bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sodium-glucose co-transporter-2 inhibitors and the risk of major arrhythmias: a meta-analysis of the cardiovascular and renal outcome trials
Authors: Boulmpou A , Patoulias D , Teperikidis E , Papadopoulos C E , Sarafidis P , Doumas M , Fragakis N , Pagourelias E , Vassilikos V 
Published: October 2021

Abstract

Background
Type 2 diabetes mellitus is closely associated with cardiovascular disease and evidence already exists on its arrhythmogenic action. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a unique class of oral antidiabetic medications which recently attracted attention for reducing the total risk of major adverse cardiovascular events in a series of recent, large placebo-controlled randomized clinical trials (RCTs). Dapagliflozin and empagliflozin additionally seem to improve survival and outcomes in patients with heart failure with reduced ejection fraction (HFrEF), irrespective of the presence of diabetes mellitus. Whether antidiabetic treatment with sodium-glucose co-transporter inhibitors could reduce the arrhythmic burden in diabetic patients still is to be clarified.

Purpose
The purpose of the present meta-analysis was to report the impact of SGLT2i on the risk for several types of cardiac arrhythmias, pooling data from all relevant cardiovascular and renal outcome, placebo-controlled, RCTs, comparing SGLT2i to placebo.

Methods
We searched PubMed for all available cardiovascular and renal outcome RCTs utilizing SGLT2i, along with grey literature sources. We sought to determine the risk of the following arrhythmias/cardiac disorders with the use of SGLT2i versus placebo: atrial fibrillation, atrial flutter, supraventricular tachycardia, ventricular tachycardia, ventricular fibrillation, ventricular extrasystoles, sinus bradycardia, sinus node dysfunction, second degree atrioventricular block, complete atrioventricular block.

Results
We extracted relevant data from 8 trials (5 dedicated cardiovascular outcome trials, 2 dedicated renal outcome trials, 1 trial enrolling patients with HFrEF), pooling data in a total of 55,966 patients. SGLT-2i treatment compared to placebo produced a significant reduction in the risk of atrial fibrillation equal to 21% (RR=0.79, 95% CI: 0.67–0.93, I2=0%) (Figure 1). A non-significant reduction in the risk of atrial flutter equal to 9% (RR=0.91, 95% CI: 0.64–1.29, I2=0%) was also observed with SGLT2i (Figure 2). No significant effect on the rest major arrhythmias was observed.

Conclusions
Antidiabetic therapy with SGLT2i seems to hold a significant impact on antiarrhythmic burden in type 2 diabetes mellitus, reducing the risk of atrial fibrillation development.

Funding Acknowledgement
Type of funding sources: None. Figure 1Figure 2
Meta-analysis of cardiovascular outcome trials assessing the cardiovascular efficacy and safety of dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes mellitus
Authors: Patoulias D , Boulmpou A , Teperikidis E , Katsimardou A , Siskos F , Tranidou A , Nikolaidis A , Mouselimis D , Doumas M , Papadopoulos C E , Vassilikos V 
Published: October 2021

Abstract

Background
Type 2 diabetes mellitus (T2DM) represents an independent risk factor for the development of cardiovascular disease, which accounts for half of deaths among the affected patients. Patients with T2DM experience higher incidence of vascular interventions compared to high-risk patients without T2DM or cardiovascular disease at baseline, underscoring the necessity for targeted therapeutic interventions. Dipeptidyl peptidase-4 (DPP-4) inhibitors constitute a safe treatment option with fair glycemic efficacy in T2DM whose cardiovascular efficacy has been doubted over recent years. A series of randomized controlled trials (RCTs) addressing cardiovascular outcomes with DPP-4 inhibitors have been recently published, while previous meta-analyses failed to show any cardiovascular benefit with their use in patients with T2DM.

Purpose
The purpose of our analysis was to report the impact of antidiabetic treatment with DPP-4 inhibitors on different cardiovascular efficacy outcomes.

Methods
We searched PubMed for all published RCTs assessing cardiovascular outcomes after antidiabetic treatment with DPP-4 inhibitors. We extracted data related to the following efficacy outcomes: fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, hospitalization for heart failure, hospitalization for unstable angina, hospitalization for coronary revascularization and cardiovascular death.

Results
We pooled data from a total of 6 trials in a total of 52,520 patients. Antidiabetic treatment with DPP-4 inhibitors did not significantly affect any of the prespecified cardiovascular efficacy outcomes. More specifically, DPP-4 inhibitors compared to control led to a non-significant increase in the risk for fatal and non-fatal myocardial infarction (RR=1.02, 95% CI: 0.94–1.11, I2=0%), hospitalization for heart failure (RR=1.09, 95% CI: 0.92–1.29, I2=65%) and cardiovascular death (RR=1.02, 95% CI: 0.93–1.11, I2=0%), as shown in figures 1a, 1c and 1f. In addition, DPP-4 inhibitors produced a non-significant decrease in the risk for fatal and non-fatal stroke (RR=0.96, 95% CI: 0.85–1.08, I2=0%) and coronary revascularization (RR=0.99, 95% CI: 0.90–1.09, I2=0%), as depicted in figures 1b and 1e. Finally, DPP-4 inhibitors demonstrated a neutral effect on the risk for hospitalization due to unstable angina (RR=1.00, 95% CI: 0.85–1.18, I2=0%), as shown in figure 1d.

Conclusions
Antidiabetic treatment with DPP-4 inhibitors does not seem to confer any significant cardiovascular benefit for patients with T2DM.

Funding Acknowledgement
Type of funding sources: None. Figure 1
Influence of cardiovascular drugs on the efficacy and safety of dapagliflozin in patients with type 2 diabetes mellitus in the DECLARE-TIMI 58 trial
Authors: Oyama K , Raz I , Cahn A , Goodrich E , Bhatt D , Leiter L , McGuire D , Wilding J , Gause-Nilsson I , Mosenzon O , Sabatine M , Wiviott S 
Published: October 2021

Abstract

Background
In DECLARE-TIMI 58, the sodium glucose co-transporter 2 inhibitor (SGLT2i) dapagliflozin reduced the risk of the composite of cardiovascular (CV) death or hospitalization for heart failure (HHF) in a broad range of patients with type 2 diabetes mellitus (T2DM). SGLT2i are known to have diuretic and anti-hypertensive effects. However, whether concomitant CV drugs influence the efficacy and safety of dapagliflozin in these populations is less well known.

Purpose
We examined whether dapagliflozin consistently reduced the risk of CV outcomes and whether the safety of dapagliflozin was similar with or without the concurrent use of various CV drugs.

Methods
DECLARE–TIMI 58 was a randomized trial of dapagliflozin versus placebo in patients with T2DM and either atherosclerotic cardiovascular disease (ASCVD) or multiple risk factors for CV disease followed for a median of 4.2 years. We stratified patients by the use of CV drugs at baseline commonly used for heart failure: angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers (ACEi/ARB), beta-blockers, diuretics, and mineralocorticoid receptor antagonists (MRA). Efficacy outcomes of interest were the composite of CV death/HHF and HHF alone. We used the Cox proportional-hazard model for these analyses.

Results
Of 17,160 patients, 13,950 (81%) used ACEi/ARB, 9,030 (53%) used beta-blockers, 6,967 (41%) used diuretics, and 762 (4%) used MRA at baseline. All were balanced by randomized treatment groups. Patients using CV drugs at baseline had a greater prevalence of atherosclerotic risk factors and established CV disease than those without. Dapagliflozin consistently reduced the risk of CV death/HHF regardless of the use of CV medications (Figure). For HHF alone, similar results were seen with no significant interactions for any of the classes. There were no significant treatment interactions by the concomitant use of any of CV drugs for adverse events including symptoms of volume depletion or acute kidney injury.

Conclusions
In this analysis from the DECLARE–TIMI 58 trial, dapagliflozin consistently reduced the risk of CV death/HHF and HHF alone irrespective of the concurrent use of various CV drugs without any treatment interaction for key safety events.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): The DECLARE–TIMI 58 trial was supported by AstraZeneca.
Frequency of antiplatelet therapy in coronary artery disease. Data from the disease management programme CAD
Authors: Hagen B , Griebenow R 
Published: October 2021

Abstract

Background
Physicians always aim to improve their patients' health and consequently also improve community health. Continued medical education (CME) should be designed to support this goal and thus not only provide knowledge transfer, but also influence clinical decision-making and close performance gaps. However, the relative weight of CME in this process needs to be determined.

Purpose
Main purpose of the study was to analyse APT prescription rates and differences between subgroups of patients in a disease management programme (DMP) for coronary artery disease (CAD).

Methods
In a retrospective study we analysed prescription rates for APT in 254,932 CAD patients (male: 64.4%), treated in a total of 3,405 practices in 2019 in a DMP in the region of North Rhine, Germany, to delineate the potential for change by CME to further improve community health. Analyses were run for the whole study population stratified by sex as well as for subgroups of patients suffering from myocardial infarction / acute coronary syndrome (MI/ACS), or who have been treated with percutaneous coronary intervention (PCI) or bypass surgery. Subgroup differences were analysed in a logistic regression model.

Results
Patients mean age was 72.7±11.2 years (mean ± 1SD), mean duration of DMP participation was 7.2±4.7 years and mean cumulative number of DMP visits was 27±17. APT prescription rates were 85.0% in male and 78.8% in female CAD patients. In subgroups of male CAD patients APT prescription rates were between 89.7% and 92.8%, in the same subgroups of female CAD patients the corresponding rates were between 87.8% and 92.0%. Rates for a missing APT prescription per practice were between 0.0044% and 0.0062% for male and female CAD patients respectively. Rates for a missing APT prescription per practice and DMP visit were 0.0002% for both sexes. In a multivariate model significant positive predictors of APT prescription were male sex (OR=1.37, 95% CI: 1.34–1.40), age ≥76 yrs (OR=1.11, 95% CI: 1.08–1.14), participation in DMP ≥4 and &lt;10 yrs (OR=1.19, 95% CI: 1.16–1.22), MI/ACS (OR=1.14, 95% CI: 1.08–1.20), PCI (OR=1.97, 95% CI: 1.88–2.06) and bypass surgery (OR=1.14, 95% CI: 1.08–1.21).

Conclusion
Our study demonstrates that a multifaceted intervention, like a DMP, can achieve high attainment rates for APT in CAD. To describe the benchmark for CME to further improve attainment rates, consideration of absolute numbers of eligible patients per practice or physician is probably more appropriate than expression of performance as percentage values. This is especially true if attainment rates show substantial variations between subgroups, if subgroups show substantial variation in size, if attainment rates are already in the order of magnitude of 80% or higher, and if there are disparities in the evidence base underlying treatment recommendations related to subgroups.

Funding Acknowledgement
Type of funding sources: None.
Aspirin vs. P2Y12 inhibitors with anticoagulation therapy for atrial fibrillation: insights from the AFIRE trial
Authors: Fukaya H , Ako J , Yasuda S , Kaikita K , Akao M , Matoba T , Nakamura M , Miyauchi K , Hagiwara N , Kimura K , Hirayama A , Matsui K , Ogawa H ,   the AFIRE Investigators
Published: October 2021

Abstract

Background
Patients with coronary artery disease (CAD) and atrial fibrillation (AF) can be treated with multiple antithrombotic therapies including antiplatelets and oral anticoagulants; however, this has the potential to increase bleeding risk.

Purpose
This sub-analysis aimed to evaluate the efficacy and safety of P2Y12 inhibitors and aspirin in patients also receiving oral anticoagulant therapy.

Methods
We evaluated patients from the Atrial Fibrillation and Ischemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease (AFIRE) trial who received combination therapy (rivaroxaban plus a single antiplatelet agent). The choice of antiplatelets was left to the physician's discretion. The primary efficacy endpoint was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, and death from any cause. The primary safety endpoint was major bleeding according to the International Society on Thrombosis and Haemostasis criteria.

Results
A total of 1,075 patients were included (P2Y12 inhibitor group, n=297; aspirin group, n=778). Approximately 60% of patients were administered proton pump inhibitors (PPIs), and there was no significant difference in PPI use in the P2Y12 inhibitor and aspirin groups. Regarding the primary efficacy endpoint, there was no significant difference between the P2Y12 inhibitor and aspirin groups (hazard ratio, 1.31; 95% confidence interval, 0.88–1.94; p=0.178). Likewise, the primary safety endpoint was not different between the groups (hazard ratio, 0.79; 95% confidence interval, 0.43–1.47; p=0.456). In the detailed subgroup analysis, there were no differences in the efficacy and safety endpoints.

Conclusions
There were no significant differences between P2Y12 inhibitors and aspirin in cardiovascular events in patients with AF and stable CAD taking rivaroxaban in the chronic phase.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): The Japan Cardiovascular Research Foundation based on a contract with Bayer Yakuhin, Ltd. Summary of this study
Antiplatelet therapy and outcome in patients with COVID-19. Results from a multi-center international prospective registry (HOPE-COVID19)
Authors: Santoro F , Vitale E , Nunez Gil I , Guerra F , El-Battrawy I , Brunetti N D 
Published: October 2021

Abstract

Background
No standard therapy is currently recommended for Corona-virus-19 disease (COVID-19). Autopsy studies showed high prevalence of platelet-fibrin rich micro-thrombi in several organs. Aim of the study was to evaluate safety and efficacy of antiplatelet therapy (APT) in COVID-19 hospitalized patients and its impact on survival.

Methods
7824 consecutive patients with COVID-19 were enrolled in a multicenter-international prospective registry (HOPE-COVID19). Clinical data and in-hospital complications were recorded. AP regimen, including aspirin and other antiplatelet drugs, was obtained for each patient.

Results
During hospitalization 730 (9.3%) patients received AP drugs with single (93%, n=680) or dual APT (7%, n=50). Patients treated with APT were older (73±12 vs 62±17 years, p&lt;0.01), more frequently male (70% vs 64%, p&lt;0.01) and had higher prevalence of diabetes (39.5% vs 17%, p&lt;0.01).
Patients treated with APT showed no differences in terms of in-hospital mortality (18% vs 19%, p=0.64, Log Rank p=0.23), need of invasive ventilation (8.7% vs 8.5%, p=0.88) and bleeding (2.1% vs 2.4%, p=0.43); However, after excluding patients treated only with anticoagulation, APT was associated with lower mortality rates (Log Rank p&lt;0.01, relative risk 0.79, 95% CI 0.70–0.94) (Figure 1).
At multivariable analysis including age, gender, diabetes, hypertension, respiratory failure, pre-hospital therapy with antiplatelet drugs, in-hospital APT, and anticoagulation therapy, in-hospital APT was associated with a lower mortality risk (relative risk 0.29, 95% CI 0.22–0.38, p&lt;0.001).

Conclusions
APT during hospitalization for COVID-19 could be associated with lower mortality risk without increased risk of bleeding. Randomized trials are needed to confirm these preliminary data.

Funding Acknowledgement
Type of funding sources: None. Figure 1
Calcium channel blockers and beta-blockers could increased mortality of patients with COVID-19
Authors: Esteban-Lucia L , Zambrano Chacon M A , Venegas Rodriguez A M , Devesa-Arbiol A , Gonzalez-Rodriguez M , Maure-Blesa L , Avila-Barahona P , Pello-Lazaro A M , Gonzalez-Lorenzo O , Kallmeyer-Mayor A M , Fernandez-Roblas R , Villar-Alvarez F , Tunon J , Acena Navarro A , Franco-Pelaez J A 
Published: October 2021

Abstract

Background
High incidence of cardiovascular events has been described among patients with COVID-19 and since the beginning of the pandemic concerns have been expressed with medical treatments for cardiovascular disease, as they could contribute to the severity of illness in patients with COVID-19. We aim to analyze the effect of chronic treatment with calcium channel blockers and beta-blockers on COVID 19 severity in a Spanish cohort during the 2020 pandemic.

Methods
Observational study including all consecutive patients (≥40 years old) diagnosed with SARS-CoV-2 through PCR in the microbiology laboratory of our hospital, from March 2nd to 20th 2020. Clinical characteristics and drugs were recorded. The Primary end-point (PE) was all-cause death and the secondary end-point (SE) was the combined of death or the need for orotracheal intubation until 30 days of infection symptoms onset.

Results
We included 704 patients in our study. Baseline characteristics of the overall cohort can be seen in the table. Median age was 61 years old (IQR 52.9–72.9); 52.7% were female. 34.7% and 12.6% had hypertension and diabetes respectively. After a median follow-up of 111.5 days, 58 patients (8.2%) needed orotracheal intubation and 133 patients (18.9%) died. Secondary endpoint (all-cause death or need for orotracheal intubation) was reached by 164 patients (23.3%). The table described clinical differences between survivors and deceased patients.
After multivariate Cox modeling, age, male gender, diabetes, previous lung disease, BMI and the chronic intake of calcium channel blockers (HR 1.74, 95% CI (1.11–2.75), p=0.016) and beta-blockers (HR 1.71, 95% CI (1.07–2.76), p=0.026) were independently related with mortality. Other cardiovascular drugs (Antiplatelets, anticoagulants, diuretics, mineralcorticoid-receptor antagonists, angiotensin-receptor blockers, angiotensin-converting enzyme inhibitors and statins) did not influence survival after SARS-CoV 2 infection (Figure).
The secondary outcome was reached by 164 patients (23.3%) and chronic treatment with calcium channel blockers remains as an independent predictor of mortality (HR 1.55, 95% CI (1.01–2.37), p=0.044).

Conclusions
Chronic treatment with calcium channel blockers and beta-blockers are independent predictors of mortality after SARS-CoV-2 infection. Further studies are needed to confirm these results.

Funding Acknowledgement
Type of funding sources: None. Description of studied populationOdds-ratio and CI for all-cause death
Factors related to hospital readmission of patients with acute coronary syndrome: a prospective cohort study
Authors: Lopes J , Russomanno L L R , Lopes C T L 
Published: October 2021

Abstract

Background
Hospital readmissions of patients with acute coronary syndrome (ACS) are frequent and associated with poor clinical outcomes and increased costs to the healthcare services. Identifying factors that might be associated with hospital readmission is important to support preventive interventions.

Purpose
To identify factors related to hospital readmission of patients with ACS.

Methods
A prospective cohort study. Patients hospitalized with ACS for the first time were included in the study. The outcome, hospital readmission for ACS, was assessed at 30 days, 6 months and 1 year after index discharge. Modifiable cardiovascular risk factors (arterial hypertension, dyslipidemia, diabetes mellitus, smoking, degree of addiction to smoking, use of alcohol, physical inactivity, obesity, stress, depression, excessive daytime sleepiness, obstructive sleep apnea syndrome, hormone replacement) and non-modifiable risk factors (age, race, family history of coronary heart disease) were evaluated as potential predictors of the outcome. Other variables that might have contributed to readmission were also included: marital status, family income, occupation, education, adherence to medication and type of treatment (clinical, percutaneous coronary intervention or coronary artery bypass grafting). The association between hospital readmission and potential predictors was assessed using the Log-Rank test and Cox's simple regression model. Factors whose associations had a p-value of less than 0.20 in the simple regression and other variables of clinical interest were evaluated in a Cox multiple regression model, with p&lt;0.05 considered significant. The study was approved by two Research Ethics Committees.

Results
216 patients were included and the incidence of readmission was 15.7%. Most of the patients were male, white, married, had an income between two and four minimum wages, and a mean age of 60 years. Half of the patients had high adherence to medication. The cardiovascular risk factors identified in most patients were sedentary lifestyle (79.6%), arterial hypertension (63.4%) and obstructive sleep apnea (51.9%). The only independent predictor for readmission was surgical treatment (p=0.026).

Conclusions
Participants had several cardiovascular risk factors and the predictor of hospital readmission was surgical treatment. Identifying the predictive factors of a given population helps nurses in planning and guiding hospital discharge.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Conselho Nacional de Desenvolvimento Científico e Tecnolόgico (CNPq)