Left ventricular diastolic function over the acute and subacute phase in the Takotsubo syndrome versus ST-elevation myocardial infarction.

Non-adherence to cardiovascular disease (CVD) treatments leads to suboptimal health outcomes and increased healthcare and societal costs. We assessed the long-term effects of adherence to CVD and diabetes medications using population data and microsimulation modelling. We developed a CVD microsimulation model using individual participant data from the SIDIAP database (2012-2021) for 152,117 adults who received new prescriptions for antihypertensive, lipid-lowering, oral glucose-lowering or antiplatelet treatments in Catalonia between January 2012 and December 2013. Model inputs included demographic and clinical characteristics, medication adherence and cardiovascular events. Costs (€, 2025) and treatment effects were sourced from the literature, and utilities were estimated using national population-based surveys. Model validity was assessed by comparing simulated and observed cumulative incidences over 8 years. The model simulated life-years (LYs), quality-adjusted life-years (QALYs) and healthcare and societal costs under three scenarios: non-adherent, observed adherence and full adherence. We estimated the maximum per-patient cost at which adherence-enhancing interventions would remain cost-effective. Simulated cumulative incidences of cardiovascular events and all-cause death closely matched observed data. Improved adherence increased survival by 0.19-0.58 years and QALYs by 0.25-0.70, while increasing lifetime healthcare costs by €2,431-€8,093 per patient. The additional cost per QALY ranged from €8,946 to €12,614 per QALY, indicating that improving adherence is likely to be a cost-effective if achieved at additional cost of up to €4,041 to €10,098 per patient. Long-term extrapolation of real-world data using microsimulation modelling shows that optimising adherence to CVD and diabetes medications can enhance health outcomes cost-effectively.

The long-term impact of common cardiovascular medications on sarcopenia in older people is unclear. The objective was to investigate whether long-term intake of statins and renin-angiotensin system inhibitors (RASi), i.e., angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB), is associated with muscle mass, strength, and physical performance in community-dwelling older adults. This exploratory observational cohort study included 1083 participants of the Berlin Aging Study II (52% women, 68.3 ± 3.5 years at baseline) with an extended follow-up of 7.4 ± 1.5 years. Statins or RASi users at baseline and follow-up were compared with nonusers. Appendicular lean mass (ALM) was measured via dual-energy X-ray absorptiometry and related to body mass index (ALM/BMI) and height2 (SMI). Hand grip strength, arm muscle quality, the Timed "up and go," and Tinetti mobility test were additionally assessed. Adjusted linear regressions of drug use on muscle-related parameters were conducted. Statin use was not associated with any of the muscle-related outcomes. RASi use was associated with modestly lower ALM/BMI (β = -0.036, p = 0.004). Sex-stratified analyses showed that RASi use was significantly associated with lower ALM/BMI in women (β = -0.033, p = 0.029) but not in men (β = -0.037, p = 0.072), without a significant sex interaction. Long-term statin use was not associated with sarcopenia-related parameters, which is clinically reassuring. RASi use showed a modest association with lower ALM/BMI, but causality cannot be inferred because of the exploratory design. These findings warrant replication in independent cohorts and suggest that the clinical relevance of this association should be further evaluated.

Thoracic aortic aneurysm (TAA) remains a high-risk vascular condition despite major advances in imaging surveillance, operative repair, and endovascular therapy. Medical management still relies largely on blood pressure control and global cardiovascular risk reduction. Renin-angiotensin-aldosterone system (RAAS) inhibitors are frequently used in TAA, but contemporary data evaluating survival and cardiovascular outcomes in broad TAA populations are limited. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) have established cardiometabolic benefits, yet their role in TAA has not been well defined. We performed a retrospective multicenter cohort study of adults with imaging-confirmed TAA diagnosed between 1 January 2018 and 1 January 2026 using a Mayo Clinic electronic data platform encompassing more than 15 million patient records. Primary exposures were documented use of RAAS inhibitors, GLP-1 RAs, and SGLT2 inhibitors, evaluated individually and in prespecified combination-therapy analyses. Propensity score matching was used to balance demographics, comorbidities, aortic procedural history, and concomitant cardiovascular medications. Primary outcomes were all-cause mortality and major adverse cardiovascular events (MACE) through 60 months. The study included 162,126 patients with TAA. After matching, RAAS inhibitor use was associated with higher 60-month overall survival (88.3% vs. 85.5%; hazard ratio [HR], 0.79; 95% CI, 0.76-0.83; p < 0.001) and MACE-free survival (86.1% vs. 84.2%; HR, 0.87; 95% CI, 0.83-0.91; p < 0.001). GLP-1 RA therapy was associated with higher overall survival (97.5% vs. 92.5%; HR, 0.32; 95% CI, 0.27-0.38; p < 0.001) and MACE-free survival (93.2% vs. 89.3%; HR, 0.62; 95% CI, 0.56-0.70; p < 0.001). SGLT2 inhibitor therapy was similarly associated with higher overall survival (89.8% vs. 81.5%; HR, 0.51; 95% CI, 0.47-0.54; p < 0.001) and MACE-free survival (86.3% vs. 79.1%; HR, 0.62; 95% CI, 0.58-0.66; p < 0.001). Combination therapy with RAAS inhibitors plus either GLP-1 RAs or SGLT2 inhibitors was associated with incremental improvements in overall survival and MACE-free survival compared with GLP-1 RA or SGLT2 inhibitor monotherapy. In this large propensity-matched TAA cohort, RAAS inhibitors, GLP-1 RAs, and SGLT2 inhibitors were each associated with improved survival and fewer major cardiovascular events, with additional benefit observed for RAAS-based combination therapy. These findings support further prospective investigation of integrated cardiometabolic and vascular-targeted therapy in TAA, while underscoring that observational associations should not be interpreted as proof of aneurysm-specific disease modification.

Safety and Outcomes of Concomitant Left Atrial Appendage Occlusion and Atrial Fibrillation Ablation.

Climate change is increasingly recognised as a threat to population health and healthcare systems, yet the effects of environmental variability on pharmaceutical prescribing remain poorly characterised in the UK. Using a wide array of open-source datasets, we examine the effect of environmental, geographic and socioeconomic factors on prescribing habits in England. We linked monthly, practice-level prescribing data for England (August 2010 - August 2025) to meteorological, air-quality, flooding and demographic datasets using spatial nearest-neighbour matching. Prescribing volumes for cardiovascular, respiratory and antibiotic medications were analysed using log-transformed outcomes in mixed-effects models with practice-level random effects, adjusting for region, seasonality, deprivation and temporal trends, using both continuous environmental measures and extreme-condition indicators. A complementary Bayesian hierarchical model jointly estimated the conditional effects of multiple correlated environmental exposures, with partial pooling across practices and support for distributed lag effects. In mixed-effects analyses, temperature showed the most consistent associations with prescribing, with higher temperatures linked to increased respiratory and cardiovascular prescriptions and reduced antibiotic use, while rainfall, flooding and most pollutants had small or negligible effects. Environmental predictors exhibited strong correlations, motivating multivariate modelling. Bayesian multivariate models confirmed temperature as the dominant environmental driver after adjustment for correlated exposures, with substantially larger variation attributable to regional and socioeconomic factors than to environmental conditions. Temperature is the most consistent environmental determinant of GP prescribing in England, with higher temperatures associated with increased cardiovascular and respiratory prescribing and reduced antibiotic use. Rainfall, flooding and most air pollutants show little evidence of meaningful effects once seasonal and meteorological structure is accounted for. Environmental associations are modest in magnitude relative to persistent socioeconomic and regional drivers of prescribing, indicating that climate-related influences operate within broader structural determinants of healthcare utilisation. These results suggest that, at monthly timescales, prescribing demand is relatively stable to environmental variability, supporting a focus on long-term adaptation and surveillance rather than short-term demand shocks in climate-resilient healthcare planning.

Background and ObjectiveA potential association between sleep disturbances and adverse cardiovascular prognoses has been proposed in patients with chronic obstructive pulmonary disease (COPD), although high-quality confirmatory evidence remains limited. Sleep disturbances may contribute to increased cardiovascular risk through multiple biological pathways, including chronic intermittent hypoxia, systemic inflammation, and metabolic dysregulation. This study aimed to examine the association between sleep disturbances and adverse cardiovascular events in patients with COPD.Materials and MethodsA prospective cohort study of 21423 UK Biobank participants with COPD. We set the research subjects as non-sleep disorder group and sleep disorder group. Outcomes included stroke, heart failure (HF), atrial fibrillation (AF), angina pectoris, and myocardial infarction (MI). Cox proportional hazards models were applied with adjustment for sociodemographic and lifestyle factors to evaluate the association between sleep disorders and subsequent cardiovascular outcomes.ResultsIn this manuscript, compared with COPD patients in the non-sleep disorder group, sleep disorder group had a 79% higher risk of HF (HR = 1.79, 95% CI: 1.57–2.03). Moreover, sleep disorder had a 49% higher HR for AF (HR = 1.49, 95% CI: 1.32–1.68) and a 44% higher HR for angina development (HR = 1.44, 95% CI: 1.23–1.68). The risk of MI was also increased by 0.24-fold in the sleep disorder group (HR = 1.24, 95% CI: 1.01–1.54). Furthermore, male sex, older age, previous cardiovascular medication use, smoking, and obesity were significantly associated with elevated cardiovascular risk among COPD patients with sleep disorders.ConclusionSleep disorders are associated with an increased risk of adverse cardiovascular outcomes in COPD patients. These findings suggest that identification and appropriate management of sleep disorders could potentially contribute to improved cardiovascular risk profiles in this population.

Prognostic value of left atrial diameter in chronic kidney disease: The KNOW-CKD study.

Ensuring equitable access to essential medicines is fundamental to universal health coverage, yet disparities in availability, pricing, and affordability persist in many low- and middle-income countries. This study assessed the availability, prices, and affordability of essential cardiovascular and antidiabetic medicines across public and private healthcare sectors in Pakistan using the WHO/Health Action International (WHO/HAI) methodology. A cross-sectional survey of 32 essential medicines was conducted across selected study areas (Rawalpindi, Muzaffargarh, Vehari, Gujranwala, Islamabad, and Azad Jammu & Kashmir). Medicine availability was measured as the percentage of facilities stocking medicines on the survey day. Prices were analyzed using median price ratios (MPRs) against international reference prices, and affordability was calculated as the number of days' wages required by the lowest-paid unskilled government worker to purchase a standard 30-day treatment. Sectoral and regional differences were evaluated using chi-square tests. The availability of the 32 cardiovascular and antidiabetic medications was generally poor, especially in government facilities; originator brands (OBs) and lowest-priced generics (LPGs) were consistently more readily available in private pharmacies (χ²=180.6, p < 0.001). There were notable geographical differences, with rural areas exhibiting very poor access (χ²=202.8, p < 0.001) and Gujranwala exhibiting the greatest availability. While certain OBs, particularly insulin analogs, were noticeably more expensive than LPGs, prices and affordability favored LPGs across all medications. Public and private sectors continued to have insufficient supplies of insulin and emergency medications, falling short of WHO objectives. This study reveals persistent inequities in the availability and affordability of essential medicines across the selected districts in Pakistan. While these findings specifically reflect the studied regions, they provide actionable evidence to strengthen Pakistan's public-sector supply systems, promote generic medicines, and inform national access policies.

Heat and hearts: An exposure-anchored computational phenotyping framework for assessing cardiovascular vulnerability during extreme heat.

Psychopharmacological treatment of patients with heart failure: A narrative review of antidepressants and anxiolytics.

In the Netherlands, community pharmacists (CPs) are required to conduct annual clinical medication reviews (CMRs) for older patients with polypharmacy. In practice, these reviews are insufficiently implemented, and opportunities to deprescribe inappropriate cardiovascular and antidiabetic medications are often missed. The LeMON study focused on deprescribing, enhancing CPs' awareness and ability to reduce unnecessary medication through close collaboration with general practitioners (GPs). The aim of the study was to evaluate the experiences of patients and CPs who participated in the LeMON study. Patient experiences and satisfaction were assessed using the Patient-Reported Experience Measure (PREM) and the Treatment Satisfaction Questionnaire for Medication (TSQM). Semistructured interviews with CPs were analysed using the extended normalization process theory (eNPT), covering potential, capability, capacity and contribution. Of 140 patients, 62 (44%) completed the questionnaires. Patients reported high satisfaction, felt their medication concerns were addressed andappreciated CP recommendations. TSQM scores were moderate to high across effectiveness, side effects, convenience andoverall satisfaction. CPs valued the online training and acknowledged the importance of deprescribing. Challenges included addressing patient concerns in the absence of symptoms and deprescribing medications initially prescribed by specialists, which could reduce CPs' confidence and patient trust. Patient and CP experiences highlight the need for specific knowledge and training, shared clinical data andclose CP-GP collaboration to implement deprescribing-focused CMRs routinely. Addressing patient concerns and deprescribing specialist-initiated medications requires effective communication skills and structured local or regional protocols for multidisciplinary collaboration between primary and secondary care.

Mobile health (mHealth) interventions have promise as low-cost tools promoting behavioral change. We evaluated the implementation and maintenance costs of 3 text messaging strategies aimed at improving cardiovascular medication adherence. The Nudge Study (NCT03973931) was a randomized pragmatic trial that evaluated prescription refill adherence across 3 health systems. We estimated costs over the 4-year study period. After adjusting for inflation to 2023 US$, we calculated net non-research-related labor and materials costs in total and by The Nudge Study arm, assigning usual care a $0 cost. We calculated incremental cost-effectiveness ratios (ICERs) using observed cost; payoffs of the median reduction in number of gap days without medications; and the study's published rates of death, hospitalization, and emergency visits. Program start-up costs were similar across the 3 health care systems (mean [SD], $2954 [$352]). Across the 53 months of the study and comprising start-up, implementation, and program delivery phases, the mean monthly cost to deliver all messaging strategies was $3949 and 1430 unique patients on average received any type of message monthly, resulting in an estimated cost of $2.76 per patient per month. ICER values were low, and there were no significant differences across treatment strategy or outcome. Providing medication adherence support via mobile messaging may be a low-cost solution for some hospital systems.

Nurse practitioners (NPs) play a major role in delivering primary and chronic care to Medicare beneficiaries, making their prescribing patterns an important area of study. This study examined national trends in NP prescribing under Medicare Part D from 2013 to 2022, focusing on overall prescribing volume, prescriptions per Medicare beneficiary, and condition-specific prescribing patterns compared with physicians and physician assistants. We conducted a retrospective analysis of the Centers for Medicare and Medicaid Services Medicare Part D Prescribers dataset from 2013 to 2022. Trends in total prescriptions, prescriptions per Medicare beneficiary, and prescribing by provider type were analyzed. Condition-specific analyses focused on cardiovascular, neuropsychiatric, and endocrine conditions, comparing prescribing patterns across provider groups. Total Medicare Part D prescriptions increased modestly between 2013 and 2022, while prescriptions per Medicare beneficiary declined. During this period, NP prescribing increased substantially, accounting for 15.6% of all Part D prescriptions by 2022, while the proportion attributed to physicians decreased. Cardiovascular, neuropsychiatric, and endocrine medications represented nearly 60% of NP prescriptions. Across these clinical areas, NP prescribing increased alongside stable or modest changes in specialist prescribing, indicating redistribution of prescribing responsibility rather than an increase in prescribing intensity. Nurse practitioner prescribing for Medicare beneficiaries expanded markedly over the past decade, particularly within key chronic disease categories. These findings point to the expanding role of NPs in medication management for older adults and emphasize the need for adequate training and support as they take on a larger share of care for Medicare beneficiaries.

Anticoagulation Services as a Model for Cardiovascular Medication Stewardship.

ABSTRACT Purpose To investigate the bidirectional association between age-related macular degeneration (AMD) and cardiovascular disease (CVD), including acute myocardial infarction (AMI) and ischemic stroke (IS), in a large Taiwanese cohort. Methods We conducted a retrospective cohort study using electronic health records from China Medical University Hospital (CMUH), Taiwan. From 2003 to 2014, we identified 9,333 AMD patients with 37,332 matched controls, and 26,897 CVD patients with 107,588 matched controls. All patients were followed through December 31, 2019. Multivariable Cox regression was used to estimate the risk of CVD in AMD patients and the risk of AMD in CVD patients. The effects of common cardiovascular medications were also analyzed. Results AMD patients had an increased risk of AMI (adjusted HR = 1.45, 95% CI = 1.25–1.69) and IS (adjusted HR = 1.78, 95% CI = 1.52–2.09) compared to controls. CVD patients had a higher risk of AMD (adjusted HR = 2.57, 95% CI = 1.30–5.09). Aspirin use among CVD patients was associated with a lower risk of AMD (HR = 0.69, 95% CI = 0.50–0.94). Several comorbidities, including diabetes, hypertension, and chronic kidney disease, further increased risks in both directions. Conclusion This population-based study demonstrates a significant bidirectional association between AMD and CVD in Taiwan. Integrated screening and management should be considered for patients with either condition.

Preoperative assessment is a key but inconsistently taught skill in internal medicine residency, particularly in the ambulatory setting. Many residents report low confidence and limited formal training. To evaluate the impact of a structured, gamified Jigsaw-based workshop on internal medicine residents' knowledge acquisition and self-reported confidence in preoperative assessment. In 2025, we conducted a quasi-experimental pilot study at the University of California, San Diego. Primary Care Track residents (intervention group) completed a three-hour interactive Jigsaw workshop on four domains of preoperative management: cardiovascular risk, medication management, anticoagulation, and considerations for special populations. Residents in the control group received standard residency training in preoperative medicine through routine clinical exposure during inpatient rotations (wards, intensive care unit, and consult services) and outpatient settings, including continuity clinic and ambulatory electives. Additional instruction occurred through the residency's protected didactic curriculum, including Wednesday School and Friday School, four-hour conference blocks covering rotating internal medicine topics. Preoperative assessment was addressed within this broader curriculum but not through a dedicated standardized program. Pre- and post-surveys assessed knowledge (multiple-choice) and confidence (Likert scale). Due to the small sample size, formal hypothesis testing with p-values was not performed. Instead, effect sizes were calculated to estimate the magnitude of differences between the intervention and control groups. A needs assessment of 159 residents (12% response) revealed low confidence in perioperative care; over half reported no structured training. In the control group (n = 11 pre, n = 10 post), notable gains are observed in special population (40% to 49%, effect size = 0.45) and anticoagulation (41.1% to 48.50%, effect size = 2.00). Cardiovascular risk and medical management remain stable (45.40% to 39.40%, effect size = 0.18, and 60.60% to 56.1%, effect size = 0.04, respectively). In the intervention group (n = 11, n = 10 post), all categories show notable gains, with special populations and cardiovascular risk reaching statistical significance: cardiovascular risk group (37.50% to 66.70%, effect size = 4.04), medication management (64.5% to 75%, effect size = 0.45), special population (45% to 95%, effect size = 4.26), and anticoagulation (45.80% to 58.30%, effect size = 0.42). In the control group (n = 11 pre, n = 10 post), mean confidence scores remained largely unchanged, with minimal effect (2.35 vs 2.38; effect size = 0.10). In contrast, the intervention group (n = 8 pre, n = 8 post) demonstrated substantial improvements in confidence across all domains following the workshop, with mean Likert scores increasing from 1.86 to 3.18 (effect size = 2.48). Qualitative feedback showed that residents valued the interactive, case-based format and the gamified "Escape the OR" activity. A single Jigsaw-based workshop integrated into a primary care residency curriculum was observed to be associated with improvements in resident knowledge and confidence in perioperative assessment. These early findings suggest that structured, interactive workshops may help address gaps in perioperative education and support further evaluation of learner-centered instructional strategies in larger training settings.

CKD is associated with a high burden of cardiovascular complications, including atrial fibrillation. While loop diuretic medications are commonly prescribed for volume and blood pressure management in CKD, their relationship with incident atrial fibrillation in this population remains poorly understood. Using data from 4,607 patients without baseline atrial fibrillation from the Chronic Renal Insufficiency Cohort (CRIC), we used adjusted Cox regression models to explore the association of baseline loop diuretic use with hospitalization with atrial fibrillation. We tested for differential associations according to sex, history of heart failure, and baseline CKD stage category. Models adjusted for demographics, cardiovascular risk factors, kidney function (eGFR), laboratory parameters (albumin, hematocrit, log 24-hour urine protein), and the use of cardiovascular medications. The mean age of subjects at baseline was 59 ±11 years, 44% were female, and 42% were Black. The mean follow-up was 9.3 years, during which time 614 participants experienced a hospitalization with atrial fibrillation. Baseline loop diuretic therapy was associated with a 41% higher risk of hospitalization with atrial fibrillation (adjusted hazard ratio 1.41, 95% CI 1.14, 1.73). There was no effect modification by sex or CKD stage (P-interactions=0.52 and 0.29, respectively). The association appeared stronger among those with vs. without heart failure (aHR 3.00; 95% CI 1.22, 7.37 vs aHR 1.33; 95% CI 1.06, 1.66), although the interaction did not reach statistical significance (P-interaction=0.06). Among patients with CKD and without a history of atrial fibrillation, the use of loop diuretics is independently associated with subsequent hospitalization with atrial fibrillation. This association appeared to be more potent among those with (vs. without) a history of heart failure. The etiology of the observed association requires further investigation.

Heart failure (HF) remains a major cause of morbidity and mortality worldwide, and acute decompensation frequently necessitates intensive care. Early identification of high-risk patients is essential, yet traditional HF risk scores were developed largely in chronic or ward-based cohorts and often fail to capture early physiologic deterioration in the ICU. Explainable machine-learning (ML) models may improve early risk stratification. Using the MIMIC-IV v3.1 database, we conducted a retrospective study of adult ICU patients with heart failure identified by ICD-10 codes (I50.x) between October 1, 2015 and 2022. Predictors included demographics, comorbidities, pre-ICU cardiovascular medications, and vital signs and laboratory tests obtained within 0-6h of ICU admission. Implausible values were removed; missing data were imputed using medians or modes. An XGBoost classifier was trained with an 80/20 stratified split and class weighting. Performance in the test cohort was assessed using AUC, average precision, sensitivity, specificity, F1-score, and Brier score. SHapley Additive exPlanations (SHAP) were used for global and feature-level interpretability. A total of 12,110 ICU patients with HF were included, of whom 2,041 (16.9%) died in hospital. In the test cohort (n = 2,422), the model achieved an AUC of 0.797 (95% CI, 0.772-0.822) and an average precision of 0.491. Sensitivity and specificity were 0.632 and 0.793 at the default threshold; using the Youden-optimal threshold increased sensitivity to 0.708. Kaplan-Meier analysis demonstrated significant separation of survival curves across predicted risk quartiles (log-rank P < 0.001), supporting the survival stratification of early risk predictions. SHAP analysis identified FiO₂, age, lactate, Charlson comorbidity index, BUN, and systolic blood pressure as the strongest predictors, revealing clinically coherent non-linear relationships and interactions. These findings suggest that an interpretable model based on routinely available early ICU data may facilitate structured and quantitative risk stratification within the first hours of admission, thereby assisting clinicians in identifying high-risk patients who may benefit from closer monitoring and timely escalation of supportive care, rather than replacing clinical judgment.

Background:Advanced pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and limited therapeutic options. Drug repurposing offers a cost-effective strategy to identify agents with potential synergistic benefits and known safety profiles. Preclinical and retrospective studies suggest that renin–angiotensin–aldosterone system inhibitors (RAASi) and statins may enhance chemotherapy efficacy by modulating the tumor microenvironment and oncogenic signaling.Objectives:To explore associations between cumulative RAASi and/or statin use and overall survival (OS) in elderly patients with advanced PDAC receiving first-line chemotherapy, as hypothesis-generating adjunct exposures.Methods:We analyzed a population-based registry using linked administrative databases from Ontario, Canada, identifying patients aged ⩾67 years with advanced PDAC who received first-line gemcitabine/nab-paclitaxel or mFOLFIRINOX between 2015 and 2024. The primary outcome was OS. Associations between cumulative RAASi or statin exposure and OS were assessed using multivariable Cox proportional hazards models, treating cumulative drug exposure as a time-varying covariate to mitigate immortal time bias.Results:Among 3226 eligible patients, the median age was 73 years, and 44% were female. Forty-one percent received both RAASi and statins, 17% statins alone, 14% RAASi alone, and 28% neither. Median OS was 7.9 months across groups. On multivariable analysis, neither cumulative RAASi (hazard ratio (HR) 1.00, 95% CI 0.98–1.02) nor statin exposure (HR 1.00, 95% CI 0.98–1.02) was associated with improved survival.Conclusion:In this large cohort of advanced PDAC patients undergoing first-line chemotherapy, real-world, non-targeted RAASi and statin use was not associated with improved OS. These findings highlight the need for rigorously designed prospective studies to validate repurposed drug candidates before clinical adoption.Design:Retrospective population-based cohort study.