EASD 2017 - Lisbon, Portugal

//Presented by Marc Sabatine (Brigham and Women’s Hospital, Boston, MA, USA) at 53rd Annual Meeting of the European Association for the Study of Diabetes (EASD) in Lisbon, Portugal//.

A new analysis of the FOURIER CV outcomes study demonstrated that lowering LDL-C levels with the PCSK9 inhibitor evolocumab significantly and consistently reduced CV events in patients with and without diabetes at baseline.

The analysis showed that diabetes was independently associated with a substantially increased risk of CV morbidity and mortality in patients with atherosclerotic CV disease. Patients with diabetes tended to have a greater absolute risk reduction of CV events with evolocumab treatment because of their heightened baseline risk. Consistent with recent trials of more intensive LDL lowering, evolocumab has not shown an effect on CV mortality. The analysis also showed that evolocumab was not associated with an increased risk of new-onset diabetes or worsening glycemia over a median of 2.2 years of follow-up in patients without diabetes or pre-diabetes. Additionally, no new safety concerns were identified in this analysis.

As part of a pre-specified analysis of the evolocumab CV outcomes study, diabetes status was defined on the basis of patient history, clinical events committee review of medical records, or baseline glycated hemoglobin (HbA1c) of 6.5 percent or greater or fasting plasma glucose (FPG) of 7.0 mmol/L (126 mg/dL) or greater. At study baseline, 40% of patients had diabetes (n=11,031) and 60% did not have diabetes (n=16,533), of whom 10,344 had pre-diabetes and 6,189 had normoglycemia. In this analysis, compared with placebo, the diabetes subgroup experienced a 57% mean reduction in LDL-C levels when treated with evolocumab (95%CI: 56-58.0; p<0.0001), and in the non-diabetes subgroup, patients treated with evolocumab experienced a 60% mean reduction at 48 weeks (95%CI: 60-61; p<0.0001), down to 0.8 mmol/L (30 mg/dL) in both groups.

The HR of evolocumab treatment for the composite primary endpoint, which included hospitalization for unstable angina, coronary revascularization, heart attack, stroke or cardiovascular death, was 0.83 (95%CI: 0.75-0.93; p=0.0008) for those with diabetes, and 0.87 (95%CI: 0.79-0.96; p=0.0052) for patients without diabetes. Because of their greater baseline risk of CV events, patients with diabetes tended to have a greater absolute risk reduction with evolocumab treatment than patients without diabetes (2.7% [95%CI: 0.7-4.8] vs. 1.6% [95%CI, 0.1-3.2]), driven largely by a greater absolute risk reduction in coronary revascularisation (2.7 [95%CI:1.1-4.2] vs. 1.8% [95%CI: 0.6–3.1]). The HR of evolocumab treatment for the secondary composite endpoint of heart attack, stroke or CV death was 0.82 (95%CI: 0.72-0.93; p=0.0021) for those with diabetes and 0.78 (95%CI: 0.69-0.89; p=0.0002) for those without diabetes. As was seen in the overall trial results, the magnitude of risk reduction in both the primary and secondary endpoints tended to increase over time beyond the first year in patients with and without diabetes.

Evolocumab, compared to placebo, did not increase the risk of new-onset diabetes in patients without diabetes at baseline (8.0% [663/8,256] versus 7.6% [631/8,254], respectively; HR 1.05, 95%CI:0.94-1.17), including those with pre-diabetes (HR 1.00, 95%CI: 0.89-1.13). Levels of HbA1c and FPG were similar between the evolocumab and placebo groups over time in patients with diabetes, pre-diabetes or normoglycemia.

The overall rates of adverse events and serious adverse events were similar between evolocumab and placebo in patients with and without diabetes. Among patients with diabetes at baseline, the proportions of patients with adverse events were 78.5% (4,327 of 5,513 patients) in the evolocumab group and 78.3% (4,307 of 5,502 patients) in the placebo group. Among patients without diabetes at baseline, the proportions with adverse events were 76.8% (6,337 of 8,256 patients) in the evolocumab group and 76.8%(6,337 of 8,254 patients) in the placebo group.

Source: press release Amgen, 15 September 2017

These data were simultaneously published in The Lancet Diabetes & Endocrinology