bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjunct remote ischemic conditioning to PCI in ST-segment elevation myocardial infraction patients: Systematic review and meta-analysis
Authors: Desouki Mariam Tarek M D , Elzankaly Osama O Z , Helmi Ahmed A H , Ramadan Shrouk S R , Hakim Diaa D H 
Published: November 2023

Abstract

Introduction
ST-segment elevation myocardial infarction (STEMI) is the most dangerous presentation of the acute coronary syndrome (ACS). Throughout the last three decades, clinicians have been attempting to reduce the short and long-term major adverse cardiac events (MACE) associated with STEMI. Remote ischemic conditioning (RIC) is one of the new adjunctive modalities to PCI in treating STEMI patients whereby brief reversible episodes of ischemia and reperfusion are applied to the tissue (by alternative cycles of inflation and deflation of a blood pressure cuff on the upper or lower limb) confers global protection and renders remote tissues resistant to ischemia/reperfusion injury.
This review aims to provide reliable evidence from published randomized controlled trials (RCTs) regarding whether RIC is beneficial for STEMI patients or not.

Methods
We followed the PRISMA guidelines during the preparation of this systematic review and meta-analysis. A computer literature search for (PubMed, Web of Science, Scopes, and Google Scholar) was carried out. We included RCT, comparing the remote ischemic conditioning, regardless of its timing of application to PCI, with either placebo or sham procedure, in terms of both short-term and long-term cardio protection. Outcomes of myocardial salvage index, myocardial infarction size, and left ventricular ejection fraction were pooled as the standardized mean difference between the two groups from baseline to endpoint.

Results
11 RCTs (7151 patients), were included in this analysis. The overall effect on short-term outcomes, was in favor of PCI only in terms of myocardial salvage index(P value=0.04, 95% CI [0.00-0.08]), and left ventricular ejection fraction(P value=0.05, 95% CI [0.02,2.16]), while the adjunctive application of remote ischemic conditioning was beneficial in terms of: myocardial infarct size ( P value=0.004, 95% CI [-3.22,-0.62]).
Regarding the long-term outcomes, the overall effect did not show any benefit in either of the two groups in terms of: major adverse cardiac and cerebrovascular events (MACCE) (P value=0.13, 95% CI [0.48,1.10]), hospitalization for heart failure (P value=1.00, 95% CI [0.83,1.20]), and cardiac death (P value=0.91, 95% CI [0.73,1.32]).

Conclusion
The adjunctive application of RIC to PCI during treatment of STEMI patients showed a beneficial effect only on short-term reduction of myocardial infarct size, nevertheless, it was not of benefit regarding the other short and long-term metrics of myocardial salvage and left ventricular function.
Eicosapentaenoic acid, arachidonic acid, and triglyceride levels mediate most of the benefit of icosapent ethyl in REDUCE-IT
Authors: Szarek M , Bhatt D , Miller M , Steg P G , Brinton E A , Jacobson T A , Tardif J C , Ballantyne C M , Ketchum S B , Pineda A L , Dunbar R L , Siri-Tarino P W , Mason R P 
Published: November 2023

Abstract

Background
In REDUCE-IT, icosapent ethyl (IPE) reduced major adverse cardiovascular (CV) events (MACE) relative to placebo (PBO) in 8179 statin-treated patients with residual hypertriglyceridemia and high CV risk. Questions have been raised about the mechanisms of benefit of IPE and the potential effects of the pharmaceutical grade mineral oil PBO on the results.

Purpose
The contributions of eicosapentaenoic acid (EPA), arachidonic acid (AA), triglycerides (TG), and other biomarkers (listed in Table 1) to MACE reduction by IPE relative to PBO were quantified via mediation analyses to illustrate the mechanisms of IPE.

Methods
Patients were randomised 1:1 to IPE 4 g/day or PBO and followed for a median 4.9 years. For a biomarker to be a mediator, there had to be both a treatment group difference on the biomarker and an association between the biomarker and risk of MACE. For the first condition, treatment group differences in change from baseline in each biomarker were analysed by mixed effects repeated measures models. For the second condition, time-varying values of each biomarker were related to the risk of MACE by calculating the time-weighted moving average (TWMA) for each variable, using all values for a given patient. Each was analysed in a Cox regression model with time to MACE as the outcome and TWMA values as time-varying covariates. The individual and joint mediation of those biomarkers determined to be mediators were assessed in Cox models that included treatment assignment. Biomarkers individually found to be ³10% mediators in absolute terms were included in the multivariable models. If biomarkers that would otherwise be included in multivariable models were strongly correlated (baseline values R2&gt;0.5), the marker with the greatest univariate mediation was included. All analyses were intention-to-treat.

Results
IPE reduced MACE by 25% (HR (95% CI) = 0.75 (0.68, 0.83), p&lt;0.0001). Treatment group differences on all potential mediators had p&lt;0.05, and all but oxLDL were significantly related to MACE (p&lt;0.05). Analyses of individual biomarkers showed EPA to be the strongest single mediator (Table 1). EPA, AA, and TG jointly mediated 78.9% of the IPE treatment effect, with EPA driving most of the mediation (57% as a single mediator). The marginal mediation by the remaining 3 biomarkers was 4.5% of the treatment effect, for total joint mediation of 83.4% (Figure 1).

Conclusion
In this mediation analysis of REDUCE-IT, most of the IPE benefit on MACE reduction was attributable to the two major mechanisms of the drug: (1) increasing EPA while reducing AA and, to a lesser extent, (2) reducing TG. The remainder of measured biomarker changes accounted for a minority of the benefit.Table 1Figure 1
Interplay among proton pump inhibitors, platelet reactivity and CYP2C19 genotyping in clopidogrel-treated patients after drug-eluting stent implantation
Authors: Kim J H , Hong S J , Cha J J , Lim S , Joo H J , Park J H , Yu C W , Jeong Y H , Ahn T H , Lim D S 
Published: November 2023

Abstract

Background
Several published data suggested that concomitant use of clopidogrel and proton pump inhibitors (PPIs) is associated with reduced antiplatelet efficacy of clopidogrel and increased adverse clinical outcomes. We sought to evaluate the interplay between PPI and clopidogrel on platelet reactivity and long-term clinical outcomes in patients after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation.

Methods
The PTRG-DES (Platelet function and genoType-Related long-term proGnosis in DES-treated patients) registry is a multi-center, real-world registry of patients who underwent PCI with DES and received dual antiplatelet therapy of aspirin and clopidogrel in South Korea. Patients prescribed with PPI were compared to those without the use of PPI (the control group). The primary outcome was a composite of all-cause death, myocardial infarction, stent thrombosis, and stroke at 5 years. Secondary outcomes included cardiac death, major bleeding, and gastrointestinal bleeding. Adjusted outcomes were compared after 1:2 propensity score (PS) matching analysis.

Results
Among 13,160 patients, 2235 (17.0%) were prescribed with concomitant PPI at the time of clopidogrel loading. Average age was 64.4 years, 67.2% were men, and 35.1% had diabetes. The PPI group demonstrated a higher on-treatment P2Y12 reaction unit than the control group (p&lt;0.001). The 5-year cumulative incidence of the composite primary outcome was higher in the PPI group (12.1% vs. 9.8%, log-rank p&lt;0.001). After PS matching, the primary outcome was similar between the two groups (12.9% vs. 12.1%, log-rank p=0.24). However, the PPI group with CYP2C19 poor metabolizers showed an increased adjusted risk of the primary outcome (hazard ratio 2.69, p&lt;0.001).

Conclusions
PPI use in patients with clopidogrel administration after DES implantation was associated with increased platelet reactivity, but similar cardiovascular outcomes in real-world practice. Physicians should be careful when administering PPI with clopidogrel in patients with CYP2C19 poor metabolizers.Distribution of P2Y12 reaction unitCumulative Incidence of outcomes
A meta-analysis on the efficacy of ticagrelor monotherapy after 3 months of dual antiplatelet therapy vs ticagrelor plus aspirin dual therapy on patients with ACS who underwent PCI
Authors: Galera L , Pestano N , Tumanan-Mendoza B , Punzalan F , Flores J , Europa M 
Published: November 2023

Abstract

Background
Major adverse cardiovascular events remain the major cause of mortality and morbidity after acute coronary syndrome, including patients who underwent percutaneous coronary intervention. Several studies have shown increased incidence of re-infarction, cardiac death, stroke, stent thrombosis, and all-cause mortality among these patients. The use of dual antiplatelet therapy has been recommended for post-procedural patients, according to guidelines. However, prolonged exposure to dual antiplatelets raised concerns on risk of bleeding. Our study aims to determine whether short term dual antiplatelet therapy followed with Ticagrelor monotherapy will benefit patients who are at higher risk of bleeding.

Objective
To determine the efficacy of Ticagrelor monotherapy after three months of Dual Antiplatelet Therapy versus 12 months of Ticagrelor plus Aspirin dual therapy in the prevention of MACE and bleeding among patients who had ACS and have undergone PCI.
METHODOLOGY
Randomized controlled trials on Ticagrelor monotherapy vs Ticagrelor + Aspirin Dual Therapy with outcomes on myocardial infarction, cardiac death, stroke, stent thrombosis, bleeding, all-cause mortality, were searched through PubMed.

Results
A total of 10,175 participants who had Acute Coronary Syndrome who have undergone Percutaneous Coronary Intervention were included in this analysis. Our results showed that discontinuing Aspirin after 3 months of Dual antiplatelet was not associated with significant increase in the risk of Major Adverse Cardiovascular Events: Myocardial Infarction (RR 0.96 95% CI 0.73-1.25), Cardiac Death (RR 0.92 95% CI 0.74-1.14), Stroke (RR 1.27 95% CI 0.69 -2.31), Stent Thrombosis (RR 0.87, 95% CI 0.48-1.59), Bleeding (RR 0.58 , 95% CI 0.49- 0.69) and All Cause Death (RR 0.77, 95% CI 0.52 – 1.14). Discontinuing Aspirin 3 months was associated with lower risk of bleeding (RR 0.58, 95% CI 0.49 - 0.69).

Conclusion
Minimizing the duration of exposure to antiplatelet agents with the use of Ticagrelor monotherapy after three months of DAPT among ACS patients who underwent PCI significantly reduced the incidence of bleeding, particularly among those who are at higher risk of bleeding. There is no significant difference in the risk for myocardial infarction, cardiac-related deaths, stroke, stent thrombosis, and all-cause mortality between the two groups.
Improvement of symptoms and quality of life in patients with coronary vasomotion disorders by endotype-based drug therapy
Authors: Kroll C , Hubert A , Seitz A , Bekeredjian R , Sechtem U , Ong P 
Published: November 2023

Abstract

Introduction
In patients with angina pectoris and/or signs of ischemia but no obstructive coronary artery disease (ANOCA) coronary vasomotion disorders are a frequent cause for their symptoms. However, the heterogeneous clinical presentation resulting from a wide spectrum of subtypes (so-called endotypes) poses a major therapeutic challenge. Many patients suffer from long-term refractory symptoms and severely reduced quality of life.

Purpose
The purpose of this study was to demonstrate that the quality of life of these patients can be improved by an endotype-based drug therapy.

Methods
A total of 50 patients (56% women, mean age 63±14 years) with a confirmed diagnosis of coronary vasomotion disorder were enrolled between April 2021 and February 2022. The endotypes were classified according to the diagnostically distinguishable subtypes (coronary spasm: n=30; vasodilatation disorder: n=3; combined vasomotion disorder: n=17). Based on the guideline recommendations of the European Society of Cardiology, an individual endotype-adapted medication was prescribed. The efficacy and tolerability of the medications were monitored over a period of 3 months. In addition, the quality of life was assessed quantitatively (score 0-100) using the Seattle Angina Questionnaire-7 (SAQ-7) at baseline and after 1, 2 and 3 months. The symptoms at home were documented weekly using a patient diary (PROM).

Results
Within the study population, arterial hypertension (74%) and dyslipidemia (80%) were among the most frequent concomitant cardiovascular risk factors. After 3 months of endotype-based antianginal therapy, a clinically relevant and significant improvement of 15 points on average in the SAQ7-score was achieved in 70% of the patients within the entire cohort (p&lt;0.001), while no change (&lt;5 points) was recorded in 14% of the study participants and 16% experienced an aggravation in the clinically relevant range (≥5 points). Accordingly, the PROM mood score (scale 1-5) also showed a significant improvement of 0.5 points (2.7±0.8 vs. 3.2±0.8; p&lt;0.001) as well as a significant decrease in monthly number of chest pain attacks by 38% (11.7±13.6 vs. 7.3±15.4; p=0.041) and nitroglycerin intake by 67% (2.7±5.9 vs. 0.9±2.6; p=0.004). When comparing the initial and final medication, a significant increase (33%) in the intake of calcium channel antagonists (non-DHP) was recorded in patients with coronary spasm (p=0.004). Within the patient group with combined vasomotion disorders, statins, ezetimibe and ranolazine were taken significantly more often by 35% respectively at the end of the observation period (p=0.031).

Conclusion
Targeted endotype-based drug therapy can contribute decisively to a clinically relevant improvement of symptoms and quality of life in ANOCA patients.Outcome of the whole patient cohortSAQ improvement during follow-up
Bailout inclisiran-based triple lipid-lowering therapy reduces plaque lipid content in stable coronary artery disease patients
Authors: Trusinskis K , Lapsovs M , Kokina B , Karantajere M , Knoka E , Caunite L , Jegere S , Narbute I , Sondore D , Grave A , Kumsars I , Erglis A 
Published: November 2023

Abstract

Background
Low-density lipoprotein cholesterol (LDL-C) has a causal role in atherosclerotic cardiovascular disease. Genetic studies and variability in individual response to lipid-lowering therapies suggest combining hypolipidaemic medications with different mechanisms of action.

Purpose
The aim of this study was to evaluate the effect of triple inclisiran-based hypolipidaemic therapy in patients not reaching LDL-C target on maximum statin/ezetimibe treatment.

Methods
This prospective study enrolled 37 stable coronary artery disease patients admitted for elective percutaneous coronary intervention after 4-6 weeks on maximum tolerated statin and/or ezetimibe therapy during run-in period. Afterwards, patients with LDL-C level &gt;1.8 mmol/l at the time of inclusion were assigned to receive add-on inclisiran (triple therapy group). In all participants near-infrared spectroscopy (NIRS) was performed at baseline and after 15 months for atherosclerotic plaque evaluation in the segment of interest, defined as 20-50% lesion in the proximal or middle third of a coronary artery. Statistical analysis was carried out with SPSS Statistics software.

Results
Average LDL-C level among screened patients was 2.81 (±1.17) mmol/l. In 19 patients LDL-C level remained &gt;1.8 mmol/l on maximally tolerated statin and/or ezetimibe treatment, and after 15 months of triple therapy mean LDL-C reached 1.81 (±1.02) mmol/l with a significant LDL-C percentage change of 35.59% (95%CI -47.31 to -9.18, P=0.006) in this group. 17 patients continued statin/ezetimibe as mono or dual treatment and at 15-month follow-up mean LDL-C level comprised 1.67 (±0.61) mmol/l among these participants. According to NIRS data, maximum lipid-core burden index within 4 mm (maxLCBI4 mm) was significantly reduced by 28.85 (95%CI -189.39 to 17.64, P=0.041) in triple therapy group and by 114.72 in mono or dual therapy group (-194.76 to 23.01, P=0.004), with no statistically significant difference established between both groups (P=0.494).

Conclusions
Triple therapy demonstrated significant atherosclerotic plaque lipid content reduction along with LDL-C level lowering in patients with insufficient effectiveness of statin/ezetimibe treatment.
Preprocedural computed tomography angiography for prediction of transcatheter aortic valve implantation outcomes. A machine learning study
Authors: Kwiecinski J , Grodecki K , Pieszko K , Dabrowski M , Chmielak Z , Slomka P , Wojakowski W , Witkowski A , Dey D 
Published: November 2023

Abstract

Background
Prediction of outcomes following transcatheter aortic valve implantation (TAVI) is challenging. While over the past decades multiple scores for risk stratification in TAVI patients have been proposed due to their limited accuracy none of them have been adopted clinically. Recently machine learning was leveraged for this purpose yet again, while new approaches showed promise in prediction of outcomes following TAVI this was only the case for models which included peri-procedural data.

Purpose
Considering that in aortic stenosis outcomes are governed by both valve degeneration and myocardial adverse remodelling which ensues, we aimed to employ the pre-procedural computed tomography (CT) to develop a machine-learning model for prediction of 1-year outcomes following TAVI.
The model was developed on data of consecutive patients who underwent TAVI at a high-volume center between January 2016 and January 2022. Machine learning by extreme gradient boosting was trained and tested with repeated 10-fold hold-out testing using CT-derived volumetric measurements including myocardial mass and quantitative fibrocalcific valve volume and attenuation measured using standardized software. We compared our CT model based on 21 imaging variables, age and gender with the EuroSCORE II for prediction of 12-month all-cause mortality. External validation was performed on unseen data of consecutive patients who underwent TAVI in 2019-2020 at an independent high volume TAVI center.

Results
The derivation cohort included 631 consecutive patients (48% men, 80±8 years old, EuroSCORE II 6.5 [4.6-10.3] %). Our model was externally tested on data of 226 patients (46% men, 78±8 years old, EuroSCORE II 7.4 [4.9-10.8] %). Over the 12 months of follow-up 86 (13%) and 29 (13%) subjects died in the derivation and validation cohort respectively. In external validation the CT-based machine learning model had an area under the receiver operator curve (AUC) of 0.70 [0.63-0.76] which was superior to the EuroSCORE 0.59 [0.53-0.66] and age 0.58 [0.52-0.65], p&lt;0.001 for a difference. The feature importance for the machine learning model are presented in Figure 1; the highest-ranked features included LV ejection fraction and mass, the noncalcific valve volume and the mean aortic valve calcification attenuation.

Conclusions
Machine-learning facilitates leveraging preprocedural CT angiography for prediction of TAVI outcomes. By combining CT derived cardiac assessment machine-learning provides superior prediction to EuroSCORE II.
Long-term outcomes of patients with late presentation STEMI undergoing percutaneous coronary revascularization
Authors: Neef P A , Loy O , Brennan A L , Ajani A E , Reid C , Dinh D , Clark D J , Freeman M , Stub D , Hiew C , Oqueli E 
Published: November 2023

Abstract

Background/Introduction
Patients with late-presentation ST-segment myocardial infarction (STEMI) (12-48hr of symptom onset) tend to have worse clinical outcomes compared to early presenters (&lt;12hr of symptom onset). The optimal management and decision for primary percutaneous coronary intervention (PCI) is limited by the current evidence, particularly in the modern revascularisation era.

Purpose
The aim of this study was to assess the short- and long-term clinical outcomes of primary PCI in patients with STEMI who present late following symptom onset (12-48hr) compared to those who present early (&lt;12hr).

Methods
Data from 4265 consecutive patients undergoing PCI for STEMI within 48hr of presentation were analysed from the Melbourne Interventional Group registry between 2014 and 2020. Patients were categorised based upon symptom-to-door time (early &lt;12hr vs late 12-48hr).. The primary endpoints were in-hospital, 30-day and long-term mortality. Secondary outcomes were major adverse cardiovascular events (MACE; composite of all-cause mortality, non-fatal myocardial infarction, non-fatal stroke or repeat revascularisation), procedural outcomes and medications at 30-day.

Results
4044 patients were early presentation and 221 patients were late presentation. The median symptom-to-door time was 1.73hr (interquartile range (IQR) 1.2, 2.8) for early presenters and 14.8hr (IQR 13.2, 18.1) for late presenters. Late presenters were less likely to have out-of-hospital cardiac arrest and require inotropic support (all p&lt;0.01). There was no significant difference in in-hospital mortality (6.5% vs 5.4%, p=0.53) and MACE (9.0% vs 7.7%, p=0.52), nor 30-day mortality (7.4% vs 7.3%, p=0.94) and MACE (11.1% vs 10.5%, p=0.77). Long-term mortality did not differ between early and late presenters with hazard ratio 1.17 (95% confidence interval 0.71-1.95, p=0.54). There was no difference in major bleeding at 30-days (p=0.42).

Conclusions
Primary PCI in patients following late presentation STEMI is not associated with worse short- or long-term clinical outcomes compared to those who present early . Further, randomised controlled trials in the modern revascularisation era are needed to guide clinical practice.