Background: Apixaban and rivaroxaban are commonly used direct oral anticoagulants for venous thromboembolism (VTE), but comparative real-world effectiveness and safety data remain limited. Methods: We conducted a retrospective cohort study using the TriNetX database. Adults with VTE were stratified into apixaban and rivaroxaban treatment groups. Propensity score matching balanced baseline characteristics. Time-to-event outcomes up to 2 years were assessed using Kaplan–Meier analysis and Cox proportional hazards models. Results: Following propensity score matching, well-balanced cohorts (8247) were obtained, with a mean age of 58.3 ± 18.0 versus 57.3 ± 18.1 years. Recurrent VTE rates were broadly comparable at 3 months (22.14% vs. 22.26%; HR 1.02, 95% CI 0.95–1.09; p = 0.6, ARD −0.001, 95% CI: −0.014 to 0.011), with small but statistically significant increases observed with apixaban at 6-month (HR 1.07, 95% CI 1.01–1.13; p = 0.016, ARD 0.009, 95% CI: −0.005 to 0.023), 1-year (HR 1.07, 95% CI 1.01–1.12; p = 0.019, ARD 0.004, 95% CI: −0.010 to 0.019), and 2-year follow-ups (HR 1.08, 95% CI 1.04–1.13; p = 0.000, ARD −0.001, 95% CI: −0.013 to 0.011). All-cause mortality was comparable through 1 year; however, a statistically significant increase was observed at the 2-year follow-up for apixaban (HR 1.20, 95% CI 1.06–1.37; p = 0.005, ARD 0.005, 95% CI: −0.002 to 0.013). Bleeding outcomes were largely comparable in the overall cohort, with no statistically significant differences in composite major bleeding (2-year ARD: −0.004, 95% CI: −0.012–0.004), major bleeding (2-year ARD: 0.002, 95% CI: −0.004 to 0.007), gastrointestinal bleeding (2-year ARD: −0.001, 95% CI: −0.004–0.003), or intracerebral hemorrhage (2-year ARD: 0.000, 95% CI: −0.002–0.003) across follow-up periods. A statistically significant reduction in non-major bleeding with regard to apixaban was observed at the 6-month follow-up only (HR 0.79, 95% CI 0.63–0.98; p = 0.033) (2-year ARD: −0.004, 95% CI: −0.010–0.002). Subgroup analyses revealed important heterogeneity: among patients with obesity, composite major bleeding was significantly lower with respect to apixaban at the 2-year follow-up (HR 0.39, 95% CI 0.20–0.76; p = 0.004), whereas among patients with cancer, composite major bleeding was significantly higher with apixaban at the 1-year (HR 1.31, 95% CI 1.02–1.70; p = 0.037) and 2-year follow-ups (HR 1.32, 95% CI 1.04–1.68; p = 0.023). Conclusions: In this real-world propensity-matched analysis, apixaban and rivaroxaban demonstrated broadly comparable effectiveness and safety for VTE treatment, with largely similar bleeding outcomes in the overall cohort. Small but statistically significant increases in recurrent VTE and 2-year mortality with apixaban, alongside subgroup-specific bleeding differences, underscore the importance of individualized treatment selection based on patient-specific risk factors.

Introduction: Advanced chronic kidney disease (CKD) patients undergoing percutaneous coronary intervention (PCI) face a high risk of renal injury. Given this vulnerability, zero- and ultra-low-contrast PCI techniques have been proposed to minimize renal damage while still enabling effective revascularization. On this basis, this meta-analysis tests whether these contrast-sparing strategies yield better clinical and renal outcomes compared with conventional PCI in CKD patients. Methods: A total of 3939 records were retrieved from PubMed, Embase, Scopus, ScienceDirect, and Cochrane from inception till November 2025. Eligible RCTs and comparative observational studies reporting renal or cardiovascular outcomes were included. Pooled analyses were conducted in RevMan Web using a random-effects model with p < 0.05 considered statistically significant. Results: Across nine included studies (464,815 patients) evaluating zero-contrast or ultra-low-contrast PCI versus conventional PCI, zero-contrast PCI significantly reduced contrast-induced acute kidney injury (CI-AKI) (OR 0.24, 95% CI 0.12–0.49; p = 0.002), decreased contrast volume (MD −110 mL, 95% CI −168.6 to −51.8; p = 0.005), lowered the need for repeat revascularization (OR 0.26, 95% CI 0.09–0.77; p = 0.005), and reduced the incidence of emergent hemodialysis (OR 0.25, 95% CI 0.13–0.49; p < 0.0001). All-cause mortality and repeat myocardial infarction were initially nonsignificant but became significant after excluding outlier studies (OR 0.49, 95% CI 0.47–0.51; p < 0.00001; OR 0.19, 95% CI 0.10–0.35; p = 0.007, respectively). No significant differences were observed for major adverse cardiovascular events, cardiovascular or non-cardiovascular mortality, renal replacement therapy, or dialysis requirement. Conclusions: Our findings demonstrate that zero- and ultra-low-contrast PCI significantly reduces the risk of CI-AKI while preserving cardiovascular and renal outcomes, supporting its use as a safe and effective alternative to conventional PCI in high-risk CKD patients.

Background: Heart failure patients are frequently prescribed SGLT2 inhibitors, but the incremental real-world benefit of adding GLP-1 receptor agonists is uncertain. Methods: A retrospective propensity-matched cohort study was conducted using the TriNetX Global Collaborative Network (171 healthcare organizations). Adults aged ≥18 years with incident heart failure who initiated either dual SGLT2 inhibitor and GLP-1 receptor agonist therapy or SGLT2 inhibitor monotherapy within 1 month of the first heart failure diagnosis were compared. Outcomes over 365 days included all-cause mortality, all-cause hospitalization, acute myocardial infarction, atrial fibrillation/flutter, acute kidney failure, pulmonary edema, new-onset diuretic use, urinary tract infection, retinopathy, and laboratory hypoglycemia (glucose ≤ 70 mg/dL). Cox proportional hazards models were used; the proportional hazards assumption was formally tested. Bonferroni and Benjamini–Hochberg adjustments were applied for multiple comparisons. E-values quantified robustness to unmeasured confounding. Appendicitis was used as a negative control outcome. Results: After 1:1 propensity score matching, 3421 patients were included in each cohort. Cohorts were well-balanced (all standardized mean differences < 0.10). Over 365 days of follow-up, no significant differences were observed between dual therapy and monotherapy in all-cause mortality (HR 0.92, 95% CI 0.77–1.09), all-cause hospitalization (HR 1.16, 95% CI 0.96–1.40), acute myocardial infarction (HR 1.20, 95% CI 0.92–1.55), atrial fibrillation/flutter (HR 1.05, 95% CI 0.85–1.30), acute kidney failure (HR 1.05, 95% CI 0.89–1.26), new-onset diuretic use (HR 0.92, 95% CI 0.78–1.09), or urinary tract infection (HR 1.16, 95% CI 0.90–1.48). Dual therapy was associated with a significant increase in retinopathy (HR 2.66, 95% CI 1.81–3.93; Bonferroni p = 0.001; E-value 4.77, lower CI bound 3.01), and a modest increase in laboratory hypoglycemia (HR 1.22, 95% CI 1.04–1.44) and pulmonary edema (HR 1.35, 95% CI 1.06–1.70), both of which survived FDR but not Bonferroni adjustment. Prespecified subgroup analyses showed lower mortality with dual therapy in patients aged 18–64 (HR 0.64, 95% CI 0.43–0.93) and in women (HR 0.60, 95% CI 0.45–0.81). The negative control outcome (appendicitis) was non-significant. Conclusions: In a propensity-matched real-world cohort with a conservative cohort definition, dual SGLT2 inhibitor and GLP-1 receptor agonist therapy was not associated with significant differences in mortality or major cardiovascular outcomes compared with SGLT2 inhibitor monotherapy. Subgroup signals favoring dual therapy in younger and female patients, alongside safety signals for retinopathy and laboratory hypoglycemia, are hypothesis-generating and should be confirmed in prospective trials.

Background: Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) usually coexist and are related to increased morbidity and mortality. Cardiovascular benefits have been demonstrated by drugs such as sodium-glucose cotransporter-2 inhibitors (SGLT2i) and GLP-1 receptor agonists including the dual GIP/GLP-1 receptor agonist tirzepatide (collectively, incretin-based therapies); however, their relative effectiveness in patients with concomitant AF and HFpEF remains undefined. Methods: We conducted a retrospective, propensity score-matched cohort study utilizing the TriNetX Global Collaborative Network. Adults with AF or atrial flutter with a diagnosis of HFpEF who initiated incretin-based therapies (GLP-1 receptor agonists or dual GLP-1/GIP receptor agonists) or SGLT2i were included; index medication was required to be initiated within 30 days of a qualifying AF/HFpEF diagnosis. 1:1 matching was performed based on baseline medications, demographics, and comorbidities. Co-primary outcomes were all-cause mortality, inpatient visits, and emergency department (ED) visits at 1 year. Secondary outcomes included myocardial infarction, ischemic stroke, acute kidney injury, transient ischemic attack, major adverse cardiovascular events (MACE; all-cause mortality/MI/stroke composite), and AF-related procedures. Agent-specific subgroup analyses were performed for semaglutide and tirzepatide separately. Sensitivity analyses were conducted at 6 months and 2 years. Results: 7624 patients were included in each cohort after matching (mean age: 70.8 years; 52% women). At 1 year, incretin-based therapy was associated with lower all-cause mortality (5.3% vs. 7.3%, HR 0.721, 95% CI 0.634–0.820; p < 0.001), fewer inpatient visits (30.0% vs. 37.4%, HR 0.743, 95% CI 0.702–0.787; p < 0.001), and no statistically significant difference in ED visits (27.0% vs. 28.0%; HR 0.946, 95% CI 0.888–1.007; p = 0.081) compared with SGLT2i. Incretin-based therapy was also associated with lower risk of MACE (HR 0.709), acute kidney injury (HR 0.751), myocardial infarction (HR 0.583), catheter ablation (HR 0.685), and electrical cardioversion (HR 0.472). No significant differences were observed in ischemic stroke or transient ischemic attack. These findings were broadly consistent at 6-month and 2-year follow-up, and directionally consistent in agent-specific subgroup analyses of semaglutide and tirzepatide. Conclusions: In this large propensity-matched cohort of patients with AF and HFpEF, initiation of incretin-based therapy (GLP-1 receptor agonists or dual GLP-1/GIP receptor agonists) was associated with lower all-cause mortality, fewer inpatient visits, and reduced cardiovascular events compared with SGLT2i. These findings, while subject to observational limitations, suggest potential benefits of incretin-based therapy in this high-risk population and support the need for prospective comparative trials.

Background: Cardiogenic shock (CS) and chronic ischemic heart disease (CIHD) remain major contributors to cardiovascular mortality in the United States. Although mortality related to ischemic disease declined in the early 2000s, recent trends suggest a resurgence. Methods: This population-based study utilized the Centers for Disease Control and Prevention’s Wide-Ranging OnLine Data for Epidemiologic Research (CDC WONDER) database from 1999 to 2023. Deaths were identified using ICD-10 codes R57.0 (CS) and I25 (CIHD). Adults aged ≥ 45 years were included. Crude mortality rates (CMRs) and age-adjusted mortality rates (AAMRs) were calculated, with temporal changes assessed using Joinpoint regression to estimate Annual Percent Change (APC) and Average Annual Percent Change (AAPC). Results: Between 1999 and 2023, deaths attributed to CS and CIHD accounted for 78,903 cases among adults ≥ 45 years. Overall AAMR ranged from 35.88 per million in 1999 to 37.44 per million in 2023, with a downward trend from 1999 to 2012 followed by an upward trend thereafter. Males (51,080 deaths) exhibited rising mortality (AAPC: +0.50, p < 0.001), while females (27,823 deaths) showed a decline (AAPC: − 0.91, p < 0.0004). Non-Hispanic Black adults demonstrated the steepest increase (AAPC: +1.85, p < 0.001). The burden was greatest in adults ≥ 65 years, but the 45–64 group showed the fastest rise (AAPC: +1.67, p < 0.001). Conclusion: Mortality from cardiogenic shock and chronic ischemic heart disease among U.S. adults ≥ 45 years declined initially but reversed after 2012. Rising mortality in middle-aged adults, persistent racial disparities, and geographic inequities highlight urgent gaps in prevention and acute care.

Background: Coronary artery disease (CAD) and heart failure with preserved ejection fraction (HFpEF) are major causes of morbidity and mortality. Systemic inflammation contributes to both, suggesting potential benefit from colchicine, though data in CAD-HFpEF are limited. Methods: We conducted a real-world study using the TriNetX Research Network, identifying 480,434 adults with CAD and HFpEF. Patients were categorized as colchicine users (n = 30,254) or non-users (n = 450,180). One-to-one propensity score matching yielded 28,941 patients per group. The primary outcome was a composite of acute myocardial infarction, stroke, all-cause mortality, and acute heart failure. Secondary outcomes included individual components, hospitalizations, atrial fibrillation, and gastrointestinal events, assessed at 1- and 3-year follow-up. Results: At 1 year, the primary outcome occurred in 16.9% of the colchicine group versus 19.8% of non-users (HR: 0.86, 95% CI: 0.81–0.91; p < 0.001). All-cause mortality was 11.4% versus 14.5% (HR: 0.77, 95% CI: 0.73–0.80; p < 0.001). At 3 years, the primary outcome occurred in 34.2% versus 39.7% (HR: 0.88, 95% CI: 0.85–0.92; p < 0.001), with acute heart failure slightly higher in the colchicine group (27.5% vs. 26.5%; HR: 1.04, 95% CI: 1.01–1.08; p = 0.009). Stroke was modestly reduced (HR: 0.93, 95% CI: 0.88–0.99; p = 0.014). No significant differences were seen in all-cause hospitalization, atrial fibrillation, or gastrointestinal events. Conclusions: In patients with CAD and HFpEF, colchicine was associated with lower short- and medium-term risk of composite cardiovascular events and mortality, with modest attenuation over time, suggesting early time-dependent association rather than sustained structural effects. Prospective randomized trials are warranted.