Inverse Probability Of Treatment Weighting Research Articles

Association of ticagrelor vs clopidogrel with net adverse clinical events in NSTEMI patients with mild thrombocytopenia

Abstract Backgrounds: Guidelines currently recommend aspirin plus ticagrelor as the preferred dual antiplatelet therapy (ADPT) for non-ST-elevation myocardial infarction (NSTEMI). However, there are no established recommendations for managing NSTEMI patients with mild thrombocytopenia, defined as a platelet count of 100~150×109/L. Purpose This study aims to investigate the association between ticagrelor and clopidogrel with ischemic and hemorrhagic events in NSTEMI patients with a platelet count of 100~150×109/L. Methods A retrospective cohort study was conducted using data from the Health and Medical Big Data Super Platform from January 2010 to June 2023. The study included NSTEMI patients with a platelet count of 100~150×109/L who received DAPT consisting of aspirin and a P2Y12 receptor antagonist (eithor clopidogrel or ticagrelor). Patients were followed up for at least one year. The inverse probability of treatment weighting (IPTW) approach based on propensity score was used to balance the observed confounders between treatments. The primary endpoint was net adverse events (NACE) at 1 year, composed of ischemic events (recurrent myocardial infarction or ischemic stroke), Bleeding Academic Research Consortium (BARC) classification ≥ 3, and cardiac death. Secondary outcomes included cardiac death, recurrent myocardial infarction and, ischemic stroke. Results The study cohort comprised 2969 participants, with a median age of 72 years and 29.2.0% female. After adjustment using inverse probability of treatment weighting, ticagrelor and clopidogrel showed similar rates of NACE (aHR, 0.84; 95%Cl, 0.58-1.21). Cardiac death (aHR, 0.99; 95%Cl, 0.54-1.83) and ischemic stroke (aHR, 0.94; 95%Cl, 0.49-1.81) did not significantly differ between the two groups. However, ticagrelor was associated with a lower rate of recurrent myocardial infarction (aHR, 0.44; 95%Cl, 0.21-0.93). Conclusion In routine clinical practice, among NSTEMI patients with a platelet count of 100~150×109/L, ticagrelor, did not showed a significant difference in the risk of NACE at 1 year compared with clopidogrel. However, ticagrelor was associated with a lower rate of recurrent myocardial infarction. Further research is warranted to confirm the this conclusion.

Association of ticagrelor vs clopidogrel with net adverse clinical events in STEMI patients with mild thrombocytopenia

Abstract Backgrounds Current guidelines advocate for aspirin plus ticagrelor as the preferred dual antiplatelet therapy (DAPT) for ST-elevation myocardial infarction (STEMI). However, there is a lack of consensus or guidelines to direct clinicians on managing STEMI patients with mild thrombocytopenia, defined as a platelet count of 100~150×109/L. Purpose This study aims to investigate the association between ticagrelor and clopidogrel with ischemic and hemorrhagic events in STEMI patients with a platelet count of 100~150×109/L. Methods A retrospective cohort study was conducted using Health and Medical Big Data Super Platform from January 2010 to June 2023.The study included STEMI-patients with a platelet count of 100~150×109/L who received DAPT consisting of aspirin and a P2Y12 receptor antagonist (either clopidogrel or ticagrelor) All STEMI patients with a platelet count of 100~150×109/L were included in the analysis with a follow-up of at least one year. The inverse probability of treatment weighting (IPTW) approach based on propensity score was utilized to balance observed confounders between treatments. The primary endpoint was net adverse events (NACE) at 1 year, including ischemic events (recurrent myocardial infarction or ischemic stroke), Bleeding Academic Research Consortium (BARC) classification ≥ 3, and cardiac death. Secondary outcomes were cardiac death, recurrent myocardial infarction, and ischaemic stroke. Results The study cohort consisted 2941 participants with median age of 69 years, and 21.0% were female. Following adjustment using the inverse probability of treatment weighting, ticagrelor and clopidogrel demonstrated similar NACE (aHR, 0.86; 95%CI, 0.60-1.23). Cardiac death (aHR, 0.69; 95%CI, 0.36-1.31), recurrent myocardial infarction (aHR, 0.94; 95%CI, 0.50-1.78), and ischaemic stroke (aHR, 0.62; 95%CI, 0.34-1.14) did not significantly differ between the two groups. Conclusion In routine clinical practice, among STEMI patients with a platelet count of 100~150×109/L ticagrelor compared with clopidogrel, was not associated with a significant difference in the risk of NACE at 1 year. Further research is warranted to assess whether ticagrelor is more effective than clopidogrel in this particular patient population.

Clinical impact of performing esophagogastroduodenoscopy before percutaneous coronary intervention in patients with acute coronary syndrome patients and anaemia

Abstract Background In patients presenting with acute coronary syndrome (ACS) and anaemia, esophagogastroduodenoscopy (EGD) is commonly performed to exclude an upper gastrointestinal source of bleeding prior to perform percutaneous coronary intervention (PCI). However, the diagnostic yield and clinical impact of EGD in this setting is uncertain. Purpose We aimed to investigate the clinical yield and impacts of EGD on the 1-year clinical outcomes in ACS patients with concomitant anaemia who underwent PCI. Methods We retrospectively analysed electronic health records of ACS patients who underwent PCI at 16 public hospitals from 2014-2018. Patients with anaemia (defined as haemoglobin (Hb) <11dl/L) and EGD before PCI during the same admission were identified. The primary outcomes were bleeding events including clinical GIB (as diagnosed by EGD), need for urgent EGD, need for transfusion, Hb drop of >3 dl/L and Hb <8 dl/L. Secondary outcomes were 12-month 4-point MACE including myocardial infarction (MI), stroke, subsequent PCI or CABG, or cardiovascular-related death. Propensity-score models with inverse probability of treatment weighting (IPTW) against EGD were developed for the comparisons. A weighted Cox Proportional Hazard Model was performed to estimate adjusted hazards ratio (aHR) with corresponding 95% confidence intervals (CI). Results Of 13,793 patients, 3625 (25%) had anaemia on admission and 12.8% (n=466/3625) underwent EGD. Most EGD findings were not accountable for overt GIB, with gastritis, gastric polyps and gastric erosion being the 3 most common EGD diagnoses. After IPTW, clinical outcomes of 466 patients with EGD were compared with 3159 patients without EGD. 12-month bleeding event rates were higher among EGD patients compared to non-EGD patients (59.7% vs. 27.6%, p< 0.01; aHR = 3.01, 95% CI 2.58-3.52, p<0.005). Overall, 12-month GIB rate was low 1.0%, with 4.1% in EGD patients and 0.57% in non-EGD patients (aHR=7.99, 95% CI 4.13-15.45, p<0.005). The 12-month cumulative MACE rate overall was 39.9% and no significant difference between EGD and non-EGD patients. Conclusion Our real-world data demonstrated that the presence of anaemia is common among ACS patients. The yield of EGD in identifying sources of upper GI bleeding was low and there was no difference in 12-month clinical outcome among EGD patients. Although EGD was associated with higher rates of 12-month bleeding events, the cause was unclear with very low incidence of upper GI bleeding events. Therefore, the benefits of routine EGD prior to PCI in ACS patients with anaemic is unclear.

Hypnotic use and the risk of cardiovascular diseases in insomnia patients

Abstract Background Insomnia, commonly treated with hypnotic agents, is an independent risk factor of cardiovascular diseases. Previous research demonstrated the detrimental effect of hypnotics on the prognosis of cardiovascular patients. Purpose We aimed to examine the association between hypnotic agents and cardiovascular outcomes in general individuals with insomnia. Methods In a propensity score matched cohort of UK Biobank (UKB) participants with insomnia, Cox proportional hazard model was used to estimate the association between regular use of hypnotic agents and predetermined cardiovascular outcomes including incident coronary heart diseases (CHD), heart failure (HF), stroke, and cardiovascular death. Inverse probability of treatment weighting and competing risk models were further performed during sensitivity analysis. Drug-target Mendelian randomization (MR) analyses were employed for further evaluation of hypnotics-related genes and cardiovascular disease association. The genome-wide association data of CHD, HF, and stroke were there large-scale genome-wide association analyses. Tissue-specified expression quantitative trait loci (eQTL) data was derived from BrainSeq phase II. Results During a median follow-up of 14.3 years, the matched cohort documented a total of 1,019 CHD cases, 406 HF cases, 285 stroke cases, and 197 cardiovascular deaths. No significant association was detected between Z-meds and CHD, stroke, and cardiovascular mortality. Benzodiazepine use was significantly associated with the increased risk of CHD, HF, and cardiovascular mortality (Figure 1). The inverse probability of treatment weighting and competing risk models didn’t alter the above associations. Moreover, drug-target MR analyses corroborated the safety of Z-meds in the general population regarding cardiovascular health. However, GABRG1—a drug target for benzodiazepines—was associated with heightened risks for heart failure, and ischemic stroke (Figure 2). Conclusions Our findings suggested the heterogeneous associations between different categories of hypnotics and incident cardiovascular events in individuals with insomnia. Z-meds are safe regarding the risk of cardiovascular outcomes in the UKB population with insomnia.Figure 1Figure 2

Association Between Dysphagia and Depressive Symptoms: Propensity Score Matching Approaches.

The co-occurrence of depression and dysphagia is obvious to clinicians and has been the focus of several research investigations. Dysphagia not only leads to physical complications but also exerts a negative emotional impact, resulting in a decline in quality of life. The purpose of the study was to investigate the association between dysphagia and depressive symptoms at the population level while accounting for various demographics and health conditions. This study was a cross-sectional design using the 2022 National Health Interview Survey. The study subjects were American adults who completed the survey questionnaires about depressive symptoms, swallowing problems, and health conditions. Regression models and three different propensity score matching approaches were utilized to estimate associations between dysphagia and depressive symptom. Data analyzed in the study showed that among 25,651 U.S. adults, 1,664 (6.48%) reported dysphagia. Among patients with dysphagia, 976 (58.65%) were women, and the average age was 55.48 years. The differences in demographics and health conditions between individuals with and without dysphagia were balanced by three propensity score matching approaches (p >.05). After adjustments using population-weighted multivariable logistic regression, the inverse probability of treatment weighting (IPTW) with both normalized weights, IPTW with stabilized weights, and Greedy algorithms with 1:1 matching method, the risks of having depressive symptom in those with dysphagia were significantly higher than those without dysphagia (odds ratios ranged from 1.763 to 2.402, p <.0001). The study supports that dysphagia and depressive symptoms frequently co-occur in U.S. adults, highlighting the need for comprehensive care that addresses both physical and mental health aspects of swallowing impairments.

Lipid lowering therapy in patients aged 90 years or older with acute myocardial infarction:a multicenter cohort study

Abstract Background Lipid-lowing therapy significantly reduce adverse cardiovascular events in patients with acute myocardial infarction (AMI). However, evidence regarding the efficacy of lipid-lowing therapy in extremely elderly patients with AMI is limited. Purpose This study aims to evaluate major adverse cardiovascular events (MACCE) at 1 year in relation to taking lipid-lowing therapy (statins) among patients aged 90 years or older. Methods The data for this study were derived from a retrospective cohort comprising patients admitted to secondary or tertiary hospitals from 2010 to 2023. Patients were grouped by lipid-lowing therapy: statins group (n=549) and not taking statins group (n=811). The primary endpoint was MACCE, a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke, at 1 year. Secondary endpoints included cardiac death (CD), stroke, and recurrence of myocardial infarction at 1 year. Inverse probability treatment weighting (IPTW) based on propensity scores was performed to balance baseline characteristics. A multivariate adjusted Cox proportional hazard model evaluated the association between lipid-lowing therapy and clinical endpoints. Results Of the 1,360 patients, 77.2% were men, and the median age was 92 years. During 1 year follow up, 35.3% of patients experienced MACCE, and 28.7% died due to CD. After IPTW, the incidence of MACCE was lower in the statins group compared to the non-statins group (33.3% vs. 42.6%, p=0.036), as was 1- year mortality due to CD (26.2% vs.35.9%, p=0.021). However, there were no differences in the incidence of stroke (2.8% vs. 4.5%, p＞0.274) or recurrence of myocardial infarction (4.7% vs. 5.1%, p=0,855) at 1 year. Kaplan-Meier analysis showed a lower probability of 1-year MACCE and CD in the statins group (log-rank test, p&amp;lt;0.001). Multivariate Cox regression analysis demonstrated that statin therapy reduced the incidence of MACCE (aHR 0.67; 95%CI, 0.40–0.91; p=0.009) and 1-year CD (aHR 0.63; 95%CI, 0.45–0.87; p=0.005). Conclusions Lipid-lowering therapy with statins was associated with a significantly lower risk of 1-year MACEE and cardiac death in elderly patients aged over 90 years with AMI. These findings support the use of lipid-lowing therapy in elderly individuals.

Association between reduced risk of gastrointestinal bleeding related to proton pump inhibitor use and subsequent all-cause death in patients with percutaneous coronary intervention

Abstract Background Gastrointestinal bleeding is the leading cause of post-percutaneous coronary intervention (PCI) bleeding complications which are associated with a high risk for subsequent clinical outcomes. The aim of this study was to estimate association between risk of gastrointestinal bleeding events related to proton pump inhibitor (PPI) use and subsequent clinical outcomes in patients with PCI. Methods The Clinical Deep Data Accumulation System (CLIDAS) is a database for inclusive of patient characteristics, medications, laboratory test, physiological test, cardiac catheterization and PCI treatment, all of which were aggregated from electronic medical records in 7 tertiary hospitals in Japan. Data of 6457 patients who underwent PCI between April 2014 and March 2020 and were then followed for 30 days after the index PCI, were analyzed. These patients were divided into two groups based on use of PPI; the PPI group (n=5285; 82%) and the non-PPI group (n=1172; 18%). Clinical outcomes, defined as gastrointestinal bleeding and all-cause death, were assessed using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) models. Results Among the 6457 PCI patients, 90 (1.7%) in the PPI group and 31 (2.6%) in the non-PPI group experienced gastrointestinal bleeding events. Adjusting for baseline demographics, comorbidities, and anti-thrombotic treatments, the multivariable Cox hazard model suggested a trend towards a lower risk of gastrointestinal bleeding with PPI use (HR, 0.70; 95%CI, 0.46-1.05; p=0.087). The PSM analysis confirmed a significant association between PPI use and a lower risk of gastrointestinal bleeding (HR, 0.13; 95%CI, 0.04-0.43; p=0.001), consistent with IPTW model results (HR, 0.60; 95%CI, 0.38-0.95; p=0.031). Subgroup analysis showed that PPI use was associated with a low risk of all-cause death in patients with acute coronary syndrome (ACS) (HR, 0.58; 95%CI, 0.36-0.93; p=0.024). Causal mediation analysis indicated an indirect effect of PPI on reducing all-cause death through the suppression of gastrointestinal bleeding events. Conclusion These findings suggested that use of PPI against gastrointestinal bleeding complications might reduce the risk of subsequent all-cause death in ACS patients undergoing PCI.

Clopidogrel versus aspirin monotherapy for secondary prevention after percutaneous coronary intervention - a nationwide population-based study

Abstract Background After percutaneous coronary intervention (PCI), patients are maintained on single antiplatelet therapy (SAPT) for secondary cardiovascular prevention after completing the guideline-recommended duration of DAPT for a period of time. We sought to compare the efficacy and safety of clopidogrel versus aspirin monotherapy for secondary prevention in patients who undergoing PCI in a population-based cohort study using the database from the National Health Insurance Service (NHIS) in Korea. Methods Of those who underwent PCI from 2009 to 2020, 133,343 patients were selected for analysis. (aspirin 65,802 patients, clopidogrel 67,653 patients). To balance between aspirin and clopidogrel users for the comparison of efficacy and safety, we applied the inverse probability of treatment weighting (IPTW) of propensity score method. The primary effectiveness outcome was major cardiovascular events (MACEs) as the composite of cardiovascular death, myocardial infarction (MI) or stroke. The primary safety outcome was any bleeding. We divided the short DAPT user (&amp;lt; 6 months of DAPT in patients with CCS or &amp;lt; 12 months of DAPT in patients with ACS) and long DAPT user (≥ 6 months of DAPT in patients with CCS or ≥ 12 months of DAPT in patients with ACS) by DAPT duration. Results After IPTW matching, overall the mean age of participants was 63.8±16.3 and the median SAPT duration was 3.3 (1.3 – 6.2). During period, the overall primary effectiveness outcome occurred in 4.1% in aspirin group and 2.8% in clopidogrel group (hazard ratio [HR], 0.684; 95% CI, 0.656 – 0.712; p-value &amp;lt;0.0001) (Figure 1-A). the overall primary safety outcome occurred in 2.4% in aspirin group and 2.1% in clopidogrel group (HR, 0.945; 95% CI, 0.899 – 0.994; p-value, 0.0287) (Figure 1-B). In short DAPT group, clopidogrel reduced the risk of MACE (HR, 0.761; 95% CI, 0.715 – 0.811; p-value, &amp;lt;0.0001) but did not reduce the risk of bleeding (HR, 0.973; 95% CI, 0.893 – 1.056; p-value, 0.5067) comaped with aspirin. However, in the long DAPT group, clopdiogrel reduced both MACE (HR, 0.633; 95% CI, 0.600 – 0.669; p-value &amp;lt;0.0001) and bleeding risk (HR, 0.931; 95% CI, 0.873 – 0.992; p-value, 0.028) compared with aspirin. (Figure 2) Conclusion Clopidogrel monotherapy, compared with aspirin monotherapy during the chronic maintenance period after PCI reduced the risk of MACEs and bleeding. As shown in randomized controlled trials, clopidogrel monotherapy was superior to aspirin monotherapy in preventing future clinical adverse events in real-world bid database.

Comparative analysis of renin-angiotensin system inhibitors/angiotensin receptor neprilysin inhibitor and mineralocorticoid receptor antagonists in heart failure with mildly reduced ejection fraction

Abstract Background Apart from sodium-glucose co-transporter 2 inhibitors, the efficacy of renin–angiotensin system inhibitors/angiotensin receptor neprilysin inhibitors (RASI/ARNI)j8788 as well as mineralocorticoid receptor antagonist (MRA) in patients with heart failure with mildly reduced ejection fraction remains uncertain. We assessed the association between these medications and outcomes in patients with heart failure with mildly reduced ejection fraction (HFmrEF). Methods Patients with HFmrEF from our university hospital-integrated Medical Database were included. Associations between the medications and cardiovascular mortality/heart failure hospitalization were evaluated using Cox regressions in a 1:1 propensity score-matched cohort. Inverse probability of treatment weighting was employed to balance baseline patient characteristics. Results Of 2584 patients with HFmrEF, 17% received MRA and 43% received RASI/ARNI. Predictors of MRA use included older age, slightly higher ejection fraction, lower NT-proBNP level, and eGFR &amp;gt;60 mL/min/1.73 m^2. Predictors of RASI/ARNI use included higher body mass index, lower NT-proBNP level, normal uric acid level, normal potassium level, and eGFR &amp;gt;60 mL/min/1.73 m^2. MRA use was not associated with a lower risk of cardiovascular death and hospitalization for heart failure (hazard ratio [HR] = 0.89, 95% confidence interval [CI]: 0.78–1.02 and HR = 1.01, 95% CI: 0.94–1.09, respectively). Conversely, RASI/ARNI use was associated with a lower risk of cardiovascular death but not hospitalization for heart failure (HR = 0.82, 95% CI: 0.71–0.94 and HR = 0.995, 95% CI: 0.924–1.07, respectively). Notably, landmark analysis revealed no significant difference in the risk of outcomes when the follow-up duration exceeded two years. Conclusions The effect of MRA on cardiovascular death and hospitalization for heart failure was neutral, whereas RASI/ARNI was associated with a lower risk of cardiovascular death. Our findings suggest that RASi use may be more beneficial than MRA use in patients with HFmrEF.

Switching from warfarin to a DOAC in frail elderly asian patients with atrial fibrillation: a nationwide population-based study

Abstract Background Recently, switching international normalized ratio guided warfarin management to a direct oral anticoagulant (DOAC) was associated with more bleeding complications than maintaining warfarin in frail elderly patients with atrial fibrillation (AF). However, there is a paucity of information on whether these results could be applied to Asian patients with AF, who are known to have relatively low time in therapeutic range (TTR) levels. Purpose To evaluate the safety and effectiveness of switching from warfarin to a DOAC in frail elderly Asian patients with AF. Methods Using a Korean health insurance database, we included patients with AF who were prescribed warfarin between January 2013 and August 2015 without significant bleeding or thromboembolic events during the window period, specifically those aged 75 or older with a Hospital Frailty Risk Score of 5 or more. Those who switched to DOACs during the window period were categorized as the DOAC group and those who continued with warfarin were categorized as the warfarin group. The primary outcome was defined as the composite of major bleeding (MB) and clinically relevant non-major bleeding (CRNMB), and secondary outcomes were defined as thromboembolic events, all-cause death, the composite of MB, CRNMB and ischemic stroke (so-called net clinical outcome [NCO]). The propensity score weighting method was utilized to compare the two groups. Results A total of 12,162 patients were included (8,108 with maintaining warfarin, 4,054 with switching to a DOAC). Baseline characteristics were well-balanced after the inverse probability of treatment weighting (mean age, 80 years; men, 50%; and mean CHA₂DS₂-VASc score, 5.6). Compared with maintaining warfarin, switching to a DOAC was associated with significantly higher risks of the primary outcome (hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.09-1.87, p=0.01), thromboembolic events (1.28, 1.01-1.62, p=0.039), all-cause death (1.38, 1.15-1.66, p&amp;lt;0.001) and the NCO (1.26, 1.01-1.58, p=0.04). (Figure A, Figure B), whereas there was no difference in the risk of intracerebral hemorrhage (0.90, 0.50-1.60, p=0.7157). When comparing each DOAC with maintaining warfarin, switching to rivaroxaban was associated with a higher risk of the composite of MB and CRNMB (1.91, 1.38-2.64, p&amp;lt;0.001) and thromboembolic events (1.40, 1.03-1.91, p=0.034) than maintaining warfarin. Conclusion In line with the non-Asian population, switching to a DOAC was associated with a significantly higher risk of MB or CRNMB, thromboembolic events, all-cause death and NCO compared with maintaining warfarin in frail elderly Asian patients with AF. Therefore, even in Asians, switching to a DOAC should be considered more cautiously in patients who are stably managed on warfarin.

Effects of airway clearance in hospitalized children with neurologic impairment.

Airway clearance therapies (ACT) are often used to optimize respiratory function for children with neurologic impairment (CNI) hospitalized with acute respiratory infections (ARI). In a five-center retrospective cohort study of CNI aged 1-18 years hospitalized between 2013 and 2015 with ARI, we assessed the association of admission ACT with hospital outcomes (days to return to baseline respiratory support and length of stay [LOS]). Generalized estimated equation (GEE) models examined the association between ACT and outcomes, while accounting for clustering. Propensity scores estimating the likelihood of receiving ACT were included in the GEE models as inverse probability of treatment weights to account for confounding. In adjusted analyses, children receiving admission ACT required similar time to return to respiratory baseline (adjusted risk ratio [aRR] 1.24, 95%CI: 0.95,1.62) and had similar LOS (aRR 1.08, 95%CI: 0.88,1.32) compared with children not receiving ACT. Future studies should seek to identify subpopulations of CNI who benefit most from ACT.

Stroke-Heart syndrome: a population-based cohort study and cluster analysis

Abstract Background The onset of acute cardiovascular complications following a stroke, also known as "Stroke-Heart Syndrome", can occur in up to 20% of patients following a stroke. The syndrome remains under-investigated and limited data exists related to the occurrence and impact of the Stroke-Heart Syndrome in an Asian population. Objectives We aimed to investigate the potential impact of the Stroke-Heart Syndrome and its associations in a retrospective population based-cohort study. Methods The analysis included patients with new-onset ischaemic stroke (IS) June 2006 and May 2022 with 5 years’ follow-up. Patients who developed acute cardiovascular complications within 28 days of their index stroke were compared to patients who did not. The association between acute cardiovascular complications and longer term outcomes were evaluated using multivariate Fine-Grey analyses to adjust for competing risk of mortality, and a Cox regression model for all-cause mortality. Inverse probability of treatment weighting was applied prior to analysis. Furthermore, a hierarchical cluster analysis was performed in the cohort of stroke patients with "Stroke-Heart Syndrome", to further evaluate associations between the identified clusters and (i) longer term outcomes, as well as (ii) the development of acute cardiovascular complications. Results A total of 141,118 patients (median age 72.4 (IQR 62.6 to80.8) years; 45.4% female) were included in the analysis, 6,457 of who developed acute cardiovascular complications, and 134,661 of whom did not. At 5 years follow-up, acute cardiovascular complications were associated with a higher risk of developing recurrent ischaemic stroke (Sub-distribution Hazard Ratio [SHR]: 1.20, 95% Confidence Interval [CI]: 0. 1.12-1.28, p= &amp;lt;0.001), haemorrhagic stroke (SHR: 1.15, 95%CI: 1.03-1.28, p=0.014), myocardial infarction (SHR: 1.53, 95%CI: 1.39-1.69, p=&amp;lt;0.001), and cardiovascular death (SHR: 1.57, 95%CI: 1.45-1.71, p=&amp;lt;0.001) as well as all-cause mortality (HR: 1.07, 95%CI: 1.07-1.07, p=&amp;lt;0.001). A total of 4 clusters were identified in the cluster analysis. Compared to Cluster 3, the other Clusters were associated with increased 5-year risk of myocardial infarction, cardiovascular death and all-cause mortality (p=&amp;lt;0.001). In this cohort, compared to Cluster 2, the other clusters had an increased risk of developing acute cardiovascular complications, in particular acute ischaemic heart disease and acute heart failure (p=&amp;lt;0.001). Cluster 3 tended to be younger with fewer comorbidities and prescribed medications. Over 90% of the patients in Cluster 2 were aged over 75 (with 43% aged 85 years or over). Conclusion Stroke-Heart Syndrome was associated with long-term adverse cardiovascular events in this Asian cohort of ischaemic stroke patients.

The effect of Glucagon-like peptide-1 receptor agonists on cardiovascular outcomes in type 2 diabetes mellitus patients with coronary artery disease

Abstract Background Cardiovascular disease is the primary cause of mortality in patients with type 2 diabetes mellitus (T2DM). Randomized controlled trials (RCT) have shown that Glucagon-like peptide-1 receptor agonists (GLP-1RA) improve cardiovascular outcomes in T2DM patients, with greater therapeutic benefits observed in patients with established atherosclerotic cardiovascular disease. However, the effect of GLP1-RA therapy on cardiovascular outcomes has been inconsistent and the RCT have not been sufficiently powered to examine the effect of GLP1-RA on mortality or their therapeutic effect in different subgroups of T2DM patients. Purpose This study aimed to examine the effect of GLP1-RA therapy on cardiovascular outcomes and mortality in a real-world cohort of T2DM patients with coronary artery disease (CAD). Methods This study included T2DM patients with CAD who were treated with metformin at a daily dose of ≥ 1g for a period of ≥ 180 days. CAD was defined as ≥ 50% luminal stenosis in any coronary artery segment according to a nationwide angiography and angioplasty registry. We performed sequential emulated target trials at monthly intervals between January 1, 2013 and December 31, 2020 to examine the effect of GLP1-RA therapy on major adverse cardiovascular outcomes (MACE), a composite of myocardial infarction, ischemic stroke and all-cause mortality. Secondary outcomes included the individual components of MACE. Marginal structural models were used to compute pooled effect estimates. This was an intention-to-treat analysis with 5 years of follow-up for each emulated target trial. Inverse probability of treatment weighting was used to adjust for confounding due to differences in patient demographics at baseline. Results This study consisted of 26,746 individuals who were treated with GLP1-RA and 74,638 controls. The 5-year cumulative risk of MACE was 27.7 % in the GLP1-RA group and 32.7 % in the control group (risk ratio 0.85 [95% confidence interval 0.82 – 0.88]). GLP1-RA therapy was associated with a lower risk of all-cause mortality (risk ratio 0.76 [95% confidence interval 0.72 – 0.79]) and myocardial infarction (risk ratio 0.95 [95% confidence interval 0.89 – 1.00]). We found little or no effect of GLP1-RA therapy on the risk of ischemic stroke (risk ratio 1.13 [95% confidence interval 0.97 – 1.27]). Conclusions In this large real-world cohort of T2DM patients with established CAD, we observed that GLP1-RA therapy was associated with a lower risk of MACE, myocardial infarction and all-cause mortality.

Performance and safety of complex percutaneous coronary intervention in centres without on-site cardiac surgery: a multi-centre australian registry study.

Abstract Background Performing complex percutaneous coronary intervention (PCI) procedures in hospitals with no on-site cardiac surgery (NOSCS) remains controversial due to a lack of contemporary data and guideline support. Methods Victorian Cardiac Outcomes Registry data was analysed including all PCI cases in the state of Victoria, Australia, from 2014 to 2022. Patients were stratified by PCI at sites with on-site cardiac surgery (OSCS) or NOSCS. Complex PCI was defined as PCI to unprotected left main, bifurcation lesions, rotational atherectomy or intravascular lithotripsy use, severe left ventricular systolic dysfunction, chronic total occlusion, or vein graft PCI. The primary outcome was composite MACCE comprising all-cause mortality, stroke, non-fatal MI, emergency CABG, unplanned revascularisation, definite stent thrombosis and major bleeding (BARC 3 &amp; 5) at 30-days. Risk ratio for average treatment effect in the NOSCS cohort was estimated using inverse probability treatment weighting. Results 94,268 total PCI procedures (32.6% NOSCS) were analysed, including 12,459 complex PCI cases (28.7% NOSCS). Patients from NOSCS were younger (65.0 vs 67.4, p&amp;lt;0.001), less likely to have had previous PCI (29.5% vs 34.5%, p&amp;lt;0.001) or CABG (4.6% vs 8.0% p&amp;lt;0.001) and presented more frequently with acute coronary syndromes (NSTEMI [32.0% vs 28.0%, p&amp;lt;0.001; STEMI [23.3% vs 15.2%], p&amp;lt;0.001). A propensity weighted sample of 30,850 OSCS patients and 30,692 NOSCS patients demonstrated no difference in adjusted 30-day MACCE (risk ratio 0.93, 95% CI 0.87-1.01, p=0.051) for all PCI procedures. In a propensity-weighted subgroup of 3,638 OSCS and 3,576 NOSCS patients who underwent complex PCI, there was also no difference in adjusted 30-day MACCE (risk ratio 0.97, 95%CI 0.86-1.09, p=0.60). Unadjusted rates of CABG at 30-days were very low (0.1 vs 0.1%, p=1.00). Conclusion Patients undergoing PCI and complex PCI at NOSCS centres had comparable 30-day outcomes to those treated at OSCS centres. Newer percutaneous therapies such as intravascular lithotripsy and percutaneous left ventricular assist devices may further improve safety and efficacy of high-risk PCI in NOSCS centres as operator experience increases. Increasing PCI and complex PCI capabilities at NOSCS is likely to increase equitable treatment access for more patients.

Luminal shape and aortic remodelling after total arch replacement for type A aortic dissection: conventional and frozen elephant trunks.

This study was performed to assess postoperative aortic remodelling (AR) after total arch replacement (TAR) for acute type A aortic dissection (AAD) with a frozen elephant trunk (FET) or conventional elephant trunk (cET). Furthermore, the shape of the residual true lumen (TL) was analyzed based on elliptical Fourier analysis (EFA) and evaluated as a predictor of AR. This study involved patients who underwent TAR with a cET or FET for AAD from December 2006 to January 2023 at five institutions. AR was assessed at the levels of the 4th thoracic vertebra (Th4), Th7, Th10, and above the coeliac trunk. The shape of the residual TL at all four levels was analyzed based on EFA to calculate shape patterns as principal component (PC) values. Inverse probability of treatment weighting (IPTW) was performed for adjustment between the groups. In total, 180 patients (88 with cET and 92 with FET) were enrolled. The complete AR rate, defined as false lumen remodelling throughout the entire descending thoracic aorta, was significantly higher in the FET than cET group (63.4% vs 32.0%, P = 0.0013). The IPTW-adjusted Fine-Gray regression model revealed that the mean PC2 (hazard ratio, 0.22; P < 0.001) and PC3 (hazard ratio, 0.24; P = 0.009) of the four levels were independent predictors of complete AR. In AAD repair, the AR rate was significantly higher with use of the FET than cET. The shape patterns of the residual TL can be an important reference for predicting postoperative AR.

Virologically suppressed switch to Dolutegravir/Lamivudine 2-Drug regimen versus switch to commonly prescribed 3-Drug regimens in the United States

BackgroundTwo-drug regimens (2DRs) have been introduced in recent years to potentially reduce antiretroviral therapy (ART) toxicities and drug-drug interactions while demonstrating comparable efficacy to three-drug regimens (3DRs) for people with HIV (PWH). The objective of this study was to compare the real-world effectiveness and durability of a single-tablet 2DR of dolutegravir/lamivudine (DTG/3TC) with that of commonly prescribed 3DRs in ART-experienced, virologically suppressed PWH during the first 24 months of DTG/3TC availability in the United States.MethodsVirologically suppressed (viral load [VL] < 200 copies/mL) adult PWH initiating DTG/3TC 2DR, bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), or a DTG-based 3DR between 01MAY2019 and 31OCT2020 were identified in the OPERA® cohort and followed through 30APR2021. Univariate Poisson regression (incidence rates) and marginal structural Cox proportional hazards models with inverse probability of treatment weights (hazard ratios) were used to quantify relationships between regimen type and confirmed virologic failure (2 consecutive VLs ≥ 200 copies/mL) or regimen discontinuation. Reasons for discontinuation were examined.ResultsA total of 8,037 ART-experienced, virologically suppressed PWH met the inclusion criteria and switched to DTG/3TC (n = 1,450), BIC/FTC/TAF (n = 5,691), or a DTG-based 3DR (n = 896). Incidence rates of confirmed virologic failure were low for all groups, at 0.66 (DTG/3TC), 0.84 (BIC/FTC/TAF), and 1.78 (DTG 3DR) per 100 person-years (py). Compared to DTG/3TC, only the DTG 3DRs were associated with a statistically significant increased hazard of confirmed virologic failure (hazard ratio: 5.21, 95% confidence interval: 1.85, 14.67). Discontinuation rates per 100 py were highest in the DTG 3DR group (24.90), followed by the DTG/3TC group (17.69) and the BIC/FTC/TAF group (8.30). Regardless of regimen, discontinuations were infrequently attributed to effectiveness (VL ≥ 200 copies/mL; 4%) or tolerability (adverse diagnoses, side effects, or lab abnormalities; 6%).ConclusionsAmong virologically suppressed PWH initiating a new regimen, few individuals experienced virologic failure in real-world clinical care. While rates of regimen discontinuation were high, most discontinuations could not be attributed to a lack of virologic control or poor tolerability. These findings suggest that DTG/3TC is an effective option for ART-experienced, virologically suppressed PWH.

Imaging characteristics and clinical outcomes of hemodialysis vs. non-hemodialysis patients undergoing transcatheter aortic valve replacement: a Japanese single-center experience.

In 2021, Japan approved transcatheter aortic valve replacement (TAVR) for end-stage renal disease patients on hemodialysis (ESRD-HD). Yet, clinical/anatomical differences and outcomes between patients with and without ESRD-HD remain underexplored. This single-center study enrolled consecutive patients who underwent TAVR with the SAPIEN 3 between 2021 and 2023. Baseline characteristics and outcomes up to 1year were compared. Inverse probability treatment weighting (IPTW) approach and Cox regression were used. Among 287 eligible patients, 59 had ESRD-HD. Patients with ESRD-HD were predominantly male (59.2% vs. 40.7%; p = 0.01), younger (78.0 [73.5-83.5] vs. 84.0 [79.8-88.0]; < 0.001), with lower body mass index (21.4 [19.6-23.3] vs. 22.9 [20.3-25.3]; p = 0.02], higher surgical risk (Society of Thoracic Surgeons Predicted Risk of Mortality ≧8%: 28 [47.5%] vs. 34 [14.9%]; p < 0.001), and more peripheral artery disease (25.4% vs. 4.8%; p < 0.001). Patients with ESRD-HD had a significantly higher prevalence of severely calcified femoral arteries (12.5% vs. 2.6%; p < 0.001). However, there were no differences in the computed-tomographic (CT) anatomical characteristics of the aortic valve complex (AVC), including the aortic valve calcium score (1995 [1372-3374] vs. 2195 [1380-3172]; p = 0.65) or the presence of moderate or severe left ventricular outflow tract calcification (4.3% vs. 5.2%; p > 0.99). Major vascular complications were rare, and technical (98.3% vs. 98.7%; p > 0.99) and device success (75.9% vs. 82.4%; p = 0.26) rates were high in both. At 1year, there were no significant differences in a composite endpoint of death, stroke, major bleeding, or myocardial infarction (32.4% vs. 33.2%; HR 1.12; 95% CI 0.45-2.80; p = 0.81), nor its components after baseline adjustment.

Renin–angiotensin system inhibition and mortality in patients undergoing dialysis with coronary artery disease: insights from a multi-center observational study

ABSTRACT Background While the survival benefits of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are firmly established in the general population, their efficacy within patient undergoing dialysis with coronary artery disease (CAD) remains controversial. Methods Between January 2015 and June 2021, 1168 patients undergoing dialysis with CAD were assessed from 30 tertiary medical centers. The primary outcome was all-cause death, and the secondary outcome was cardiovascular death. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for between-group differences. Results Overall, ACEI or ARB were prescribed to 518 patients (44.3%) upon discharge. After a median follow-up of 22.2 months, 361 (30.9%) patients died, including 243 cardiovascular deaths. The use of ACEI or ARB was associated with a significantly lower risk of all-cause (25.3% vs 35.4%, hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.52–0.82, p < 0.001) and cardiovascular death (17.0% vs 23.8%; HR 0.64, 95% CI 0.48–0.83, p = 0.001). These findings remained consistent across IPTW and PSM analyses. Sensitivity analyses for ACEI and ARB use separately yielded similar results. Conclusions Our findings suggested that among patients undergoing dialysis with CAD, ACEI or ARB use was associated with a lower risk of all-cause and cardiovascular death.

Fluticasone Furoate/Umeclidinium/Vilanterol Initiation Following a COPD Exacerbation: Benefits of Prompt Initiation on COPD Outcomes.

Previous real-world evidence suggests that prompt versus delayed initiation of single-inhaler triple therapy (SITT) with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) following an exacerbation results in improved clinical outcomes for patients with chronic obstructive pulmonary disease (COPD). This prior study was conducted in the first 2years following FF/UMEC/VI approval, representing early trends. The current updated analysis aims to further elucidate the real-world evidence for FF/UMEC/VI. This was a retrospective cohort study using the IQVIA PharMetrics® Plus database. Patients with COPD initiating SITT with FF/UMEC/VI within 6months of an exacerbation (index date) were classified as prompt (≤ 30days following exacerbation) or delayed (31-180days) initiators. The baseline period comprised the 12months prior to index. Inverse probability of treatment weighting was used to balance differences in baseline characteristics between cohorts. COPD exacerbations, hospital readmission rates, and healthcare costs were compared between cohorts post-index. Overall, 5421 patients (prompt, 2057; delayed, 3364) were included. After weighting, baseline characteristics were well balanced between cohorts. For up to 12months post-index, prompt initiators of FF/UMEC/VI had significantly lower rates of exacerbations per person-year versus delayed initiators (0.74 vs. 1.06; rate ratio 0.70, 95% confidence interval [CI] 0.64-0.77; P < 0.001). A 1-day delay in FF/UMEC/VI initiation was associated with a 0.31% increase in the rate of exacerbations. At 90days post-index, Kaplan-Meier rates of all-cause (hazard ratio [HR] 0.62, 95%CI 0.45-0.86; P = 0.004) and COPD-related (HR 0.58, 95%CI 0.35-0.98; P = 0.042) hospital readmissions were significantly lower in the prompt versus delayed cohort. Total COPD-related healthcare costs per person per year were significantly lower for patients in the prompt versus delayed cohort. Healthcare providers should consider the positive impact of prompt FF/UMEC/VI initiation on exacerbation rate, hospital readmission rate, and costs when treating patients with COPD at risk of exacerbations.

A comprehensive organ protection strategy in total arch replacement: a propensity-weighted analysis.

To report the outcomes and determine the effectiveness of a comprehensive organ protection strategy in total arch replacement. A total of 350 patients who underwent total arch replacement were enrolled. 54 patients underwent the comprehensive organ protection strategy with bilateral antegrade cerebral perfusion (bACP) and aortic balloon occlusion (ABO) technique (comprehensive strategy group) and 296 patients underwent the standard strategy with unilateral antegrade cerebral perfusion (standard strategy group). Inverse probability of treatment weighting (IPTW) was used to balance the baseline characteristics. After IPTW, the comprehensive strategy group had lower incidences of 30-day mortality (0.9% vs 4.9%, P = 0.002), continuous renal replacement therapy (CRRT) (0.6% vs 10.3%, P < 0.001), renal failure (4.6% vs 13.7%, P < 0.001), hepatic dysfunction (11.6% vs 21.1%, P = 0.001), and shorter duration of mechanical ventilation [16 (13, 31) vs 20 (14, 48) hours, P = 0.011]. Multivariable logistic analysis showed the comprehensive strategy was an independent protective factor of 30-day mortality (odds ratio (OR): 0.242, 95% confidence interval (CI): 0.068-0.867, P = 0.029), CRRT (OR: 0.045, 95% CI: 0.008-0.264, P = 0.001), renal failure (OR: 0.351, 95% CI: 0.156-0.788, P = 0.011), and mechanical ventilation >20 hours (OR: 0.531, 95% CI: 0.319-0.883, P = 0.015). Kaplan-Meier analysis showed mid-term survival was comparable. The comprehensive organ protection strategy might improve early survival, reduce the use of CRRT, have protective effects on the kidney, and shorten mechanical ventilation time in total arch replacement. This strategy might be considered a viable alternative in total arch replacement.