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Appropriate blood pressure control in hypertensive and normotensive type 2 diabetes mellitus: a summary of the ABCD trial

Nature Clinical Practice Nephrology volume 3, pages 428–438 (2007)Cite this article

Abstract

The hypertensive and normotensive Appropriate Blood Pressure Control in Diabetes (ABCD) studies were prospective, randomized, interventional clinical trials with 5 years of follow-up that examined the role of intensive versus standard blood pressure control in a total of 950 patients with type 2 diabetes mellitus. In the hypertensive ABCD study, a significant decrease in mortality was detected in the intensive blood pressure control group when compared with the standard blood pressure control group. There was also a marked reduction in the incidence of myocardial infarction when patients were randomly assigned to initial antihypertensive therapy with angiotensin-converting-enzyme inhibition rather than calcium channel blockade. The results of the normotensive ABCD study included associations between intensive blood pressure control and significant slowing of the progression of nephropathy (as assessed by urinary albumin excretion) and retinopathy, and fewer strokes. In both the hypertensive and normotensive studies, mean renal function (as assessed by 24 h creatinine clearance) remained stable during 5 years of either intensive or standard blood pressure intervention in patients with normoalbuminuria (<30 mg/24 h) or microalbuminuria (30–300 mg/24 h) at baseline. By contrast, the rate of creatinine clearance in patients with overt diabetic nephropathy (>300 mg/24 h; albuminuria) at baseline decreased by an average of 5 ml/min/year in spite of either intensive or standard blood pressure control. Analysis of the results of 5 years of follow-up revealed a highly significant correlation of all-cause and cardiovascular mortality with left ventricular mass and severity of albuminuria.

Key Points

  • The primary hypothesis of the 5-year prospective Appropriate Blood Pressure Control in Diabetes (ABCD) trial was that intensive (as opposed to moderate) control of blood pressure, via randomization to either nisoldipine or enalapril treatment, would prevent or slow the progression of diabetic complications and cardiovascular events in individuals with type 2 diabetes mellitus

  • The prevalences of diabetic complications and cardiovascular disease at baseline were significantly greater among enrollees whose diastolic blood pressure exceeded 90 mmHg; trial data for the hypertensive and normotensive cohorts were, therefore, analyzed separately

  • Comparison of the angiotensin-converting-enzyme inhibitor enalapril and the calcium channel blocker nisoldipine was halted after 4 years in the hypertensive cohort because treatment with the former was associated with significantly fewer myocardial infarctions than was treatment with the latter

  • In the hypertensive cohort, open-label treatment with enalapril for a further year was associated with preservation of renal function in patients with normoalbuminuria or microalbuminuria in both the moderate and intensive blood pressure control groups; this finding was replicated in the normotensive cohort

  • All-cause mortality in the hypertensive cohort after 5 years was markedly lower in the intensive than in the moderate blood pressure control group

  • The progression of microvascular retinopathy and the incidence of stroke were decreased by intensive blood pressure control in the normotensive cohort

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Figure 1: Complications at baseline in patients enrolled in the ABCD randomized clinical trial
Figure 2: Randomization protocol for the hypertensive ABCD study
Figure 3: Cardiovascular complications in patients receiving enalapril or nisoldipine
Figure 4: Interactions by which obesity and insulin resistance might lead to hypertension in patients with type 2 diabetes
Figure 5: Randomization protocol for the normotensive ABCD study
Figure 6: Progressive increases in urinary albumin excretion rate are associated with decreased survival in patients with type 2 diabetes
Figure 7: Results of the randomized UKPDS trial show that strict control of blood pressure is more effective than strict control of blood glucose level in decreasing the incidence of both microvascular and macrovascular complications in patients with type 2 diabetes
Figure 8: Mean blood pressure achieved in diabetic patients in the UKPDS, HOT and ABCD trials
Figure 9: Left ventricular mass (as adjusted Cornell voltage) across the three stages of albuminuria (P <0.0001) in patients from the ABCD trial with type 2 diabetes
Figure 10: Potential effects of increased levels of plasminogen activator inhibitor in type 2 diabetes on cardiovascular and renal mortality

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Acknowledgements

The ABCD trial was supported by Bayer and the National Institute of Diabetes, Digestive, and Kidney Diseases (DK50298-02). The valsartan study was supported by Novartis Pharmaceutical Company. We sincerely thank Jan Darling for her excellent support in the preparation of the manuscript. Désirée Lie, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

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Authors and Affiliations

  1. at the University of Colorado School of Medicine. RO Estacio is also Director of the Medical Affairs Department at The Colorado Prevention Center. PS Mehler is the Medical Director of the Acute Comprehensive Urgent Treatment for Eating Disorders program in Denver, RW Schrier is Professor of Medicine, and RO Estacio is Associate Professor of Medicine, Chief of Internal Medicine at Denver Health Medical Center, and Professor of Medicine at the University of Colorado Health Center. WR Hiatt is President of the Colorado Prevention Center, Professor of Medicine, and Chief of the Vascular Medicine Section at the University of Colorado Health Sciences Center, CO, USA.,

    Robert W Schrier, Raymond O Estacio, Philip S Mehler & William R Hiatt

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  1. Robert W Schrier
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  2. Raymond O Estacio
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Correspondence to Robert W Schrier.

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Competing interests

Dr Schrier has been a Consultant for Amgen and Otsuka America Pharmaceuticals, and has received Speaker's honoraria from Astellas Pharma and Otsuka America Pharmaceuticals.

The other authors declared no competing interests.

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Schrier, R., Estacio, R., Mehler, P. et al. Appropriate blood pressure control in hypertensive and normotensive type 2 diabetes mellitus: a summary of the ABCD trial. Nat Rev Nephrol 3, 428–438 (2007). https://doi.org/10.1038/ncpneph0559

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