Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study

• Published in: BMJ Vol. 321; no. 7274; pp. 1440 - 1444
• Main Authors: Mogensen, Carl Erik, Neldam, Steen, Tikkanen, Ilkka, Oren, Shmuel, Viskoper, Reuven, Watts, Richard W, Cooper, Mark E
• Format: Journal Article
• Language: English
• Published: London British Medical Journal Publishing Group 09.12.2000; British Medical Association; BMJ Publishing Group LTD; BMJ
• Subjects: Adult; Aged; Albumins; Albuminuria - drug therapy; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Antihypertensive agents; Antihypertensive Agents - therapeutic use; Benzimidazoles - therapeutic use; Biological and medical sciences; Blood pressure; Cardiovascular system; Diabetes complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetic nephropathies; Diastolic blood pressure; Humans; Hypertension; Hypertension - drug therapy; Lisinopril - therapeutic use; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Prospective Studies; Receptors; Renin angiotensin system; Renin-Angiotensin System - drug effects; Tetrazoles - therapeutic use; Treatment Outcome; Type 1 diabetes mellitus; Type 2 diabetes mellitus; Endocrinopathy; Human; Hypertension; Urinary system disease; Lisinopril; Candesartan; Cardiovascular disease; Controlled therapeutic trial; Receiver; Non insulin dependent diabetes; Concomitant disease; Randomization; Treatment; Antihypertensive agent; Complication; Antagonist; Angiotensin II; Comparative study; ACE inhibitor; Proteinuria
• ISSN: 0959-8138; 0959-8146; 1468-5833; 1756-1833
• DOI: 10.1136/bmj.321.7274.1440

Abstract Objectives: To assess and compare the effects of candesartan or lisinopril, or both, on blood pressure and urinary albumin excretion in patients with microalbuminuria, hypertension, and type 2 diabetes. Design: Prospective, randomised, parallel group, double blind study with four week placebo run in period and 12 weeks' monotherapy with candesartan or lisinopril followed by 12 weeks' monotherapy or combination treatment. Setting: Tertiary hospitals and primary care centres in four countries (37 centres). Participants: 199 patients aged 30-75 years. Interventions: Candesartan 16 mg once daily, lisinopril 20 mg once daily. Main outcome measures: Blood pressure and urinary albumin:creatinine ratio. Results: At 12 weeks mean (95% confidence interval) reductions in diastolic blood pressure were 9.5 mm Hg (7.7 mm Hg to 11.2 mm Hg, P<0.001) and 9.7 mm Hg (7.9 mm Hg to 11.5 mm Hg, P<0.001), respectively, and in urinary albumin:creatinine ratio were 30% (15% to 42%, P<0.001) and 46% (35% to 56%, P<0.001) for candesartan and lisinopril, respectively. At 24 weeks the mean reduction in diastolic blood pressure with combination treatment (16.3 mm Hg, 13.6 mm Hg to 18.9 mm Hg, P<0.001) was significantly greater than that with candesartan (10.4 mm Hg, 7.7 mm Hg to 13.1 mm Hg, P<0.001) or lisinopril (mean 10.7 mm Hg, 8.0 mm Hg to 13.5 mm Hg, P<0.001). Furthermore, the reduction in urinary albumin:creatinine ratio with combination treatment (50%, 36% to 61%, P<0.001) was greater than with candesartan (24%, 0% to 43%, P=0.05) and lisinopril (39%, 20% to 54%, P<0.001). All treatments were generally well tolerated. Conclusion: Candesartan 16 mg once daily is as effective as lisinopril 20 mg once daily in reducing blood pressure and microalbuminuria in hypertensive patients with type 2 diabetes. Combination treatment is well tolerated and more effective in reducing blood pressure.