bluuebunny/crossref_metadata_2025_split huggingface dataset:
The gender gap in prescription pattern of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes
Authors: Hammer A , Hofer F , Kazem N , Koller L , Steinacher E , Niessner A , Sulzgruber P 
Published: October 2022

Abstract

Background
The major benefit of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in type 2 diabetes mellitus (T2DM) on cardiovascular outcome has been undoubtably proven in several landmark trials and different populations. In consideration of emerging evidence that there are clinically relevant gender-related differences in the course of T2DM and subsequent cardiovascular outcomes, it is unknown if SGLT2i therapy is gender independent utilized in clinical practice. In this regard, real-world data are needed to determine whether there is a gender gap in SGLT2i prescription and if this influences long-term outcome.

Methods
Patients with T2DM admitted to a tertiary academic center between 01/2014 and 04/2020 were identified through a search of electronic health records. Data on antidiabetic therapy was acquired at discharge, and were screened for SGLT2i prescription. Subsequently, the entire cohort was prospectively followed.

Results
In total, 812 patients (median age 70 years, 29.7% female) were included in the present analysis. Only 17.3% of the study population received an SGLT2i. In direct comparison between sexes, females show lower rates of SGLT2i prescription (11,2% vs. 19,8%, p=0.003), despite comparable patient characteristics. Furthermore, males show a significantly higher probability of SGLT2i prescription, illustrated as an adjusted odds ratio of 2.59 (CI 95% 1.29–5.19; p=0.008). During a median follow-up time of 2.3 years, a total of 142 patients died due to cardiovascular causes – corresponding to 103 (18.0%) male and 39 (16.2%) female participants. Females who did not receive a SGLT2i showed higher rates of chronic kidney disease (CKD, 25.2% vs. 7.4%, p=0.039) and greater levels of proBNP (2092 pg/ml (IQR: 738–5279) vs. 825 pg/ml (IQR: 298–2479), p=0.011) as compared to non-SGLT2i females.

Conclusion
Despite clear evidence on the beneficial effect of SGLT2i, the present data suggest a gender-gap in SGLT2i prescription and thus missed potential in female patients. The most common reason for not prescribing a SGLT2i in females was the presence of CKD. However, SGLT2i (i.e. Empagliflozin) are approved to use in individuals with a glomerular filtration rate (GFR) as low as ≥20ml/min, and therefore more awareness has to be raised, that SGLT2i are feasible to prescribe in such vulnerable patients with present cardiovascular comorbidities, to achieve a benefit as shown in several landmark trials. Additionally, more attention is needed to address this gender-gap and ensure that both sexes receive equal attention, in terms of state of the art T2DM therapy to reduce mortality and morbidity.

Funding Acknowledgement
Type of funding sources: None.
Adherence and discontinuation of sglt2-inhibitors and glp1-r agonists in patients with type 2 diabetes with and without cardiovascular disease
Authors: Malik M , Falkentoft A , Jensen J , Andersson C , Parveen S L , Koeber L , Schou M E M 
Published: October 2022

Abstract

Background
Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucacon-like-peptide-1 receptor (GLP-1R) agonists are two novel therapies in type 2 diabetes (T2D) that are recommended in patients with manifestations of cardiovascular disease or high risk of cardiovascular disease due to their cardioprotective benefits. Despite the increasing use of these drugs, there is still limited knowledge on the adherence patterns and the risk of discontinuation, according to the presence or absence of different cardiovascular conditions.

Purpose
To investigate the adherence and estimate the risk of discontinuation of SGLT2 inhibitors and GLP1-R agonists in patients with T2D with and without cardiovascular disease.

Methods
From Danish nationwide registers, we included all individuals &gt;40 years with T2D who redeemed the first prescription of a SGLT2 inhibitor or GLP1-R agonist, between December, 2012 and December, 2018. Patients were divided into subgroups according to the presence or absence of different cardiovascular conditions (heart failure, ischemic heart disease, peripheral artery disease, atrial fibrillation), at the time of inclusion. Adherence over the course of one year after initiation of treatment was estimated by the proportion of days covered (PDC) for each subgroup, and adherence was defined as PDC 80%. The risk of discontinuation was estimated using multivariable cause-specific Cox regression models, and was defined as a break in treatment of 90 days. The Aalen-Johansen estimator was used to account for censoring and competing risks. Patients were followed until date of emigration, death or study end (December 31, 2019).

Results
We included 24,061 patients with T2D who initiated treatment with a SGLT2 inhibitor, and 13,899 patients with T2D who initiated treatment with a GLP1-R agonist, for the first time between December 10, 2012 and December 31, 2018. Median age at inclusion was 62 years (IQR 54–70) and 40% were female. In the analyses, 67% of the patients treated with SGLT2 inhibitors were adherent to therapy throughout the first year, whereas the same proportion of patients, 67%, were adherent to therapy with GLP-1R agonists. Mean PDC was 77% (SD 33) and 79% (31) for patients in therapy with SGLT2 inhibitors and GLP1-R agonists, respectively. No significant difference was observed related to the presence or absence of cardiovascular disease (SGLT2 inhibitor: mean PDC 77 (33) vs. 77 (33), GLP1-R agonist: 78 (32) vs. 79 (31)).

Conclusions
In this nationwide cohort study, we found that patients with T2D who initiated therapy with a SGLT2 inhibitor and those who initiated therapy with a GLP1-R agonist were almost equally adherent to therapy throughout the first year. Adherence in both treatment groups did not differ according to the presence or absence of cardiovascular disease.

Funding Acknowledgement
Type of funding sources: None.
Frailty and outcomes in octogenarians with atrial fibrillation treated with edoxaban: ESCAPE study
Authors: Denas G , Zoppellaro G , Granziera S , Pagliani L , Iliceto S , Pengo V 
Published: October 2022

Abstract

Background
Frailty is associated with significant morbidity and mortality among elderly adults. Whether frailty predicts adverse outcomes in patients treated with oral anticoagulants for stroke prevention in atrial fibrillation remains uncertain.

Purpose
To examine the impact of frailty in clinical outcomes in elderly patients with non-valvular atrial fibrillation treated with edoxaban.

Methods
This is an observational prospective single centre cohort study enrolling consecutive naïve to anticoagulation patients of age ≥80 years starting oral anticoagulation with edoxaban for stroke prevention in non-valvular atrial fibrillation and followed up for 2 years. At baseline, all patients were evaluated for frailty, comorbidities, medications, and stroke and bleeding risk factors. Frailty was assessed using the Survey of Health Ageing and Retirement in Europe Frailty Index (SHARE-FI) tool, a validated frailty measure centred on health resource utilisation, with the cohort stratified into non-frail, pre-frail and frail. The clinical outcomes were the cumulative incidence of stroke/systemic embolism, major bleeding, and clinically relevant non-major bleeding (CRNMB), and individual components part of the composite outcome.

Results
Among 160 patients who received edoxaban for stroke prevention in atrial fibrillation, 34% were frail, 20% pre-frail, 46% non-frail. The mean age of the cohort was 85±4 years and 58% were female. The mean CHA2DS2VASc score was 4±1. Mean Cockroft-Gault creatinine clearance (CrCl) was 52±17 mL/min, and edoxaban 30mg was administered to 59% of patients as per indications (weight ≤60 kg and/or, CrCl 15–50 ml/min). The follow up extended for 681±289 days. Primary endpoint occurred in 46 patients (28.7%; annualised rate 15.4%patient-years): 19 events occurred in non-frail, 9 in pre-frail, and 18 in frail patients (p=0.6). Stroke/systemic embolism occurred in 2.2%, major bleeding in 5.0%, and CRNM bleeding in 10.0% of patients. Frailty was not a predictor of the events part of the composite outcome (non-frail 5.4% vs pre-frail 0% vs frail 1.9%, p=0.27; non-frail 5.4% vs pre-frail 9.4% vs frail 1.9%, p=0.29; and non-frail 13.5% vs pre-frail 3.1% vs frail 9.3%, p=0.25; for stroke/systemic embolism, major bleeding, and CRNMB, respectively). Cumulative rate of events (Figure) did not differ in frail versus the rest (non-frail and pre-frail) of patients (p=0.521).

Conclusions
Frailty status was not a predictor of events among the elderly with atrial fibrillation treated with edoxaban. Anticoagulation with edoxaban is feasible in octogenarians even if frail.

Funding Acknowledgement
Type of funding sources: None.
Prognostic utility of left ventricular global longitudinal strain in patients with systemic amyloidosis
Authors: Bhatia K , Aggarwal D , Ochoa-Jimenez R , Lopez P , Konje S , Argulian E 
Published: October 2022

Abstract

Background
Myocardial deposition of amyloid proteins results in restrictive cardiomyopathy. Left ventricular global longitudinal strain (GLS) has emerged as a sensitive measure for detecting subclinical cardiac dysfunction over traditional echocardiographic parameters. However, multiple studies have provided differing conclusions regarding prognostic utility of impaired GLS in patients with systemic amyloidosis.

Purpose
We conducted a systematic review and meta-analysis to evaluate whether impaired GLS was associated with increased mortality or major adverse cardiovascular events (MACE) in patients with systemic amyloidosis.

Methods
We performed a literature search of Embase, Medline and Web of Science databases to identify studies that reported the association of GLS with clinical outcomes in patients with systemic amyloidosis (light chain or TTR amyloidosis). Outcomes of interest included all-cause mortality and MACE, defined as a composite of death or heart transplant or heart failure hospitalization. Unadjusted and adjusted hazard ratio (uHR and aHR respectively) were pooled using a random effects model. Heterogeneity among the studies was assessed using the Higgins I2 value.

Results
Out of 2139 initial citations, 28 observational studies with a total of 2713 patients were included in the analysis. The mean age ranged between 58–78 years and 62% of the patients were male. Most patients had cardiac amyloidosis (83%) and light-chain amyloidosis accounted for 69% of cases. Mean follow-up ranged between 1 and 5 years. GLS was significantly higher (less negative) (mean difference (MD) −3.69 [−5.94, −1.44], I2=87, p&lt;0.01) in non-survivors compared with survivors. Similarly, patients who experienced MACE had a significantly higher mean GLS (MD −3.22, [−5.21, −1.22,], I2=82, p&lt;0.01]. The risk of both mortality and MACE increased significantly for every −1% increase in GLS. In unadjusted models, a GLS above the defined threshold value was associated with a significantly higher risk of mortality (uHR: 1.66 [1.22, 5.21], I2=85.2, p&lt;0.01) and MACE (uHR: 2.24 [1.28, 3.92], I2=39, p&lt;0.01). In multivariable models an increase in GLS by −1% was an independent predictor of mortality (aHR: 1.09 [1.01,1.16], I2=53, p=0.02) and MACE (aHR: 1.24 [1.14,1.36], I2=0, p&lt;0.01).

Conclusion
In patient with amyloidosis, the baseline left ventricular GLS may help identify patients with a higher risk of mortality and MACE.

Funding Acknowledgement
Type of funding sources: None.
The use of warfarin as part of antithrombotic strategy after transcutaneous aortic valve replacement is not associated with better medium-term outcomes
Authors: Naser J , Gochanour B R , Scott C G , Luis S A , Greason K L , Crestanello J A , Gulati R , Eleid M F , Nkomo V T , Pislaru S V 
Published: October 2022

Abstract

Background
Bioprosthetic valve thrombosis is currently a well-recognized cause of bioprosthetic valve dysfunction. It was found to be associated with accelerated degeneration of the bioprosthesis with higher rates of valve re-replacement, even after treatment with anticoagulation. We hypothesized that the use of warfarin for three months after transcatheter aortic valve replacement (TAVR) protects against accelerated valve degeneration and is therefore associated with better outcomes compared to dual antiplatelet therapy (DAPT).

Methods
Consecutive adult patients who underwent TAVR in our clinic between 2012 and 2019 were identified retrospectively. Patients with atrial fibrillation were excluded. Subsequently, patients who received DAPT were propensity matched to up to 2 patients who received three months of warfarin as part of their anti-thrombotic regimen. Matching was performed for variables that were significantly different at baseline between the two groups and included diabetes mellitus, prior myocardial infarctions, chronic lung disease, peripheral arterial disease, hemoglobin at time of TAVR, kidney function [creatinine&gt;2], use of angiotensin-converting enzyme inhibitors / angiotensin II receptor blockers, beta blockers, the Society of Thoracic Surgeons (STS) score [STS ≥8, STS 4–8, STS&lt;4], and valve size. The two groups were then compared for outcomes of ischemic stroke, death, valve re-replacement/intervention, the composite endpoint of the aforementioned three outcomes, as well as the three-month outcome of hemorrhagic strokes. Kaplan Meier was used for outcome analysis, and discharge date was considered time zero. Patients who had their anti-thrombotic therapy interrupted were censored at that time point.

Results
A total of 1,373 patients who underwent TAVR were identified. Of these, 576 patients with atrial fibrillation were excluded. Baseline characteristics were compared between 633 patients who received three months of warfarin and 164 patients who received DAPT after TAVR. After matching the two groups, 435 patients were included in the final analysis [warfarin in 281, DAPT in 154; median time to last follow up 2.61 years], Table 1. There was no difference in matched (Figure 1) or unmatched analysis (not shown) in outcomes of ischemic stroke, death, valve re-replacement/intervention, their composite endpoint, or hemorrhagic strokes (p&gt;0.05 for all).

Conclusion
Antithrombotic regimen including three months of warfarin after TAVR was not associated with better outcomes of ischemic strokes, deaths, and valve re-replacement/intervention or with increased risk of hemorrhagic strokes compared to DAPT.

Funding Acknowledgement
Type of funding sources: None.
Previous antithrombotic therapy does not have an impact on the in-hospital mortality of patients with upper gastrointestinal bleeding
Authors: Hozman M , Hassouna S , Grochol L , Waldauf P , Hracek T , Zborilova Pazdiorova B , Adamec S , Osmancik P 
Published: October 2022

Abstract

Background
The association between antithrombotic therapy due to concomitant cardiovascular disorders and the risk of gastrointestinal bleeding is well known; however, data regarding the influence of antithrombotics on outcomes and further management after a bleeding episode are scarce.

Purpose
This study was conducted to assess the impact of concomitant antithrombotic therapy and other variables on in-hospital and 6-month outcomes and to determine the re-initiation rate of the antithrombotic treatment after a bleeding event.

Methods
We retrospectively analysed all patients with upper gastrointestinal bleeding (UGB) who underwent urgent gastroscopy in 3 centres from 1 January 2019 to 31 December 2019. Demographic and medical data were collected from the electronic hospital database system.

Results
Among 333 patients (60% males, mean age 69±16 years), 44% were receiving antithrombotics. The in-hospital mortality rate was 12%, and the 6-months was 32%. In logistic regression we observed no association between antithrombotics and worse in-hospital outcomes. Haemorrhagic shock (OR 5.7, 95% CI 2.7 to 12.2; p&lt;0.001), as well as a history of cancer (OR 2.7, 95% CI 1.1 to 6.9; p=0.03) and higher comorbidity (mean Charlson comorbidity index 5.6 vs. 6.9, OR 1.3, 95% CI 1.1 to 1.6; p=0.005) led to higher in-hospital mortality (tab. 1). In terms of 6-months outcomes, higher age (OR 1.03, 95% CI 1.00 to 1.05; p=0.02), higher comorbidity (OR 1.4, 95% CI 1.2 to 1.6; p&lt;0.001), a history of cancer (OR 4.5, 95% CI 2.0 to 10.1; p&lt;0.001) and a history of liver cirrhosis (OR 2.3, 95% CI 1.2 to 4.6; p=0.02) were associated with higher mortality. Other tested variables such as ischemic heart disease, heart failure or diabetes did not influence 6-month outcomes at statistically significant level (tab. 2). After a bleeding episode, antithrombotic treatment in patients with lasting indication from cardiovascular reasons was re-initiated in 81% of cases. One patient with atrial fibrillation was referred for a left atrial appendage closure.

Conclusions
Based on our observations, previous antithrombotic therapy does not worsen in-hospital outcomes in patients with UGB. Development of haemorrhagic shock during hospitalization predicted poor prognosis. Higher 6-month mortality was observed in older patients and patients with a history of liver cirrhosis. A history of cancer and higher comorbidity negatively affected the short- as well as long-term prognosis.

Funding Acknowledgement
Type of funding sources: None.
Myocardial deformation in athletes measured with feature tracking cardiovascular magnetic resonance
Authors: Silva C , Marcos-Carrion A , Garcia-Lopez M P , Lopez-Lereu M P , Monmeneu J V , Higueras L , Ferreira A M , Maceira A M 
Published: October 2022

Abstract

Background
Morphological changes of the heart associated with exercise are well studied. However, changes in myocardial mechanics of athlete's heart are less understood. The aim of this study was to analyze myocardial deformation parameters in athletes and controls, using feature tracking cardiac magnetic resonance (FT-CMR).

Methods
In a cohort of 73 athletes who had been submitted to CMR at 1.5T and 3 T (mean age 31±12 years, 69% males), we used CMR-FT to measure longitudinal, circumferential and radial strain and strain rates of both ventricles. Left ventricle (LV) longitudinal, circumferential and radial dyssynchrony index (L-SDI, C-SDI and R-CDI, respectively) was calculated as the standard deviation of the calculated time to peak strain percentages of the cardiac cycle with segmental strain analysis. We also measured these parameters in 73 age-matched healthy subjects.

Results
In comparison to the control subjects, athletes revealed lower left and right ventricle global longitudinal strain (−14.24% vs. −13.31%, p=0.03, and −18.12% vs. −15.95% p=0.01, respectively) and right ventricular (RV) global radial strain (19.28 vs 15.74, p&lt;0.05) – Figure 1. There were no significant differences in LV global radial and circumferential strain. LV longitudinal, radial and circumferential systolic strain rate were also lower in athletes compared to controls (−0.69 s–1 vs. −0.78 s–1, p=0.04; 1.35 s–1 vs. 1.50 s–1, p=0.03: −0.92 s–1 vs −0.98 s–1, p=0.05, respectively). Regarding LV dyssynchrony index, we found no significant difference for L-SDI (10.76% vs. 10.72%, p=0.956), but athletes group showed lower C-SDI and R-SDI values (5.99% vs 4.84%, p=0.006, and 5.53% vs 4.47%, p=0.002).

Conclusion
Our study revealed attenuation of biventricular strain values and lower circumferential and radial LV dyssynchrony indexes in athletes, compared with healthy controls. We hypothesize that these differences may be related with exercise physiologic cardiac adaptations.

Funding Acknowledgement
Type of funding sources: None.
Influence of obesity on the safety and efficacy of antithrombotic therapy: a systematic review and meta-analysis
Authors: Rocha Darze B , Borges De Oliveira Q , Santos Viana M , Sahade Darze E , Fonteles Ritt L E 
Published: October 2022

Abstract

Background/Introduction
The prevalence of obesity has increased in recent decades and, considering its association with a higher risk of Venous Thromboembolism (VTE) and Acute Coronary Syndromes (ACS), it is necessary to establish an anticoagulation regimen suitable for this group of patients. The obese population is historically underrepresented in clinical trials, so the effect of obesity on the efficacy and safety of antithrombotic treatment is still uncertain.

Purpose
To evaluate the influence of obesity on the safety and efficacy of antithrombotic therapy in patients with ACS or VTE.

Methods
This is a systematic review and meta-analysis, using the MEDLINE/PubMed, Scielo, Cochrane, EMBASE and Lilacs databases. Articles characterized as randomized, cohort or case-control studies that compared the occurrence of clinical outcomes (mortality or bleeding) between obese and non-obese patients using parenteral anticoagulants for the treatment of ACS or VTE were selected. To assess the risk of bias, the Cochrane Risk of Bias Tool and the Newcastle-Ottawa Scale were used. Statistical analysis was performed using Revman 5.4 software with relative risk and 95% CI as analytical parameters.

Results
Six articles, with a total of 40.939 patients, were eligible for this review, being 3 randomized clinical trials and 3 retrospective cohorts. Of the patients, 87.7% had ACS. The mortality rate was 2.6% (95% CI 2.2–3.0%) in obese patients and 3.6% (95% CI 3.3–4.0%) in non-obese patients, while the rate of major bleeding was 6.0% (95% CI 5.6–6.4%) in the obese group and 6.2% (95% CI 5.9–6.5%) in the non-obese group. The incidence of major bleeding was similar between groups with RR: 0.90, 95% CI: 0.77–1.04, p=0.14. The outcome incidence remained comparable when studies were analyzed separately by anticoagulant: enoxaparin (RR: 0.87, 95% CI, 0.70–1.08, p=0.21) or UFH (RR: 0.96, 95% CI, 0.79–1.17, p=0.67). The mortality rate, measured by only 2 studies, was lower in obese patients, with RR: 0.71, 95% CI 0.59–0.87, p=0.0007.

Conclusion
In patients treated for VTE or ACS, rates of thrombotic complications, death and bleeding were comparable between obese and non-obese patients, regardless of the antithrombotic used.

Funding Acknowledgement
Type of funding sources: None.