Does early intensive multifactorial treatment reduce total cardiovascular burden in individuals with screen-detected diabetes? Findings from the ADDITION-Europe cluster-randomized trial

AIMS: To describe the total cardiovascular burden (cardiovascular morbidity or mortality, revascularization or non-traumatic amputation) in individuals with screen-detected diabetes in the ADDITION-Europe trial and to quantify the impact of the intervention on multiple cardiovascular events over 5 years. METHODS: In a pragmatic, cluster-randomized, parallel-group trial in four centres (Denmark; Cambridge, UK; the Netherlands; and Leicester, UK), 343 general practices were randomized to screening plus routine care (n = 1379 patients), or screening and promotion of target-driven, intensive treatment of multiple risk factors (n = 1678). We estimated the effect of the intervention on multiple cardiovascular events after diagnosis of diabetes using the Wei, Lin and Weissfeld method. RESULTS: Over 5.3 years, 167 individuals had exactly one cardiovascular event, 53 exactly two events, and 18 three or more events. The incidence rates (95% CI) of first events and any event per 1000 person-years were 14.6 (12.8–16.6) and 20.4 (18.2–22.6), respectively. There were non-significant reductions in the risk of a first (hazard ratio 0.83, 95% CI 0.65–1.05) and second primary endpoint (hazard ratio 0.70, 95% CI 0.43–1.12). The overall average hazard ratio for any event was 0.77 (95% CI 0.58–1.02). CONCLUSIONS: Early intensive multifactorial treatment was not associated with a significant reduction in total cardiovascular burden at 5 years. Focusing on first events in cardiovascular disease prevention trials underestimates the total cardiovascular burden to patients and the health service.