Background: Atrial fibrillation (AF) and congestive heart failure (CHF) remain major contributors to cardiovascular mortality in the United States. When accompanied by underlying ischemic heart disease (IHD), mortality risk is amplified. Although IHD mortality declined in the early 2000s, recent data suggest a resurgence. Methods: This population-based study used the CDC Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database from 1999 to 2023. Deaths were identified using ICD-10 codes I48 (AF) and I50.0 (CHF) as multiple causes of death and I20–I25 (IHD) as the underlying cause. Adults aged ≥ 65 years were included. Crude mortality rates (CMRs) and age-adjusted mortality rates (AAMRs) were calculated. Temporal trends were analyzed using Joinpoint regression to estimate annual percent change (APC) and average annual percent change (AAPC). Future mortality trends were projected using autoregressive integrated moving average (ARIMA) model. Results: From 1999 to 2023, AF, CHF, and IHD accounted for 219,188 deaths among adults ≥ 65 years. The overall AAMR increased from 193.8 per million in 1999 to 220.1 per million in 2023, with a decline from 1999 to 2010 followed by a sustained rise. Males (108,732 deaths) showed the steepest increase (AAPC + 1.40%, p < 0.001), whereas females (110,456 deaths) experienced a modest decline (AAPC − 0.55%, p < 0.001). Non-Hispanic Black adults had the largest racial increase (AAPC + 1.21%, p < 0.001). Non-metropolitan areas showed the greatest geographic rise (AAPC + 1.67%, p < 0.001). Conclusion: Mortality involving AF and CHF with underlying IHD among U.S. adults ≥ 65 years declined only temporarily before reversing after 2010. Persistent racial and geographic disparities underscore gaps in prevention and acute cardiovascular care. Clinical Trial Registration: Not applicable.

Background: Atherosclerotic heart disease (AHD) remains a leading cause of global mortality and a major driver of fatal cardiac syndromes. Ischemic myocardial injury from AHD can lead to ventricular remodeling and myocyte loss, progressing to heart failure (HF) and, in advanced stages, cardiogenic shock (CS). However, long-term national mortality trends for deaths involving the combined burden of AHD, HF, and CS remain insufficiently characterized. Methods: Mortality data from 1999 to 2023 were obtained from the CDC WONDER Multiple Cause of Death database. Deaths involving CS (ICD-10 R57.0), HF (I50, I50.1, I50.9), and AHD (I25.1) in adults were identified. Age-adjusted mortality rates (AAMRs) per 1,000,000 population were calculated and stratified by sex, race/ethnicity, and geographic region. Temporal trends were analyzed using Joinpoint regression to estimate annual percent changes (APCs) and average annual percent changes (AAPCs). Autoregressive integrated moving average (ARIMA) modeling was used to forecast mortality trends through 2035. Results: A total of 15,631 deaths were attributed to AHD-associated HF and CS during the study period. Overall AAMRs increased significantly (AAPC 3.75%; 95% CI 3.32–4.29; p < 0.01). Mortality rates declined between 1999 and 2006 (APC −7.55%; 95% CI −13.15 to −5.23; p < 0.01), increased modestly from 2006 to 2013 (APC 3.94%; 95% CI −1.47 to 8.91), and rose sharply from 2013 to 2023 (APC 12.33%; 95% CI 11.27–14.46; p < 0.01). Males had higher AAMRs than females in 2023 (9.26 vs. 3.39 per 1,000,000). Non-Hispanic White individuals accounted for the highest number of deaths (11,878), followed by non-Hispanic Black individuals (1708), while non-Hispanic American Indian populations had the lowest counts (39). Regionally, the West (7.31) and South (5.92) exhibited the highest final AAMRs. State-level AAMRs ranged from 2.49 in Minnesota to 8.27 in Nevada. Conclusions: Mortality involving AHD, HF, and CS has risen substantially in the United States since 2013, with marked demographic and geographic disparities. These findings highlight a growing burden of advanced ischemic heart disease and heart failure and underscore the need for earlier intervention and improved access to advanced HF therapies to prevent progression to cardiogenic shock and death.

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.

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: Finerenone and sodium–glucose cotransporter-2 inhibitors provide cardiovascular and renal benefits in patients with chronic kidney disease (CKD) and heart failure (HF), but real-world comparative evidence is limited. Methods: This retrospective study used the TriNetX database. Adults ≥ 40 years with CKD stages 1–5 and HF [LVEF > 40%; excluding end-stage renal disease (ESRD) or dialysis] receiving finerenone were compared with those on SGLT2 inhibitors. Propensity score matching (1:1) yielded 333 patients per cohort. Kaplan–Meier and Cox models estimated hazard ratios (HRs) with 95% confidence intervals. Results: After matching, baseline characteristics were reasonably balanced, with some residual imbalance remaining. All-cause mortality was similar between finerenone and SGLT2 inhibitors at 6 months (HR 0.98; 95% CI 0.50–1.90) and 1 year (HR 0.93; 95% CI 0.53–1.66). All-cause hospitalization or ER visits were also comparable at 6 months (HR 1.07; 95% CI 0.84–1.36) and 1 year (HR 1.04; 95% CI 0.83–1.29). Finerenone was associated with a modest, borderline reduction in HF hospitalization at 1 year, without consistent effects across timepoints or a mortality benefit; thus, this finding is hypothesis-generating (HR 0.81; 95% CI 0.66–0.99). Safety outcomes were similar between groups. Conclusions: In this real-world analysis, finerenone was associated with similar all-cause mortality, overall hospitalization, and renal safety outcomes compared with SGLT2 inhibitors, with a modest reduction in HF hospitalization at 1 year that should be interpreted cautiously given the exploratory nature of the study. These findings are hypothesis-generating and underscore the need for prospective head-to-head trials to better define optimal therapy sequencing in patients with HFpEF and CKD.

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.