bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical impact of switching or continuation of apixaban or rivaroxaban among patients with non-valvular atrial fibrillation
Authors: Deitelzweig S , Kang A , Jiang J , Gao C , Luo X , Atreja N , Han S , Cheng D , R S , Lip G 
Published: November 2023

Abstract

Background
Numerous studies have demonstrated varied clinical outcomes with initiation of different direct oral anticoagulants (DOACs) among patients with non-valvular atrial fibrillation (NVAF). Although switching of DOACs either for medical or non-medical reasons occurs among some NVAF patients in real-world clinical practice, there has been a lack of evidence on the clinical outcomes of those switchers.

Purpose
Assess the risk of stroke/systemic embolism (SE) and major bleeding (MB) among NVAF patients who switched from apixaban therapy to rivaroxaban or switched from rivaroxaban therapy to apixaban.

Methods
This retrospective study identified NVAF patients who initiated the most commonly used DOACs (apixaban or rivaroxaban) between 01 Jan 2013 and 31 December 2021 using a large US administrative claims database (Optum’s de-identified Clinformatics® Data Mart Database) representing patients in commercial or Medicare Advantage insurance plans. Patients who switched from one DOAC to the other within 30 days before or 90 days after discontinuation of initial DOAC and patients who continued receiving the initial DOAC were included. For switchers, the switch date was the index date. For continuers, a hypothetic index date was randomly assigned based on the distribution of the time from initial DOAC prescription to the switch date in the switchers group. Two final cohorts (switchers and continuers) within apixaban initiators and rivaroxaban initiators were further propensity score matched (PSM) based on pre-index characteristics up to a 1:5 ratio. The risks of stroke/SE and MB after the index date were compared between patients who continued the initial DOAC and patients who switched to the other DOAC.

Results
There were 167,868 apixaban initiators and 65,888 rivaroxaban initiators. After PSM, 2,884 patients who switched from apixaban to rivaroxaban were matched to 14,296 patients who continued apixaban, and 2,853 patients who switched from rivaroxaban to apixaban were matched to 13,330 patients who continued rivaroxaban. Patient characteristics were balanced between the continuers and switchers for both apixaban and rivaroxaban initiators. Patients who switched from apixaban to rivaroxaban were associated with a higher risk of stroke/SE (Hazard Ratio (HR):1.54, 95% Confidence Interval (CI): 1.06-2.24) and MB (HR: 1.73, 95% CI: 1.40-2.14) than those who continued apixaban. Patients who switched from rivaroxaban to apixaban were associated with a similar risk of stroke/SE (HR:0.75, 95% CI: 0.45-1.24) and a lower risk of MB (HR:0.58, 95%CI: 0.44-0.76) compared to those who continued rivaroxaban.

Conclusion
Bleeding outcomes associated with switching or continuation of apixaban or rivaroxaban in NVAF patients were consistent with existing evidence supporting a better safety profile for apixaban vs rivaroxaban.
Acetylsalicylic acid challenge or desensitization in sensitive patients with cardiovascular disease
Authors: Galli M , Cortellini G , Raiteri A , Lotrionte M , Fabio F , Romano A 
Published: November 2023

Abstract

Background
The use of acetylsalicylic acid (ASA) is problematic in subjects with histories of hypersensitivity reactions (HRs) to it or with cross-reactive types of nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity.

Purpose
To evaluate the efficacy of low-dose ASA challenge (LDAC) and desensitization to allow ASA therapy at an antiplatelet dose in patients with atherosclerotic cardiovascular disease (ASCVD) or multiple related risk factors and histories of HRs to ASA or ≥ 2 chemically unrelated NSAIDs.

Methods
We studied prospectively all patients with such histories and ≥ 3 risk factors for ASCVD (group I), chronic coronary syndrome (CCS, group II), and acute coronary syndrome (ACS) with indication for ASA desensitization (group III). Patients from groups I and II underwent LDACs (cumulative dose of 110 mg), while those from group III were desensitized (cumulative dose of 100.1 mg).

Results
We evaluated 103 patients: 62 from group I, 24 from group II, and 17 from group III. Eighty-two of the 86 patients from the first two groups underwent LDACs and 2 reacted. Subsequently, 22 (27.5%) of the 80 patients with negative LDACs were administered dual antiplatelet therapy with ASA after successful percutaneous coronary interventions, thus sparing desensitizations. The remaining 4 patients with CCS and all 17 patients from group III were successfully desensitized.

Conclusions
LDAC proved to be a safe and reliable diagnostic tool for identifying patients with histories of HRs to ASA or ≥ 2 different NSAIDs who can tolerate ASA at antiplatelet doses. Routine LDAC is advisable in all patients at high risk for ASCVD or with CCS who report HRs to ASA or ≥ 2 NSAIDs. ASA desensitization remains a safe and effective option in patients with ACS.
Superiority of CS585 as a selective prostacyclin receptor agonist in prevention of thrombosis
Authors: Stanger L , Lambert S , Yamaguchi A , Yalavarthi P , Dahlof B , Bergh N , Holinstat M 
Published: November 2023

Abstract

Background
A major challenge with development of new targets for antithrombotic treatment is the sustained effect on the platelet and the target selectivity. While increasing cAMP in the platelet through activation of the prostacyclin (IP) receptor represents a viable antiplatelet target for prevention of thrombosis, current IP receptor agonists lack stability and selectivity. Development of a selective IP receptor agonist that is stable in the blood and selective for the IP receptor would represent a new approach for prevention of platelet activation and thrombosis in the blood and expand the utility of IP receptor agonists which are currently used for the treatment of pulmonary arterial hypertension (PAH).

Purpose
Develop an IV and oral IP receptor agonist, CS585, with sustained activity in vivo in the blood and eliminating the off-target effects observed with other IP agonists not having selective activation of the IP receptor. These characteristics would make CS585 an attractive new therapeutic approach for limiting platelet activation and thrombosis.

Methods
We assessed platelet activation and thrombosis in human blood ex vivo and mouse models in vivo. For mouse models, platelets and fibrin were labelled and accumulation at the site of injury was measured using intravital microscopy. Thrombosis in the vessel was assessed in the laser-induced cremaster thrombosis assay. Selectivity was assessed in human blood pharmacologically using prostaglandin receptor inhibitors and in mouse with an IP receptor knockout mouse. Flow cytometry, aggregometry, and western blot techniques were used to assess selectivity.

Results
IV and oral administration of CS585 resulted in sustained inhibited clot formation and fibrin formation at the site of injury in the laser-induced cremaster arteriole thrombosis assay in wild-type mice but was unable to alter platelet function in IP knockout mice. CS585 inhibition of platelet activation was fully prevented in platelets from IP knockout mice as assessed by flow cytometry (integrin activation and granule secretion) and by VASP phosphorylation. Inhibition of human platelet activation by CS585 was inhibited by pharmacological inhibition of the IP receptor, but not by inhibition of the DP1, EP2, or EP4 receptors as assessed by aggregation, flow cytometry, and VASP phosphorylation.

Conclusions
We have shown for the ﬁrst time that CS585, a novel IP receptor agonist, not only inhibits platelet activation and clot formation, but gives sustained inhibition through multiple routes of administration in an in vivo mouse model of thrombosis. Importantly, the challenge in selectivity observed with other IP receptor agonists is not observed with CS585 supporting its development for a number of diseases in the cardiovascular system including thrombosis, VTE, secondary prevention after MI and stroke, and PAH.CS585 inhibition of thrombosis in vivoCS585 selectively signals through IP
Variability of the antithrombotic effect of acetylsalicylic acid with the administration of different dosages: reality or myth?
Authors: Lima Lopes J , Passos M , Mateus C , Fialho I , De Oliveira V , Sousa Mendes D , Roque D 
Published: November 2023

Abstract

Introduction
We rely on the antithrombotic effect of acetylsalicylic acid (ASA) in a number of pathologies, although other beneficial effects are known, such as its anti-inflammatory properties, when administered in higher doses (500mg, 1000mg per os). However, whether the anti-inflammatory effect decreases the antithrombotic potency of ASA is not known. This gap in evidence may lead to an unnecessary use of two drugs (one antithrombotic and one anti-inflammatory) that could be replaced by ASA alone. This scenario presents frequently: post-infarct pericarditis or when in doubt between non-ST segment elevation myocardial infarction vs myopericarditis. In such cases, the use of ASA could assure both antithrombotic and anti-inflammatory effects. Since the antithrombotic effect of ASA is not scientifically proved for higher doses, currently we use ASA 100mg as an antithrombotic agent and ibuprofen as an anti-inflammatory. This experimental study intends to assess whether ASA maintains its antithrombotic effect when administered in an anti-inflammatory dose.

Methods
Twenty healthy volunteers were recruited. They all had their platelet function assessed in a qualitative manner, using PFA-200 Innovance technology. The volunteers were randomized into four groups, with 5 participants each. The participants of groups 1, 2, 3 and 4 ingested ASA 100mg, 300mg, 500mg and 1000mg respectively, in a blind experiment. One hour after ingestion (peak of action), the volunteers’ platelet function was reassessed. PFA-200 evaluates platelet function through platelet occlusion time (OT), which is measured in milliseconds (ms). Normal platelet function translates into OT of 82-150ms. If the OT is higher than 150ms, the patient is anti-aggregated.

Results
Prior to ASA administration, 19/20 volunteers had OT within the reference range. Afterwards, in all four groups, volunteers reached OT &gt; 150ms, regardless of the ASA dose administered. Mean OT values for each group were 188ms [SD-23] , 205ms [SD-63], 262ms[SD-44] and 232ms [SD-47], respectively. Overall SD was 32ms.

Conclusion
ASA maintains its antithrombotic effect when administered in an anti-inflammatory dose. There is no clear correlation between the potency of antithrombotic effect and the ASA dose administered. This was a pilot study that supports the maintenance of the antithrombotic effect of ASA in higher doses, but further and larger studies are required to corroborate these results.
The effect of discontinuing long-term beta-blockers following acute myocardial infarction in optimally treated, stable patients without heart failure - a Danish, nationwide cohort study
Authors: Halili A , Holt A , Eroglu T E , Haxha S , Zareini B , Torp-Pedersen C , Bang C 
Published: November 2023

Abstract

Aims
We studied the effect of discontinuing beta-blockers following myocardial infarction in optimally treated, stable patients without heart failure.

Methods and results
Using nationwide registers, we identified first-time myocardial infarction patients treated with beta-blockers following percutaneous coronary intervention or coronary angiography.
The analysis was based on landmarks selected as 1, 2, 3, 4, and 5 years after the first redeemed beta-blocker prescription date. The outcomes included all-cause death, cardiovascular death, recurrent myocardial infarction, and a composite outcome of cardiovascular events and procedures. We used logistic regression and reported standardized absolute 5-year risks and risk differences at each landmark year. Among 21,220 first-time myocardial infarction patients, beta-blocker discontinuation was not associated with an increased risk of all-cause death, cardiovascular death, or recurrent myocardial infarction compared with patients continuing beta-blockers (landmark year 5; absolute risk difference [95% confidence interval]), correspondingly; -4.19% [-8.95%; 0.57%], -1.18% [-4.11%; 1.75%], and -0.37% [-4.56%; 3.82%]). Further, beta-blocker discontinuation within two years after myocardial infarction was associated with increased risk of the composite outcome but there was no risk difference associated with discontinuation hereafter.

Conclusion
Discontinuation of beta-blockers one year or later after myocardial infarction without heart failure was not associated with increased serious adverse events.
Impact of CYP2C19 genotype status on clinical outcomes in patients with symptomatic coronary artery disease, stroke, and peripheral arterial disease
Authors: Maas D , Willems L , Kranendonk J , Kramers C , Warle M 
Published: November 2023

Abstract

Background
Coronary artery disease (CAD), stroke, and peripheral arterial disease (PAD) are clinical manifestations of atherosclerosis. Clopidogrel is widely used for the secondary prevention of atherothrombotic events in these patients. CYP2C19 plays a pivotal role in the conversion of clopidogrel to its active metabolite. Clopidogrel-treated carriers of a CYP2C19 loss-of-function allele (LOF) may have a higher risk of new atherothrombotic events. Previous studies on genotype-guided treatment were mainly performed in CAD and showed mixed results.

Purpose
To simultaneously investigate the impact of CYP2C19 genotype status on the rate of atherothrombotic events in the most common types of atherosclerotic disease (CAD, stroke, PAD).

Methods
A comprehensive search in Pubmed, EMBASE and MEDLINE from their inception to April 8th 2022 was performed. For CAD, randomized controlled trials (RCTs) comparing genotype-guided and standard antithrombotic treatment were included. For stroke and PAD, cohort studies and post-hoc analyses of RCTs concerning the association between CYP2C19 genotype status and clinical outcomes in clopidogrel-treated patients were included. The primary efficacy endpoint was major adverse cardiovascular events (MACE) and the safety end point major bleeding. Secondary endpoints were myocardial infarction, stent thrombosis, and ischemic stroke.

Results
Forty-two studies were identified: 11 studies on CAD, 27 studies on stroke, and 4 studies on PAD. In CAD, genotype-guided therapy significantly reduced the risk of MACE (RR 0.60, 95% CI 0.43 – 0.83), myocardial infarction (RR 0.53, 95% CI 0.42 – 0.68), and stent thrombosis (RR 0.64, 95% CI 0.43 – 0.94) compared to standard antithrombotic treatment. The rate of major bleeding did not differ significantly (RR 0.93, 95% CI 0.70 – 1.23). Most RCTs were performed in patients after percutaneous coronary intervention (9/11). In stroke, LOF carriers had a significantly higher risk of MACE (RR 1.62, 95% CI 1.24 – 2.11) and recurrent ischemic stroke (RR 2.00, 95% CI 1.49 – 2.67) compared to non-carriers. No significant differences were found in major bleeding (RR 0.90, 95% CI 0.43 – 1.89). In the 6955 patients with symptomatic PAD treated with clopidogrel in the EUCLID trial, no differences in MACE or major bleeding were found between LOF carriers and non-carriers. In three smaller studies on patients with PAD treated with clopidogrel after endovascular therapy, CYP2C19 genotype status was significantly associated with atherothrombotic events.

Conclusion
The available evidence in PAD is too limited to draw meaningful conclusions. In stroke patients, LOF carriers treated with clopidogrel had a higher risk of MACE and recurrent stroke. Genotype-guided treatment significantly decreased the rate of atherothrombotic events in patients with CAD, especially after PCI.
Empagliflozin restores autophagy and ameliorates ponatinib-induced cardiomyocyte death
Authors: Madonna R , Ghelardoni S , Moscato S , Mattii L , Barachini S , Novo G , Zucchi R , De Caterina R 
Published: November 2023

Abstract

Background
The tyrosine kinase inhibitor ponatinib has proven cardiovascular toxicity, for which no counteractive treatment is available at the moment. Sodium-glucose cotransporter type 2 (SGLT-2) inhibitors are approved drugs treat patients with chronic heart failure of different aetiologies. They play direct anticancer activity in SGLT2-expressing cancer cells, independent of glucose metabolism and through inhibition of oxidative phosphorylation. Ongoing studies are now testing empagliflozin (EMPA) in the prevention of left ventricular dysfunction in patients receiving high cumulative doses of anthracyclines.

Aims
To determine the effect of EMPA on cardiomyocytes in an in vitro model of PON-induced cardiac toxicity, and to assess underlying cardioprotective mechanisms.

Methods and Results
We exposed cardiomyocytes to PON (1.7 nM) or vehicle (DMSO) in the presence or absence of EMPA (100 and 500 nM) for 24 hours. Compared with vehicle, incubations with PON significantly reduced cell viability at 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, decreased autophagic cells at immunofluorescence assay (1±0.5 vs 6±1 fluorescence intensity/total area, p=0.0006, Figure 1), and increased cell senescence (15±5 vs 4±2 β-gal positivity/tissue area, p&lt;0.02), effects all reverted by EMPA (p&lt;0.01). We observed no significant effects of PON or EMPA on formation of reactive oxygen species. Compared with vehicle, PON significantly reduced serum response factor (SRF)/serum response elements (SRE) binding activity (25±9 vs 218±15 SRE complex abundance, arbitrary units, p&lt;0.001), in parallel with a reduction in cardiac actin expression (0.32±0.06 vs 0.98±0,12 cardiac actin/GAPDH ratio, arbitrary units, p=0.001), which was reversed by EMPA (p=0.001).

Conclusion
EMPA attenuates PON cardiotoxicity by reducing senescence and enhancing autophagy, apparently independent of antioxidant mechanisms. This study suggests the design of clinical studies aimed at assessing the effects of EMPA on PON-induced cardiotoxicity.Legend to Figure 1.CON, control (vehicle, DMSO); PON, ponatinib; EMPA 100, empagliflozin 100 nM; EMPA 500, empagliflozin 500 nM
Influence of cholesterol levels on NSAID-associated risks after myocardial infarction: a nationwide population-based cohort study
Authors: Abdallah M B , Bonnesen K , Pedersen L , Sorensen H T , Schmidt M 
Published: November 2023

Abstract

Introduction
Non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat pain, fever, and inflammation, but they can increase the risk of recurrent myocardial infarction (MI), ischemic stroke, atrial fibrillation, and death in patients with MI. Consequently, the European Society of Cardiology warns against using NSAIDs in patients with manifest cardiovascular disease and in high-risk individuals, such as those with dyslipidemia. However, no study has investigated whether NSAID-associated cardiovascular risks differ according to patients’ low-density lipoprotein cholesterol (LDL-C) levels.

Purpose
To examine whether LDL-C levels influence the cardiovascular risk associated with NSAID use after first-time MI.

Methods
Using Danish health registries, we conducted a population-based cohort study of all adult patients with a first-time MI hospitalization during 2010–2020 with an LDL-C value before discharge. Based on the latest LDL-C value, we categorized patients into a low and high LDL-C group (&lt;3 vs. ≥3 mmol/L). We used multivariate Cox regression to compute adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between NSAID use (modelled in time-varying manner) and a major adverse cardiovascular event (MACE), defined as a composite of recurrent MI, ischemic stroke, and all-cause death. We repeated the analysis by changing the cut-off value for LDL-C to 1.8 and 1.4 mmol/L.

Results
We followed 50,573 patient with a first-time MI for a mean of 3.5 years (66% males, median age of 68 years. During NSAID use, 521 patients experienced a MACE: 312 in the low LDL-C group and 209 in the high LDL-C group. The HRs for MACE comparing NSAID use with non-use were 1.21 (1.11–1.32) overall, 1.19 (1.06–1.33) in the low LDL-C group, and 1.23 (1.07–1.41) in the high LDL-group. The HRs in the low and high LDL-C groups were 1.09 (0.88–1.34) vs. 0.94 (0.74–1.19) for recurrent MI, 0.97 (0.66–1.41) vs. 1.27 (0.86–1.87) for ischemic stroke, and 1.22 (1.07–1.39) vs. 1.54 (1.30–1.83) for all-cause death. Changing the cut-off value for LDL-C to 1.8 and 1.4 mmol/L showed consistent results.

Conclusion
In patients with a first-time MI, NSAID use was associated with an increased risk of MACE. The LDL-C level did not influence the association between NSAID use and MACE, but it might influence the association between NSAID use and all-cause death. Thus, healthcare providers should be mindful of the increased cardiovascular risk associated with NSAID use in patients with previous MI, regardless of LDL-C values.
Effects of nurse-led self-care interventions on health outcomes among people with heart failure: a systematic review and meta-analysis
Authors: Huang Z , Chair S , Liu T , Gao R 
Published: November 2023

Abstract

Background
Suboptimal self-care is associated with adverse patient outcomes. Nurse-led self-care interventions, strategies used to support self-care, are essential to heart failure management. However, research evidence of the effects of nurse-led heart failure self-care interventions on patient outcomes (quality of life, anxiety, symptom burden, sleep quality, healthcare service utilization, and mortality) is scant.

Purpose
To evaluate the effects of nurse-led self-care interventions on quality of life, anxiety, symptom burden, sleep quality, healthcare service utilization, and mortality in people with heart failure.

Methods
Six databases (MEDLINE, Embase, Web of Science, CENTRAL, CINAHL, and PsycINFO) were searched from the inception to December 2022 to identify eligible studies. Randomized controlled trials estimating the effectiveness of nurse-led self-care interventions on quality of life, anxiety, symptom burden, sleep quality, healthcare service utilization, and mortality in people with heart failure published in English were included. The risk of bias of included studies was assessed using RoB 2.0. We conducted data syntheses by means of R software and graded the quality of the evidence using the GRADE approach.

Results
Twenty-five studies with 2746 subjects were included. Our findings demonstrated that compared to the controls, nurse-led self-care interventions improved quality of life (standardized mean difference [SMD]: 0.83, 95% confidence interval [CI]: 0.50 to 1.15, moderate certainty of evidence), anxiety (mean difference [MD]: 1.83, 95% CI: 1.10 to 2.56, high certainty of evidence), and symptom burden (SMD: 0.81, 95% CI: 0.24 to 1.38, low certainty of evidence) in people with heart failure. No significant effects were found in all-cause hospital readmission and all-cause emergency department visit. Research evidence on sleep quality, cardiac-related hospital readmission, cardiac-related emergency department visit, and all-cause mortality remained unclear.

Conclusions
Our review suggests that nurse-led heart failure self-care interventions have favorable effects on the quality of life, anxiety, and symptom burden. Further well-designed randomized controlled trials are warranted to address the gaps identified in this review.