European Heart Journal Advance Access originally published online on March 11, 2009
European Heart Journal 2009 30(9):1128-1135; doi:10.1093/eurheartj/ehp055
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Risks of cardiovascular events and effects of routine blood pressure lowering among patients with type 2 diabetes and atrial fibrillation: results of the ADVANCE study
1 The George Institute for International Health, University of Sydney, Level 10, King George V Building, Royal Prince Alfred Hospital, PO Box M201, Missenden Road, Camperdown, Sydney, NSW 2050, Australia
2 Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
3 Mount Sinai Medical Center, New York City, NY, USA
4 Danielle Alberti Memorial Centre for Diabetes Complications, Baker Heart Research Institute, Melbourne, Australia
5 Department of Physiology, University of Melbourne, Melbourne, Australia
6 Research Centre, Centre hospitalier de l'Université de Montréal, Canada
7 International Centre for Circulatory Health, Imperial College London, NHLI, Faculty of Medicine, St Mary's Campus, London, UK
8 University Department of Medicine, City Hospital, Birmingham, UK
Received 5 October 2008; revised 18 January 2009; accepted 22 January 2009; online publish-ahead-of-print 11 March 2009.
* Corresponding author. Tel: +61 2 9993 4564, Fax: +61 2 9993 4502, Email: apatel{at}george.org.au or apatel{at}thegeorgeinstitute.org
Aims: The aim of this study was to investigate serious clinical outcomes associated with atrial fibrillation (AF) and the effects of routine blood pressure lowering on such outcomes in the presence or absence of AF, among individuals with type 2 diabetes.
Methods and results: About 11 140 patients with type 2 diabetes (7.6% of whom had AF at baseline) were randomized to a fixed combination of perindopril and indapamide or placebo in the Action in Diabetes and Vascular Disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study. We compared total mortality and cardiovascular disease outcomes and effects of randomized treatment for 4.3 years on such outcomes between patients with and without AF at baseline. After multiple adjustments, AF was associated with a 61% (95% confidence interval 31–96, P < 0.0001) greater risk of all-cause mortality and comparable higher risks of cardiovascular death, stroke, and heart failure (all P < 0.001). Routine treatment with a fixed combination of perindopril and indapamide produced similar relative, but greater absolute, risk reductions for all-cause and cardiovascular mortalities in patients with AF, compared with those without AF. The number of patients needed to be treated with perindopril–indapamide for 5 years to prevent one cardiovascular death was 42 for patients with AF and 120 for patients without AF at baseline.
Conclusion: Atrial fibrillation is relatively common in type 2 diabetes and is associated with substantially increased risks of death and cardiovascular events in patients with type 2 diabetes. This arrhythmia identifies individuals who are likely to obtain greater absolute benefits from blood pressure-lowering treatment. Atrial fibrillation in diabetic patients should be regarded as a marker of particularly adverse outcome and prompt aggressive management of all risk factors.
Key Words: Atrial fibrillation • Randomized controlled trial • Diabetes mellitus • Cardiovascular events • Mortality • Perindopril–indapamide
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