title: Combined effects of routine blood pressure lowering and intensive glucose control on macrovascular and microvascular outcomes in patients with type 2 diabetes: New results from the ADVANCE trial.
abstract: OBJECTIVE
  To assess the magnitude and independence of the effects of routine blood pressure lowering and intensive glucose control on clinical outcomes in patients with long-standing type 2 diabetes.
  
  
  METHODS
  This was a multicenter, factorial randomized trial of perindopril-indapamide versus placebo (double-blind comparison) and intensive glucose control with a gliclazide MR-based regimen (target A1C <or=6.5%) versus standard glucose control (open comparison) in 11,140 participants with type 2 diabetes who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial. Annual event rates and risks of major macrovascular and microvascular events considered jointly and separately, renal events, and death during an average 4.3 years of follow-up were assessed, using Cox proportional hazards models.
  
  
  RESULTS
  There was no interaction between the effects of routine blood pressure lowering and intensive glucose control for any of the prespecified clinical outcomes (all P > 0.1): the separate effects of the two interventions for the renal outcomes and death appeared to be additive on the log scale. Compared with neither intervention, combination treatment reduced the risk of new or worsening nephropathy by 33% (95% CI 12-50%, P = 0.005), new onset of macroalbuminuria by 54% (35-68%, P < 0.0001), and new onset of microalbuminuria by 26% (17-34%). Combination treatment was associated with an 18% reduction in the risk of all-cause death (1-32%, P = 0.04).
  
  
  CONCLUSIONS
  The effects of routine blood pressure lowering and intensive glucose control were independent of one another. When combined, they produced additional reductions in clinically relevant outcomes.
authors: The George Institute for International Health, University of Sydney, Sydney, New South Wales, Australia. szoungas@george.org.au.
authors: Sophia
authors: S
authors: Zoungas
authors: Bastiaan E
authors: BE
authors: de Galan
authors: Toshiharu
authors: T
authors: Ninomiya
authors: Diederick
authors: D
authors: Grobbee
authors: Pavel
authors: P
authors: Hamet
authors: Simon
authors: S
authors: Heller
authors: Stephen
authors: S
authors: MacMahon
authors: Michel
authors: M
authors: Marre
authors: Bruce
authors: B
authors: Neal
authors: Anushka
authors: A
authors: Patel
authors: Mark
authors: M
authors: Woodward
authors: John
authors: J
authors: Chalmers
authors: Alan
authors: A
authors: Cass
authors: Paul
authors: P
authors: Glasziou
authors: Stephen
authors: S
authors: Harrap
authors: Liu
authors: L
authors: Lisheng
authors: Guiseppe
authors: G
authors: Mancia
authors: Avinesh
authors: A
authors: Pillai
authors: Neil
authors: N
authors: Poulter
authors: Vlado
authors: V
authors: Perkovic
authors: Florence
authors: F
authors: Travert
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000453:epidemiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D003925:Diabetic Angiopathies / Q000188:drug therapy / Q000517:prevention & control*; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D005907:Gliclazide / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007190:Indapamide / Q000627:therapeutic use; D008297:Male; D008833:Microcirculation / Q000502:physiology*; D008875:Middle Aged; D020913:Perindopril / Q000627:therapeutic use; D010919:Placebos
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001786:Blood Glucose; D004338:Drug Combinations; D007004:Hypoglycemic Agents; D010919:Placebos; C494243:indapamide, perindopril drug combination; D007190:Indapamide; D005907:Gliclazide; D020913:Perindopril