In screen-detected type 2 diabetes, intensive therapy did not differ from usual care for CV events at 10 years

Despite the lack of observed benefit in this analysis, primary care physicians should continue to operate under the reasonable assumption that addressing cardiovascular (CV) risk factors improves longevity, said an ACP Journal Club commentary.

A follow-up analysis found that after 10 years, patients who had received intensive therapy for five years after diabetes diagnosis had similar rates of cardiovascular (CV) events and mortality as those who had been randomized to five years of usual care. The between-group differences in glycemic control and CV risk factors that had been seen during the intervention were attenuated at 10-year follow-up, and there was no significant difference in the primary outcome, a composite of first CV event, including CV mortality and morbidity (nonfatal myocardial infarction and nonfatal stroke), revascularization, and nontraumatic amputation.

The study was published Dec. 1, 2019, by The Lancet Diabetes & Endocrinology. The following commentary by Michael Tanner, MD, FACP, was published in the ACP Journal Club section of the April 21 Annals of Internal Medicine.

The original ADDITION-Europe trial sought to determine whether intensive treatment of all CV risk factors improved outcomes at 5 years in newly diagnosed, screen-detected type 2 diabetes. It showed a nonsignificant reduction in the primary composite outcome (hazard ratio [HR] 0.83, 95% CI 0.65 to 1.05). Because the findings were close to statistical significance and the Kaplan–Meier curves began to diverge markedly at 4 years, the authors extended the trial for another 5 years.

The post hoc extended ADDITION-Europe trial showed a nonsignificant reduction in the composite primary outcome (HR 0.87, CI 0.73 to 1.04). It was unable to replicate the favorable results of 2 earlier trials of multifactorial interventions for diabetes for several reasons. The intervention targeted general practices rather than individual patients and patients in both groups received similar prescribed medications, with the exception of increased use of angiotensin-converting enzyme inhibitors and aspirin in the intensive group. The follow-up study was observational, with no attempt to maintain between-group differences in treatment protocols after 5 years. Event rates were lower than expected in both groups, and not surprisingly, hemoglobin A1c, blood pressure, total cholesterol, and weight did not differ between groups at 10 years. Three of the 4 geographical practice areas had no unscreened control groups. Finally, 95% of participants self-identified as white, so generalizability to other racial groups is limited.

The results of ADDITION-Europe are unlikely to change practice. In primary care, we operate under the reasonable assumption that addressing all CV risk factors improves longevity. Strong evidence supports the CV benefit of controlling each risk factor—blood pressure, glucose, cholesterol, and weight. During follow-up, the treatments received by the intensive- and routine-care groups became too similar to demonstrate the benefit of intensive multifactorial treatment.