Daily Cardiology Research Analysis

BACKGROUND: Peripheral artery disease (PAD) is a prevalent and debilitating complication of diabetes and obesity, yet it remains underrecognized and undertreated. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as semaglutide, have shown cardiovascular benefits, but their impact on peripheral vascular outcomes remains unclear. OBJECTIVE: We conducted a systematic review and meta-analysis to evaluate the effect of semaglutide on limb events (LEs) in individuals with type 2 diabetes and/or overweight or obesity. METHODS: Following PRISMA guidelines, 19 randomized controlled trials encompassing 51,557 participants were included. Major limb events, prespecified and reported as safety outcomes in the original trials, were defined a priori as the primary outcome of this meta-analysis, comprising revascularizations, amputations, and PAD progression. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: Semaglutide significantly reduced the risk of LEs compared to control interventions (OR 0.70; 95% CI 0.60-0.82; p < 0.0001), with no heterogeneity across studies (I² = 0%). Benefits were consistent across patient subgroups, in patients with diabetes (OR 0.70; 95% CI: 0.57-0.87; p = 0.001) or obesity (OR 0.71; 95% CI: 0.56-0.89; p = 0.003); oral formulation (0.71; 95% CI: 0.53-0.94; p = 0.02) or subcutaneous (0.68; 95% CI: 0.49-0.95; p = 0.02 and 0.71; 95% CI: 0.57-0.89; p = 0.003, for 1.0 mg and 2.4 mg, respectively); and regardless of background SGLT2 inhibitor use. Meta-regression showed no significant effect modification by age, BMI, HbA1c, follow-up duration, or SGLT2i use. CONCLUSIONS: This meta-analysis suggest that semaglutide is associated with a significant reduction in major limb events across diverse populations and treatment settings, supporting a potential protective effect on limb-related vascular safety. This meta-analysis evaluates whether semaglutide can reduce the risk of peripheral artery disease (PAD) complications in people with diabetes or obesity. By analyzing data from 19 randomized controlled trials involving over 51,000 participants, the findings highlight semaglutide’s potential role in lowering the risk of amputations, revascularizations, and disease progression, beyond its established benefits on weight loss and glicemic control. Key findings:Semaglutide reduced the risk of PAD-related events by about 30% compared with other treatments.The protective effect was consistent across patient subgroups, formulations (oral or injectable), and irrespective of concomitant SGLT2 inhibitor use.

BACKGROUND: Stressor-associated atrial fibrillation (AF), defined as newly diagnosed AF in the setting of a reversible physiological stressor, is common. However, risk factors, outcomes, and current management practices remain poorly understood. METHODS: We analyzed data from VITAL-AF, a pragmatic, cluster-randomized AF screening trial conducted in 2018 and 2019 comprising adults ≥65 years of age across 16 primary care practices affiliated with Massachusetts General Hospital. All participants had longitudinal follow-up for adjudicated incident AF (including whether stressor-associated versus nonstressor-associated ["primary"]) and clinical outcomes. We compared associations between clinical AF risk factors and incident AF group (stressor-associated versus primary) using Fine-Gray models handling death and each AF group as competing risks. We also quantified oral anticoagulant initiation rates after AF diagnosis. We then fit Cox proportional hazards models to quantify associations between incident AF group (as a time-varying covariate) and a composite end point of major bleeding, stroke, and all-cause mortality, with adjustment for CHA₂DS₂-VASc (congestive heart failure, hypertension, age >74, diabetes, stroke or transient ischemic attack or thromboembolism, vascular disease, age 65-74, sex category; stroke) and ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation; bleeding) scores and time-varying oral anticoagulant exposure. RESULTS: We analyzed 30 265 patients (41% men, 83% White, and mean age 74 years). Of 988 incident AF events, 290 (29%) were stressor associated. Clinical risk factors, including age, hypertension, and heart failure, showed similar associations with both primary and stressor-associated AF. Oral anticoagulant initiation within 90 days of new AF diagnosis was lower for stressor-associated versus primary AF (56% versus 75%, CONCLUSIONS: Among >30 000 primary care patients with adjudicated AF events, nearly one-third of incident AF cases were stressor associated. Despite similar risk factor profiles and comparably high rates of adverse outcomes, oral anticoagulant initiation is lower when AF is stressor associated. Future work is needed to define optimal approaches to prevention, surveillance, and management of stressor-associated AF.

AIMS: Mixed aortic valve disease poses unique haemodynamic challenges. This study compared the clinical outcomes of concomitant moderate aortic stenosis (AS) and moderate aortic regurgitation to isolated AS. METHODS AND RESULTS: We analysed a multicentre cohort of valvular heart disease between 2008 and 2022 at three tertiary centres. The entire cohort was divided into three groups: moderate AS accompanied by moderate aortic regurgitation (moderate ASR), isolated severe AS, and isolated moderate AS. The primary outcome was a composite of cardiac death and hospitalization for heart failure. The final analysis included 4395 patients (median age: 76 years, 50.8% male), comprising 224 patients with moderate ASR, 1996 with severe AS, and 2175 with moderate AS. Over a median follow-up of 3.4 years, aortic valve replacement (AVR) rates were 11.1, 57.2, and 7.8 per 100 person-years in the moderate ASR, severe AS, and moderate AS groups, respectively (P < 0.001). Patients with moderate ASR had a significantly higher risk of the primary outcome compared with moderate AS [adjusted hazard ratio (aHR) 1.49; 95% confidence interval (CI) 1.15-1.92; P = 0.002] and a risk comparable to severe AS (aHR 1.28; 95% CI 1.00-1.64; P = 0.052). These results remained consistent even when AVR was included as a time-varying covariate. Older age, male sex, renal dysfunction, and lower left ventricular ejection fraction were independent predictors of the primary outcome in patients with moderate ASR. CONCLUSION: Moderate ASR should not be considered a benign condition, as it is associated with poor clinical outcomes comparable to those of severe AS.