Applying REWIND cardiovascular disease criteria to SUSTAIN 6 and PIONEER 6: An exploratory analysis of cardiovascular outcomes with semaglutide

Abstract

In the REWIND trial, dulaglutide reduced cardiovascular (CV) risk versus placebo in patients with type 2 diabetes in both the "established CV disease" (CVD) and "CV risk factor" subgroups. The SUSTAIN 6 and PIONEER 6 trials of semaglutide used different criteria for established CVD from those used in REWIND. The present post hoc analysis assessed the effect of semaglutide on major adverse CV events (MACE) in a pooled population of SUSTAIN 6 and PIONEER 6 patients, re-categorized into CV risk subgroups using the REWIND CVD criteria. In the pooled analysis (n = 6480), a lower percentage of patients were in the established CVD subgroup, when using the REWIND CVD criteria, compared with the original trial CVD criteria (66.5% vs. 83.8%, respectively). After re-categorization, the risk of MACE was significantly lower with semaglutide versus placebo in the established CVD subgroup (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.59, 0.92) and nonsignificantly lower in the CV risk factor subgroup (HR 0.84, 95% CI 0.55, 1.28) (P-interaction = 0.60). These results suggest that the CV effects of semaglutide may extend to patients with type 2 diabetes across the CV risk continuum.

Trial registration: ClinicalTrials.gov NCT01720446 NCT02692716.

Keywords: GLP-1 analogue; antidiabetic drug; cardiovascular disease; incretin therapy.

FIGURE 1

Primary and secondary endpoints with semaglutide versus placebo in patients from SUSTAIN 6 and PIONEER 6 re‐categorized as having established cardiovascular disease (CVD) or cardiovascular (CV) risk factors using REWIND criteria. Established CVD, n = 4310; CV risk factors, n = 2170. *Major adverse CV events (MACE) = death from CV causes, nonfatal myocardial infarction (MI), nonfatal stroke. ^†Expanded MACE = MACE plus coronary or peripheral revascularization and hospitalization for unstable angina (UA) or heart failure (HF). Established CVD = MI, ischaemic stroke, UA, coronary heart disease or asymptomatic cardiac ischaemia, arterial revascularization and >50% stenosis of coronary, carotid or lower extremity arteries. CV risk factors = microalbuminuria/proteinuria, hypertension and left ventricular hypertrophy, left ventricular dysfunction, ankle‐brachial index <0.9, chronic kidney disease, HF or transient ischaemic attack/haemorrhagic stroke. CI, confidence interval; IR, incidence rate (events/100 patient‐years of observation); n, number of patients with event