bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trimetazidine reduces stroke risk in ischemic atrial fibrillation: a territory-wide, propensity-matched study
Authors: Cheng Y T , Cheung B M Y , Yiu K H , Tse H F , Chan Y H 
Published: October 2024

Abstract

Introduction
Trimetazidine ameliorates myocardial ischemia via potentiating glucose oxidation. Whether such metabolic reprogramming protects against stroke risk in atrial fibrillation (AF) with ischemic heart disease (IHD) was unknown.

Purpose
To investigate the therapeutic impact of trimetazidine dihydrochloride on ischemic stroke in AF associated with IHD.

Methods
We collected data from a territory-wide clinical data registry (January 1999 to December 2020) with a coverage of 7.5 million population. 200,563 patients with IHD were identified. Amongst them, 13,092 (6.5%) had baseline AF (mean [SD] age: 79.7 [10.3] years, 44.8% female), and were identified as trimetazidine users (n=1,488) versus non-users (long-acting nitrates as control, n=11,604). Propensity matching at 1:1 was performed. Multivariable Cox regression was used to derive hazard ratios (HRs) for new-onset ischemic stroke.

Result
Over mean follow-up over 53.5 +/- 50.4 months, trimetazidine use was associated with a lower incidence of ischemic stroke (3.4% vs 7.6%, P&lt;.001). Kaplan-Meier analyses showed trimetazidine use was associated with increased stroke-free survival period (Mean survival: 227.9 [4.9] versus 217.5 [3.6] months, Chi-square=39.0 P&lt;.001). After adjusting for confounding factors, trimetazidine use remained an independent predictor of reduced ischemic stroke risk (adjusted HRs, 0.54, 95% CI, 0.37-0.78, P&lt;.001).

Conclusion
Trimetazidine may reduce the risk of ischemic stroke in ischemic AF. These findings will need to be confirmed by randomized controlled trials.
Safety, tolerability, and basic pharmacokinetic parameters of AUX-001, a once-daily extended release nicorandil in healthy volunteers under fasting and fed conditions
Authors: Tigoer U , Chabowski D , Fonseca M 
Published: October 2024

Abstract

Introduction
Chronic-stable angina pectoris (CSAP) is one of the most common cardiovascular conditions in the developed world with a rising prevalence in both Europe and North America. Mounting evidence from chronic angina outcomes studies, including COURAGE, BARI, ORBITA and recently ISCHEMIA, has reemphasized optimized medical therapy (OMT) as first-line treatment for most chronic-stable angina pectoris (CSAP) patients over coronary revascularization. Yet, there has been a lack of development of new antianginal medications since 2006. To lessen polypharmacy and enable better long-term compliance in CSAP patients, AUX-001, a once-daily (QD), extended-release (ER) nicorandil is in clinical development for treating CSAP as an innovative, novel version of the immediate-release (IR) antianginal.

Objective
To test the safety, tolerability, and basic pharmacokinetic (PK) parameters of AUX-001 QD in fasting and fed conditions in healthy volunteers during this first-in-human phase 1a study.

Methods
16 healthy adult volunteers were enrolled. Vital signs (HR, BP, respiratory rate) and any adverse events were collected during screening, pre-dose, 1, 2, 6, 12, 24-h, and 48-h post-dose and at end-of-study for the two respective periods (fasting and fed).

Results
Evaluable information was available on 16 patients for fasting and 15 for fed conditions with one patient excluded due to protocol violation. No patient discontinued due to safety or tolerability. No severe AEs were recorded. AEs observed during period 1 included headaches (n=12), asymptomatic hypotension (n=3), palpitation (n=1) and nasal congestion (n=1). In period 2, leading AEs were headaches (n=11), neck pain (n=1) and decreased hemoglobin (n=1). Most AEs were mild and transitory and did not trigger medical intervention or discontinuation.
AUX-001 pharmacokinetics exhibited a reduced Cmax, a right-hand shift in Tmax, and an extension of T1/2 beyond 9 hours compared to the historical data of the commercially available IR nicorandil.
AUX-001 had a small, temporary effect on heart rate and systolic and diastolic blood pressure but within the normal compensatory haemodynamic steady-state stability. The peak effect with the current AUX-001 prototype was at 6 hours, independent of the food effect.

Conclusion
AUX-001 was safe and well tolerated. Initial vasodilator-induced headaches were manageable by using simple OTC NSAIDs and led to no dropouts. No patients discontinued due to AEs or tolerability issues. There were no lasting significant haemodynamic effects of AUX-001 beyond 24hours. PK parameters of AUX-001 are characteristic of an ER formulation. Observed pharmacokinetics indicates that the achieved T1/2 is substantially longer than with IR nicorandil (~1hour vs &gt;9h) and shows promise for a potential once daily treatment of exercise induced chronic angina.AUX-001 Study Data ESC Abstract 2024
Common ECG abnormalities pose increased risks of out-of-hospital cardiac arrest
Authors: Hindborg M , Andersen M P , Sondergaard M M , Hasselbalch R B , Torp-Pedersen C 
Published: October 2024

Abstract

Background
It is known that 40%-60% of all sudden cardiac deaths occur as the first sign of unrecognized heart disease which poses a challenge in preventing early cardiac death (1). While many common ECG abnormalities have previously been associated with an increased risk of cardiac morbidity and mortality, knowledge of what abnormalities are associated with out-of-hospital cardiac arrest (OHCA) is lacking (2,3).

Purpose
To investigate the association between a range of common ECG abnormalities and the risk of subsequent OHCA.

Methods
From 2000 to 2020, patients acquiring an ECG at a Danish hospital or in an ambulance in Denmark were followed until either having OHCA, emigrating, death from other causes or end of study (01-01-2021), whichever came first. Only the index ECG and first occurrence of OHCA for each patient were considered for analysis. Data on patient age and gender were obtained through the Danish Civil Registration System. A multivariable Cox regression, adjusted for patient gender and age at ECG acquisition, was performed to assess the risk (hazard ratio [HR] with 95% confidence interval [95% CI]) of OHCA for various common ECG abnormalities. P-values less than 0.05 were considered significant.

Results
In total 2,037,003 patients were included, of which 26,446 (13.0%) had OHCA during follow-up after ECG acquisition. Patient characteristics and distribution of ECG abnormalities between the OHCA and non-OHCA patients are shown in Table 1. Patients with OHCA were older and more frequently male (both p &lt; 0.001). ECG abnormalities were also generally more frequent among OHCA patients than non-OHCA patients. Median follow-up time for the entire cohort was 2063 days. The results of the multivariable Cox regression are shown in Figure 1. All assessed ECG abnormalities resulted in significantly higher risk of later OHCA with HR (95% CI) ranging between 1.0521 (1.0512-1.0531) and 1.0554 (1.0544-1.0563) when also adjusting for patient age and gender.

Conclusion
Common ECG abnormalities were associated with a significantly increased risk of OHCA. Further research is needed to investigate the mechanisms behind specific ECG abnormalities and OHCA occurrence and to determine the validity of ECG screening in preventing OHCA.Table 1Figure 1, SL = Sokolow-Lyon
Efficacy and safety of inclisiran in real-world clinical practice. Results from the CHOLINET Registry
Authors: Gargiulo P , Fontanarosa S , Marzano F , Cotticelli C , Crisci M , Marcucci R , Maloberti A , Sarullo F M , Galasso G , Musumeci G , Indolfi C , Varbella F , Calabro' P , Carugo S , Perrone-Filardi P 
Published: October 2024

Abstract

Background/Introduction
Inclisiran has been recently introduced in clinical practice. Thus, efficacy and safety data from real-world settings are limited.

Purpose
Cholinet (Cholesterol inclisiran Italian network) is an Italian multicenter prospective phase 4 registry including 36 Italian centers, designed to assess efficacy, safety, adherence and persistence of inclisiran treatment, and clinician’s behavior on LLT in very high CV risk patients with atherosclerotic CV disease and/or familial hypercholesterolemia (FH).

Methods
From November 2022 through February 2024, the Cholinet registry enrolled patients receiving inclisiran according to standard clinical practice. Clinical and demographic characteristics, concomitant therapies, blood chemistry, were recorded at the time of first prescription and at subsequent follow-up.

Results
We enrolled 668 patients in treatment with inclisiran (15.1% with FH, 30.7% female, mean age 63 years), Data on follow-up at 3 months (booster time) were available for 495 of them. At the time of inclisiran first prescription median LDL-C was 102 mg/dl and reached 51 mg/dl at the time of 3 months observation (50% mean reduction, 51 mg/dl absolute median reduction). None of the 495 patients reaching 3 months follow up missed the reinjection dose administration. Of 668 patients enrolled, 553 patients (82.7%) were on LLT, of them 107 (19.3%) were on ezetimibe alone, 67 (12.1%) on statin alone and 379 (68.5%) on a statin and ezetimibe combination. Of the enrolled patients, 45 (6.7%) were previously treated with evolocumab and 34 (5%) with alirocumab.
Among the patients evaluated at the 3-month follow-up, 307 patients (62%) achieved the LDL cholesterol target; of them, 450 (91%) were treated with inclisiran and statin±ezetimibe. Evaluating the distribution of the percentage reduction in LDL cholesterol values, a heterogeneity emerged that was partly explainable by the concomitant lipid-lowering therapy and partly by the previous exposure to PCSK9 inhibitors.

Conclusions
These preliminary data from the Cholinet Italian registry show that inclisiran effectively reduces (50%) LDL-C in real-world settings. The LDL-C target was achieved in 62% of patients; of them 91% were on lipid-lowering therapy, showing that combination therapy is necessary in most of these patients.
Empaglifozin modifies the arterial stiffness in type-2 diabetic patients: a preliminary report.
Authors: Feola M , Pastorini G , Anastasio F 
Published: October 2024

Abstract

Background
Sodium-glucose cotransporter-2 (SGLT2) inhibitors demonstrated beneficial effects on cardiovascular and renal events in patients with type 2 diabetes mellitus. The mechanisms underlying these effects are not fully elucidated. Aim of this study was to investigate whether empagliflozin is able to modify the arterial stiffness in type 2 diabetic patients.

Methods
Pulse wave velocity (PWV) and other parameters of arterial stiffness were assessed before and after adding empagliflozin to a traditional antidiabetic treatment in 16 consecutive T2DM outpatients folowed for 3 months. Arterial stiffness were evaluted using SphygmoCor ECEL measuring the pulse waveform of the arterial pulse moving from tha descending aorta to the femoral artery (PWV). Data obtained from the diabetic population has been compared to 16 T2DM outpatients not treated with SGLT2 inhibitors.

Results
In the two groups differences according gender distribution or duration of diabetes mellitus did not emerge. However the empagliflozin group was younger compared to controls (64.1±8.68 vs 74.45±8.13, P &lt; 0.05). Empagliflozin treatment significantly decreased HbA1c after 12 weeks of treatment (7.9±0.78 vs 7.04±1.09%, P &lt; 0.008.). After 12 weeks’ treatment, empagliflozin significantly improved PWV compared to controls not treated with SGLT2-i (ΔPWVV -0.68±1.1 vs 0.89±1,6 p &lt;0.004, P = 0.0065 with age and HbA1c as covariates). Moreover body weight significantly decreased in the empagliflozin group (86.75±16.16 vs 81.71±16.5 kg, p =0.001) compared to controls (in whom remained unchanged) as long as BMI (30.48±5.4 versus 28.75±5.66 kg/m2, P &lt; 0.002) compared to controls (in whom remained unchanged). Estimated glomerular filtration rate (eGFR) remained unchanged in the two groups during the study whereas urine Albumin to Creatinine ratio significantly improved using empagliflozin (17.8±46.8 vs 12.2±35.7 mg/mmol, P = 0.049).

Conclusion
In this ‘real clinical practice’ experience, the potential effect of empagliflozin treatment on arterial stiffness in T2DM patients was extensively investigated. Arterial stiffness was significantly decreased adding empaglifozin to the traditional treatment and this result has been obtained after 3-month. Significantly improvement in urine Albumin to Creatinine ratio might suggest an amelioration of endothelial function in those patients that could be involved in reducing arterial stiffness.
The role of sodium-glucose cotransporter 2 (SGLT2) inhibitors in epicardial adipose tissue modulation: a meta-analysis
Authors: Theofilis P , Vlachakis P K , Antonopoulos A S , Sagris M , Mantzouranis E , Sakalidis A , Oikonomou E , Siasos G , Tsioufis K , Tousoulis D 
Published: October 2024

Abstract

Introduction
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as a groundbreaking class of antidiabetic medications, renowned for their glucose-lowering effects and cardiovascular benefits. Recent studies have suggested that SGLT2 inhibitors may extend their influence beyond glycemic control to impact adipose tissue physiology, particularly within the epicardial adipose depot. Epicardial adipose tissue (EAT), an actively secretory organ surrounding the heart, has been implicated in the modulation of cardiovascular risk.

Purpose
This meta-analysis aims to systematically review and synthesize existing literature on the effects of SGLT2 inhibitors on epicardial adipose tissue.

Methods
We performed a literature search for studies assessing epicardial adipose tissue before and after treatment with a SGLT2 inhibitor compared to a control group. We excluded reviews, editorials, case reports/case series, and studies that did not use SGLT2 inhibitors or did not have a control group for comparison. The main outcome of interest was the change in EAT volume/thickness at follow-up. Effect sizes are presented as standardized mean difference (SMD) with their corresponding 95% confidence intervals (CIs) and were pooled based on a random-effects model. The leave-one-out sensitivity analysis was used for further validation of the findings. Publication bias was assessed by funnel plot inspection and egger’s regression test.

Results
The literature search yielded 49 results. After application of the exclusion criteria, a total of 6 studies were selected for data extraction and inclusion in the meta-analysis. Accordingly, we detected that treatment with an SGLT2 inhibitor was associated with decreased EAT volume/thickness (SMD -1.79, 95% CI -2.91 to -0.66, p&lt;0.01). There was substantial between-study heterogeneity (I2: 94%, p&lt;0.01). Results remained robust even after exclusion of any single study. Funnel plot inspection and egger’s regression test did not indicate the presence of publication bias.

Conclusion
This meta-analysis suggests that SGLT2 inhibitors use is associated with a reduction in EAT volume/thickness, posing as a potential mechanism of their beneficial effects in heart failure outcomes.Figure
All cause mortality in people with type 2 diabetes using SGLT-2 inhibitors compared to DPP4 inhibitors using the danish registries
Authors: Yazdanfard P , Soerensen K , Pedersen-Bjerregaard U , Andersen M , Zareini B , Torp-Pedersen C 
Published: October 2024

Abstract

Background
The SGLT-2 inhibitors outcome trials such as EMPA-REG have had significant impact on the treatment and management of patients with type 2 diabetes. Using real world danish data simulating EMPA-REG criteria can demonstrate the efficacy of SGLT-2 in real world clinical settings.

Aim
The purpose of this study is to evaluate the efficacy of SGLT-2 in reducing all-cause mortality in people with type 2 diabetes (T2D) over a 5-year period, using real world data. We compared all cause mortality between those prescribed SGLT-2 and DPP4 inhibitors in a population resembling the EMPA-REG trial. DPP4 is selected as a comparator to SGLT-2 given it is known to be neutral with regards to cardiovascular disease (CVD).

Methods
Individuals were identified using Danish nationwide registries. This estimate was performed using in/exclusion criteria from EMPA-REG. We defined time zero as the first date the patient redeems either SGLT-2/DPP4. Individuals &gt;=50 years of age with verified T2D and established CVD were included. CVD included myocardial infarctions, ischemic heart disease, stroke and heart failure. Individuals were only included if they had Hba1c at baseline &gt; 53 mmol/mol (7.0%) The primary endpoint was all cause mortality. Survival was estimated using a Kaplan-Meier estimator in both arms. P values of less than 5% are considered significant.

Results
A total of 150.313 patients were identified to be on either DPP4-inhibitors or SGLT2 between 2012 and 2022. After applying EMPA-REG inclusion and exclusion criteria 15.461 patients remained (8518 on DPP4 and 6943 on SGLT2). The 5 year survival rate of SGLT2 and DPP4 was 0.780 and 0.657 respectively (p-value&lt;0.0001).

Conclusion
In conclusion, we demonstrate, using EMPA-REG trial criteria in real-world data based on Danish nationwide registries, that five year mortality of people with T2D treated with SGLT-2 inhibitor was lower than those treated with DPP4 inhibitor.
A prospective analysis of the efficacy and safety of ethacizine during premature atrial contractions and premature ventricular contractions
Authors: Kuridze N , Etsadashvili K , Minadze E 
Published: October 2024

Abstract

Background
Ethacizine, a class Ic antiarrhythmic agent, is prescribed for managing severe or refractory supraventricular and ventricular arrhythmias, including premature atrial (PACs) and ventricular contractions (PVCs). Despite its use, there is a lack of substantial research exploring the therapeutic effects of ethacizine at present.

Purpose
The study evaluated the efficacy and safety of ethacizine in addressing PACs and PVCs, in cases where other antiarrhythmic medications proved ineffective.

Methods
We performed a prospective analysis of ethacizine treatment (50 mg. b.i.d.) for early (30-45 days) and late periods (150-210 days), in male (n=58; 59.2%) and female (n=40; 40.8%) patients aged ≥ 18 years (18-72 y.o; mean age 45 years), with 46 cases of PACs and 52 cases of PVCs, who had previously been treated with another antiarrhythmic medication (bisoprolol, metoprolol, sotalol, verapamil, amiodarone, or propafenone) and had not achieved the target rate of extrasystoles (≤1000/24h).

Results
The findings reveal a substantial decrease in the mean parameters of PACs during both, the early period (initial 6877 ± 2432, following 761 ± 341); (88,9%); t([45]) = [13,336], p = [&lt; .001) and the late period (initial 6877 ± 2432, following 574 ± 294); (91,7%); t([45]) = [15,124], p = [&lt; .001). The quantitative reduction in PACs reached a maximum of 93.8% in the early period (19406 PACs □ 1211 PACs) and 94.3% in the late period (19406 PACs □ 1105 PACs). The mean parameters of PVCs in the early period experienced a significant reduction (initial 3205 ± 1145, following 550 ± 194); (82,8%); t([51]) = [8,284], p = [&lt; .001). Similarly, the mean PVC values in the late period exhibited a noteworthy decrease (initial 3205 ± 1145, following 490 ± 181); (84,8%); t([51]) = [8,553], p = [&lt; .001). For PVCs, the maximum effect observed in the early period was 94.8% (18929 PVCs □ 989 PVCs), and in the late period, it reached 95% (18929 PVCs □ 950 PVCs). The target rate in the late period (≤1000/24h.) for PACs reached 89%, and for PVCs - 86% (Figure 1). Adverse effects were noted in a mere four subjects (4%). These events manifested as 2nd-degree AV block (Mobitz 1), sustained ventricular tachycardia, asymptomatic nonsustained polytopic ventricular tachycardia, and asymptomatic transient ST-segment elevation observed through 24-hour ECG holter monitoring.

Conclusion
A prospective study on ethacizine treatment (50 mg. b.i.d.) confirmed its effectiveness and safety in reducing PACs and PVCs. It demonstrated a sustained reduction in extrasystole occurrences for an extended period, achieving the target rate with minimal side effects. Ethacizine merits consideration for addressing extrasystolic arrhythmia, particularly in cases where other antiarrhythmic medications prove ineffective.Results of the study
Antithrombotic strategies after cryptogenic stroke: a systematic review, pairwise, and network meta-analysis of randomized controlled trials
Authors: Abuelazm M , Mazen A M , Ali H T , Nazir A , Ayyad M , Ramadan S , Tanashat M , Abouzid M , Abdelazeem B 
Published: October 2024

Abstract

Background
No definite etiology is identified in 30-40% of ischemic stroke cases, which is known as cryptogenic stroke. Several antithrombotic strategies have been investigated for cryptogenic stroke management; however, the optimal strategy remains unknown.

Purpose
We aim to assess the efficacy and safety of oral anticoagulants (OACs) versus aspirin, and the comparative efficacy and safety of different OACs after cryptogenic stroke.

Methods
A systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) obtained from PubMed, Embase Cochrane, Scopus, and WOS until February 2024. We used the fixed-effects model to report dichotomous outcomes using a risk ratio (RR), with a 95% confidence interval (CI). Analysis was conducted using R, version 4.2.0.

Results
Seven RCTs with 15.240 patients were included. In pairwise analysis, there was no difference between OACs and aspirin regarding all-cause mortality (RR: 1.13, CI [0.89, 1.43], P= 0.33) and stroke recurrence (RR: 0.93, CI [0.82, 1.07], P= 0.31). However, OACs were associated with a significantly increased incidence of major bleeding (RR: 1.6, CI [1.24, 2.05], P= 0.01), with no difference regarding the incidence of intracranial hemorrhage (RR: 1.09, CI [0.3, 3.97], P= 0.9). Moreover, in network analysis, none of the OACs showed a significant efficacy in preventing all-cause mortality and stroke recurrence compared to aspirin. However, only rivaroxaban significantly increased the incidence of major bleeding (RR: 2.69, CI [1.67, 4.33]).

Conclusion
OACs did not protect against stroke recurrence or decrease the incidence of all-cause mortality but increased the incidence of major bleeding in patients with cryptogenic stroke.