Aims: This meta-analysis aims to evaluate the effect of semaglutide, a glucagon-like peptide-1 receptor agonist, on new-onset atrial fibrillation (AF) in randomized clinical trials (RCTs). Methods and results: Twenty-six RCTs involving 48 583 participants (of whom 25 879 on semaglutide) with 541 new-onset AF were analyzed. Semaglutide treatment resulted in a 17% reduction in AF incidence compared to controls (odds ratio [OR] 0.83, 95% confidence interval [CI] 0.70–0.98, P = 0.03) with no heterogeneity (I² = 0%). The effect was more pronounced with the oral formulation, which reduced AF incidence by 52% (OR 0.48, 95% CI 0.24–0.95, P = 0.04), while studies with active comparators showed a 59% reduction in AF risk (OR 0.41, 95% CI 0.20–0.83, P = 0.01). In trials without sodium-glucose co-transporter 2 inhibitors (SGLT2i) concomitant therapy, there was a significant reduction of 21% in new-onset AF (OR 0.79, 95% CI, 0.63–0.99; P = 0.04). Meta-regression revealed no influence of baseline covariates, including BMI and HbA1c. An additional meta-regression analysis evaluating the percentage of patients on SGLT2 inhibitors as a potential moderator revealed no statistically significant association (P = 0.336). Conclusion: Treatment with semaglutide significantly reduces the incidence of new-onset AF. This effect appears more evident with the oral formulation and independent of baseline characteristics.

Introduction Accurate risk assessment is critical in cardiovascular (CV) prevention, yet physicians often underestimate CV risk, leading to inadequate preventive measures. Aim This study evaluates the concordance between physician-perceived CV risk and calculated CV risk in a primary prevention setting. Methods This cross-sectional study included primary prevention patients from the Cardiology Outpatient Clinic of Caserta Hospital, Italy. Two independent cardiologists evaluated the physician-perceived risk, and a third resolved discrepancies. CV risk was calculated using SCORE2 for patients with 70 years or less and SCORE2-OP for those with more than 70 years. The concordance between perceived and calculated risks was assessed using Cohen’s kappa coefficient. Multivariate logistic regression analysis was performed to examine the influence of risk estimation on achieving low-density lipoprotein cholesterol (LDL-C) targets recommended by the ESC. Results 389 patients had complete data for CV risk calculation. Physician-perceived risk categorized 8.7% of patients as low/moderate, 37.8% as high, and 53.5% as very-high risk. In contrast, calculated CV risk according to the SCORE2/SCORE2-OP classified 8% as low/moderate, 5.7% as high, and 86.4% as very-high risk. The concordance between perceived and calculated CV risk was poor (Cohen’s kappa 0.208, p < 0.001). Underestimated patients reached LDL-C targets in 16% of cases, well-estimated in 34.5%, and overestimated in 76.9%. Statin use was significantly lower in patients with underestimated CV risk (29.2%) compared to well-estimated (50%) and overestimated (76.9%) groups (p < 0.001). Multivariate analysis showed that patients with overestimated risk were more likely to achieve LDL-C targets (OR 5.33, CI 1.33–21.42, p = 0.018), whereas underestimated patients were 47% less likely (OR 0.53, CI 0.3–0.93, p = 0.027). Conclusions A significant discrepancy exists between physician-perceived and calculated CV risk, leading to risk underestimation in over one-third of patients. This underestimation is associated with lower LDL-C target achievement and reduced statin use.

Coronary artery disease (CAD) is the most common cause of heart failure with reduced ejection fraction (HFrEF). Advances and innovations in medical therapy have been shown to play a crucial role in improving the prognosis of patients with CAD and HFrEF; however, mortality rate in these patients remains high, and the role of surgical and/or percutaneous revascularization strategy is still debated. The Surgical Treatment for Ischemic Heart Failure (STICH) trial and the Revascularization for Ischemic Ventricular Dysfunction (REVIVED) trial have attempted to provide an answer to this issue. Nevertheless, the results of these two trials have generated further uncertainties. Their findings do not provide a definitive answer about the ideal clinical phenotype for surgical or percutaneous coronary revascularization and dispute the historical dogma on myocardial viability and the theory of myocardial hibernation, raising new questions about the proper selection of patients who are candidates for coronary revascularization. The aim of this review is to provide an overview on the actual available evidence of coronary artery revascularization in patients with CAD and left ventricular dysfunction and to suggest new insights on the proper selection and management strategies in this high-risk clinical setting.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were initially developed for the treatment of diabetes due to their antihyperglycemic activity. However, in the light of the most recent clinical studies, they are revolutionizing the approach to cardiovascular disease in patients with and without diabetes. We aimed to generate real-world data about the use of SGLT2i in patients with T2DM and coronary artery disease (CAD), focusing on their effectiveness in glycemic control, adherence, long-term efficacy, and safety outcomes. On the basis of the inclusion and exclusion criteria, 143 patients were enrolled. Patients were treated with canagliflozin (n = 33 patients; 23%), dapagliflozin (n = 52 patients, 36.4%), empagliflozin (n = 48 patients; 33.6%), or ertugliflozin (n = 10 patients; 7%) as monotherapy or in combination with other antidiabetic drugs. All patients performed a clinical visit, and their medical history, blood sampling, and anthropometric parameters were measured at discharge and at 1-year follow-up. The reduction in HbA1c % value at 12 months was significant (8.2 vs. 7.4; p < 0.001). Trends in body weight and body mass index also confirmed the positive effect of the treatment (p < 0.0001), as did the reduction in abdominal adiposity (expressed via waist circumference). At 1-year follow-up, 74.1% of patients were adherent to the treatment, and 81.1% were persistent to the treatment. A total of 27 patients (18.8%) had to discontinue treatment early due to drug intolerance caused by genitourinary infections (11.9%), the drub being permanently ineffective (HbA1c not at target or decreasing: 4.9%), or because of expressing. a desire not to continue (2%). No major drug-related adverse events (diabetic ketoacidosis, Fournier’s gangrene, lower-limb amputations) occurred at follow-up, while MACE events occurred in 14 patients (9.8%). In real-world patients with T2DM and CAD, SGLT2i have been effective in long-term glycemic control and the improvement in anthropometric indices with good tolerance, high adherence, persistence to treatment, and no major adverse events at 1-year follow-up.

Aims: 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, 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 and results: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 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. Semaglutide significantly reduced the risk of LEs compared with 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 and 2.4 mg, respectively); and regardless of background SGLT2 inhibitor use. Meta-regression showed no significant effect modification by age, body mass index, HbA1c, follow-up duration, or sodium-glucose co-transporter 2 inhibitors use. Conclusion: This meta-analysis suggests that semaglutide is associated with a significant reduction in major LEs across diverse populations and treatment settings, supporting a potential protective effect on limb-related vascular safety. Lay summary: This meta-analysis evaluates whether semaglutide can reduce the risk of peripheral artery disease (PAD) complications in people with diabetes or obesity. By analysing 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 glycaemic 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.

Beta-blockers represent a key treatment pillar for reducing mortality and morbidity in patients with myocardial infarction (MI) and stable heart failure with a reduced ejection fraction (HFrEF)