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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

BMJ 2000; 321 doi: (Published 09 December 2000) Cite this as: BMJ 2000;321:1440
  1. Carl Erik Mogensen, professor of medicine (cem{at},
  2. Steen Neldam, general practitionerb,
  3. Ilkka Tikkanen, associate professor of medicine (nephrology)c,
  4. Shmuel Oren, physiciand,
  5. Reuven Viskoper, physiciand,
  6. Richard W Watts, physiciane,
  7. Mark E Cooper, professor of medicinef

    for the CALM study group

  1. a Department of Medicine, M, Kommunehospitalet, University Hospital, DK-8000 Aarhus C, Denmark
  2. b Rødovre Centrum 294, DK-2610, Denmark
  3. c Helsinki University Hospital, Clinic of Internal Diseases, Helsinki, FIN-00029 HYKS, Finland,
  4. d Barzilai Medical Centre, Ashkelon, Israel,
  5. e 19 Oxford Terrace, Port Lincoln, SA 5606, Australia,
  6. f Department of Medicine, University of Melbourne (Repatriation Campus), W Heidelberg, Victoria 3084, Australia
  1. Correspondence to: C E Mogensen
  • Accepted 26 June 2000


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.


  • Conflict of interest CEM and MEC have received fees for speaking at symposia supported by AstraZeneca, the manufacturers of lisinopril and candesartan cilexetil. CEM has received funds for research and consulting fees from AstraZeneca.

  • Funding AstraZeneca, Mölndal, Sweden.

  • Accepted 26 June 2000
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