title: The role of antihypertensive therapy in reducing vascular complications of type 2 diabetes. Findings from the DIabetic REtinopathy Candesartan Trials-Protect 2 study.
abstract: BACKGROUND
  Recent trials question previously accepted low blood pressure targets in type 2 diabetes to reduce complication risk. We explored this question in the DIabetic REtinopathy Candesartan Trials-Protect 2 clinical trial.
  
  
  METHODS
  A total of 1905 normoalbuminuric participants with type 2 diabetes and mild-moderate retinopathy were randomized to candesartan or placebo. Participants were normotensive [untreated, blood pressure (BP) < 130/85 mmHg] or treated hypertensive [(62%), BP < 160/90 mmHg]. The effects of candesartan on microvascular and macrovascular endpoints alone and in combination were analysed, including subgroup analyses by baseline hypertension status.
  
  
  RESULTS
  Mean age was 57 ± 8 years, 50% were men, mean diabetes duration was 9 ± 5 years and baseline HbA1c was 8.2 ± 1.6%. Mean randomization BP was 123/75 mmHg in the normotensive, and 139/79 mmHg in the treated hypertensive subgroups. During the median 4.7-year follow-up, achieved systolic pressure on candesartan was 128 mmHg in baseline normotensive individuals, and 136 mmHg in treated hypertensive patients. Candesartan reduced combined macrovascular and microvascular complication risk; the age and baseline SBP overall adjusted hazard ratio for candesartan vs. placebo was 0.85 [95% confidence interval (CI) 0.72-0.99], P = 0.040, reflecting hazard ratios of 0.86 (0.66-1.13) for baseline normotensive individuals and 0.83 (0.68-1.02) for hypertensive patients. Hazard ratios were 0.87 (0.74-1.04) for microvascular and 0.84 (0.57-1.25) for macrovascular complications, when analysed separately. However, an interaction (P = 0.06) between hypertensive [hazard ratio 0.67 (0.42-1.07)] and normotensive (1.45, 0.71-2.94) subgroups was observed for macrovascular events.
  
  
  CONCLUSIONS
  Candesartan modestly reduces vascular complication risk in treated hypertensive diabetic individuals at low risk of cardiovascular disease. Separate analyses of microvascular and macrovascular events suggest that candesartan may not reduce macrovascular events in normotensive persons with type 2 diabetes.
authors: International Centre for Circulatory Health, Imperial College London, London, UK.
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