bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison between ticagrelor and clopidogrel in high bleeding risk patients with acute coronary syndrome
Authors: Tjerkaski J , Jernberg T , Alfredsson J , Erlinge D , James S , Lindahl B , Mohammad M A , Omerovic E , Venetsanos D , Szummer K 
Published: October 2022

Abstract

Background
Potent antiplatelet agents such as ticagrelor are associated with a lower risk of ischemic events than clopidogrel in patients with acute coronary syndrome (ACS). However, it is uncertain whether the benefits of more intensive anti-ischemic therapy outweigh the risks of major bleeding in individuals who have a high bleeding risk (HBR). This study aimed to assess treatment outcomes following dual antiplatelet therapy (DAPT) using either ticagrelor or clopidogrel in ACS patients with HBR.

Methods
All HBR patients enrolled in the SWEDEHEART registry who were discharged with DAPT using ticagrelor or clopidogrel following ACS between 2010 and 2017 were included in this study. Bleeding risk was assessed using the 4-item PRECISE-DAPT score, which consists of age, prior bleeding, haemoglobin concentration and creatinine clearance. HBR was defined as a PRECISE-DAPT score ≥25. Inverse-probability of treatment weighting was used to adjust for baseline differences between the treatment groups. The main analysis consisted of a doubly robust estimation of causal effect using Cox proportional hazards models. Data on major bleeding, recurrent myocardial infarction (MI), ischemic stroke and all-cause mortality was obtained from national registries, with 365 days of follow-up. Additional outcomes include major adverse cardiovascular events (MACE), a composite of MI, ischemic stroke and all-cause mortality, and net adverse clinical events (NACE), a composite of MACE and major bleeding.

Results
Of all ACS patients, 36% (n=25,042) had a PRECISE-DAPT score ≥25. Approximately half of the study participants were treated with ticagrelor (n=11,848). Ticagrelor reduced the risk of MI (hazard ratio [HR], 0.82 [95% CI 0.74–0.91]), ischemic stroke (HR, 0.73 [95% CI 0.60–0.88]) and MACE (HR, 0.90 [95% CI 0.84–0.97]), while also increasing the risk of major bleeding compared to clopidogrel (HR, 1.30 [95% CI 1.16–1.47]). We found no significant differences in all-cause mortality (HR 1.02 [95% CI 0.92–1.12]) and NACE (HR 0.98 [95% CI 0.92–1.05]).

Conclusions
Ticagrelor was associated with a lower risk of recurrent ischemic events, but a higher risk of major bleeding compared to clopidogrel. There were no significant differences in all-cause mortality and NACE between the treatment groups. These results suggest that more potent antiplatelet agents might not be superior to clopidogrel in ACS patients with HBR.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Stockholm county council
Effect of alirocumab added to high-Intensity statin therapy on endothelial function in patients with acute myocardial infarction: a sub-study of the randomized placebo-controlled PACMAN-AMI trial
Authors: Rexhaj E , Soria R , Baer S , Kavaliauskaite R , Yasushi U , Tatsuhiko O , Temperli F , Shibutani H , Siontis Cm G , Haener D J , Stortecky S , Windecker S , Koskinas C K , Losdat S , Raeber L 
Published: October 2022

Abstract

Background
Endothelial dysfunction is involved early in the development of vascular dysfunction leading to atherosclerosis and cardiovascular diseases. Statins have shown to improve endothelial function. The role of the protein convertase subtilisin/kexin type 9-inhibitor (PCSK9) alirocumab on endothelial function among patients with acute myocardial infarction (AMI) remains unknown.

Purpose
We investigated the effect of alirocumab on endothelial function among AMI patients receiving PCSK9i alirocumab in addition to high intensity statin therapy.

Methods
This is a pre-specified, sub-study nested within the PACMAN-AMI (effects of the PCSK9 antibody AliroCuMab on coronary Atherosclerosis in patieNts with Acute Myocardial Infarction) trial, a randomized trial that compared the effects of biweekly PCSK9-inhibitor alirocumab 150 mg vs. placebo, initiated within 24h of presentation in patients with AMI on top of high-intensity statin. Patients recruited at Bern University Hospital and adherent to the study drug (alirocumab or placebo) were analysed for the current study. Endothelial function was assessed by flow mediated dilation (FMD) of the brachial artery at week 4 and 52 after treatment initiation.

Results
Among 139 patients (68 alirocumab, 71 placebo) completing the sub-study, baseline characteristics were well balanced between groups (alirocumab vs. placebo: mean age 57.5±10.1 years vs. 58.7±8.4 years, p=0.45; mean LDL-C 4.03±0.93 mmol/L vs. 4.05±0.74 mmol/L, p=NS). At week 52 LDL-C levels decreased to 0.65±0.71 mmol/L in the alirocumab group and to 1.98±0.71 mmol/L in the placebo group (p&lt;0.001). There was no difference in FMD at 52 weeks in the alirocumab (5.44±2.24%) versus placebo (5.45±2.19%) group (between groups difference FMD, −0.21% (95% CI −077 to 0.35), p=0.47). Compared to baseline, follow-up FMD was improved in both groups (from 4.52±1.87 to 5.44±2.24%, p&lt;0.001 in the alirocumab group and from 4.32±1.62 to 5.45±2.19%, p&lt;0.001 in the placebo group).

Conclusion
Among patients with acute myocardial infarction, the addition of subcutaneous biweekly alirocumab, compared with placebo, to high-intensity statin therapy did not result in additional improvement of endothelial function after 52 weeks of treatment.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): The PACMAN-AMI study was supported by a research grant from Sanofi, Regeneron and Infraredx. This substudy was funded by the University of Bern.
Efficacy and safety of proprotein covertase subtilisin/kexin type 9 inhibitors among patients with acute coronary syndrome: a meta-analysis of randomized controlled trials
Authors: Delgado S , Tiongco R H 
Published: October 2022

Abstract

Background
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have formed part of the armamentarium of lipid-lowering therapy, most especially low-density lipoprotein-cholesterol (LDL-C) reduction, which in turn decreases the risk of atherosclerotic cardiovascular diseases and adverse cardiovascular events. However, studies are sparse on the benefit of initiating PCSK9 inhibitors during the early phase of an acute coronary sydrome (ACS).

Purpose
The objective of this meta-analysis is to investigate the efficacy and safety of the PCSK9 inhibitors evolocumab and alirocumab in the acute setting of an ACS.

Methods
A systematic search for randomized controlled trials (RCTs) that involve the use of PCSK9 inhibitors in ACS was done using MEDLINE/PubMed and Cochrane Library.

Results
Three RCTs (n=385 participants) were included in this meta-analysis comparing PCSK9 inhibitors versus placebo in patients hospitalized for ACS. Among patients being managed for ACS, PCSK9 inhibitors demonstrated a greater reduction in LDL-C compared to placebo as early as day 3 (WMD −41.65%, 95% CI [−60.09, −23.21], p&lt;0.00001), and was maintained until week 4 (WMD −45.67%, 95% CI [−64.82, −26.53], p&lt;0.00001). The occurrence of adverse events did not significantly differ between the two groups in terms of hospitalization for recurrent ACS (OR 0.99, 95% CI 0.10–9.98, p=1.0), hospitalization for heart failure (OR 6.18, 95% CI 0.26–146.78, p=0.26), or cerebrovascular events (OR 3.12, 95% CI 0.31–31.30, p=0.33).

Conclusion
In patients admitted for ACS, the early administration of PCSK9 inhibitors such as evolocumab and alirocumab during the first 24 hours of hospitalization resulted in a rapid and significant reduction of LDL-C without any significant adverse event as compared to placebo. Further validation of the role of PCSK9 inhibitors in the setting of ACS is needed to robustly investigate its contribution in improving hard cardiovascular outcomes.

Funding Acknowledgement
Type of funding sources: Private hospital(s). Main funding source(s): St. Luke's Medical Center Global City
Infarct size, inflammatory burden and admission hyperglycemia in diabetic patients with acute myocardial infarction treated with SGLT2-inhibitors: a multicenter international registry
Authors: Sansonetti A , Paolisso P , Bergamaschi L , Santulli G , Gallinoro E , Cesaro A , Gragnano F , Sardu C , Mileva N , Mauro C , Vassilev D , Marfella R , Calabro' P , Barbato E , Pizzi C 
Published: October 2022

Abstract

Background
Sodium-glucose co-transporter 2 inhibitors (SGLT2-I) currently receive intense clinical interest in patients with and without diabetes mellitus (DM) with pleiotropic beneficial effects. Nowadays, the inflammation response in the setting of acute myocardial infarction (AMI) has been proposed as a potential pharmacological intervention target. In this setting, we tested the hypothesis that the SGLT2-I displays anti-inflammatory effect along with glucose-lowering properties. We investigated the relationship between stress hyperglycemia, inflammation burden and infarct size in a cohort of type 2 diabetic AMI patients treated with SGLT2-I versus other oral anti-diabetic (OAD) agents alone.

Methods
In this multicenter international registry, all diabetic patients with AMI treated with percutaneous coronary intervention (PCI) between 2018 and 2021 were enrolled. Based on the admission anti-diabetic therapy, patients were divided into those receiving SGLT2-I versus other OAD agents alone. Patients on insulin therapy alone or combined with OAD agents were excluded from the study. The following inflammatory markers were evaluated at different time points: total white blood cell, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and neutrophil-to-platelet ratio (NPR), C-reactive protein. Infarct size was assessed by peak troponin levels and echocardiographic parameters.

Results
The final study population consisted of 583 patients hospitalized for AMI (both STEMI and NSTEMI) classified as SGLT2-I users (n=98) versus other OAD agents alone (n=485). Admission hyperglycemia was more prevalent among the other OAD agents group. Reduced infarct size was detected in patients treated with SGLT2-I compared to those treated with other OAD agents alone. Both at admission, and after 24 hours, inflammatory indices were significantly higher in patients treated with other OAD agents alone, with a significant increase in neutrophils levels at 24 hours, compared to the SGLT2-I group. In multivariate analysis, SGLT2-I emerged as a significant predictor of reduced inflammatory response (OR 0.45, 95% CI 0.27–0.75, p=0.002), together with peak troponin values, independently of age, admission creatinine values and admission glycemia.

Conclusions
Type 2 Diabetic patients hospitalized for AMI and receiving SGLT2-I exhibited modest inflammatory response and myocardial damage/infarct size compared to other OAD agents alone, independently of glucose-metabolic control. Our findings pave the way for new pathophysiological and therapeutic insights regarding the cardioprotective effect of SGLT2-I in the setting of coronary artery disease.

Funding Acknowledgement
Type of funding sources: None.
Long-term assessment and target achievement of LDL-C and systolic blood pressure in primary care after acute coronary syndrome
Authors: Schubert J , Svensson M , Denstedt G , Johnston N , Cars T , Gustafsson S , Schalin L , Hagstrom E 
Published: October 2022

Abstract

Background
Hospital-based cardiac rehabilitation and risk factor control decreases the risk of recurrent events after acute coronary syndrome (ACS). Little is known on long-term assessment and target achievement after referral to primary care. Patients with diabetes, regardless of ACS, have yearly follow-up visits in primary care, whereas there is no structured follow-up after ACS for patients without diabetes.

Purpose
To describe long-term assessment and target achievement of LDL-C and systolic blood pressure (SBP) in ACS patients after referral to primary care. Further, to compare patients with and without diabetes at the time of index ACS.

Methods
A non-interventional population-based observational study of patients with first ever ACS in a Swedish region with 390,000 inhabitants. Data on clinical measurements after ACS were collected from the electronic medical records between 2012 and 2020. Patients were followed until new ACS event, death, moving out of the county, or end of study. Target levels studied were LDL-C &lt;1.8 mmol/L and SBP &lt;140 mmHg. The same assessments with the addition of target levels of HbA1c ≤70 mmol/mol were evaluated in patients with diabetes.

Results
Median follow-up was 2.9 years (inter quartile range [IQR]: 1.0–5.4) and 4,733 patients were detected. Median age was 72 years (IQR 63–80) and 34% were female. Follow-up data were available for 3,579 (76%) patients any time during the first, 2,891 (61%) during the second, and 2,308 (49%) during the third year after the index ACS event. The number of patients with diabetes was 1311 (28%), and of these 921, 723, and 562 could be followed for the first, second, and third year. During the first three years, 898 (19%) of all patients with available follow-up died.
The proportion of patients with assessments of LDL-C and SBP declined for each year of follow-up and target achievement was low (Table). Among patients with diabetes a larger proportion had measurements for LDL-C and SBP, while the target achievement was similar to that of the whole study population. HbA1c was measured equally frequently as SBP and was at target in 81% of patients with diabetes during the three years of follow-up (Table).

Conclusion
The proportion of patients with follow-up assessment and measurements in primary care declined each year after the index ACS event. Patients with diabetes had more frequent LDL-C and SBP measurements but the same low target achievement after an ACS compared with patients without diabetes. This could potentially be due to an increased focus on glycaemic control at these visits. A structured long-term follow-up for ACS patients in primary care might improve both assessment and target achievement and prevent recurrent ACS events.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): AmgenSwedish Heart Lung Foundation
Prevalence of reaching target low-density lipoprotein cholesterol (LDL-C) in very high-risk patients using high intensity lipid-modifying therapy
Authors: Omar Khader A , Van Der Brug S , Liem A , Hamer B , Groenemeijer B , Martens F , Alings M 
Published: October 2022

Abstract

Background
Hyperlipidemia is an important risk factor for developing cardiovascular disease. Lowering LDL-C reduces the risk for coronary heart disease: the longer LDL-C remains low, the better. We studied the effect of implementing a guideline based, stepwise approach of lipid-modifying therapy to achieve target LDL-C levels in very high-risk patients in daily clinical practice in the Netherlands.

Methods
Nine hundred and ninety-nine (999) patients with a type I (N)STEMI and a history of Atherosclerotic Cardiovascular Disease and/or Diabetes mellitus II were included. Patients with LDL-C &gt;1.8 mmol/L were treated with high-intensity statin (HIST) monotherapy. If target LDL-C level was not reached, first ezetimibe and subsequently a PCSK9i was added. The primary objective was to assess the prevalence of reaching LDL-C ≤1.8mmol/L with HIST and/or ezetimibe.

Results
Nine hundred and thirty-nine (939) patients were treated with HIST and/or ezetimibe, of whom 89% reached LDL-C ≤1.8 mmol/L. Yet thirty four (34) of the 40 patients (85%) who received additional treatment with PCSK9i, reached the target LDL. After treatment with HIST, HIST plus ezetimibe, and HIST plus ezetimibe and PCSK9i in the per protocol population the cumulative prevalence of reaching target LDL-C was 71%, 89% and 99% respectively.

Conclusion
Using an ESC guideline-based flowchart with stepwise intensification of lipid-lowering drugs, using HIST and/or ezetimibe, 89% of the very high-risk patients reached an LDL-C ≤1.8 mmol/L in 57 days ± 38 (mean ± SD). Including patients in whom additional PCSK9i was started, success rate of meeting target LDL-C rose to 99%.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Sanofi-Aventis Netherlands B.V.
Association of malnutrition with in-hospital and long-term outcomes among ST-elevation myocardial infarction patients receiving primary PCI
Authors: Hosseini F , Pitcher I , Kang M , MacKay M , Singer J , Lee T , Madden K , Cairns J , Wong G , Fordyce C 
Published: October 2022

Abstract

Background
The impact of malnutrition on outcomes in a contemporary ST-segment-elevation myocardial infarction (STEMI) population is unclear. We hypothesized that malnutrition severity amongst STEMI patients undergoing primary percutaneous coronary intervention (pPCI) is associated with worse long-term outcomes.

Purpose
The aim of this study was 2-fold: 1) to establish the prevalence of malnutrition among STEMI patients undergoing pPCI; 2) to determine the association of malnutrition severity on in-hospital and 1-year outcomes in STEMI patients receiving pPCI

Methods
We retrospectively identified 1,169 STEMI patients of age ≥65 years who had received pPCI (2013–2020). Patients who had presented with out-of-hospital cardiac arrest or those who received fibrinolytic therapy were excluded. The Controlling Nutritional Status (CONUT) score, based on serum albumin, total cholesterol and lymphocyte count, was used as a tool to assess the nutritional status of included patients. Malnourished patients were defined as those with a CONUT score of 5 to 12. To account for the impact of frailty, a frailty index (FI) was determined using the health deficit accumulation model (Table 1). The primary outcome was 1-year all-cause mortality. The secondary outcome was a composite of in-hospital heart failure, cardiogenic shock, re-infarction, major bleeding, stroke, and all-cause mortality. A multivariable model adjusting for baseline covariates, including frailty index score, was performed (Figure 1).

Results
Among 1,169 STEMI patients receiving pPCI, 315 (26.9%) were classified as malnourished. Malnourished patients were older (mean 77.4 vs. 76.0 years, p=0.009) and had a higher comorbidity burden. After multivariable adjustment, worsening malnutrition was associated with increased 1-year all-cause mortality (odds ratio [OR] = 1.29, p&lt;0.001). Worsening malnutrition was also associated with a higher incidence of the in-hospital composite adverse outcome (OR = 1.12, p=0.003) and increased in-hospital all-cause mortality (OR=1.41, p&lt;0.001).

Conclusion
Among STEMI patients receiving pPCI, 1 in 4 were malnourished. Malnutrition was associated with increased rate of in-hospital composite adverse outcome and worse long-term outcomes, even when accounting for frailty. Efforts to routinely identify malnourished STEMI patients and to implement best practices to reduce the risk of adverse events in this vulnerable population are warranted.

Funding Acknowledgement
Type of funding sources: None.
Specific characteristics of STEMI in COVID-19 patients and their practical implications: a systematic review
Authors: Gitto M , Novelli L , Cozzi O , Reimers B , Condorelli G , Stefanini G G 
Published: October 2022

Abstract

Introduction
STEMI is one of the cardiac emergencies whose management has been mostly challenged by the COVID-19 pandemic. Patients presenting with the “lethal combo” of STEMI and concomitant SARS-CoV-2 infection have faced dramatic issues related to need for self-isolation, systemic inflammation with multi-organ disease, and difficulties to obtain timely diagnosis and treatment.

Methods
We performed a systematic search of three electronic databases from February 1st 2020 to January 31st 2022. We included all studies reporting crude rates of in-hospital outcomes of STEMI patients with concomitant COVID-19.

Results
A total of 9 observational studies were identified, mainly conducted during the first wave of the pandemic. STEMI patients with COVID −19 were more likely Afro-American and displayed higher rates of hypertension and diabetes with lower smoking prevalence. Associated comorbidities, including coronary artery disease, prior stroke and chronic kidney disease were also more common in those with SARS-CoV-2 infection.
At coronary angiography, a higher thrombus burden in COVID-19 positive STEMI patients was highlighted, with up to 10-fold higher rates of stent thrombosis and greater need for glycoprotein IIb/IIa inhibitors and aspiration thrombectomy; this was not always associated with prolonged times from symptom onset to hospital admission and door-to-balloon. COVID-19 positive STEMI patients were less likely to receive coronary angiography and primary PCI, and more likely to be treated with fibrinolytics only. At the same time, patients with Covid-19 were more prone to present MINOCA.
In-hospital mortality ranged from 15% to 40%, with consistent variability across different studies and subjects who tested positive for SARS-CoV-2 did also present higher rates of cardiogenic shock, cardiac arrest, prolonged ICU stay, mechanical ventilation, major bleeding, and stroke.

Conclusion
The coexistence of STEMI and COVID-19 was associated with increased in-hospital mortality and poor short-term prognosis. This was not entirely attributable to logistic issues determining delayed coronary revascularization, since patients' specific clinical and angiographic characteristics, including higher burden of cardiovascular risk factors and greater coronary thrombogenicity might have substantially contributed to this trend.

Funding Acknowledgement
Type of funding sources: None.