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Studies assessing the treatment of refractory no-reflow in patients with ST-elevation myocardial infarction (STEMI) are limited to clinical cases and pilot studies. This study aimed to evaluate the efficacy and safety of intracoronary adrenaline administration in such patients. Ninety consecutive patients with refractory coronary no-reflow during percutaneous coronary intervention (PCI) were prospectively included after the initial failure of conventional treatment. They were randomized into 2 groups: 45 patients in Group 1 received adrenaline, and 45 patients in Group 2 (control) received conventional treatments alone. After intracoronary drug administration, the adrenaline group demonstrated significantly higher rates of coronary flow restoration in the infarct-related artery to the level of thrombolysis in myocardial infarction grade 3 (56% vs 29% [p = 0.01]) and resolution of STEMI >50% after PCI (78% vs 36% [p <0.001]). Additionally, the adrenaline group showed a lower indexed microvascular obstruction (MVO) volume compared with the control group (0.9 [0.3; 3.1] % vs 1.9 [0.6; 7.9] % [p = 0.048]). A significant improvement in ejection fraction (EF) was observed in the adrenaline group (p = 0.025). Intracoronary adrenaline administration during PCI in patients with STEMI with refractory no-reflow is more effective compared with conventional treatments. This approach improves coronary flow in the infarct-related artery, facilitates a faster resolution of STEMI, enhances EF, and reduces MVO volume. Intracoronary adrenaline administration demonstrates a comparable safety profile to conventional treatment strategies in terms of life-threatening arrhythmias occurrence. The study suggests that intracoronary adrenaline administration during PCI could be an effective treatment strategy for patients with STEMI with refractory no-reflow., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, improves cardiovascular outcomes in heart failure patients, but data regarding the efficacy of empagliflozin in the setting of acute myocardial infarction (AMI) is still unclear. The current study aimed to evaluate whether treatment with empagliflozin before primary percutaneous coronary intervention (PCI) improves parameters associated with patients' outcomes., Methods: We randomly assigned 101 non-diabetic and non-heart failure patients with ST-elevation myocardial infarction (STEMI) who underwent primary PCI to receive either empagliflozin (10 mg before PCI and once daily for 40 days) or placebo, in addition to the standard treatment. The primary outcomes were changes in left ventricular ejection fraction (LVEF) 40 days after PCI, changes in cardiac troponin I (cTnI) and estimates of its area under the curve (AUC) and the peak level, and resolution of ST-segment in > 50% of leads 90 min after PCI., Results: No significant difference was observed in terms of the occurrence of ST-segment resolution > 50% (46.0% versus 45.0%; p = 0.92) and the mean level of cTnI at each time point between the two groups. The estimated mean [standard deviation (SD)] AUC of cTnI was 955.0 (595.7) ng h/ml in the intervention and 999.7 (474.7) ng h/ml in the control groups (p = 0.85) without any significant difference in peak cTnI level. The mean (SD) LVEF 40 days after primary PCI was significantly higher in empagliflozin-treated patients than the placebo group [43.2% (5.8%) versus 39.2% (6.7%); p = 0.002]., Conclusion: In this study, no significant differences were observed across the groups in terms of cTnI levels and ST-segment resolution in patients with STEMI undergoing primary PCI. However, it shed light on the potential benefits of empagliflozin in improving LVEF following STEMI., Registration: Iranian Registry of Clinical Trials Platform ( https://irct.behdasht.gov.ir/ ) identifier number IRCT20111206008307N42., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Tongxinluo, a traditional Chinese medicine compound, has shown promise in improving outcomes for patients with ST-segment elevation myocardial infarction (STEMI). This randomized, double-blind, placebo-controlled trial investigated the efficacy of Tongxinluo in reducing major adverse cardiac and cerebrovascular events (MACCEs) in STEMI patients. The study enrolled 3777 patients from 124 hospitals in China, all of whom received standard STEMI treatments in addition to either Tongxinluo or placebo for 12 months. The primary endpoint was the occurrence of MACCEs at 30 days, with secondary endpoints including individual components of MACCEs, severe STEMI complications, major bleeding, and all-cause mortality at 1 yr. Results showed that Tongxinluo significantly reduced the 30-day MACCE rate compared to placebo (3.4 % vs 5.2 %), and this benefit persisted at 1 year (5.3 % vs 8.3 %). Cardiac death and myocardial reinfarction rates were also significantly lower in the Tongxinluo group. These findings underscore the importance of integrating traditional Chinese medicine with conventional Western medical treatments, providing significant evidence to support the development of evidence-based practices in traditional Chinese medicine. This study represents a pivotal advancement in the field of TCM, demonstrating its potential to contribute meaningfully to modern clinical practice and highlighting the necessity for further high-quality research in this area., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: no-reflow can complicate up to 25% of pPCI and is associated with significant morbidity and mortality. We aimed to compare the outcomes of intracoronary epinephrine and verapamil with intracoronary adenosine in the treatment of no-reflow after primary percutaneous coronary intervention (pPCI)., Methods: 108 STEMI patients had no-reflow during pPCI were assigned into four groups. Group 1, in which epinephrine and verapamil were injected through a well-cannulated guiding catheter. Group 2, in which same drugs were injected in the distal coronary bed through a microcatheter or perfusion catheter. Group 3, in which adenosine was injected through a guiding catheter. Group 4, in which adenosine was injected in distal coronary bed. Primary end point was the achievement of TIMI III flow and MBG II or III. Secondary end point was major adverse cardiovascular and cerebrovascular events (MACCEs) during hospital stay., Results: The study groups did not differ in their baseline characteristics. Primary end point was achieved in 15 (27.8%) patients in the guide-delivery arm compared with 34 (63%) patients in the local-delivery arm, p < 0.01. However, the primary end point did not differ between the epinephrine/verapamil group and the adenosine group (27 (50%) vs 22 (40.7%), p = 0.334). The secondary end points were similar between the study groups., Conclusion: Local delivery of epinephrine, verapamil and adenosine in the distal coronary bed is more effective in achieving TIMI III flow with MBG II or III compared with their guide-delivery in patients who suffered no-reflow during pPCI. There was no difference between epinephrine/verapamil Vs. adenosine., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A middle-aged man presented with inferior wall ST-elevation myocardial infarction and underwent primary percutaneous coronary intervention with tirofiban administered due to extensive thrombus. He developed sudden-onset dyspnoea, bilateral crepitations, haemoptysis, desaturation and hypotension an hour after starting tirofiban infusion. The tirofiban, antiplatelet medications and heparin were stopped immediately. Chest X-ray showed patchy opacities in the left upper, middle and lower zones. High-resolution CT showed confluent areas of consolidation with surrounding ground glass opacities and interlobular septal thickening (crazy pavement appearance) representing diffuse alveolar haemorrhage (DAH). He was managed with inotropes, non-invasive ventilation and intravenous furosemide. He was asymptomatic with complete resolution of lung opacities in chest X-ray done 2 months follow-up. DAH is a rare but potentially life-threatening complication which is often misidentified with other respiratory syndromes. Treatment includes stopping tirofiban and anticoagulant medication, blood transfusion, and institution of mechanical ventilation., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Conflict of interest: R.C.W. has received research grants from AstraZeneca, Edwards Lifesciences, and Novartis and honoraria from AstraZeneca, Bayer, GSK, and Novartis. R.C.W. is a site principal investigator for the CELEBRATE trial.

Background: Several clinical studies have produced diverse results regarding the efficacy and safety of early intravenous beta-blockers in patients with acute ST-segment elevation myocardial infarction (STEMI). A study-level meta-analysis of randomized clinical trials (RCTs) comparing early intravenous beta-blockers versus placebo or routine care in STEMI patients undergoing primary percutaneous coronary intervention (PCI) was performed., Methods: A database search was conducted using PubMed, EMBASE, the Cochrane Library, and Clinicaltrials.gov for randomized clinical trials (RCTs) that compared intravenous beta-blockers versus placebo or routine care in STEMI patients who underwent primary PCI. The efficacy outcomes were infarct size (IS, % of LV) and the myocardial salvage index (MSI) based on magnetic resonance imaging, electrocardiographic findings, heart rate, ST-segment reduction percent (STR%), and complete STR. Safety outcomes included arrhythmias in the first 24 h (ventricular tachycardia and fibrillation [VT/VF], atrial fibrillation [AF], bradycardia, and advanced atrioventricular [AV] block), cardiogenic shock and hypotension during hospitalization, left ventricular ejection fraction (LVEF), and major adverse cardiovascular events (cardiac death, stroke, reinfarction, and heart failure readmission) at follow-up., Results: Seven RCTs with 1428 patients were included in this study, with 709 patients in the intravenous beta-blockers and 719 in the control group. Intravenous beta-blockers improved MSI compared to the control group (weighted mean difference [WMD] 8.46, 95% confidence interval [CI] 3.12-13.80, P = 0.002, I 2 = 0%), but no differences were observed in IS (% of LV) between groups. Compared to the control group, the intravenous beta-blockers group had a lower risk of VT/VF (relative risk [RR] 0.65, 95% CI 0.45-0.94, P = 0.02, I 2 = 35%) without an increase of AF, bradycardia, and AV-block and significantly decreased HR, hypotension. LVEF at 1 week ± 7 days (WMD 2.06, 95% CI 0.25-3.88, P = 0.03, I 2 = 12%) and 6 months ± 7 days (WMD 3.24, 95% CI 1.54-4.95, P = 0.0002, I 2 = 0%) was improved in the intravenous beta-blockers group compared to the control group. Subgroup analysis showed that intravenous beta-blockers before PCI decreased the risk of VT/VF and improved LVEF compared to the control group. Furthermore, sensitivity analysis showed that patients with a left anterior descending (LAD) artery lesion had a smaller IS (% of LV) in the intravenous beta-blockers group compared to the control group., Conclusion: Intravenous beta-blockers improved the MSI, decreased the risk of VT/VF in the first 24 h, and were associated with increased LVEF at 1 week and 6 months following PCI. In particular, intravenous beta-blockers started before PCI is beneficial for patients with LAD lesions., (© 2023. The Author(s).)

Background: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarction (MI) size in the preclinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction in patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention., Methods: This was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted between November 2017 to November 2021 in 6 cardiac centers in Singapore. Patients were randomized to receive either cangrelor or placebo initiated before the primary percutaneous coronary intervention procedure on top of oral ticagrelor. The key exclusion criteria included presenting <6 hours of symptom onset; previous MI and stroke or transient ischemic attack; on concomitant oral anticoagulants; and a contraindication for cardiovascular magnetic resonance. The primary efficacy end point was acute MI size by cardiovascular magnetic resonance within the first week expressed as percentage of the left ventricle mass (%LVmass). Microvascular obstruction was identified as areas of dark core of hypoenhancement within areas of late gadolinium enhancement. The primary safety end point was Bleeding Academic Research Consortium-defined major bleeding in the first 48 hours. Continuous variables were compared by Mann-Whitney U test (reported as median [first quartile-third quartile]), and categorical variables were compared by Fisher exact test. A 2-sided P <0.05 was considered statistically significant., Results: Of 209 recruited patients, 164 patients (78%) completed the acute cardiovascular magnetic resonance scan. There were no significant differences in acute MI size (placebo, 14.9% [7.3-22.6] %LVmass versus cangrelor, 16.3 [9.9-24.4] %LVmass; P =0.40) or the incidence (placebo, 48% versus cangrelor, 47%; P =0.99) and extent of microvascular obstruction (placebo, 1.63 [0.60-4.65] %LVmass versus cangrelor, 1.18 [0.53-3.37] %LVmass; P =0.46) between placebo and cangrelor despite a 2-fold decrease in platelet reactivity with cangrelor. There were no Bleeding Academic Research Consortium-defined major bleeding events in either group in the first 48 hours., Conclusions: Cangrelor administered at the time of primary percutaneous coronary intervention did not reduce acute MI size or prevent microvascular obstruction in patients with ST-segment-elevation MI given oral ticagrelor despite a significant reduction of platelet reactivity during the percutaneous coronary intervention procedure., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03102723., Competing Interests: L.T. is on the Astra Zeneca international advisory board of management of adverse events with the new antibody drug conjugate T-DXd in Asian patients with metastatic breast cancer, Roche Singapore immunotherapy in early stage NSCLC patient journey advisory board. L.T. has received a Philips speaker honorarium in kind and a Siemens Healthineers speaker honorarium. Y.K.K. has received research funding from Amgen, Astra Zeneca, Abbott Vascular, Bayer, Boston Scientific, Shockwave Medical, and Novartis (via institution); consulting fees from Abbott Vascular, Medtronic, Novartis, and Peijia Medical; and speaker fees from Shockwave Medical, Abbott Vascular, Boston Scientific, Medtronic, Alvimedica, Biotronik, Orbus Neich, Amgen, Novartis, Astra Zeneca, Microport, Terumo, and Omnicare. Y.K.K. is also cofounder and owns equity in Trisail, for which OrbusNeich is an investor. D.J.H. has received consultant fees from Faraday Pharmaceuticals Inc and Boehringer Ingelheim International GmbH, honoraria from Servier, and research funding from Astra Zeneca and Merck Sharp & Dohme Corp. C.Y.C. has received speaker fees from Novartis and consultancy fees from Boston Scientific and Philips. The other authors report no conflicts.

While the efficacy of GpIIb-IIIa-inhibitors during primary PCI (pPCI) for ST-elevated myocardial infarction (STEMI) has previously been demonstrated, its ongoing role and safety in combination with newer P2Y12-inhibitors is unclear. We therefore sought to compare outcomes between two centers with divergent approaches to the use of GpIIbIIIa antagonists in pPCI. We performed a retrospective chart review of all-comer STEMI patients treated with pPCI at two high-volume Montreal academic tertiary care centers. One center tended to use GpIIb-IIIa-inhibitors up-front in a large proportion of patients (liberal strategy) and the other preferring a bail-out approach (conservative strategy). Baseline patient characteristics and procedural data were compared between the two groups. The main efficacy outcome was rate of no-reflow/slow-reflow and the main safety outcome was BARC ≥ 2 bleeding events. A total of 459 patients were included, of whom 167 (36.5%) were exposed to a GpIIb-IIIa-antagonist. There was a significant overall difference in use of GpIIb-IIIa-antagonist between the two centers (60.5% vs. 16.1%, p < 0.01). Rate of no-reflow/slow-reflow was similar between groups (2.6% vs. 1.4%, p = 0.22). In-hospital rates of unplanned revascularization, stroke and death were also not different between groups. Use of a liberal GpIIb--IIIa-antagonist strategy was however associated with a higher risk of bleeding (OR 3.16, 95% CI 1.57-6.37, p < 0.01), which persisted after adjustment for covariables (adjusted OR 2.85, 95% CI 1.40-5.81, p < 0.01). In this contemporary retrospective cohort, a conservative, bail-out only GpIIb--IIIa-antagonist strategy was associated with a lower incidence of clinically relevant bleeding without any signal for an increase in no-reflow/slow-reflow or ischemic clinical events., (© 2024. The Author(s).)

Background: Secreted glycoproteins of the Dickkopf (DKK) family modify Wnt signaling and may influence plaque destabilization but their modulation by statins in MI patients is not known., Methods: We measured plasma DKK-1 and DKK-3 in patients with acute ST-segment elevation MI (STEMI) before percutaneous coronary intervention (PCI) and after 2 and 7 days and 2 months in patients receiving short-term high-dose (40 mg rosuvastatin, given before PCI; n = 25) and moderate dose (20 mg simvastatin, given the day after PCI; n = 34). In vitro modulation of DKK-1 in human umbilical vein endothelial cells (HUVECs) by statins were assessed., Results: (i) Patients receiving high dose rosuvastatin had a marked decline in DKK-1 at day 2 which was maintained throughout the study period. However, a more prevalent use of β-blockers in the simvastatin group, that could have contributed to higher DKK-1 levels in these patients. (ii) There was a strong correlation between baseline DKK-1 levels and change in DKK-1 from baseline to day 2 in patients receiving high dose rosuvastatin treatment. (iii) DKK-3 increased at day 2 but returned to baseline levels at 2 months in both treatment groups. (iv) Statin treatment dose-dependently decreased DKK-1 mRNA and protein levels in HUVEC., Conclusions: Our findings suggest that high dose statin treatment with 40 mg rosuvastatin could persistently down-regulate DKK-1 levels, even at 2 months after the initial event in STEMI patients., Competing Interests: Declaration of competing interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The impact of statin therapy on cardiovascular outcomes after ST-elevation acute myocardial infarction (STEMI) in real- world patients is understudied., Aims: To identify predictors of low adherence and discontinuation to statin therapy within 6 months after STEMI and to estimate their impact on cardiovascular outcomes at one year follow-up., Methods: We evaluated real-world adherence to statin therapy by comparing the number of bought tablets to the expected ones at 1 year follow-up through pharmacy registries. A total of 6043 STEMI patients admitted from 2012 to 2017 were enrolled in the FAST STEMI registry and followed up for 4,7 ± 1,6 years; 304 patients with intraprocedural and intrahospital deaths were excluded. The main outcomes evaluated were all-cause death, cardiovascular death, myocardial infarction, major and minor bleeding events, and ischemic stroke. The compliance cut-off chosen was 80% as mainly reported in literature., Results: From a total of 5744 patients, 418 (7,2%) patients interrupted statin therapy within 6 months after STEMI, whereas 3337 (58,1%) presented >80% adherence to statin therapy. Statin optimal adherence (>80%) resulted as protective factor towards both cardiovascular (0.1% vs 4.6%; AdjHR 0.025, 95%CI 0.008-0.079, p < 0.001) and all-cause mortality (0.3% vs 13.4%; Adj HR 0.032, 95%CI 0.018-0.059, p < 0.001) at 1 year follow-up. Further, a significant reduction of ischemic stroke incidence (1% vs 2.5%, p = 0.001) was seen in the optimal adherent group. Statin discontinuation within 6 months after STEMI showed an increase of both cardiovascular (5% vs 1.7%; AdjHR 2.23; 95%CI 1.37-3.65; p = 0,001) and all-cause mortality (14.8% vs 5.1%, AdjHR 2.32; 95%CI 1.73-3.11; p 〈0,001) at 1 year follow-up. After multivariate analysis age over 75 years old, known ischemic cardiopathy and female gender resulted as predictors of therapy discontinuation. Age over 75 years old, chronic kidney disease, previous atrial fibrillation, vasculopathy, known ischemic cardiopathy were found to be predictors of low statin adherence., Conclusions: n our real-world registry low statin adherence and discontinuation therapy within 6 months after STEMI were independently associated to an increase of cardiovascular and all-cause mortality at 1 year follow-up. Low statin adherence led to higher rates of ischemic stroke., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

The use of intravenous antiplatelet therapy during primary percutaneous coronary intervention (PPCI) is not fully standardized. The aim is to evaluate the effectiveness and safety of periprocedural intravenous administration of cangrelor or tirofiban in a contemporary ST-segment elevation myocardial infarction (STEMI) population undergoing PPCI. This was a multicenter prospective cohort study including consecutive STEMI patients who received cangrelor or tirofiban during PPCI at seven Italian centers. The primary effectiveness measure was the angiographic evidence of thrombolysis in myocardial infarction (TIMI) flow < 3 after PPCI. The primary safety outcome was the in-hospital occurrence of BARC (Bleeding Academic Research Consortium) 2-5 bleedings. The study included 627 patients (median age 63 years, 79% males): 312 received cangrelor, 315 tirofiban. The percentage of history of bleeding, pulmonary edema and cardiogenic shock at admission was comparable between groups. Patients receiving cangrelor had lower ischemia time compared to tirofiban. TIMI flow before PPCI and TIMI thrombus grade were comparable between groups. At propensity score-weighted regression analysis, the risk of TIMI flow < 3 was significantly lower in patients treated with cangrelor compared to tirofiban (adjusted OR: 0.40; 95% CI: 0.30-0.53). The risk of BARC 2-5 bleeding was comparable between groups (adjusted OR:1.35; 95% CI: 0.92-1.98). These results were consistent across multiple prespecified subgroups, including subjects stratified for different total ischemia time, with no statistical interaction. In this real-world multicenter STEMI population, the use of cangrelor was associated with improved myocardial perfusion assessed by coronary angiography after PPCI without increasing clinically-relevant bleedings compared to tirofiban., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Although major guidelines recommend the routine introduction of angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) and beta-blockers for patients with ST-segment elevation myocardial infarction (STEMI), evidence regarding the target blood pressure (BP) or pulse rate (PR) at hospital discharge is sparse. This retrospective study aimed to compare the clinical outcomes in patients with STEMI between those with good BP and PR control and those with poor BP or PR control., Methods: We included 748 patients with STEMI who received both ACE inhibitors/ARBs and beta-blockers at hospital discharge, and divided them into a good control group (systolic BP ≤140 mmHg and PR ≤80 bpm, n = 564) and a poor control group (systolic BP >140 mmHg or PR >80 bpm, n = 184). The primary endpoint was major cardiovascular events (MACE) defined as the composite of all-cause death, non-fatal myocardial infarction, and re-admission for heart failure., Results: During the median follow-up duration of 568 days, a total of 119 MACE were observed. The Kaplan-Meier curves showed that MACE were more frequently observed in the poor control group (p = 0.009). In the multivariate Cox hazard analysis, the good control group was inversely associated with MACE (HR 0.656, 95 % CI: 0.444-0.968, p = 0.034) after controlling for multiple confounding factors., Conclusions: The good control of systolic BP and PR at discharge was inversely associated with long-term adverse events in STEMI patients treated with both ACE inhibitors/ARBs and beta blockers. This study suggests the importance of titration of ACE inhibitors/ARBs and beta-blockers for better clinical outcomes in patients with STEMI., Competing Interests: Declaration of competing interest Dr. Sakakura has received speaking honoraria from Abbott Vascular, Boston Scientific, Medtronic Cardiovascular, Terumo, OrbusNeich, Japan Lifeline, Kaneka, and NIPRO. Dr. Jinnouchi has received speaking honoraria from Abbott Vascular. Prof. Fujita has served as a consultant for Mehergen Group Holdings, Inc., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The early unfractionated heparin (UFH) treatment in patients with ST-elevation myocardial infarction (STEMI) is a single-center, open-label, randomized controlled trial. The study population are patients with STEMI that undergo primary percutaneous coronary intervention (PPCI). The trial was designed to investigate whether early administration of unfractionated heparin immediately after diagnosis of STEMI is beneficial in terms of patency of infarct-related coronary artery (IRA) when compared to established UFH administration at the time of coronary intervention. The patients will be randomized in 1:1 fashion in one of the two groups. The primary efficacy endpoint of the study is Thrombolysis in myocardial infarction (TIMI) flow grades 2 and 3 on diagnostic coronary angiography. Secondary outcome measures are: TIMI flow after PPCI, progression to cardiogenic shock, 30-day mortality, ST-segment resolution, highest Troponin I and Troponin I values at 24 hours. The safety outcome is bleeding complications. The study of early heparin administration in patients with STEMI will address whether pretreatment with UFH can increase the rate of spontaneous reperfusion of infarct-related coronary artery., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fister et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Over the past decade, major society guidelines have recommended the use of newer P2Y 12 inhibitors over clopidogrel for those undergoing percutaneous coronary intervention for acute coronary syndrome. It is unclear what impact these recommendations had on clinical practice., Methods and Results: All percutaneous coronary intervention procedures (n=534 210) for acute coronary syndrome in England and Wales (April 1, 2010, to March 31, 2022) were retrospectively analyzed, stratified by choice of preprocedural P2Y 12 inhibitor (clopidogrel, ticagrelor, and prasugrel). Multivariable logistic regression models were used to examine odds ratios of receipt of ticagrelor and prasugrel (versus clopidogrel) over time, and predictors of their receipt. Overall, there was a significant increase in receipt of newer P2Y 12 inhibitors from 2010 to 2020 (2022 versus 2010: ticagrelor odds ratio, 8.12 [95% CI, 7.67-8.60]; prasugrel odds ratio, 6.14 [95% CI, 5.53-6.81]), more so in ST-segment-elevation myocardial infarction than non-ST-segment-elevation acute coronary syndrome indication. The most significant increase in odds of receipt of prasugrel was observed between 2020 and 2022 ( P <0.001), following a decline/plateau in its use in earlier years (2011-2019). In contrast, the odds of receipt of ticagrelor significantly increased in earlier years (2012-2017, P trend <0.001), after which the trend was stable ( P trend =0.093)., Conclusions: Over a 13-year-period, there has been a significant increase in use of newer P2Y 12 inhibitors, although uptake of prasugrel use remained significantly lower than ticagrelor. Earlier society guidelines (pre-2017) were associated with the highest rates of ticagrelor use for non-ST-segment-elevation acute coronary syndrome and ST-segment-elevation myocardial infarction cases while the ISAR-REACT 5 (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome) trial and later society guidelines were associated with higher prasugrel use, mainly for ST-segment-elevation myocardial infarction indication.

Background: The purpose of this study was to investigate a therapeutic approach targeting the inflammatory response and consequent remodeling from ischemic myocardial injury., Methods and Results: Coronary thrombus aspirates were collected from patients at the time of ST-segment-elevation myocardial infarction and subjected to array-based proteome analysis. Clinically indistinguishable at myocardial infarction (MI), patients were stratified into vulnerable and resilient on the basis of 1-year left ventricular ejection fraction and death. Network analysis from coronary aspirates revealed prioritization of tumor necrosis factor-α signaling in patients with worse clinical outcomes. Infliximab, a tumor necrosis factor-α inhibitor, was infused intravenously at reperfusion in a porcine MI model to assess whether infliximab-mediated immune modulation impacts post-MI injury. At 3 days after MI (n=7), infliximab infusion increased proregenerative M2 macrophages in the myocardial border zone as quantified by immunofluorescence (24.1%±23.3% in infliximab versus 9.29%±8.7% in sham; P <0.01). Concomitantly, immunoassays of coronary sinus samples quantified lower troponin I levels (41.72±7.34 pg/mL versus 58.11±10.75 pg/mL; P <0.05) and secreted protein analysis revealed upregulation of injury-modifying interleukin-2, -4, -10, -12, and -18 cytokines in the infliximab-treated cohort. At 4 weeks (n=12), infliximab treatment resulted in significant protective influence, improving left ventricular ejection fraction (53.9%±5.4% versus 36.2%±5.3%; P <0.001) and reducing scar size (8.31%±10.9% versus 17.41%±12.5%; P <0.05)., Conclusions: Profiling of coronary thrombus aspirates in patients with ST-segment-elevation MI revealed highest association for tumor necrosis factor-α in injury risk. Infliximab-mediated immune modulation offers an actionable pathway to alter MI-induced inflammatory response, preserving contractility and limiting adverse structural remodeling.

Background and Aims: The evidence for beta-blocker therapy after myocardial infarction (MI) is randomized trials conducted more than 30 years ago, and the continued efficacy has been questioned., Design and Methods: The ongoing Danish (DANBLOCK) and Norwegian (BETAMI) randomized beta-blocker trials are joined to evaluate the effectiveness and risks of long-term beta-blocker therapy after MI. Patients with normal or mildly reduced left ventricular ejection fraction (LVEF ≥ 40%) will be randomized to open-label treatment with beta-blockers or no such therapy. The event-driven trial will randomize ∼5700 patients and continue until 950 primary endpoints have occurred. As of July 2023, 5228 patients have been randomized. Of the first 4000 patients randomized, median age was 62 years, 79% were men, 48% had a ST-segment elevation myocardial infarction (STEMI), and 84% had a normal LVEF. The primary endpoint is a composite of adjudicated recurrent MI, incident heart failure (HF), coronary revascularization, ischaemic stroke, all-cause mortality, malignant ventricular arrhythmia, or resuscitated cardiac arrest. The primary safety endpoint includes a composite of recurrent MI, HF, all-cause mortality, malignant ventricular arrhythmia, or resuscitated cardiac arrest 30 days after randomization. Secondary endpoints include each of the components of the primary endpoint, patient-reported outcomes, and other clinical outcomes linked to beta-blocker therapy. The primary analysis will be conducted according to the intention-to-treat principle using a Cox proportional hazards regression model. End of follow-up is expected in December 2024., Conclusion: The combined BETAMI-DANBLOCK trial will have the potential to affect current clinical practice for beta-blocker therapy in patients with normal or mildly reduced LVEF after MI., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aim: The efficacy and safety of bivalirudin when used concurrently with glycoprotein IIb/IIIa inhibitors (GPI) is uncertain. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of bivalirudin versus heparin in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) and to explore the impact of differential use (greater and balanced) of GPI., Methods: Online databases were queried from inception to March 2023 to identify eight randomized controlled trials (n = 22,483) for inclusion. The primary outcomes included all-cause mortality, major bleeding, major adverse cardiovascular events (MACE), and net adverse clinical events (NACE). Secondary efficacy endpoints included cardiac death, reinfarction, stent thrombosis (ST), and stroke. Data were pooled using a random-effects model to derive risk ratios (RRs) and 95% confidence intervals (CIs)., Results: When compared to heparin, bivalirudin was associated with a significant reduction in all-cause mortality (RR 0.83; 95% CI 0.72-0.97; P = 0.02), major bleeding (RR 0.73; 95% CI 0.57-0.93; P = 0.01), cardiac death (RR 0.79; 95% CI 0.66-0.94; P = 0.01), and NACE (RR 0.80; 95% CI 0.72-0.89; P < 0.0001). However, while the bivalirudin arm showed an increased likelihood of ST in the greater GPI subgroup (RR 1.70; 95% CI 1.13-2.56; P = 0.01), it was associated with a decreased likelihood of ST in the balanced GPI subgroup (RR 0.40; 95% CI 0.24-0.65; P = 0.0003)., Conclusion: Overall, our findings suggest that bivalirudin may be a more efficacious intervention than heparin for reducing certain adverse events in patients with STEMI undergoing primary PCI., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Postprocedural anticoagulation (PPA) is frequently administered after primary percutaneous coronary intervention in ST-segment-elevation myocardial infarction, although no conclusive data support this practice., Methods: The RIGHT trial (Comparison of Anticoagulation Prolongation vs no Anticoagulation in STEMI Patients After Primary PCI) was an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled, superiority trial conducted at 53 centers in China. Patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention were randomly assigned by center to receive low-dose PPA or matching placebo for at least 48 hours. Before trial initiation, each center selected 1 of 3 PPA regimens (40 mg of enoxaparin once daily subcutaneously; 10 U·kg·h of unfractionated heparin intravenously, adjusted to maintain activated clotting time between 150 and 220 seconds; or 0.2 mg·kg·h of bivalirudin intravenously). The primary efficacy objective was to demonstrate superiority of PPA to reduce the primary efficacy end point of all-cause death, nonfatal myocardial infarction, nonfatal stroke, stent thrombosis (definite), or urgent revascularization (any vessel) within 30 days. The key secondary objective was to evaluate the effect of each specific anticoagulation regimen (enoxaparin, unfractionated heparin, or bivalirudin) on the primary efficacy end point. The primary safety end point was Bleeding Academic Research Consortium 3 to 5 bleeding at 30 days., Results: Between January 10, 2019, and September 18, 2021, a total of 2989 patients were randomized. The primary efficacy end point occurred in 37 patients (2.5%) in both the PPA and placebo groups (hazard ratio, 1.00 [95% CI, 0.63 to 1.57]). The incidence of Bleeding Academic Research Consortium 3 to 5 bleeding did not differ between the PPA and placebo groups (8 [0.5%] vs 11 [0.7%] patients; hazard ratio, 0.74 [95% CI, 0.30 to 1.83])., Conclusions: Routine PPA after primary percutaneous coronary intervention was safe but did not reduce 30-day ischemic events., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03664180., Competing Interests: Disclosures Dr Yan was funded by grants from the National Natural Science Foundation of China (82100260) and Beijing Hospitals Authority Youth Program (QML20210605). Dr X. Wang was funded by grants from National Key Research & Development Program of China (2022YFC2505600), Beijing Nova Program (Z201100006820087), Interdisciplinary Cooperation Project of Beijing Nova Program (Z211100002121165), and Natural Science Foundation of Beijing, China (7222046). Dr Ma reports honoraria from Bristol-Myers Squibb, Pfizer, Johnson & Johnson, Boehringer-Ingelheim, Bayer, and AstraZeneca for giving lectures. Dr Vicaut reports consulting fees from Abbott and Bristol-Myers Squibb. Dr Montalescot reports research grants to the institution or consulting or lecture fees from Abbott, Amgen, AstraZeneca, Ascendia, Bayer, Bristol-Myers Squibb, Boehringer-Ingelheim, Boston-Scientific, Celecor, CSL Behring, Idorsia, Lilly, Novartis, Novo, Opalia, Pfizer, Quantum Genomics, Sanofi, and Terumo. Dr Nie was funded by Beijing Hospitals Authority Clinical Medicine Development of Special Funding support (grant ZLRK202318), National Natural Science Foundation of China (grant 82270258), and Beijing Municipal Science & Technology Commission, China (grant Z221100003522027), and reports research grants to the institution from Boston Scientific, Abbott, Jiangsu Hengrui Pharmaceuticals, China Resources Sanjiu Medical & Pharmaceuticals, and East China Pharmaceuticals. The other authors have no conflicts of interest to declare.

Background: The effect of administering a crushed prasugrel loading dose is uncertain in patients presenting with a large myocardial infarction and ST-segment elevation myocardial infarction (STEMI)., Aims: The aim of this study was to investigate if patients with a large myocardial infarction may benefit from prehospital administration of a crushed prasugrel loading dose., Methods: Patients from the CompareCrush trial with an available ambulance electrocardiography (ECG) were included in the study. An independent core laboratory confirmed a prehospital large myocardial area. We compared pre- and postprocedural angiographic markers, including Thrombolysis in Myocardial Infarction (TIMI) 3 flow in the infarct-related artery, high thrombus burden, and myocardial blush grade 3, in STEMI patients with and without a prehospital large myocardial area., Results: Ambulance ECG was available for 532 patients, of whom 331 patients were identified with a prehospital large myocardial area at risk. Crushed prasugrel significantly improved postprocedural TIMI 3 flow rates in STEMI patients with a prehospital large myocardial area at risk (92% vs 79%, odds ratio [OR] 3.00, 95% confidence interval [CI]: 1.50-6.00) but not in STEMI patients without a prehospital large myocardial area at risk (91% vs 95%, OR 0.47, 95% CI: 0.14-1.57; p interaction =0.009)., Conclusions: Administration of crushed prasugrel may improve postprocedural TIMI 3 flow in STEMI patients with signs of a large myocardial area at risk on the ambulance ECG. The practice of crushing tablets of prasugrel loading dose might, therefore, represent a safe, fast and cost-effective strategy to improve myocardial reperfusion in this high-risk STEMI subgroup undergoing primary percutaneous coronary intervention.

Competing Interests: Conflict of interest: A.S. received lecture fees and honoraria from Abiomed, Amgen, Astra Zeneca, Daiichi-Sankyo, Boehringer Ingelheim, Bayer, Berlin Chemie, BMS, Pfizer, and ZOLL as well as research support by Abiomed and Daiichi-Sankyo. J.B. received lecture fees and honoraria from Novartis, Vifor, Bayer, Pfizer, Boehringer Ingelheim, AstraZeneca, Cardior, CVRx, BMS, Amgen, and Corvia as well as research support by Zoll, CVRx, and Abiomed. All other authors have no conflict of interest to declare.

Aims: People in remote areas may have more difficulty accessing healthcare following myocardial infarction (MI) than people in metropolitan areas. We determined whether remoteness was associated with initial and 12-month use of secondary prevention medications following MI in Victoria, Australia., Methods and Results: We included all people alive at least 90 days after discharge following MI between July 2012 and June 2017 in Victoria, Australia (n = 41 925). We investigated dispensing of P2Y12 inhibitors (P2Y12i), statins, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs), and beta-blockers within 90 days after discharge. We estimated 12-month medication use using proportion of days covered (PDC). Remoteness was determined using the Accessibility/Remoteness Index of Australia (ARIA). Data were analysed using adjusted parametric regression models stratified by ST elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI). There were 10 819 STEMI admissions and 31 106 NSTEMI admissions. Following adjustment across NSTEMI and STEMI, there were no medication classes dispensed in the 90-day post-discharge that differed in a clinically significant way from the least remote (ARIA = 0) to the most remote (ARIA = 4.8) areas. The largest difference for NSTEMI was ACEI/ARB, with 71% (95% confidence interval 70-72%) vs. 80% (76-83%). For STEMI, it was statins with 89% (88-90%) vs. 95% (91-97%). Predicted PDC for STEMI and NSTEMI was not clinically significant across remoteness, with the largest difference in NSTEMI being P2Y12i with 48% (47-50%) vs. 55% (51-59%), and in STEMI, it was ACEI/ARB with 68% (67-69%) vs. 76% (70-80%)., Conclusion: Remoteness does not appear to be a clinically significant driver for medication use following MI. Possible differences in cardiovascular outcomes in metropolitan and non-metropolitan areas are not likely to be explained by access to secondary prevention medications., Competing Interests: Conflict of interest: A.C.L., Z.A., D.P., and J.I.M. have no conflicts to declare relevant to this publication. J.I. has received grants from the NHMRC, National Breast Cancer Foundation, Dementia Australia Research Foundation, AstraZeneca. and Amgen. J.S.B. is supported by a National Health and Medical Research Council (NHMRC) Boosting Dementia Research Leadership Fellowship and has received grant funding or consulting funds from the NHMRC, Medical Research Future Fund, Victorian Government Department of Health, Dementia Australia Research Foundation, Yulgilbar Foundation, Aged Care Quality and Safety Commission, Dementia Centre for Research Collaboration, Pharmaceutical Society of Australia, Society of Hospital Pharmacists of Australia, GlaxoSmithKline Supported Studies Programme, Amgen, and several aged care provider organizations unrelated to this work. All grants and consulting funds were paid to the employing institution., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: None declared

Background: Patients who sustain an acute myocardial infarction (AMI), including ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI), remain at high risk for heart failure (HF), coronary events, and death. Angiotensin-converting enzyme inhibitors have been shown to significantly decrease the risk for cardiovascular events in both STEMI and NSTEMI patients., Objectives: The objectives were to determine whether angiotensin-receptor blockade and neprilysin inhibition with sacubitril/valsartan, compared with ramipril, has impact on reducing cardiovascular events according to the type of AMI., Methods: The PARADISE-MI (Prospective ARNI versus ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction) trial enrolled patients with AMI complicated by left ventricular dysfunction and/or pulmonary congestion and at least 1 risk-enhancing factor. Patients were randomized to either sacubitril/valsartan or ramipril. The primary endpoint was death from cardiovascular causes or incident HF. In this prespecified analysis, we stratified patients according to AMI type., Results: Of 5,661 enrolled patients, 4,291 (75.8%) had STEMI. These patients were younger and had fewer comorbidities and cardiovascular risk factors than NSTEMI patients. After adjustment for potential confounders, the risk for the primary outcome was marginally higher in NSTEMI vs STEMI patients (adjusted HR: 1.19; 95% CI: 1.00-1.41), with borderline statistical significance (P = 0.05). The primary composite outcome occurred at similar rates in patients randomized to sacubitril/valsartan vs ramipril in STEMI (10% vs 12%; HR: 0.87; 95% CI: 0.73-1.04; P = 0.13) and NSTEMI patients (17% vs 17%; HR: 0.97; 95% CI: 0.75-1.25; P = 0.80; P interaction = 0.53)., Conclusions: Compared with ramipril, sacubitril/valsartan did not significantly decrease the risk for cardiovascular death and HF in patients with AMI complicated by left ventricular dysfunction, irrespective of the type of AMI. (Prospective ARNI vs ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After MI; NCT02924727)., Competing Interests: Funding Support and Author Disclosures The PARADISE-MI trial was funded by Novartis. Dr Braunwald has received research grants through his institution from AstraZeneca, Daiichi-Sankyo, Merck, and Novartis; and has consultancies with Amgen, Bristol Myers Squibb, Boehringer Ingelheim/Lilly, Cardurion, and Verve. Dr Claggert has received consultancy fees from Novartis, Amgen, Boehringer Ingelheim, Cardurion, Corvia, and Myokardia. Dr Granger has received research grants from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, Duke Clinical Research Institute, FDA, GlaxoSmithKline, Janssen Pharmaceutical Products, L.P., Medtronic Foundation, Novartis Pharmaceutic Company, and Pfizer; has received consulting fees from Abbvie, Abiomed, Alnylam Pharm, Bayer Corporation US, Boehringer Ingelheim, Boston Scientific Corporation, Bristol Myers Squibb, Cardionomic, CeleCor Therapeutics, HengRui USA, Janssen Pharmaceutica Products, L.P., Medscape, LLC, Medtronic Inc, Merck, NIH, Novo Nordisk, Novartis Pharmaceutic Company, Pfizer, Phillips, and REATA; and owns equity in Tenac.io. Dr Kerkar has received speaker fees from Novartis, AstraZeneca, Bayer Zydus, Boehringer Ingelheim, Cipla, Dr Reddy’s, Emcure, Intas, Johnson and Johnson, Mankind, Pfizer, Torrent, and USV. Dr Kober has received speaker honorarium from Nova, Novartis, AstraZeneca, Bayer, and Boehringer. Dr Lewis has received personal fees from Amgen and Dal-Cor. Dr Maggioni has received personal fees for participation in committees of studies supported by Bayer, Novartis, AstraZeneca, and Fresenius, outside the present work. Dr Mann has received consulting fees from Cardurion, HAYA Therapeutics, Tenaya, and Novo Nordisk. Dr Mehran has received institutional research payments from Abbott, Abiomed, Alleviant Medical, AM-Pharma, Applied Therapeutics, Arena, AstraZeneca, BAIM, Bayer, Beth Israel Deaconess, Biosensors, Biotronik, Boston Scientific, Bristol Myers Squibb, CardiaWave, CellAegis, CeloNova, CERC, Chiesi, Concept Medical, CSL Behring, Cytosorbents, DSI, Duke University, Element Science, Faraday, Humacyte, Idorsia, Insel Gruppe AG, Magenta, Medtronic, Novartis, OrbusNeich, Philips, RenalPro, Vivasure, and Zoll; has received personal fees from Cine-Med Research and WebMD; has received consulting fees paid to the institution from Abbott, Janssen, Medtronic, and Novartis; has equity <1% in Applied Therapeutics, Elixir Medical, STEL, and CONTROLRAD (spouse); and is on the Scientific Advisory Board for AMA, ACC (BOT Member), SCAI (Women in Innovations Committee Member), and JAMA Associate Editor; and Faculty CRF (no fee). Dr McMurray has received payments through Glasgow University from work on clinical trials, consulting, and other activities from Amgen, AstraZeneca, Bayer, Cardurion, Cytokinetics, GSK, KBP Biosciences, and Novartis; has received personal consultancy fees from Alnylam Pharma, Bayer, BMS, George Clinical PTY Ltd, Ionis Pharma, Novartis, Regeneron Pharma, and River 2 Renal Corporation; has received personal lecture fees from Abbott, Alkem Metabolics, AstraZeneca, Blue Ocean Scientific Solutions Ltd., Boehringer Ingelheim, Canadian Medical and Surgical Knowledge, Emcure Pharma. Ltd, Eris Lifesciences, European Academy of CME, Hikma Pharmaceuticals, Imagica health, Intas Pharma, J.B. Chemicals & Pharma. Ltd, Lupin Pharma, Medscape/Heart.Org, ProAdWise Communications, Radcliffe Cardiology, Sun Pharma., The Corpus, Translation Research Group, and Translational Medicine Academy; and he is a director of Global Clinical Trial Partners Ltd. Dr Nunez has received personal fees from or is on the advisory boards for Alleviant, AstraZeneca, Boehringer Ingelheim, Bayer, Cytokinetics, Novartis, Novo Nordisk, Rovi, and Vifor Pharma. Dr Pfeffer has received research grant support through his institution from Novartis; has been a consultant to Alnylam, AstraZeneca, Boehringer Ingelheim and Eli Lilly Alliance, Corvidia, DalCor, GlaxoSmithKline, Lexicon, NHLBI CONNECTs (Master Protocol Committee), Novartis, Novo Nordisk, Peerbridge, and Sanofi; and has equity in DalCor. Dr Rouleau has received consultant fees from Novartis, BMS, Bayer, and AstraZeneca. Dr Sim has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, BMS, Celladon, Cytokinetics, Eidos, Gilead, GSK, Ionis, Lilly, Mesoblast, MyoKardia, NIH/NHLBI, Neurotronik, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI; and has consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GSK, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Puretech Health. Dr Solomon has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lilly, Mesoblast, MyoKardia, National Institutes of Health/NHLBI, Neurotronik, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI; and has consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellPro-Thera, Moderna, American Regent, and Sarepta. Dr Steg has received research grants from Amarin, Bayer, Sanofi, and Servier; and has received speaker or consultant fees from Amarin, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Janssen, Kowa, Idorsia, Lexicon, Merck, Novartis, Novo Nordisk, PhaseBio, Pfizer, Regeneron, Sanofi, and Servier. Dr Van der Meer has received consultancy fees and/or grants, through the University Medical Center Groningen, from Novartis, Pharmacosmos, Vifor Pharma, AstraZeneca, Pfizer, Pharma Nord, BridgeBio, Novo Nordisk, Daiichi-Sankyo, Boehringer Ingelheim, and Ionis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Introduction: ST-segment elevation myocardial infarction (STEMI) is a fatal disease with significant burden worldwide. Despite advanced medical treatment performed, STEMIrelated morbidity and mortality remains high due to ischemia reperfusion injury after primary angioplasty mediated by NLRP3 inflammasome. Adding colchicine expected to reduce inflammation both in vitro and in vivo. We want to evaluate the effect of colchicine administration on the NLRP3 level of STEMI patient who undergo primary cutaneous intervention (PCI)., Materials and Methods: Randomised controlled trial was conducted on STEMI patients who undergo PCI in two hospitals in Jakarta, 104 patients enrolled to this study, and 77 patients completed the trial. 37 patients were randomly assigned to receive colchicines (2 mg loading dose; 0.5 mg thereafter every 12 hour for 48 hours) while 40 patients received placebo. NLRP3 level was measured from venous blood at baseline (BL), after procedure (AP), dan 24-hour post procedure (24H)., Results: No NLRP3 difference was observed initially between colchicine arm and placebo arm 38,69 and 39,0138, respectively (p >0.05). Measurement conducted at 24H, patients received colchicine demonstrate reduction in NLRP3 level (37.67), while placebo arm results increase in NLRP3 level (42.89) despite not statistically significant (p >0,05)., Conclusion: Colchicine addition to standard treatment of STEMI patients undergo PCI reduce NLRP3 level despite statistically insignificant.

Background: Interleukin-1 blockade with anakinra reduces C-reactive protein (CRP) levels and prevents heart failure (HF) events after ST-segment myocardial infarction (STEMI). The effectiveness of anakinra according to the degree of systemic inflammation in STEMI has not been addressed., Methods: We analyzed 139 patients from three Virginia Commonwealth University Anakinra Response Trial randomized clinical trials to assess whether CRP levels predicted HF hospitalization or death in patients with STEMI, and if CRP levels influenced the effects of treatment with anakinra., Results: CRP cut-off levels for prediction of the composite of death or HF hospitalization for CRP at admission, 3 and 14 days were, respectively 6.45 mg/L (100% of sensitivity and 66.1% specificity), 26 mg/L (100% of sensitivity and 78% specificity) and 9.56 mg/L (100% of sensitivity and 80% specificity). More patients with elevated CRP levels died or had a HF hospitalization (5/47 [11%] vs 0/82 [0%], p = 0.004 for CRP at admission; 5/32 [15.6%] vs 0/92 [0%], p < 0.001 for day 3 and 5/26 [19%] vs 0/89 [0%], p < 0.001 for day 14). A greater number of patients treated with anakinra had low CRP levels at 3 and 14 days compared to placebo (Odds Ratio 0.11 [95% IC 0.04-0.28], p < 0.0001 and OR 0.35 [95% CI 0.14-0.86], p = 0.02, respectively). Anakinra significantly prevented death or HF hospitalization in patients with high inflammatory burden (p = 0.04 for admission, p = 0.24 for day 3, and p = 0.05 for day 14)., Conclusion: Patients with elevated CRP had higher incidence of HF hospitalization or death. Anakinra reduced the number of patients with elevated CRP levels and prevented death or HF hospitalization in patients with elevated CRP levels., Competing Interests: Declaration of Competing Interest Dr. Abbate and Dr. Van Tassell have served as consultants to Swedish Orphan Biovitrum LLC in the past. Dr. Abbate has also served as a consultant to Cardiol Therapeutics, Kiniksa Pharmaceuticals, Implicit Biosciences, Novo Nordisk, Olatec, and R-Pharm. The remaining authors have no disclosures to report., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aim: Based on data from the Russian REGION-IM registry, to study the features of reperfusion therapy in patients with ST-segment elevation myocardial infarction (STEMI) in real-life clinical practice., Material and Methods: REGION-IM is a multicenter prospective observational study. The observational period is divided into 3 stages: during the stay in the hospital and at 6 and 12 months after inclusion in the registry. The patient's records contain demographic and history data; information about the present case of MI, including the time of the first symptom onset, first contact with medical personnel, and admission to the hospital; coronary angiography (CAG) data, percutaneous coronary intervention (PCI) data, and information about the thrombolytic therapy (TLT)., Results: Reperfusion therapy was performed in 88.9 % of patients with STEMI. Primary PCI (pPCI) was performed in 60.6 % of patients. The median time from the onset of symptoms to pPCI was 315 minutes [195; 720]. The median time from ECG to pPCI was 110 minutes [84;150]. Isolated TLT was performed in 7.4 %, pharmaco-invasive treatment tactics were used only in 20.9 % of cases. The median time from ECG to TLT (prehospital and in-hospital) was 30 minutes [10; 59], whereas the median time from ECG to prehospital TLT was 18 minutes [10; 39], and in 63 % of patients, TLT was performed more than 10 minutes after diagnosis. PCI followed TLT in 73 % of patients., Conclusion: The frequency of reperfusion therapy for STEMI in the Russian Federation has increased considerably in recent years. The high frequency of pPCI is noteworthy, but the timing of pPCI does not always comply with clinical guidelines. The results of this registry confirm the high demand for pharmaco-invasive strategies in real-life clinical practice. Taking into account geographical and logistical features, implementing timely myocardial reperfusion requires prehospital TLT. However, the TLT frequency in the Russian Federation is still insufficient despite its proven maximum effectiveness in the shortest possible time from the detection of acute MI.

Background: A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI., Methods: In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints., Results: From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA ( n = 384) or rt-PA ( n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a -15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: -3.4%; 95% confidence interval [CI]: -11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: -0.5%; 95% CI: -5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups., Conclusion: rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI., Trial Registration: www.ClinicalTrials.gov (No. NCT02835534)., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

The new guidelines of the European Society of Cardiology (ESC) on the management of acute coronary syndrome (ACS) in 2023 encompass updates for both the guidelines pertaining to ST elevation myocardial infarction (STEMI) and acute coronary syndrome without ST segment elevation (NSTE-ACS). The previously separated guidelines from 2017 and 2020 were therefore revised and summarized. These guidelines address various topics, including diagnostics, acute management, antithrombotic treatment, out-of-hospital cardiac arrest, cardiogenic shock, invasive strategies, and long-term treatment. The notable updates compared to earlier guidelines address the recommendation regarding the timing of invasive diagnostics in NSTE-ACS (Non-ST elevation acute coronary syndrome), the procedure of revascularization in multivessel coronary artery disease and alternative regimens for antithrombotic treatment in patients with a high risk of bleeding., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Interleukin-1 blockade with anakinra reduces high-sensitivity C-reactive protein (hsCRP) levels and prevents heart failure (HF) events after ST-segment myocardial infarction (STEMI). Sex-based differences in STEMI patients have been reported, but no data are available regarding response to anakinra., Methods: We analyzed the systemic inflammation and composite end-point of new-onset HF or death in women and men with STEMI treated with anakinra from three different Virginia Commonwealth University Anakinra Response Trial (VCUART) randomized clinical trials., Results: We analyzed 139 patients, 29 (21%) were women while 110 (79%) were men. Baseline hsCRP was higher in women compared to men (8.9 [5.2-13.5] vs. 4.2 [2.1-7.7] mg/L, P<0.001). Eighty-four patients were treated with anakinra (22 [75%] women and 62 [56%] men). The area under the curve of hsCRP (hsCRP-AUC) after 14 days was numerically lower in patients receiving anakinra versus placebo both in men (86 [37-130] vs. 223 [119-374] mg day/L) and in women (73 [46-313] vs. 242 [102-988] mg day/L) (P<0.001 for multiple groups, P for interaction 0.22). The incidence of the composite endpoint was also numerically lower in the anakinra group compared to placebo, both in men (4 [6.4%] vs. 14 [29.1%]) and in women (3 [13.6%] vs. 2 [28.5%]) (P=0.019 for multiple groups, P for interaction 0.44). There were no statistically significant differences between women and men in hsCRP-AUC and death or HF events when comparing separately the anakinra and placebo groups (all P>0.05)., Conclusions: Women were underrepresented in the VCUART trials, they appeared to have higher hsCRP levels at time of presentation, yet to benefit similar to men by treatment with anakinra in STEMI.

Atorvastatin is widely recommended for long-term secondary prevention in STEMI patients with no contraindication. Although high-dose atorvastatin has been shown to reduce important patient outcomes such as MACE, there is still doubt that high-dose atorvastatin could have the same protective effect in patients undergoing PCI in the short and long term. We searched the following electronic databases: Scopus, Web of Science, MEDLINE, EMBASE, and Cochrane Central considering studies that enrolled adult patients with a confirmed diagnosis of STEMI or NSTEMI undergoing PCI. The intervention must have been atorvastatin alone compared to a placebo, standard care, or a different atorvastatin dose. A total of (n = 11) studies were included in the quantitative analysis. Information on (N = 5,399) patients was available; 2,654 were assigned to receive high-dose atorvastatin therapy, and 2,745 comprised the control group. High-dose atorvastatin pre-loading significantly reduced MACE at one month of follow-up (RR: 0.78; 95% CI: 0.67-0.91; p = 0.014) in both STEMI and NSTEMI. All-cause mortality was reduced in patients with STEMI (RR: 0.28; 95% CI: 0.10-0.81; p = 0.029). The quality of the body of evidence was rated overall as moderate. Patients presenting with STEMI or NSTEMI benefit from high-dose atorvastatin pre-loading before PCI by reducing MACE at 30 days. The use of high-dose atorvastatin in STEMI patients reduced all-cause mortality. The beneficial effects of atorvastatin pre-loading are limited to 30 days post-PCI., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 García-Campa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The efficacy of intracoronary (IC) antithrombotic therapy, which may best prevent the no-reflow phenomenon during percutaneous coronary intervention (PCI), remains unclear. Therefore, we compared the efficacy and safety of different IC antithrombotic agents., Materials and Methods: This systematic review and network meta-analysis of randomized controlled trials (RCTs) compared IC fibrinolytic agents (recombinant tissue plasminogen activators [rtPAs] and non-rtPAs) or glycoprotein IIb/IIIa inhibitors (small molecules and monoclonal antibodies) with placebo by searching the relevant studies published before September 21, 2022. Bayesian network meta-analyses were performed using random-effects models., Results: Twenty-five RCTs with 4546 patients were included. Non-rtPAs and small molecules were significantly more effective in achieving thrombolysis in myocardial infarction (TIMI) grade 3 flow than placebo (odds ratio [OR] 2.28, 95 % credible intervals [CrI] 1.24-4.13; OR 2.06, 95 % CrI 1.17-3.46). Moreover, these agents' efficacy was observed in other microcirculation-related outcomes, including TIMI myocardial perfusion grade 3, complete ST-segment resolution, and corrected TIMI frame counts. Within 6 months, small molecules were associated with both an improved left ventricular ejection fraction (MD 3.90, 95 % CrI 0.48-7.46) and major adverse cardiac events (MACE) reduction (OR 0.36, 95 % CrI 0.20-0.61). Non-rtPAs demonstrated a reduced MACE incidence within 6 months (OR 0.51, 95 % CrI 0.31-0.81). The results were consistent in the subgroup with a total ischemic time > 6 h. No significant differences in mortality or bleeding events were observed., Conclusions: IC non-rtPAs and small molecules may be effective for adjunctive therapy to PCI, particularly in patients with longer ischemia periods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This study investigated the efficacy and safety of pharmaco-invasive strategy with half-dose recombinant human prourokinase (PHDP) during hospitalization for patients with ST-segment elevation myocardial infarction (STEMI) to provide references for the treatment of STEMI. Patients with STEMI who fulfilled the inclusion and exclusion criteria and attended Chengde Central Hospital, Hebei Province, China, between September 3, 2019, and December 28, 2021, were included in this study. The experimental group received PHDP and the control group underwent primary percutaneous coronary intervention (PPCI). This study enrolled 150 patients with STEMI, 75 in the experimental group and 75 in the control group. Coronary angiography revealed successful thrombolysis in 64 (85.33%) patients. Compared with the control group, the experimental group had shorter first medical contact-reperfusion time ( P  < 0.001), less slow flow/no-reflow ( P  < 0.001), and a lower utilization rate of Tirofiban ( P  < 0.001). Validity endpoints: no statistically significant differences between the two groups. Safety endpoints: no statistically significant differences between bleeding and major adverse cardiovascular and cerebrovascular events (MACCEs), but the experimental group was more prone to arrhythmias ( P  = 0.040), particularly premature ventricular beats (PVB) ( P  = 0.008). In conclusion, the efficacy and safety of PHDP in the treatment of patients with STEMI were positive. Complete epicardial and myocardial reperfusion rates, risk for bleeding during hospitalization, and incidence of MACCEs were similar to those of the PPCI strategy. Although the PHDP group has a higher incidence of PVB, it does not increase the incidence of malignant arrhythmia. This study aimed to provide a new therapeutic strategy for the treatment of STEMI in hospitals without adequate PPCI resources condition., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: It has been demonstrated that there is a significant reduction in the incidence of cardiovascular events, mortality rates, and worsening kidney disease in patients using sodium-glucose cotransporter 2 inhibitors (SGLT2i). However, there is limited information about the effect of SGLT2i on the incidence of contrast-induced acute kidney injury (CI-AKI) in patients undergoing primary percutaneous intervention (pPCI)., Aims: Our research was focused on examining how SGLT2i exposure impacts CI-AKI occurrence in patients with ST-segment elevation myocardial infarction (STEMI) and undergoing pPCI., Results: This retrospective, single-center, case-control study included diabetic patients diagnosed with STEMI who underwent pPCI in a tertiary healthcare center between 2021 and 2022. The study population included SGLT2i users (n = 130) and non-SGLT2i users (n = 165). Inverse probability propensity score weighting and doubly robust estimation were performed to decrease bias and to balance covariate distribution for estimating average treatment for those treated. In a doubly robust inverse probability weighted regression model, in which covariates were balanced, CI-AKI risk was also found to be lower in the SGLT2i-user group (OR: 0.86 [0.76-0.98]; 95% CI; P = 0.028). In addition, ejection fraction, admission creatinine, albumin, and volume of contrast media were found to be independent predictors of CI-AKI in patients presenting with STEMI and undergoing pPCI., Conclusion: Our study provides evidence supporting the potential protective effect of SGLT2i against CI-AKI in diabetic patients presenting with STEMI and undergoing pPCI.

Purpose: There is accumulating evidence regarding the potential benefits of empagliflozin in individuals with acute myocardial infarction (MI). Based on the literature, colchicine could also reduce the risk of MI and death in individuals with cardiovascular disease (CVD). However, trials investigating the effects of the combination of empagliflozin with colchicine and high-dose empagliflozin monotherapy in this setting are lacking., Methods: In this trial, 106 non-diabetic participants with reduced left ventricular ejection fraction (LVEF) following recent ST-elevation MI were randomly assigned to empagliflozin 10 mg/day, empagliflozin 10 mg/day plus colchicine 0.5 mg twice daily, or empagliflozin 25 mg/day groups within 72 h after primary percutaneous coronary intervention (PCI). The study's primary outcomes were the changes in New York Heart Association (NYHA) functional class and high-sensitivity C-reactive protein (hs-CRP) over 12 weeks., Results: The baseline characteristics of individuals were statistically similar between the study groups. Changes in NYHA functional class over 12 weeks were not significantly different between the study groups. hs-CRP was significantly reduced in all groups (all P < 0.001); however, there was no significant change between the groups over the study period. Changes in tumor necrosis factor-alpha (TNF-α), LVEF, and left ventricular end-diastolic dimension (LVEDD) during the research period did not differ significantly between groups., Conclusion: This study showed that neither the combination treatment of empagliflozin 10 mg/day with colchicine nor the monotherapy of empagliflozin 25 mg/day was superior to empagliflozin 10 mg/day in terms of changes in clinical, inflammatory, and echocardiographic outcome parameters in patients with recent MI with reduced LVEF over 3 months. Further studies are warranted to confirm the findings., Trial Registration: Clinical trial ID: IRCT20111206008307N39. Registration date: 27 October 2022. https://www.irct.ir/trial/66216., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

It was to explore the application value of individualized nursing oriented by solution-focused nursing mode in postoperative nursing of patients with pelvic fractures. 90 patients with ST-segment elevation myocardial infarction (STEMI) undergoing emergency percutaneous coronary intervention (PCI) were enrolled. They were randomly grouped into a control group and an experimental group, with 45 cases in each group. Patients in the general group were treated with conventional treatment, and patients in the enhancement group were treated with high-dose rosuvastatin based on conventional treatment. The experimental group was compared for indicators such as serum inflammatory factors, cardiac function, overall efficacy, and follow-up prognosis before and after the operation. After treatment, the total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in the enhancement group were better as against the control group (P<0.05). Through treatment, the concentration of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the enhancement group was lower compared to the general group. The total effective rate of the enhancement group (95.56%) was higher relative to the general group (86.67%) (P<0.05). In patients with STEMI, preoperative intensive statin therapy can improve the efficacy of PCI, and reduce the inflammatory response and the incidence of cardiovascular events.

Background: The use of bivalirudin-based anticoagulation over heparin-based anticoagulation for coronary percutaneous intervention has been debated for a long time. Multiple trials have shown promising benefits of bivalirudin over heparin therapy with the most recent addition being the BRIGHT-4 trial. We performed a meta-analysis to assess evidence from these trials, focusing on the coronary intervention of the STEMI population., Methods: This meta-analysis was performed based on PRISMA guidelines after registering in PROSPERO (CRD42023394701). Databases were searched for relevant articles published before January 2023. Pertinent data from the included studies were extracted and analyzed using RevMan v5.4., Results: Out of 2375 studies evaluated, 13 randomized control trials with 24 360 acute ST-elevation myocardial infarction patients were included for analysis. The bivalirudin-based anticoagulation reduced the net clinical events (OR 0.75, CI 0.61-0.92), major adverse cardiac or cerebral events (OR 0.85, CI 0.74-0.98), any bleeding (OR 0.61, CI 0.45-0.83), major bleeding (OR 0.54, CI 0.39-0.75), all-cause mortality (OR 0.79, CI 0.67-0.92) and cardiac mortality (OR 0.78, CI 0.65-0.93) significantly without increasing the risk of any stent thrombosis (OR 0.92, 95% CI 0.52-1.61), definite stent thrombosis (OR 1.17, 95% CI 0.62-2.22) and acute stent thrombosis (OR 2.06, 95% CI 0.69-6.09) significantly at 30 days., Conclusion: Based on this meta-analysis, bivalirudin plus a post-PCI high-dose infusion-based anticoagulation during STEMI PCI has significant benefits over heparin therapy for cardiovascular outcomes without a significant increase in the risk of thrombotic outcomes., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Biodegradable polymer sirolimus-eluting stents improve early stent-related clinical outcomes compared to durable polymer everolimus-eluting stents in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. The long-term advantages of biodegradable polymer sirolimus-eluting stents after complete degradation of its polymer coating in patients with STEMI remains however uncertain., Methods: BIOSTEMI Extended Survival (BIOSTEMI ES) was an investigator-initiated, follow-up extension study of the BIOSTEMI prospective, multicentre, single-blind, randomised superiority trial that compared biodegradable polymer sirolimus-eluting stents with durable polymer everolimus-eluting stents in patients with STEMI undergoing primary percutaneous coronary intervention at ten hospitals in Switzerland. All individuals who had provided written informed consent for participation in the BIOSTEMI trial were eligible for this follow-up study. The primary endpoint was target lesion failure, defined as a composite of cardiac death, target vessel myocardial re-infarction, or clinically indicated target lesion revascularisation, at 5 years. Superiority of biodegradable polymer sirolimus-eluting stents over durable polymer everolimus-eluting stents was declared if the Bayesian posterior probability for a rate ratio (RR) of less than 1 was greater than 0·975. Analyses were performed according to the intention-to-treat principle. The study was registered with ClinicalTrials.gov, NCT05484310., Findings: Between April 26, 2016, and March 9, 2018, 1300 patients with STEMI (1622 lesions) were randomly allocated in a 1:1 ratio to treatment with biodegradable polymer sirolimus-eluting stents (649 patients, 816 lesions) or durable polymer everolimus-eluting stents (651 patients, 806 lesions). At 5 years, the primary composite endpoint of target lesion failure occurred in 50 (8%) patients treated with biodegradable polymer sirolimus-eluting stents and in 72 (11%) patients treated with durable polymer everolimus-eluting stents (difference of -3%; RR 0·70, 95% Bayesian credible interval 0·51-0·95; Bayesian posterior probability for superiority 0·988)., Interpretation: In patients undergoing primary percutaneous coronary intervention for STEMI, biodegradable polymer sirolimus-eluting stents were superior to durable polymer everolimus-eluting stents with respect to target lesion failure at 5 years of follow-up. The difference was driven by a numerically lower risk for ischaemia-driven target lesion revascularisation., Funding: Biotronik., Competing Interests: Declaration of interests JFI reports a research grant to their institution, speaker fees, and support for attending meetings from Biotronik; research grants to their institution from Abbott Vascular, Astra Zeneca, Biosensors, Concept Medical, Philips, and Terumo Corporation, outside the submitted work; and speaker fees from AstraZeneca, Biosensors, Biotronik, Bristol Myers Squibb, Cordis, Concept Medical, Medalliance, Medtronic, Novartis, Terumo Corporation, Pfizer, and Philips, outside the submitted work. MR reports research grants to the institution from Biotronik, Boston Scientific, Cordis, Medtronic, and Terumo Corporation, outside the submitted work. SL and DH are employed by the CTU Bern, University of Bern, which has a staff policy of not accepting honoraria or consultancy fees. However, CTU Bern is involved in design, conduct, or analysis of clinical studies funded by not-for-profit and for-profit organisations. In particular, pharmaceutical and medical device companies provide direct funding to some of these studies. An up-to-date list of CTU Bern's conflicts of interest can be found online. OM reports a research grant to their institution, and speaker and personal fees from Edwards Lifesciences, outside the submitted work; and speaker fees from Abbott Vascular, outside the submitted work. SD reports research grants to their institution from Abbott Vascular and Biotronik, outside the submitted work; and speaker fees from Biotronik, Medalliance, and Medtronic, outside the submitted work. LH reports research grants to their institution from Abbott Vascular, Abiomed, Amarin, Amgen, AstraZeneca, Bayer, Biosense Webster, Biotronik, Boston Scientific, Bracco, Bristol Myers Squibb, B-Braun, Daiichi-Sankyo, Edwards Lifesciences, GE HealthCare, Medtronic, Microport, Novartis, Pfizer, Vascular Medical, and Zoll, outside the submitted work; speaker fees from Medtronic, outside the submitted work; and support for attending meetings from Daiichi-Sankyo and Biotronik. CK reports consulting fees to the institution from Unimedtec Switzerland; and support for attending meetings from Medtronic, outside the submitted work. SW reports research, travel, or educational grants to their institution from Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Bbraun, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardinal Health, CardioValve, Cordis Medical, Corflow Therapeutics, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Farapulse, Fumedica, Guerbet, Idorsia, Inari Medical, InfraRedx, Janssen-Cilag, Johnson & Johnson, Medalliance, Medicure, Medtronic, Merck Sharp & Dohme, Miracor Medical, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pharming Tech, Pfizer, Polares, Regeneron, Sanofi-Aventis, Servier, Sinomed, Terumo Corporation, Vifor, and V-Wave; and served as an advisory board member or member of the steering or executive group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Boston Scientific, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo Corporation, and V-Wave, with payments to the institution but no personal payments. He is also a member of the steering or executive committee group of several investigator-initiated trials that receive funding by industry without impact on his personal remuneration. TP reports a research grant to their institution from Biotronik; research, travel, or educational grants to their institution without personal remuneration from Biotronik, Boston Scientific, Edwards Lifesciences, and ATSens, outside the submitted work; and speaker fees and consultancy fees to their institution from Abbott Vascular, Biotronik, Biosensors, Boston Scientific, Edwards Lifesciences, Highlife, and Medtronic, outside the submitted work. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: We demonstrated that circulating microparticles (MPs) are increased in patients with coronary heart disease (both chronic coronary syndrome (CCS) and acute coronary syndrome). Whether thrombolysis affects MPs in patients with ST-segment elevation myocardial infarction (STEMI) with or without percutaneous coronary intervention (PCI) is unknown., Methods: This study was divided into three groups: STEMI patients with thrombolysis ( n = 18) were group T, patients with chronic coronary syndrome ( n = 20) were group CCS, and healthy volunteers ( n = 20) were the control group. Fasting venous blood was extracted from patients in the CCS and control groups, and venous blood was extracted from patients in the T group before (pre-T) and 2 hours after (post-T) thrombolysis. MPs from each group were obtained by centrifugation. After determining the concentration, the effects of MPs on endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in rat myocardial tissue in vitro were detected by immunohistochemistry and western blotting. Changes in nitric oxide (NO) and oxygen free radicals (O 2 •- ) were also detected. The effect of MPs on vasodilation in isolated rat thoracic aortae was detected., Results: Compared with that in the control group (2.60 ± 0.38 mg/ml), the concentration of MPs was increased in patients with CCS (3.49 ± 0.72 mg/ml) and in STEMI patients before thrombolysis (4.17 ± 0.58 mg/ml). However, thrombolysis did not further increase MP levels (post-T, 4.23 ± 1.01 mg/ml) compared with those in STEMI patients before thrombolysis. Compared with those in the control group, MPs in both CCS and STEMI patients before thrombolysis inhibited the expression of eNOS (both immunohistochemistry and western blot analysis of phosphorylation at Ser1177), NO production in the isolated myocardium and vasodilation in vitro and stimulated the expression of iNOS (immunohistochemistry and western blot analysis of phosphorylation at Thr495), and the generation of O 2 •- in the isolated myocardium. The effects of MPs were further enhanced by MPs from STEMI patients 2 hours after thrombolysis., Conclusion: Changes in MP function after thrombolysis may be one of the mechanisms leading to ischemia-reperfusion after thrombolysis., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2023 Zhe Li et al.)