Clinical Context

Atrial fibrillation (AF) is associated with increased risk of stroke, heart failure, and cardiovascular mortality. Obesity is a well-established risk factor for both incident and recurrent AF, and weight reduction has been associated with improved AF outcomes.

The SELECT trial previously demonstrated that semaglutide reduced major adverse cardiovascular events (MACE) and body weight in patients with atherosclerotic cardiovascular disease (ASCVD) and overweight or obesity without diabetes. This analysis evaluated AF burden and cardiovascular outcomes based on baseline AF status.

Study Design

SELECT was a double-blind, placebo-controlled trial including 17,604 patients aged 45 years or older with established ASCVD and overweight or obesity without diabetes.

A total of 1,614 patients (9%) had a history of AF at baseline. AF status was defined based on medical history or baseline documentation, as assessed by site investigators.

Time-to-event analyses were performed for:

• First MACE (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke)
• Heart failure outcomes (cardiovascular death or HF hospitalization/urgent visit)
• Incident AF events recorded as adverse events

Key Findings

Patients with a history of AF were older (median age 67 vs 61 years) and had higher baseline body weight compared with those without AF.

A higher incidence of first MACE was observed in patients with prior AF. Semaglutide reduced MACE risk compared with placebo in both groups:

• With AF: hazard ratio (HR) 0.76 (95% CI: 0.57-1.02)
• Without AF: HR 0.81 (95% CI: 0.72-0.91)
• No significant interaction between groups

Across the overall study population, semaglutide was associated with a lower risk of first AF event (HR 0.83; 95% CI: 0.70-0.99; P = 0.040).

Among patients with a history of AF, semaglutide reduced AF events:

• HR 0.73 (95% CI: 0.54-0.96)

In patients without prior AF, the reduction was not statistically significant:

• HR 0.93 (95% CI: 0.74–1.16; interaction not significant)

Patients with prior AF also had higher rates of HF outcomes. Semaglutide reduced HF outcomes compared with placebo:

• With AF: HR 0.68 (95% CI: 0.40–1.12)
• Without AF: HR 0.85 (95% CI: 0.62–1.16)
• No significant interaction between groups

Study Limitations

• AF events were captured as adverse events rather than systematically adjudicated endpoints
• Subgroup analyses were not powered for definitive comparisons
• Interaction analyses were not statistically significant

Clinical Perspective

Patients with a history of AF had higher risks of MACE, AF recurrence, and heart failure outcomes compared with those without AF. Semaglutide consistently reduced cardiovascular risk across both groups, with a signal toward reduction in AF events, particularly in those with prior AF.

These findings support the broader cardiometabolic benefits of semaglutide beyond weight reduction and highlight its potential role in patients with elevated AF risk.

Key Takeaway

Semaglutide reduced MACE, AF events, and HF outcomes compared with placebo irrespective of AF history, with greater absolute event burden observed in patients with prior AF.

Author

Vivek Pathak is Founder and Editorial Lead at MedApt, a physician-focused platform covering clinical updates, congress insights, and expert perspectives.