BMJ. 2000 Dec 9;321(7274):1440-4. 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.

Mogensen CE， Neldam S， Tikkanen I， Oren S， Viskoper R， Watts RW， Cooper ME.

Department of Medicine， M， Kommunehospitalet， University Hospital， DK-8000 Aarhus C， Denmark. cem@afdm.au.dk

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.