Effect of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with type 2 diabetes detected by screening (ADDITION-Europe): a cluster-randomised trial

Abstract

SummaryBackgroundIntensive treatment of multiple cardiovascular risk factors can halve mortality among people with established type 2 diabetes. We investigated the effect of early multifactorial treatment after diagnosis by screening.MethodsIn a pragmatic, cluster-randomised, parallel-group trial done in Denmark, the Netherlands, and the UK, 343 general practices were randomly assigned screening of registered patients aged 40–69 years without known diabetes followed by routine care of diabetes or screening followed by intensive treatment of multiple risk factors. The primary endpoint was first cardiovascular event, including cardiovascular mortality and morbidity, revascularisation, and non-traumatic amputation within 5 years. Patients and staff assessing outcomes were unaware of the practice's study group assignment. Analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00237549.FindingsPrimary endpoint data were available for 3055 (99·9%) of 3057 screen-detected patients. The mean age was 60·3 (SD 6·9) years and the mean duration of follow-up was 5·3 (SD 1·6) years. Improvements in cardiovascular risk factors (HbA1c and cholesterol concentrations and blood pressure) were slightly but significantly better in the intensive treatment group. The incidence of first cardiovascular event was 7·2% (13·5 per 1000 person-years) in the intensive treatment group and 8·5% (15·9 per 1000 person-years) in the routine care group (hazard ratio 0·83, 95% CI 0·65–1·05), and of all-cause mortality 6·2% (11·6 per 1000 person-years) and 6·7% (12·5 per 1000 person-years; 0·91, 0·69–1·21), respectively.InterpretationAn intervention to promote early intensive management of patients with type 2 diabetes was associated with a small, non-significant reduction in the incidence of cardiovascular events and death.FundingNational Health Service Denmark, Danish Council for Strategic Research, Danish Research Foundation for General Practice, Danish Centre for Evaluation and Health Technology Assessment, Danish National Board of Health, Danish Medical Research Council, Aarhus University Research Foundation, Wellcome Trust, UK Medical Research Council, UK NIHR Health Technology Assessment Programme, UK National Health Service R&D, UK National Institute for Health Research, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, Novo Nordisk, Astra, Pfizer, GlaxoSmithKline, Servier, HemoCue, Merck.

The clinical characteristics at diagnosis of type 2 diabetes in a multi-ethnic population: the South London Diabetes cohort (SOUL-D)

“…Both populations were predominantly white. It is of interest to compare the SOUL-D participants with the wellcharacterised patient cohort of the UKPDS, which recruited people with newly diagnosed type 2 diabetes from primary care across the UK between 1977 and 1991 [2,22] and the recent European Anglo-Danish-Dutch study of Intensive Treatment In PeOple with screeN detected diabetes in primary care (ADDITION-Europe) study, which recruited people diagnosed according to local diabetes screening policies in three European countries into an intervention targeting cardiovascular risk [6]. Looking first at the historical perspective, the SOUL-D cohort has a higher mean BMI than UKPDS (32.3 vs 27.5 kg/m 2 ), presumably a reflection of the known increase in obesity over the 20 years since the UKPDS sample was recruited [23], but smoking was less prevalent (19.8% vs 35% in UKPDS), perhaps reflecting the success of recent public health interventions [24].…”

“…ADDITION-Europe provides a more contemporary comparator for SOUL-D [6]. Early ACTID, an intervention study examining the effects of exercise in new-onset type 2 diabetes in south west England, which also recruited patients with diabetes of short duration, did not report HbA 1c at diagnosis, or prevalence of retinopathy [4,5].…”

“…Clinical practice has changed, with more aggressive screening in primary care. Two recent studies of people with new-onset diabetes, identified by screening, have not reported retinopathy data and both study populations, in common with UKPDS, were of predominantly white ethnicity [4][5][6]. A third study that purposefully recruited British Asians, and which included 40% with diabetes duration of less than 4 years, also did not report retinopathy status [7].…”

Implementation of the automated Leicester Practice Risk Score in two diabetes prevention trials provides a high yield of people with abnormal glucose tolerance

“…Both patients and healthcare professionals have reported that the OGTT is a barrier to attending screening [19]. The ADDITION-Europe study used a variety of screening methods to establish a cohort with screen-detected type 2 diabetes [20]. Centres that used a three-step approach, combining a risk score followed by a random blood glucose test followed by an OGTT, had a significantly greater uptake compared with a one-step approach using the OGTT only [15].…”

Effect of population screening for type 2 diabetes and cardiovascular risk factors on mortality rate and cardiovascular events: a controlled trial among 1,912,392 Danish adults

“…Participants diagnosed with type 2 diabetes were subsequently managed according to the treatment regimen to which their practice had been allocated: routine care or intensive treatment [18]. For individuals found to have impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) [17], and/ or a high CVD risk (SCORE >5 points), practitioners were encouraged to manage cardiovascular risk factors according to national guidelines [19], including annual cardiovascular risk assessment and diabetes tests.…”