Semaglutide effects on incidence and reoccurrence of atrial fibrillation in the SELECT trial

Abstract Background Atrial fibrillation (AF) is associated with substantial cardiovascular (CV) complications including stroke and worsening heart failure (HF). Obesity is an established risk factor for initial and recurrent AF, whereas weight loss is reported to reduce recurrent AF after successful interventions. SELECT was a double-blind, placebo-controlled trial in 17,604 patients aged ≥45 years with atherosclerotic CV disease (ASCVD) and overweight or obesity without diabetes randomised to once-weekly semaglutide or placebo. In SELECT, semaglutide-treated patients had a 20% reduced risk of major adverse CV events (MACE: CV death, nonfatal myocardial infarction or nonfatal stroke) and placebo-corrected weight loss of 8.5%. Purpose To analyse AF and clinical outcomes among those with/without a medical history of AF in SELECT. Methods SELECT patients were identified as having a history of AF (defined as medical history of AF or atrial flutter or AF at baseline), as determined by medical history form query obtained at enrolment and under the site investigator’s discretion. Time from randomisation to first MACE, HF outcome (CV death or HF hospitalisation/urgent HF visit) or AF event (recorded as an adverse event) were analysed among those with and without a history of AF. Cumulative incidence rates were calculated using the Aalen–Johansen estimator. Results Among SELECT patients, 1614 (9%) had a history of AF at baseline. Those with a history of AF were older (median age 67 vs 61 years) and had higher body weight (mean 98.1 vs 94.0 kg) versus those without AF, respectively. Patients with a history of AF had a higher incidence of first MACE than those without a history of AF, with similar treatment effect of semaglutide versus placebo in both groups (HR 0.76; 95% CI 0.57–1.02 and HR 0.81; 95% CI 0.72–0.91, respectively; p for interaction not significant NS; Fig. 1). The risk of first AF event in the entire cohort, independent of AF history, was less in semaglutide versus placebo groups (HR 0.83; 95% CI 0.70–0.99; p=0.040). Patients with a history of AF had a higher incidence of AF events during the trial, which was reduced by semaglutide versus placebo (HR 0.73; 95% CI 0.54–0.96), as compared with those without a history of AF (HR 0.93; 95% CI 0.74–1.16; p for interaction NS; Fig. 2). Patients with a history of AF also had a higher incidence of a first HF outcome, which was reduced by semaglutide versus placebo (HR 0.68; 95% CI 0.40–1.12) as compared with those without a history of AF (HR 0.85; 95% CI 0.62–1.16; p for interaction NS). Conclusions In SELECT, patients with a history of AF had increased incidences of MACE, AF events and HF outcomes compared with those without a history of AF. Patients on semaglutide had a reduced risk of MACE, AF events and HF outcomes versus placebo, irrespective of history of AF status.