To test whether microalbuminuria in patients with type 2 diabetes and hypertension is primarily dependent on the severity of hypertension, and to compare the effectiveness of two antihypertensive drugs with opposite effects on the renin–angiotensin system [the diuretic, indapamide sustained release (SR), and an angiotensin-converting enzyme inhibitor, enalapril] in reducing microalbuminuria.
A multinational, multicentre, controlled, double-blind, double-dummy, randomized, two-parallel-groups study over 1 year.
After a 4-week placebo run-in period, 570 patients (ages 60.0 ± 9.9 years, 64% men) with type 2 diabetes, essential hypertension [systolic blood pressure (SBP) 140–180 mmHg, and diastolic blood pressure (DBP) < 110 mmHg], and persistent microalbuminuria (20–200 μg/min) were allocated randomly to groups to receive indapamide SR 1.5 mg (n = 284) or enalapril 10 mg (n = 286) once a day. Amlodipine, atenolol, or both were added, if necessary, to achieve the target blood pressure of 140/85 mmHg.
There was a significant reduction in the urinary albumin : creatinine ratio. Mean reductions were 35% [95% confidence interval (CI) 24 to 43] and 39% (95% CI 30 to 47%) in the indapamide SR and enalapril groups, respectively. Equivalence was demonstrated between the two groups [1.08 (95% CI 0.89 to 1.31%); P = 0.01]. The reductions in mean arterial pressure (MAP) were 16.6 ± 9.0 mmHg for the indapamide SR group and 15.0 ± 9.1 mmHg for the enalapril group (NS); the reduction in SBP was significantly greater (P = 0.0245 ) with indapamide SR. More than 50% of patients in each group required additional antihypertensive therapy, with no differences between groups. Both treatments were well tolerated.
Indapamide-SR-based therapy is equivalent to enalapril-based therapy in reducing microalbuminuria with effective blood pressure reduction in patients with hypertension and type 2 diabetes.
aHôpital Bichat, Service de Diabétologie et d'Endocrinologie, bHospital La Paz, Servicio de Medicina Interna, Madrid, Spain, cSlaska Akademia Medyczna, Klinika Nefrologii, Katowice, Poland, dInstituto Nacional de la Nutrición ‘Salvador Zubrian’ Mexico, Mexico, eBajcsy Zsilinszky Korhaz III, Budapest, Hungary, fGroote Schuur Hospital, Cape Heart Centre, Department of Medicine, Medical School, Cape Town, South Africa, gHospital no. 64, Therapevticheski korpus, Moscow, Russian Federation, hCHU du Sart Tilman, Service de Diabétologie, Sart Tilman, Belgium, iInstitute of Nutrition and Metabolic Diseases ‘N. Paulescu’ Bucarest, Romania, jHUC, Serviço de Medicina I, Coimbra, Portugal, kInternal Medicine Ward E, Edith Wolfson Medical Centre, Giborim, Holon, Israel, lDepartment of Medicine and Therapeutics, University of Leicester, School of Medicine, Leicester, UK, mCentro de Estudos de Nefrologia e Hipertensao Arterial, Hospital das Clinicas, Instituto Central Cerqueira Cesar, Sao Paulo, Brasil, nHospital de Clinicas, Departamento de Medicina Interna, Division Diabetologia, Buenos Aires, Argentina, oMedicinsk afdeling C, Aarhus Amtssygehus Hospital, Aarhus, Denmark, pNational Public Health Institute, Helsinki, Finland, qASCARDIO, Barquisimeto, Estado Lara, Venezuela, rCentre Hospitalier Universitaire, Service de Médecine B, Angers, sU. 508 INSERM, Département d'étude des lipides/lipoprotéines, Institut Pasteur de Lille, Lille, tService de Cardiologie, Hôpital Militaire du Val-de-Grâce, Paris, France and uInstitut CardioVasculaire.
*Natrilix SR versus Enalapril Study in hypertensive Type 2 diabetics with MicrOalbuminuRia
Sponsorship: This study was supported by an unrestricted grant from Institut de Recherches Internationales Servier.
Potential conflicts of interest: Michel Marre had a financial agreement with Servier for the urinary albumin excretion measurements made during this study.
Correspondence and requests for reprints to Prof. M. Marre, Service de Diabétologie et d'Endocrinologie, Hôpital Bichat, 46 rue Henri Huchard, 75018 Paris, France. Tel: +33 1 40 25 73 01; fax: +33 1 40 25 8842; e-mail: email@example.com
Received 14 April 2003 Revised 31 March 2004 Accepted 22 April 2004
Previously presented in Abstract form to the International Society of Hypertension/European Society of Hypertension, Prague 2002.