87; P=0.017) and 0.52 (0.27–0.99; P=0.048), respectively. Glucose disposal rate decreased from 5.8±2.4 to 5.3±1.9 mg/kg per min on placebo (P=0.03) but did not change on combined or delapril therapy. Treatment was well tolerated. In hypertensive type 2 diabetic patients, combined manidipine and delapril therapy failed to slow GFR decline but safely ameliorated cardiovascular disease, retinopathy, and neuropathy and stabilized insulin sensitivity.