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Aims: The benefit of long-term beta-blocker therapy after acute coronary syndromes (ACS) without heart failure in the reperfusion era is uncertain. Two recent randomized trials found conflicting results. The present study assessed the safety of beta-blocker discontinuation within 12 months following ACS with LVEF ≥40%., Methods: In a multicentre prospective real-world cohort (N=3,762) of patients hospitalized for ACS, patients with LVEF ≥40% and beta-blockers at discharge were included. Patients who continued beta-blockers at one year were compared with those who discontinued beta-blockers within 12 months post-ACS using target trial emulation and inverse probability weighting over an additional four-year follow-up. The primary endpoint was major adverse cardiovascular events (MACE), a composite of four-year cardiovascular death, myocardial infarction, stroke, transient ischemic attack, unplanned coronary revascularization, or unstable angina hospitalization., Results: Of 2,077 patients, 1,758 (85%) continued beta-blockers and 319 (15%) had discontinued beta-blockers at one year. The risk of primary endpoint was similar in both groups (14.1% versus 14.3% with beta-blocker discontinuation versus continuation; adjusted hazard ratio [aHR]=0.98; 95% confidence interval, 0.72-1.34, P=0.91). Subgroup analysis suggested a higher risk of primary endpoint with beta-blocker discontinuation after STEMI (aHR=1.46 [0.99-2.16]) compared to NSTEMI (aHR=0.70 [0.40-1.22], Pinteraction=0.033), whereas there was no interaction with LVEF (Pinteraction=0.68)., Conclusions: Beta-blocker discontinuation within 12 months following ACS with LVEF ≥40% was not associated with an increased risk of MACE compared to long-term beta-blocker therapy. Subgroup analysis suggested potential risk in STEMI patients. Discontinuing beta-blockers 12 months after ACS appears safe in patients with LVEF ≥40%, particularly after NSTEMI., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: There is a paucity of data evaluating early initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with diabetes following acute coronary syndrome (ACS) and coronary artery bypass graft surgery (CABG)., Objectives: To describe the efficacy and safety of SGLT2i initiated early after CABG in patients with type 2 diabetes who experienced ACS., Methods: This is a retrospective cohort study of patients with type 2 diabetes (T2DM) who experienced ACS and subsequent CABG with follow up at 3 and 12 months. Patients who filled a SGLT2i prescription within 14 days of discharge were allocated to the SGLT2i group and those who did not were included in the no SGLT2i group. The primary efficacy end point was first occurrence of a 4-point Major Adverse Cardiovascular Event (MACE), and the primary safety end point was a composite of hypoglycemia, hypotension, diabetic ketoacidosis, acute kidney injury, and urinary tract infection. Secondary end points included a comparative analysis of the primary outcome, 30-day readmission rates, and subgroup analyses of key populations., Results: A total of 1629 patients were included: 226 received a SGLT2i within 14 days of discharge and 1403 did not. At 12 months, 8.9% and 15.3% of patients experienced MACE in the SGLT2i and no SGLT2i groups, respectively (adjusted Hazard Ratio [aHR] 0.65, 95% confidence interval [CI] 0.41-1.04). The primary safety outcome occurred in 12.0% of the SGLT2i group and 19.1% of the no SGLT2i group at 12 months (aHR 0.68, 95% CI 0.45-1.01)., Conclusion: Early initiation of SGLT2i use was not associated with a reduction in MACE in patients with T2DM who experienced ACS and underwent subsequent CABG surgery. However, no apparent safety concerns were identified. Adequately powered trials are required to confirm this finding., (© 2024 Pharmacotherapy Publications, Inc.)

Aims: Radiation therapy (RT) is an integral component of cancer therapy but associated with adverse events. Our goal was to establish risk prediction models for major adverse cardiovascular and cerebrovascular events (MACCE) after chest RT., Methods and Results: A retrospective study of lung/breast cancer patients who had chest RT with planning CT at Mayo Clinic between 01/2010 and 01/2014. Predictive models were developed based on weighted independent predictors using a derivation (406 lung and 711 breast cancer) and validation cohort (179 lung and 234 breast cancer). Patient characteristics, pre-RT CT for coronary artery calcification (CAC), and post-RT MACCE data were reviewed. Post-RT MACCE occurred in 6.1 and 5.6% in the derivation and validation cohort over a mean follow-up of 42 ± 13 months. Post-therapy model (C2AD2) included CAC (two points), MACCE history (two points), age ≥74 (three points), DM (two points), and mean heart radiation dose ≥ 850 mGy (two points), and pre-therapy model (C2AD) included post-therapy model parameters minus mean heart radiation dose. Both models stratified patients into three risk groups: low (0-2), intermediate (3-5), and high (≥6). Post-RT MACCE across these groups were 2.7, 8.9, and 19.8% in the derivation, and 3.9, 6.6, and 16.4% in the validation cohort for post-therapy model (C2AD2) and 2.8, 9.2, and 20.4% in the derivation and 3.7, 9.2, and 13.2% in the validation cohort for pre-therapy model. Both models showed statistically significant graded survival outcome., Conclusion: Post-therapy (C2AD2) and pre-therapy (C2AD) models are simple, easy to use and effective tools to stratify breast and lung cancer patients undergoing chest radiation for post-RT MACCE., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Disclaimer: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time., Purpose: Key pharmacotherapeutic modalities and considerations for the patient with ST-elevation myocardial infarction (STEMI) across the later phases of inpatient care are reviewed., Summary: Published descriptions and validation of clinical pharmacist roles specific to the acute management of STEMI are limited. This high-risk period from presentation through revascularization, stabilization, and hospital discharge involves complex pharmacotherapeutic decision points, many operational medication needs, and multiple layers of quality oversight. A companion article reviewed STEMI pharmacotherapy from emergency department presentation through revascularization. Herein we complete the pharmacotherapy review for the STEMI patient across the inpatient phases of care, including the management of peri-infarction complications with vasoactive and antiarrhythmic agents, considerations for postrevascularization antithrombotics, and assessments of supportive therapies and secondary prevention. Key guideline recommendations and literature developments are summarized from the clinical pharmacist's perspective alongside suggested pharmacist roles and responsibilities. Considerations for successful hospital discharge after STEMI and pharmacist involvement in associated institutional quality improvement efforts are also provided. We aim to support inpatient pharmacy departments in advancing clinical services for this critical patient population and call for further research delineating pharmacists' impact on patient and institutional STEMI outcomes., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Disclaimer: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time., Purpose: Key pharmacotherapeutic modalities and considerations for the patient with ST-elevation myocardial infarction (STEMI) across the critical initial phases of care are reviewed., Summary: Despite established value in the emergency department (ED), cardiac care, and intensive care settings, there is currently little published literature describing or supporting clinical pharmacist roles in the acute management of STEMI. The high-risk period from hospital presentation through revascularization and stabilization involves complex pharmacotherapeutic decision points, many operational medication needs, and multiple layers of quality oversight. While rife with opportunities for pharmacists to optimize care, this timeframe appears inconsistently targeted by clinical pharmacy services, which may halt after ED evaluation and then resume upon postcatheterization cardiac unit admission. Herein we review the key pharmacotherapeutic modalities and considerations for the patient with STEMI across the critical initial phases of care. These include supportive therapies prior to revascularization, the host of antithrombotics involved in revascularization by percutaneous coronary intervention and/or fibrinolysis, and other periprocedural medications. Important practice guidelines and clinical resources are summarized from the clinical pharmacist perspective, and roles and responsibilities of the responding pharmacist are suggested. A companion article will extend the review to periprocedural adverse event management, key early decision-making regarding long-term risk reduction, and pharmacist involvement in institutional quality improvement efforts. We aim to support inpatient pharmacy departments in advancing clinical services for this critical patient population, and we call for further research delineating pharmacist impact on patient and institutional STEMI outcomes., Conclusion: Patients presenting with STEMI rapidly traverse multiple phases of care and receive a host of antithrombotic and supportive medications during acute management, presenting many important pharmacotherapeutic decision points and roles for pharmacists., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Identifying patients with chest pain potentially due to acute coronary syndrome (ACS) early is crucial for triage nurses. They need a reliable, validated screening tool., Aims: This study aims to develop an initial screening scale to detect ACS in patients presenting with chest pain in the emergency department., Methods: We analyzed electronic medical records of 3131 chest pain patients from 103,041 emergency department visits between January 2018 and December 2019. ACS diagnosis was confirmed by cardiologists through clinical symptoms, electrocardiograms, and cardiac enzyme levels. The study proceeded in four stages: (1) identifying potential ACS predictors through a literature review, (2) validating these predictors with experts, (3) comparing data between ACS and non-ACS patients and (4) developing a screening scale based on identified predictors. Statistical methods included univariate analysis and binary logistic regression. The scale's accuracy was assessed using ROC curve analysis and compared to existing tools., Results: Eight significant ACS predictors were identified: male sex, age over 49 for males and over 65 for females, typical symptoms, initial pain scale score of 6 or higher, pain duration of at least 10 min, history of ACS, hypertension, and dyslipidemia. Each predictor was scored, with typical symptoms and severe pain receiving higher scores, totaling up to 10 points. A score of 6 or more indicated high ACS risk, demonstrating accuracy comparable to the HEART and TIMI score systems., Conclusion: This study developed a new ACS screening scale for use by triage nurses in emergency departments. This scale can facilitate early detection and intervention for patients at high risk of ACS., (© 2024 John Wiley & Sons Ltd.)

Background: Since 2000, the definition of myocardial infarction (MI) has evolved with reliance on cardiac troponin (cTn) tests. The implications of this change on trends of acute coronary syndrome (ACS) subtypes obtained from routinely collected hospital morbidity data are unclear. Using person-linked hospitalisation data, we compared International Classification of Diseases (ICD)-coded data with biomarker-classified admission rates for ST-segment elevation MI (STEMI), non-STEMI (NSTEMI) and unstable angina (UA) in Western Australia (WA)., Methods: We used linked hospitalisation data from all WA tertiary hospitals to identify patients with a principal diagnosis of STEMI, NSTEMI or UA between 2002 and 2016. Linked biomarker results were classified as 'diagnostic' for MI according to established criteria. We calculated age-standardised and sex-standardised rates (ASSRs) for ICD-coded versus biomarker-classified admissions by ACS subtypes and estimated annual change in admissions using Poisson regression adjusting for age and sex., Results: There were 37 272 ACS admissions in 30 683 patients (64.2% male), and 96% of cases had linked biomarker data, predominantly conventional cTn at the start and high-sensitive cTn from late 2013. Despite lower ASSRs, trends in MI classified with a diagnostic biomarker were concordant with ICD-coded admissions rates for both STEMI and NSTEMI. Between 2002 and 2010, STEMI rates declined by 4.1% (95% CI 5.0%, 3.1%) and 3.4% (95% CI 4.6%, 2.3%) in ICD-coded and biomarker-classified admissions, respectively, and both plateaued thereafter. For NSTEMI between 2002 and 2010, the ICD-coded and biomarker-classified rates increased 8.0% per year (95% CI 7.2%, 8.9%) and 8.0% (95% CI 7.0%, 9.0%), respectively, and both subsequently declined. For UA, both ICD-coded and biomarker-classified UA admission rates declined in a steady and concordant manner between 2002 and 2016., Conclusions: The present study supports the validity of using administrative data to monitor population trends in ACS subtypes as they appear to generally reflect the redefinition of MI in the troponin era., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Few studies have investigated the potential predictive value of glycosylated hemoglobin A (HbA1c) and clinical outcomes in diabetic patients after percutaneous coronary intervention (PCI), and the results of the reports have often been inconclusive and contradictory. We have organized a study to investigate the relationship between HbA1c and the occurrence of major adverse cardiovascular events (MACE) in diabetic patients after PCI., Methods: This case-cohort study was conducted on 563 diabetic patients who underwent PCI. All studied patients had an HbA1c level measured within 24 h before angioplasty. All patients were followed for six months regarding the occurrence of MACE, and the HbA1c level was measured again at the end of the sixth month of follow-up. In the case of MACE, the subjects were considered the case group, and other non-MACE patients were included in the control group., Results: 505 patients remained in the study at the end of follow-up. MACE occurred in 23 (4.6%) patients during the first month and in 57 (11.3%) patients by the end of the sixth month. Baseline HbA1c was an independent predictor of MACE and mortality at the end of month-6 (P = 0.008 and 0.001, respectively)., Conclusions: The level of HbA1c at the time of admission has a significant predictive value for the occurrence of MACE in diabetic patients who undergo PCI. However, post-PCI glycemic control may not effectively reduce the risk of MACE in this population., Clinical Trial Registration: Not applicable., (© 2024. The Author(s).)

Introduction: Elevated low-density lipoprotein cholesterol (LDL-C) is a major residual risk factor among patients with acute coronary syndrome (ACS). In the absence of sufficient real-world evidence, this observational (noninterventional) study investigated the effectiveness and safety of evolocumab in patients with hyperlipidemia treated with evolocumab for ACS in a real-world clinical setting in Korea., Methods: Between January 2022 and February 2023, patients from 10 hospitals in Korea who initiated evolocumab within 24 weeks of an ACS event were enrolled. Data collected at visit 1 (evolocumab initiation) included patients' characteristics, comorbidities, and lipid-lowering therapies. LDL-C reduction from visit 1 (week 0) to visit 2 (week 8) was assessed. The primary outcome was the proportion of patients who achieved LDL-C < 1.4 mmol/L (55 mg/dL) at follow-up; the secondary outcome was the proportion who achieved LDL-C < 1.8 mmol/L (70 mg/dL) at follow-up., Results: In this study, 89 out of 142 enrolled patients were included in the effectiveness analysis. The mean (SD) age of the included patients was 59.3 (12.3) years, with the majority being male (87.6%). Sixty-one patients received statin-ezetimibe combination therapy (68.5%). The median [Q1, Q3] LDL-C level at the start of the study was 2.5 [2.0, 3.0] mmol/L (98 [77, 115] mg/dL), which decreased to 1.3 [0.7, 1.7] mmol/L (49 [29, 67] mg/dL) after 8 weeks of evolocumab treatment, resulting in an mean (SD) 50.9 (28.6) % reduction and 1.4 (1.0) mmol/L (55.1 (37.9) mg/dL) absolute reduction. At follow-up, 55.1% and 78.7% of patients achieved LDL-C goals of < 1.4 mmol/L (55 mg/dL) and < 1.8 mmol/L (70 mg/dL), respectively. No adverse or serious adverse drug reactions were reported., Conclusion: Evolocumab treatment was associated with significant LDL-C lowering and favorable safety and guideline-recommended LDL-C goal achievement rates among patients with ACS in the real-world clinical practice setting in South Korea., (© 2024. The Author(s).)

Objective: As a biomarker of inflammation and a core component in the coagulation pathway, fibrinogen contributes to atherosclerosis and subsequent adverse cardiovascular events and is modified by the occurrence of diabetes mellitus. However, the association between fibrinogen, diabetes status, and mortality in patients with end-stage renal disease (ESRD) and acute coronary syndrome (ACS) remains scarce., Methods: A multi-center cohort study enrolled 1079 patients with ESRD and ACS between January 2015 and June 2021. Patients were classified into three groups based on fibrinogen tertiles and were further categorized by diabetes status. The primary outcome was all-cause mortality, while the secondary outcome was cardiovascular mortality., Results: During a median 21.5 months of follow-up, 386 cases of all-cause mortality were recorded, including 262 cases of cardiovascular mortality. Multivariable Cox regression model revealed that patients with the third tertile of fibrinogen and those with diabetes experienced a significantly increased risk of all-cause mortality (fibrinogen: hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.32-2.19; diabetes: HR, 1.36; 95% CI, 1.10-1.68). When patients were stratified by both fibrinogen levels and diabetes status, patients in the third fibrinogen tertile with diabetes had the highest risk of all-cause mortality (HR 2.43, 95% CI 1.69-3.48) compared to those in the first fibrinogen tertile without diabetes. Similar associations were observed for cardiovascular mortality. Notably, incorporating the combined fibrinogen and diabetes status into the Global Registry of Acute Coronary Events (GRACE) score or baseline risk model led to significant improvements in the C-statistics for predicting mortality, surpassing the advancements achieved with any single biomarker., Conclusion: In patients with ESRD and ACS, elevated fibrinogen and diabetes were associated with an increased risk of all-cause and cardiovascular mortality. Categorizing patients based on fibrinogen levels and diabetes status could provide valuable information for risk stratification of these patients., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Xie et al.)

Key Clinical Message: Microvascular angina (MVA) can present with recurrent chest pain and normal coronary angiography. Recognizing MVA is crucial as it significantly impacts patient morbidity and mortality. Early diagnosis and management with antianginal medications are essential for improving outcomes and quality of life., Abstract: Cardiovascular diseases are still the main cause of death in many parts of the world. Chest pain and dyspnea are always concerning due to the implications of cardiovascular disease. However, in patients with the involvement of the small coronary vessels (Microvascular Angina), symptoms might be recurrent and persistent despite the presence of normal coronary vessel evaluations. A 45-year-old man with a 25-year smoking history presented with recurrent chest pain, especially during physical activity, and mild shortness of breath. He was admitted, and a coronary angiography the next day appeared normal. However, a cardiac PET scan revealed the involvement of small coronary vessels not visible on angiography. The Patient was a 45-year-old man who presented with recurrent chest pain, more prominent during physical activity. He also had mild shortness of breath. The patient was admitted, and the next day, he underwent normal coronary angiography. The cardiac positron emission tomography (PET scan) showed the involvement of small coronary vessels that were not obvious on angiography., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are novel medications for reducing low-density lipoprotein cholesterol (LDL-C) levels. In 2020, the Australian Pharmaceutical Benefits Scheme (PBS) began subsidising PCSK9 inhibitors for secondary prevention of cardiovascular disease in patients with LDL-C >2.6 mmol/L despite statin and ezetimibe therapy. This criterion was expanded to LDL-C >1.8 mmol/L in 2022., Method: A retrospective analysis was conducted on patients admitted to a quaternary hospital with acute coronary syndrome (ACS) between 2020-2022. PCSK9 inhibitor eligibility and prescribing patterns were compared between recurrent ACS patients (≥2 events within 5 years) and first-presentation ACS patients. Australian PBS 2020 and 2022 criteria were applied to assess eligibility., Results: Of 817 ACS patients with LDL-C >1.8 mmol/L, 118 (14.4%) were categorised as recurrent ACS (33.9% female, mean age 67 years, LDL-C 2.9 mmol/L). When compared with first-presentation ACS patients (n=699), recurrent ACS patients had significantly higher proportions already on statin therapy (49.2% vs 6.0%, p<0.001) and ezetimibe (20.3% vs 2.4%, p<0.001). Recurrent ACS patients had significantly higher proportions of 2020 PBS-eligible patients (11.0% vs 1.3%, p<0.001) and 2022 PBS-eligible patients (20.3% vs 2.2%, p<0.001). There were no significant differences in PCSK9 inhibitor prescription rates among eligible patients (four of 13, 30.8% vs four of nine, 44.4%, p=0.51). Univariate binary logistic regression demonstrated that statin intolerance was significantly associated with PCSK9 inhibitor prescription (odds ratio 10; 95% confidence interval 1.3-79.3; p=0.029)., Conclusions: Despite significantly higher eligibility rates, PCSK9 inhibitor uptake remains low in recurrent ACS patients, demonstrating the need to raise further awareness about eligibility criteria and encourage proactive prescription to prevent recurrent cardiovascular events., Competing Interests: Conflicts of Interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Hemophilia is a disease characterized by a high risk of bleeding. With advances in treatment, life expectancy and aging-associated diseases such as coronary artery disease have increased. Our primary objective is to assess for major adverse outcomes, mortality, and length of hospital stay in individuals with hemophilia presenting for acute coronary syndrome (ACS) and undergoing percutaneous coronary intervention (PCI)., Methods: Our retrospective cohort study analyzed data from the Nationwide Inpatient Sample Database (NIS) for 2018 to investigate the outcomes of ACS management with PCI in adults with and without hemophilia. We used ICD-10 codes to exclude patients with significant comorbidities and identify those with ACS undergoing PCI. Propensity score matching and multivariable logistic regression were employed to account for over 20 baseline characteristics, mitigating confounding factors., Results: The incidence of gastrointestinal bleeding (11.0% vs. 2.8%, p < 0.001), hemorrhagic stroke (10.0% vs. 1.4%, p < 0.001), and retroperitoneal hemorrhage (5.6% vs. 1.4%, p < 0.001) was significantly higher in individuals with hemophilia undergoing PCI compared to those without hemophilia. Additionally, venous thromboembolism (VTE) incidence was notably higher in the hemophilia cohort (6.6% vs. 2.4%, p = 0.027). The hemophilia cohort also experienced a higher mortality rate (7.1% vs. 3.3%, p = 0.037) and longer hospital stays., Conclusion: Patients with hemophilia undergoing PCI are at a significantly greater risk of adverse events, increased mortality, and longer hospital stays than the general population. To mitigate the risk of unfavorable outcomes, it is crucial to ensure adequate replenishment of coagulation factors and establish close collaboration between cardiologists and hematologists., (© 2024 Wiley Periodicals LLC.)

Introduction and Importance: Spontaneous coronary artery dissection is a rare cause of acute coronary syndromes not related to atherosclerosis. It involves the sudden tearing of the coronary artery wall, separating the inner intimal lining from the outer vessel wall, typically affecting a single coronary vessel. In 20% of cases, the cause of spontaneous coronary artery dissection is unknown. The other cases often occur in pregnant or postpartum women or in individuals with conditions such as connective tissue disorders or vasculitis., Case Presentation: Here, we describe a case of a 69-year-old African female presenting with non-ST-segment elevation myocardial infarction. Coronary angiography revealed an unusual triple-vessel spontaneous coronary artery dissection affecting peripheral segments, with further investigations suggesting polyarteritis nodosa., Conclusion: While triple-vessel spontaneous coronary artery dissection and polyarteritis nodosa (PAN) are individually rare, their coexistence is exceptionally uncommon and presents diagnostic and therapeutic challenges. Clinicians should be alert to vasculitic causes in patients with spontaneous coronary artery dissection, especially with atypical clinical features., (© 2024. The Author(s).)

Competing Interests: Dr Libby is an unpaid consultant to or involved in clinical trials for Amgen, Baim Institute, Beren Therapeutics, Esperion Therapeutics, Genentech, Kancera, Kowa Pharmaceuticals, Novo Nordisk, Novartis, and Sanofi-Regeneron. Dr Libby is a member of the scientific advisory board for Amgen, Caristo Diagnostics, CSL Behring, Elucid, Kancera, Kowa Pharmaceuticals, Olatec Therapeutics, Novartis, PlaqueTec, Polygon Therapeutics, TenSixteen Bio, Soley Thereapeutics, and XBiotech, Inc. Dr Libby’s laboratory has received research funding in the last 2 years from Novartis, Novo Nordisk and Genentech. Dr Libby is on the Board of Directors of XBiotech, Inc. Dr Libby has a financial interest in Xbiotech, a company developing therapeutic human antibodies; in TenSixteen Bio, a company targeting somatic mosaicism and clonal hematopoiesis of indeterminate potential to discover and develop novel therapeutics to treat age-related diseases; and in Soley Therapeutics, a biotechnology company that is combining artificial intelligence with molecular and cellular response detection for discovering and developing new drugs, currently focusing on cancer therapeutics. Dr Libby’s interests were reviewed and are managed by Brigham and Women’s Hospital and Mass General Brigham in accordance with their conflict-of-interest policies.

Background: Optimal duration and choice of antiplatelet therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention remain controversial., Methods and Results: Digital databases (PubMed, Cochrane, and Embase) were queried to select all randomized controlled trials on a post-percutaneous coronary intervention population with acute coronary syndrome. Dual-antiplatelet therapy (DAPT) with aspirin and clopidogrel for 12 months was compared with 4 major strategies: high-potency, high- to low-potency, low-dose, and short-duration DAPT. A network meta-analysis was performed to compare the safety and efficacy of different antiplatelet strategies. This study was the second updated manuscript under the International Prospective Register of Systematic Review registration (CRD42021286552). Thirty-two randomized controlled trials comprising 103 459 (51 750 experimental, 51 709 control) patients were included. Compared with DAPT with aspirin and clopidogrel for 12 months, high- to low-potency DAPT (risk ratio [RR], 0.69 [95% CI, 0.52-0.92]) and aspirin+prasugrel containing DAPT for 12 months (RR, 0.84 [95% CI, 0.72-0.98]) had a significantly lower, whereas DAPT for 1 month followed by clopidogrel only (RR, 1.59 [95% CI, 1.06-2.39]) had a higher, incidence of major adverse cardiovascular events at 1 year (median follow-up). Prasugrel (RR, 1.35 [95% CI, 1.09-1.66]) and ticagrelor (RR, 1.38 [95% CI, 1.17-1.62]) containing DAPT for 12 months had significantly higher rates, whereas high- to low-potency DAPT (RR, 0.85 [95% CI, 0.63-1.15]) had no significant risk of major bleeding., Conclusions: Aspirin and ticagrelor for 3 months, followed by aspirin and clopidogrel for the remaining duration, can be considered the optimal strategy for treating post-percutaneous coronary intervention patients with acute coronary syndrome because of a significantly reduced risk of major adverse cardiovascular events without increasing the risk of bleeding.

Background: Acute coronary syndrome and atrial fibrillation are common cardiovascular diseases in elderly individuals. Patients with comorbidities face increased risks of bleeding and ischemia; however, there is a lack of prognostic models for quantifying these risks in this special population., Methods and Results: In this retrospective cohort study, 1851 patients (≥65 years old) with acute coronary syndrome and atrial fibrillation from 2 hospitals in China were included in the development cohort (1252 individuals) and 2 external validation cohorts (284 and 315 individuals). During 1-year follow-up, 96 Bleeding Academic Research Consortium type 3 or 5 bleeding events and 245 thromboembolic events were observed. In the development cohort, the concordance indexes for bleeding at 3, 6, and 12 mo ranged from 0.737 to 0.845 and for ischemia ranged from 0.723 to 0.777. The calibration curve and decision curve analysis indicated adequate calibration and clinical practicability. The concordance indexes varied from 0.679 to 0.809 in the validation cohorts. Subgroup analyses focusing on anticoagulant drugs and antithrombotic therapy were conducted, revealing similar discrimination and calibration. Kaplan-Meier curves demonstrated significant differences (log-rank P <0.001). Additionally, the models outperformed conventional models in concordance indexes, integrated discrimination improvement, and net reclassification improvement., Conclusions: Our study provides 2 robust prognostic models with easily available clinical factors for predicting bleeding and ischemia in elderly patients with acute coronary syndrome and atrial fibrillation. Furthermore, we provide online calculators to facilitate individualized risk evaluation and clinical decision-making., Registration: URL: www.chictr.org.cn/. Unique Identifier: ChiCTR2200067185.

A single high-sensitivity troponin-T (hs-TnT) measurement may be sufficient to risk-stratify emergency department (ED) patients with possible acute coronary syndrome (ACS) using the recalibrated History, Electrocardiogram, Age, Risk Factors, Troponin (rHEART) score. We sought to validate this approach in a multiethnic population of United States patients and investigate gender-specific differences in performance. We conducted a secondary analysis of a prospective cohort study of adult ED patients with possible ACS at a single, urban, academic hospital. We investigated the diagnostic performance of rHEART for the incidence of type-1 acute myocardial infarction (AMI) and other major adverse cardiac events (MACE) at 30 days, using both single (19 ng/L) and gender-specific (14 ng/L for women, 22 ng/L for men) 99th percentile hs-TnT thresholds. The 821 patients included were 54% women, 57% Hispanic, and 26% Black. Overall, 4.6% of patients had MACE, including 2.4% with AMI. Single-threshold rHEART ≤3 had a sensitivity of 94.4% (95% confidence interval 81% to 99%) and negative predictive values of 99.3% (98% to 100%) for MACE; gender-specific thresholds performed nearly identically. Sensitivity and negative predictive values for AMI were 90.0% (67% to 98%) and 99.3% (97% to 100%). Excluding patients presenting <3 hours from symptom onset improved sensitivity for MACE and AMI to 97.0% (84% to 100%) and 94.1% (71% to 100%). Logistic regression demonstrated odds of MACE increased with higher rHEART scores at a similar rate for men and women. In conclusion, a single initial hs-TnT and rHEART score can be used to risk-stratify male and female ED patients with possible ACS, especially when drawn >3 hours after symptom onset., Competing Interests: Declaration of competing interest Edward Suh reports a relationship with Roche Diagnostics that includes: funding grants. Bryn Mumma reports a relationship with Roche Diagnostics that includes: consulting or advisory. Marc Probst reports a relationship with Roche Diagnostics that includes: non-financial support. Andrew Einstein reports a relationship with Ionetix that includes: speaking and lecture fees. Andrew Einstein reports a relationship with WL Gore and Associates that includes: consulting or advisory and funding grants. Andrew Einstein reports a relationship with Canon Medical Systems Corporation that includes: consulting or advisory and funding grants. Lauren Ranard reports a relationship with Boston Scientific Corporation that includes: funding grants. Andrew Einstein reports a relationship with Attralus, Inc. that includes: funding grants. Andrew Einstein reports a relationship with BridgeBio that includes: funding grants. Andrew Einstein reports a relationship with GE Healthcare that includes: funding grants. Andrew Einstein reports a relationship with Intellia Therapeutics Inc that includes: funding grants. Andrew Einstein reports a relationship with Ionis Pharmaceuticals Inc that includes: funding grants. Andrew Einstein reports a relationship with Neovasc Inc that includes: funding grants. Andrew Einstein reports a relationship with Roche Medical Systems that includes: funding grants. Andrew Einstein reports a relationship with Pfizer that includes: funding grants. Co-author, AJE, has recieved authorship fees from Wolters Kluwer Healthcare - UpToDate. If there are other authors, they 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 Elsevier Inc. All rights reserved.)

Background: To determine whether granulocyte colony-stimulating factor (G-CSF) improves clinical outcomes after large ST-elevation myocardial infarction (STEMI) when administered early in patients with left ventricular (LV) dysfunction after successful percutaneous coronary intervention (PCI)., Methods: STEM-AMI OUTCOME was designed as a prospective, multicentre, nationwide, randomised, open-label, phase III trial (ClinicalTrials.gov ID: NCT01969890) to demonstrate the efficacy and safety of early G-CSF administration in reducing 2-year cardiac mortality and morbidity in patients with STEMI with LV ejection fraction ≤45% after PCI. The primary outcome was a composite of all-cause death, recurrence of myocardial infarction and hospitalisation for heart failure. Due to low recruitment and event rates, the study was discontinued and did not achieve adequate statistical power to verify the hypothesis., Results: Patients were randomly allocated to G-CSF (n=260) or standard of care (SOC; n=261). No difference was found in the composite primary outcome between study groups (HR 1.20; 95% CI 0.63 to 2.28). The 2-year mortality was 2.31% in the G-CSF and 2.68% in the control group (HR 0.88; 95% CI 0.29 to 2.60). Adverse events did not differ between the G-CSF (n=65) and SOC groups (n=58; OR 1.17; 95% CI 0.78 to 1.75). In post hoc analyses on the intervention group, we observed a trend towards fewer composite primary outcomes in patients with low bone marrow (BM) cell mobilisation (n=108) versus those with high mobilisation (n=152, with peak leucocyte count >50×10 9 /L; HR 2.86; 95% CI 0.96 to 8.56). Primary outcomes were lower in patients with severe LV systolic dysfunction at discharge treated with G-CSF than in controls (interaction β±SE, -0.08±0.04; p=0.034)., Conclusions: Although inconclusive, this is the largest trial in the field of cell-based cardiac repair after STEMI providing evidence of the tolerability and long-term safety of G-CSF treatment. The results prompt further studies to understand which patient can benefit most from BM cell mobilisation., Trial Registration Number: NCT01969890., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Acute coronary syndrome (ACS) is frequently reported in patients with coronavirus disease 2019 (COVID-19). Cytokine storm induced by interleukin-6 (IL-6) has been suggested to potentially cause myocardial injury in COVID-19. We investigated the association between baseline level of IL-6 and development of ACS in COVID-19 patients., Methods: Demographic and clinical data of hospitalized COVID-19 patients from 2020 to 2022 were reviewed. Extracted data including patient characteristics, laboratory biomarkers, and systemic inflammation indexes in patients with or without ACS were reviewed and analyzed. Logistic regression models were applied to analyze predictors of ACS development and receiver-operating characteristic (ROC) curves were used to assess discriminatory power of IL-6 and other risk factors for predicting ACS development., Results: Among 1,753 COVID-19 patients, 37 cases experienced ACS and 159 patients without main COVID-19 complications were randomly selected as controls. ACS patients were older (p = 0.001) and suffered from more comorbidities including diabetes (43% vs. 18%, p = 0.001), hypertension (40.5% vs. 24.5%, p = 0.050), ischemic heart disease (49% vs. 9%, p = 0.001), and hyperlipidemia (19% vs. 5%, p = 0.010). Also, decreased level of consciousness (31.6% vs. 2.5%, p = 0.001), ICU admission (65% vs. 2%, p = 0.001), and mortality events (70% vs. 0.6%, p = 0.001) were more prevalent in the ACS group. Baseline levels of IL-6 (p = 0.001), D-dimer (p = 0.026), troponin (p = 0.001), blood urea nitrogen (p = 0.002), and creatinine (p = 0.008) were higher in ACS patients but erythrocyte sedimentation rate (p = 0.013), hemoglobin (p = 0.033), and red blood cells (p = 0.028) were lower compared with controls. Also, age (OR: 1.06, p = 0.019), IL-6 (OR: 1.44, p = 0.047), and cardiovascular disease (CVD) (OR: 3.66, p = 0.043) were associated with ACS development. The area under the curve (AUC) of IL-6 and combined predictors respectively was 0.661 (p = 0.002) and 0.829 (p = 0.001)., Conclusions: High IL-6 concentration at baseline is a strong predictor for ACS development in COVID-19 patients. Also, elderly and concurrent CVD are significantly associated with ACS development., (© 2024. The Author(s).)

Early vascular healing after drug-eluting stent (DES) implantation is associated with better outcomes and lower incidence of in-stent thrombosis. To examine vascular healing response in patients with non-ST elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI) guided by optical coherence tomography (OCT) versus angiography alone. Sixty patients were randomized 1:1:1 to OCT-guided PCI with 3-month OCT follow-up (O3 group, n = 20), angiography-guided PCI with 3-month OCT follow-up (A3 group, n = 20), or angiography-guided PCI with 6-month OCT follow-up (A6 group, n = 20). The primary endpoint was the proportion of covered struts at 3- or 6-month follow-up. The proportion of covered struts in the O3 group was significantly higher than in the A3 group (95.2% vs. 92.3%, p < 0.001), but lower than in the A6 group (95.2% vs. 97.4%, p < 0.001). The O3 group had a lower proportion of incomplete strut apposition (ISA) than the A3 group (0.46% vs. 0.76%, p = 0.006), and higher than the A6 group (0.46% vs. 0.27%, p = 0.018) at follow-up. The optimal cut-off value of ISA after implantation of DES for predicting stent coverage at 3 and 6-month follow-up was 200 μm and 308 μm, respectively. Only one patient experienced target lesion revascularization in the A3 group during a 3-year clinical follow-up. In patients with NSTE-ACS undergoing PCI with DES, OCT guidance achieved higher strut coverage compared with angiography guidance at 3-month follow-up. However, the difference in the strut coverage between the OCT-guided group and the angiography-guided group at 6 months indicates that the degree of endothelialization may be more time-dependent instead of invasive device guidance., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Low serum albumin levels increase coronary morbidity, mortality, and postoperative cardiovascular risk. Therefore, this study investigated the relationship between these levels and the length of hospital stay in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome. A total of 350 patients were divided into quartiles according to serum albumin levels. Univariate and multivariate analyses were performed to identify factors associated with the length of hospital stay. A non-linear regression analysis of serum albumin and length of hospital stay was also performed. The results of the multifactorial analysis revealed low serum albumin levels as an independent predictor of longer hospital stay, even in the fully adjusted model. In the segmented linear regression model, serum albumin level showed a U-shaped relationship with the length of hospital stay. In conclusion, low serum albumin level was an independent predictor of longer hospital stay in patients undergoing PCI for acute coronary syndrome, with shorter stays observed for increasing serum albumin levels. Low serum albumin can be used to identify patients who require longer hospitalization and may need additional nutritional support or interventions to improve their prognosis., (© 2024. The Author(s).)

Background: The prognostic significance of obstructive sleep apnea (OSA) in patients with unstable angina (UA) based on remnant cholesterol (RC) or triglyceride (TG) levels remains unclear. This study aims to evaluate the effects of the interaction between RC, TG, and OSA on cardiovascular outcomes in UA patients., Methods: In this prospective cohort study, OSA was diagnosed when apnea-hypopnea index of ≥ 15 events/h. Patients with high RC (HRC, n = 370) or high TG (HTG, n = 362) included RC or TG in the highest tertile, and those in the middle and lowest tertiles were defined as normal RC (NRC, n = 736) or normal TG (NTG, n = 744). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including cardiovascular death, myocardial infarction, ischemia stroke, ischemia-driven revascularization, or hospitalization for UA., Results: A total of 1,106 eligible UA patients were enrolled, among which 560 (50.6%) had OSA. RC and TG levels were increased in OSA patients, but there was no difference in the prevalence of OSA between the NRC and HRC or NTG and HTG groups. During a median follow-up of 1.9 (1.1, 3.0) years, OSA was associated with an increased risk of MACCE occurrence compared to non-OSA in UA patients with HRC (adjusted HR 2.06; 95% CI 1.20-3.51, P = 0.008), but not in those with NRC (adjusted HR 1.21; 95% CI 0.84-1.75, P = 0.297). The incremental risk in HRC was attributable to higher rates of hospitalization for UA and ischemia-driven revascularization. Results for HTG and NTG were similar., Conclusion: OSA was associated with a worse prognosis in UA patients with HRC or HTG, emphasizing the necessity of identifying OSA presence in this population., Trial Registration: Clinicaltrials.gov; No: NCT03362385., (© 2024. The Author(s).)

Consecutive suspected acute coronary syndrome (ACS) cases were categorized into three groups: Group-1 (ST-depression), Group-2 (T-inversion), and Group-3 (remaining cases). Group-3 was subclassified into isoelectric horizontal ST-segment with sharp ST-T-angle (IHST) positive and IHST negative groups. They underwent serial high-sensitive Troponin-I testing. ACS incidence was 77.96 %, with 33.02 %, 15.96 %, and (15.04 %, 35.96 %) of patients in Groups 1, 2, and 3 (IHST positive, IHST negative), respectively. The presence of IHST exhibited higher sensitivity than T-inversion and greater specificity than ST-depression in detecting ACS. The presence of IHST sign additionally detected 15.04 % of ACS. The presence of IHST was significant among group-3 (p = 0.008) as well as the overall ACS cases (p = 0.048)., 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 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Background: Recent neutral randomised clinical trials have created clinical equipoise for treating obstructive sleep apnoea (OSA) for managing cardiovascular risk. The importance of defining the links between OSA and cardiovascular disease is needed with the aim of advancing the robustness of future clinical trials. We aimed to define the clinical correlates and characterise surrogate cardiovascular markers in patients with acute coronary syndrome (ACS) and OSA., Method: Overall, 66 patients diagnosed with ACS were studied. Patients underwent an unattended polysomnogram after hospital discharge (median [interquartile range] 62 [37-132] days). The Epworth Sleepiness Scale, Berlin, and STOP-BANG questionnaires were administered. Surrogate measures of vascular structure and function, and cardiovascular autonomic function were conducted. Pulse wave amplitude drop was derived from the pulse oximetry signals of the overnight polysomnogram., Results: OSA (apnoea-hypopnea index [AHI] ≥5) was diagnosed in 94% of patients. Moderate-to-severe OSA (AHI≥15) was observed in 68% of patients. Daytime sleepiness (Epworth Sleepiness Scale ≥10) was reported in 17% of patients. OSA screening questionnaires were inadequate to identify moderate-to-severe OSA, with an area under the receiver operating characteristic curve of approximately 0.64. Arterial stiffness (carotid-femoral pulse wave velocity, 6.1 [5.2-6.8] vs 7.4 [6.6-8.6] m/s, p=0.002) and carotid intima-media thickness (0.8 [0.7-1.0] vs 0.9 [0.8-1.0] mm, p=0.027) was elevated in patients with moderate-to-severe OSA. After adjusting for age, sex and body mass index, these relationships were not statistically significant. No relationships were observed in other surrogate cardiovascular markers., Conclusions: A high prevalence of OSA in a mostly non-sleepy population with ACS was identified, highlighting a gross underdiagnosis of OSA among cardiovascular patients. The limitations of OSA screening questionnaires highlight the need for new models of OSA screening as part of cardiovascular risk management. A range of inconsistent abnormalities were observed in measures of vascular structure and function, and these appear to be largely explained by confounding factors. Further research is required to elucidate biomarkers for the presence and impact of OSA in ACS patients., Competing Interests: Conflicts of Interest PAC has an appointment as an endowed Academic Chair at the University of Sydney that was created from ResMed funding; he receives no personal fees, and this relationship is managed by an Oversight Committee of the University. Additionally, he has received research support from ResMed, and SomnoMed, and is a consultant/adviser to SomnoMed, ResMed, and Sunrise Medical. The other authors do not have any conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

(1) Background: Lipid accumulation product (LAP) is an anthropometric index of abdominal adiposity that has been associated with increased cardiovascular risk. We aimed to explore the association of LAP with cardiovascular hospitalizations and compare its predictive accuracy with other indices such as body mass index (BMI) and waist circumference. (2) Methods: LAERTES was a prospective, population-based cohort that recruited consecutive patients with stable ischemic heart disease (SIHD) from two Greek hospitals in Athens. Data from 770 participants (13% women, median age 62 years) with a median follow-up of 4.3 years were analyzed in relation to the occurrence of adverse cardiovascular events mandating hospital admission (non-fatal myocardial infarction [MI], non-fatal ischemic stroke and malignant ventricular arrhythmias). (3) Results: A total of 127 (16.5%) of the participants were admitted to cardiology clinics over the follow-up period; 12.4% of them developed MI, 2.6% ventricular arrhythmia and 1.5% ischemic stroke. Patients with cardiovascular hospitalization had higher BMI, larger waist circumference, higher LAP and triglycerides and lower HDL-cholesterol than patients without hospitalization. Upper LAP quartile and hypertension were independent predictors for cardiovascular hospitalization (HR: 2.20, 95% CI: 1.12-4.34, p = 0.02 and HR: 1.57, 95% CI: 1.03-2.39, p = 0.03, respectively). (4) Conclusions: Higher LAP quartiles are predictive of adverse cardiovascular events leading to hospital admission and deserve further evaluation in dedicated studies.

Background: Traditional prognostic models for ST-segment elevation myocardial infarction (STEMI) have limitations in statistical methods and usability., Objective: We aimed to develop a machine-learning (ML) based risk score to predict in-hospital mortality, intensive care unit (ICU) admission, and left ventricular ejection fraction less than 40% (LVEF < 40%) in STEMI patients., Methods: We reviewed 1,863 consecutive STEMI patients undergoing primary percutaneous coronary intervention (pPCI) or rescue PCI. Eight supervised ML methods [LASSO, ridge, elastic net (EN), decision tree, support vector machine, random forest, AdaBoost and gradient boosting] were trained and validated. A feature selection method was used to establish more informative and nonredundant variables, which were then considered in groups of 5/10/15/20/25/30(all). Final models were chosen to optimise area under the curve (AUC) score while ensuring interpretability., Results: Overall, 128 (6.9%) patients died in hospital, with 292 (15.7%) patients requiring ICU admission and 373 (20.0%) patients with LVEF < 40%. The best-performing model with 5 included variables, EN, achieved an AUC of 0.79 for in-hospital mortality, 0.78 for ICU admission, and 0.74 for LVEF < 40%. The included variables were age, pre-hospital cardiac arrest, robust collateral recruitment (Rentrop grade 2 or 3), family history of coronary disease, initial systolic blood pressure, initial heart rate, hypercholesterolemia, culprit vessel, smoking status and TIMI flow pre-PCI. We developed a user-friendly web application for real-world use, yielding risk scores as a percentage., Conclusions: The STEMI-ML score effectively predicts in-hospital outcomes in STEMI patients and may assist with risk stratification and individualising patient management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Sritharan, Nguyen, Ciofani, Bhindi and Allahwala.)

Aim: To identify incidence, type of drug abuse study clinical and angiographic profile in very young population presenting with acute coronary syndrome (ACS)., Materials and Methods: All consecutive patients less than 30 years with ACS included and segregated into Group 1 and 2 (with and without drug abuse respectively) RESULT: n = 153; n = 17 in group 1 of whom 35.29 % consumed opium, 17.64 % energy drinks, 17.64 % whey protein supplements, 17.64 % inhaled marijuana, 5.88 % heroin and spasmoproxyvon and 23.52 % multi-substance abusers. STEMI, Single vessel disease and urban domicile were predominant. Rising trends of drug abuse were identified in prospective (28.20 %) versus retrospective (5.30 %) timeframe (p = 0.011)., Conclusion: Rising trends of drug abuse, a potentially modifiable risk factor of ACS in the young are alarming. Strict regulations are needed to curb this menace., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Shibba Chhabra reports was provided by Dayanand Medical College and Hospital. NONE., (Copyright © 2024 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Background and Aims: Statin therapy reduces myocardial infarction rate but whether it is associated with a shift of ST-elevation myocardial infarction (STEMI) towards non-ST-elevation myocardial infarction (non-STEMI) remains unknown. Thus, we tested the hypothesis that statin use is associated with less STEMI relative to non-STEMI in first-time myocardial infarction., Methods: In a nationwide study, including 66,896 patients with first-time myocardial infarction between 2010 and 2021, we obtained multivariable risk estimates for STEMI versus non-STEMI according to any statin use, cumulated statin use, and daily statin dose. Furthermore, we obtained hazard ratios for 60-day mortality (5545 deaths) following myocardial infarction according to type of infarction., Results: Odds ratios for STEMI versus non-STEMI were 0.81 (95 % CI:0.77-0.85) and 1.07 (1.01-1.13) in current and previous statin users compared to never statin users. Cumulated statin exposure yielded odds ratios of 0.96 (0.87-1.07) for <2 statin-years, 0.87 (0.79-0.95) for 2-4.9 statin-years, 0.80 (0.74-0.87) for 5-10 statin-years, and 0.75 (0.70-0.80) for >10 statin-years compared to never users. Corresponding odds ratios for statin dose intensity were 0.89 (0.84-0.95) for low-intensity, 0.77 (0.73-0.82) for moderate-intensity, and 0.70 (0.63-0.77) for high-intensity. Results were similar in multiple sensitivity analyses and using a cohort design. The hazard ratio for 60-day mortality after first-time STEMI versus non-STEMI was 2.24 (2.13-2.37)., Conclusions: In this nationwide study, prior statin use is associated with less STEMI relative to non-STEMI in a dose dependent manner. This indicates that statin therapy, in addition to reducing myocardial infarction event rates, also result in a less severe presentation of myocardial infarctions., Competing Interests: Conflict of interest All authors have completed the ICMJE uniform disclosure form and declare: support from the Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark for the submitted work; BGN declares consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Ionis, Amgen, Kowa, Amarin, Denka, Mankind, Novartis, Novo Nordisk, Esperion, Abbott, Ultragenix, Silence Therapeutics, USV, Lilly, Arrowhead, Marea. MBM has received lecture honoraria from Novo Nordisk, AstraZeneca, Amarin and Sanofi. SBS and SA declare no competing interests. AL has received consultancies or talks from Amarin and Novartis. SBS has after finishing work on this paper been employed by Novo Nordisk., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Rationale: Although obstructive sleep apnea (OSA) is a prevalent condition among patients with acute coronary syndrome (ACS), the impact of OSA on cardiovascular event (CVE) recurrence is not homogeneous. We previously defined a specific phenotype of first-ACS patients without previous cardiovascular disease who are at increased risk of OSA-related CVE recurrence. However, the pathobiological mechanisms whereby OSA leads to adverse cardiovascular outcomes in this singular ACS phenotype remain to be investigated., Objective: To characterize the molecular pathways that relate OSA with CVE recurrence., Methods: This post hoc analysis of the ISAACC study (NCT01335087) included subjects without previous cardiovascular disease who were hospitalized for a first ACS and developed a recurrent CVE during the follow-up. Patients underwent respiratory polygraphy and fasting blood extraction during hospitalization. Two study groups were established on the basis of the apnea-hypopnea index (AHI): untreated severe OSA (AHI≥30events/h) and non-OSA (AHI<15events/h) groups. Proteomic profiling analysis included 276 cardiovascular and inflammatory-related plasma proteins via Olink® technology., Results: Proteomics was performed in 58 patients (77.6% male, median [p25;p75] age 58.0 [51.2;65.8] years, and median BMI 28.6 [25.8;31.2]kg/m 2 ). Thirty patients had severe OSA, and 28 subjects were considered non-OSA controls. A total of 24 plasma proteins were differentially expressed between the groups. Among these proteins, 18 were significantly associated with OSA severity parameters derived from respiratory polygraphy. Further bioinformatic analyses of OSA-related proteins revealed their involvement in several molecular pathways, mostly related to immune function, cell signaling, and inflammatory processes., Conclusion: A specific proteomic profile related to OSA presence and severity was identified in the plasma of ACS patients who developed recurrent CVEs. This analysis suggests the activation of key OSA-mediated molecular pathways with potential implications for cardiovascular prognosis., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: Lipids play key role in coronary atherosclerosis. The role of non-high-density lipoprotein cholesterol (non-HDL-C) in atherosclerotic plaques using intravascular imaging remains unclear. This study aimed to assess its relationship with coronary plaque features using intravascular ultrasound (IVUS) in acute coronary syndrome (ACS)., Methods: A total of 601 patients divided into two groups: normal non-HDL-C≤130 mg/dl (n = 410) and high non-HDL cholesterol >130 mg/dl (n = 191). IVUS performed before coronary intervention., Results: Mean age 53.18 ± 12.29 years. No significant differences in hypertension, diabetes, and smoking between groups. Plaque burden was significantly higher among normal versus high non-HDL-C groups (79.59 ± 9.98 % vs. 81.61 ± 5.39 %; p = 0.001). At minimal luminal site, fibrofatty percentage was higher in normal non-HDL-C group (p = 0.027), while necrotic core greater in high non-HDL-C group (p = 0.033). Segmental analysis, necrotic core was significantly higher in percentage (p = 0.006) and volumes (p = 0.011) in normal versus high non-HDL-C groups. Total cholesterol (r = 0.099, p = 0.015), LDL-C (r = 0.081, p = 0.046), triglycerides (r = 0.083, p = 0.041),and non-HDL-C (r = 0.099, p = 0.015) positively correlated with plaque burden. Total cholesterol (r = 0.115, p = 0.005), LDL-C (r = 0.107, p = 0.009), and non-HDL-C (r = 0.105, p = 0.010) positively correlated with necrotic core volume. Linear regression analysis showed age and non-HDL-C as predictors of higher plaque burden. Multiple linear regression analysis; age, body mass index, and non-HDL-C were predictors of larger necrotic core volume., Conclusion: Non-HDL-C levels were positively associated with plaque burden, measure of extent of atherosclerosis. It is closely associated with and is a predictor of necrotic core volume; a marker of plaque vulnerability. This IVUS study demonstrates potential role of non-HDL-C in causation of plaque in ACS., 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 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Background: Gender differences in acute coronary syndrome (ACS) outcomes have been noted in global data, which however did not analyse Indian data. No prior systematic review and meta-analysis (SRM) has addressed this important aspect of gender bias in Indian women with ACS. Hence this SRM aimed to address this knowledge gap., Methods: Electronic databases were searched for studies in ACS comparing cardiovascular disease presentation, treatment received and outcomes in women and men from India. Primary outcomes were to evaluate gender-differences in 30-day death and major adverse cardiovascular events (MACE). Secondary outcomes were to evaluate gender-differences in presentation, management and mortality. The SRM is registered with PROSPERO (CRD42023477286)., Results: From initially screened 3753 articles, data from 9 studies (61,185 patients) were analysed. Women with ACS had higher prevalence of diabetes [Odds ratio (OR) 1.65(95%CI:1.33-2.04); p < 0.001; I 2  = 95 %] and hypertension [OR2.06(95%CI:1.88-2.25); p < 0.001; I 2  = 42 %]. Smoking was significantly lower in women [OR 0.05(95%CI:0.03-0.07); p < 0.001; I 2  = 87 %]. Non-ST elevation myocardial infarction (NSTEMI) was significantly higher in women [OR 1.92(95%CI:1.66-2.21); p < 0.001; I 2  = 0 %]. Diagnostic angiography [OR 0.64(95%CI:0.56-0.74); p < 0.001; I 2  = 46 %] and percutaneous coronary interventions [OR0.71(95%CI:0.55-0.92); p = 0.01; I 2  = 92 %] were significantly lower in women. Women had significantly higher 30-day mortality [Hazard ratio (HR)2.26(95%CI:2.01-2.55); p < 0.001; I 2  = 6 %], 1-year mortality [HR2.41(95%CI:1.89-3.07); p < 0.001; I 2  = 53 %], in-hospital death [HR1.88(95%CI:1.19-2.96); p = 0.007; I 2  = 92 %], stroke [HR 1.84 (95%CI:1.34-2.52); p < 0.001; I 2  = 0 %] and MACE outcomes [OR 2.05 (95%CI:1.78-2.35); p < 0.001]. Use of aspirin, clopidogrel, beta-blockers and nitrates were significantly lower in women., Conclusion: Our study highlights worse outcomes in Indian women with ACS. Higher burden of diabetes and hypertension, decreased used of PCI and lesser aggressive pharmacotherapy may be some of the contributing factors., 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 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Background: Prompt recognition of symptoms and response to acute coronary syndrome (ACS) are crucial for reducing pre-hospital delay. This study compares culturally and linguistically diverse (CALD) and non-CALD Australian populations in terms of their (i) ACS symptom knowledge and (ii) intention to call emergency medical services (EMS) for ACS., Method: This cross-sectional study used data from HeartWatch, an online survey collected by the National Heart Foundation of Australia between 2018 and 2020 for Australian adults aged ≥18 years. CALD respondents were defined as non-Indigenous individuals who reported speaking a language other than English at home. Characteristics associated with ACS symptom knowledge and EMS calling intentions were analysed using multivariable logistic regression., Results: Of 31,919 respondents, 16.3% were from CALD backgrounds (n=5,212). Compared with non-CALD, CALD respondents were less likely to name any ACS symptom (63.0% vs 76.0%; adjusted odds ratio [AOR] 0.66; 95% confidence interval [CI] 0.61-0.70) and were less likely to state that they would call an ambulance for ACS (50.2% vs 72.1%; AOR 0.53; 95% CI 0.50-0.57). Almost one-quarter (23.0%) of CALD respondents reported not knowing what they would do. In both groups, males, individuals aged ≤60 years, and those with diabetes were less likely to name an ACS symptom and had lower intention to call an ambulance. Those unable to list a single ACS symptom also had a lower intention to call an ambulance., Conclusions: Knowledge of ACS symptoms and intention to call an ambulance were lower among CALD respondents. The demographics of those with low ACS symptom knowledge and EMS calling intention were similar in the two groups. Future education efforts in Australia should focus on promoting ACS symptom knowledge and EMS use and should target these groups., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This study evaluated the safety, tolerability, pharmacodynamics, and pharmacokinetics of recombinant neorudin (EPR-hirudin [EH]) in patients with acute coronary syndrome (ACS), providing a basis for further therapeutic research. This open-label, single-center, nonrandomized, nonblinded, and noncontrolled trial categorized 24 patients with nonprogressive ACS who met the screening criteria into 3 groups. They received an intravenous injection of neorudin (0.4 mg/kg), followed by an intravenous drip at doses of 0.15, 0.30, and 0.45 mg/kg/h for 3 days in the low-, medium-, and high-dose groups, respectively. The safety, tolerability, pharmacodynamics, and pharmacokinetics of EH were assessed after treatment, indicating that neorudin was safe and well tolerated in nonprogressive ACS. No serious adverse events or clinical composite end points were observed. The activated partial thromboplastin time and thrombin time increased significantly and dose dependently following EH administration across all groups compared to pretreatment values. Conversely, thrombin activity significantly decreased after drug administration but returned to baseline levels shortly after drug withdrawal. Within the administered dose range, neorudin exposure increased with the dose, and its half-life was approximately 2 hours. Neorudin was found to be safe and tolerable for treating patients with nonprogressive ACS, demonstrating therapeutic efficacy at doses up to 0.45 mg/kg/h over a 3-day period., (© 2024 The Author(s). Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Background: Reduced estimated glomerular filtration rate (eGFR) is associated with lower use of invasive management and increased mortality after acute coronary syndrome (ACS). The reasons for this are unclear., Methods: A retrospective clinical cohort study was performed using data from the English National Institute for Health Research Health Informatics Collaborative (2010-2017). Multivariable logistic regression was used to investigate whether eGFR<90 mL/min/1.73 m 2 was associated with conservative ACS management and test whether (a) differences in care could be related to frailty and (b) associations between eGFR and mortality could be related to variation in revascularisation rates., Results: Among 10 205 people with ACS, an eGFR of <60 mL/min/1.73m 2 was found in 25%. Strong inverse linear associations were found between worsening eGFR category and receipt of invasive management, on a relative and absolute scale. People with an eGFR <30 mL compared with ≥90 mL/min/1.73 m 2 were half as likely to receive coronary angiography (OR 0.50, 95% CI 0.40 to 0.64) after non-ST-elevation (NSTE)-ACS and one-third as likely after STEMI (OR 0.30, 95% CI 0.19 to 0.46), resulting in 15 and 17 per 100 fewer procedures, respectively. Following multivariable adjustment, the ORs for receipt of angiography following NSTE-ACS were 1.05 (95% CI 0.88 to 1.27), 0.98 (95% CI 0.77 to 1.26), 0.76 (95% CI 0.57 to 1.01) and 0.58 (95% CI 0.44 to 0.77) in eGFR categories 60-89, 45-59, 30-44 and <30, respectively. After STEMI, the respective ORs were 1.20 (95% CI 0.84 to 1.71), 0.77 (95% CI 0.47 to 1.24), 0.33 (95% CI 0.20 to 0.56) and 0.28 (95% CI 0.16 to 0.48) (p<0.001 for linear trends). ORs were unchanged following adjustment for frailty. A positive association between the worse eGFR category and 30-day mortality was found (test for trend p<0.001), which was unaffected by adjustment for frailty., Conclusions: In people with ACS, lower eGFR was associated with reduced receipt of invasive coronary management and increased mortality. Adjustment for frailty failed to change these observations. Further research is required to explain these disparities and determine whether treatment variation reflects optimal care for people with low eGFR., Trial Registration Number: NCT03507309., Competing Interests: Competing interests: YB-S is partly funded as the Data Science co-lead by the National Institute for Health and Care Research Applied Research Collaboration West (NIHR ARC West) and University of Bristol. RL reports funding unrelated to this work from the Royal Marsden Cancer charity, Cancer Research UK, Innovate UK (co-funded by Roche), RM Partners Cancer Alliance, the NIHR and NHS England and consulting fees from Royal Marsden Private Care for personal private practice and is NHS England Joint National Clinical Lead for the Targeted Lung Health Check Programme and NIHR Clinical Research Network National Specialty Lead for Screening, Prevention and Early Detection., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Purpose: This study aimed to investigate the dynamic changes in monocytic myeloid-derived suppressor cells (M-MDSCs) and their implications in the pathogenesis of acute coronary syndrome (ACS), shedding light on potential therapeutic targets., Experimental Design: Peripheral blood samples were collected from 68 ACS patients, 35 stable angina pectoris (SAP) patients, and 30 healthy controls (HC). Multi-parameter flow cytometry was employed for analysis of M-MDSCs, explored with disease characteristics and progression., Results: ACS patients exhibited an increased frequency of circulating M-MDSCs compared to SAP patients and HC. M-MDSCs levels demonstrated associations with ACS type, coronary artery lesions, multi-vessel disease, and cardiac dysfunction severity. Higher M-MDSCs levels were found in obese patients. Notably, therapy led to a significant decrease in M-MDSCs frequency. Furthermore, ACS patients exhibited elevated levels of interleukin (IL)-6, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor- α (TNF- α ) in the cytokine profile associated with M-MDSCs. Increased expression of arginase-1(Arg-1) was observed in ACS patients, with positive correlations between M-MDSCs levels and IL-6, GM-CSF, and Arg-1 expression. The diagnostic performance of triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and M-MDSCs levels varied in predicting the severity of coronary artery stenosis, with TG showing higher specificity, HDL-C displaying higher sensitivity, and M-MDSCs levels demonstrating balanced sensitivity and specificity., Conclusions: Assessment of M-MDSCs frequency holds promise as a predictive marker for disease progression and therapy response of coronary artery stenosis. The elevated presence of M-MDSCs suggests their potential role in modulating ACS-related inflammation., Competing Interests: The authors declare there are no competing interests., (©2024 Tan et al.)

Background: Globally, diseases of the cardiovascular system stand as the principal contributors to mortality and are anticipated to show an upward trajectory. The occurrence of Acute Coronary Syndrome (ACS) has been linked to underlying inflammatory processes. The monocyte-to-high-density lipoprotein-cholesterol (MHR) ratio has garnered significant attention as a prognostic biomarker, encapsulating the synergistic roles of inflammation and lipid metabolism in the pathophysiology of cardiovascular diseases, including ACS., Aims: This meta-analysis examines the prognostic MHR ratio in ACS patients., Methods: We systematically searched PubMed, Embase, Scopus, Web of Science, and the Cochrane Library databases to identify the relevant meta-analyses up to February 26, 2024. The findings were aggregated into risk ratios with 95% confidence intervals., Results: Eleven studies, with 7421 patients, were included. Low MHR levels compared to high MHR levels were associated with statistically significantly lower in-hospital mortality (0.9% vs. 5.5%; respectively; p<0.001), 3-month mortality (4.4% vs. 11.2%; p = 0.02), 6-month follow-up mortality (4.0% vs. 10.2%; p = 0.03), 1-year mortality (4.2%, vs. 10.2%; p<0.001), as well as long-term follow-up mortality (7.5% vs. 13.7%; p<0.001)., Conclusions: MHR has both good predictive properties for mortality and MACE (short- and long-term). Data indicate that MHR may improve in-hospital and long-term cardiovascular risk prediction. It may, therefore, be an effective tool for risk re-estimation and the selection of patients for whom intensive lipid-lowering treatment may be particularly useful.

Introduction: Telephone triage is pivotal for evaluating the urgency of patient care, and in the Netherlands, the Netherlands Triage Standard (NTS) demonstrates moderate discrimination for chest pain. To address this, the Safety First Prediction Rule (SFPR) was developed to improve the safety of ruling out acute coronary syndrome (ACS) during telephone triage., Methods: We conducted an external validation of the SFPR using data from the TRACE study, a retrospective cohort study in out-of-hours primary care. We evaluated the diagnostic accuracy assessment for ACS, major adverse cardiovascular events (MACE), and major events within 6 weeks. Moreover, we compared its performance with that of the NTS algorithm., Results: Among 1404 included patients (57.3% female, 6.8% ACS, 8.6% MACE), the SFPR demonstrated good discrimination for ACS (C-statistic: 0.79; 95%-CI: 0.75-0.83) and MACE (C-statistic: 0.79; 95%-CI: 0.0.76-0.82). Calibration was satisfactory, with overestimation observed in high-risk patients for ACS. The SFPR (risk threshold 2.5%) trended toward higher sensitivity (95.8% vs. 86.3%) and negative predictive value (99.3% vs. 97.6%) with a lower negative likelihood ratio (0.10 vs. 0.34) than the NTS algorithm., Conclusion: The SFPR proved robust for risk stratification in patients with acute chest pain seeking out-of-hours primary care in the Netherlands. Further prospective validation and implementation are warranted to refine and establish the rule's clinical utility., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Takotsubo cardiomyopathy (TC) is an established differential diagnosis of myocardial infarction with non-obstructive coronaries with significant interest but limited data on prognostication. We reviewed the characteristics and in-hospital outcomes and developed a novel risk score for TC., Methods: Using the National Inpatient Sample data from 2016 to 2020, we identified adult patients (≥18 years) with acute coronary syndrome (ACS) and TC. We divided the cohort into ACS with and without TC and retrieved baseline data. Multivariable regression analysis was conducted to identify factors associated with TC diagnosis and adverse outcomes, leading to the development of a risk-scoring system., Results: Among 7 219 004 adult ACS admissions, 78 214 (1.0%) were diagnosed with TC, with a mean age of 68.2 years, 64 526 (82.5%) being female and 5475 (7.0%, compared with 8.4% for other ACS) in-hospital mortality events. Factors significantly associated with TC were female sex (OR 6.78 (95% CI 6.47 to 7.09), p<0.001) and chronic heart failure (OR 1.60 (95% CI 1.54 to 1.66), p<0.001). A novel risk score was developed, including the following parameters: male sex, age >70 years, non-white race, hypertension, hyperlipidemia, history of coronary artery bypass grafting, history of percutaneous coronary intervention, cardiac arrhythmias, renal failure, cardiogenic shock and vasopressor use. The area under curves for in-hospital mortality was 0.716 in the derivation and 0.725 in the validation cohorts., Conclusions: TC remains a high-risk diagnosis in a minority of ACS cases, with mortality rates similar to other ACS causes. Our novel risk score offers a valuable tool for risk stratification in patients with TC, but external validation is needed to confirm its utility., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Elderly patients diagnosed with acute coronary syndromes (ACS) represent a growing demographic population. These patients typically present more comorbidities and experience poorer outcomes compared to younger patients. Furthermore, they are less frequently subjected to revascularization procedures and are less likely to receive evidence-based medications in both the short and long-term periods. Assessing frailty is crucial in elderly patients with ACS because it can influence management decisions, as well as risk stratification and prognosis. Indeed, treatment decisions should consider geriatric syndromes, frailty, polypharmacy, sarcopenia, nutritional deficits, prevalence of comorbidities, thrombotic risk, and, at the same time, an increased risk of bleeding. Rigorous clinical assessments, clear revascularization criteria, and tailored approaches to antithrombotic therapy are essential for guiding personalized treatment decisions in these individuals. Assessing frailty helps healthcare providers identify patients who may benefit from targeted interventions to improve their outcomes and quality of life. Elderly individuals who experience ACS remain significantly underrepresented and understudied in randomized controlled trials. For this reason, the occurrence of ACS in the elderly continues to be a particularly complex issue in clinical practice, and one that clinicians increasingly have to address, given the general ageing of populations. This review aims to address the complex aspects of elderly patients with ACS to help clinicians make therapeutic decisions when faced with such situations.

Background: Following acute coronary syndrome (ACS), up to 40% of patients report elevated depressive symptoms which is associated with a two-fold increase in mortality risk due to behavioral and biological mechanisms. Mindfulness-Based Cognitive Therapy (MBCT) delivered via synchronous group videoconferencing could help reduce depressive symptoms., Objective: To guide MBCT adaptation for ACS patients for a future clinical trial, this qualitative study aimed to explore ACS patients' (1) symptoms after ACS, (2) needs for behavioral health treatment, (3) perspectives on mindfulness intervention and group videoconference delivery, and (4) willingness to self-collect dried blood spots in a research study., Methods: We compared ACS patients with and without depressive symptoms to highlight particularly relevant treatment topics for patients developing depression following ACS experience. From 2/2019-11/2019, we conducted semi-structured individual telephone interviews with N = 23 patients after ACS (N = 13 with and N = 10 without elevated depressive symptoms; 63.4 (SD = 8.5) years, 87% male, 96% non-Hispanic white, 7.1 (SD = 7.5) years since ACS). In qualitative content analyses, four independent coders coded each interview., Results: Participants with depressive symptoms experienced emotional, physical, social, and health behavior problems, while those without depressive symptoms made positive health behavior changes and struggled with anxiety symptoms. Both groups were interested in a behavioral health treatment for emotional and social support. Most were willing to participate in a mindfulness group via videoconferencing; some preferred in-person, but accessibility and convenience outweighed these cons. Almost all were willing to self-collect dried blood spots and some were already familiar with this technique., Conclusion: ACS patients, especially those with depressive symptoms, need help managing a multitude of quality of life concerns that can be targeted with an adapted MBCT approach. A videoconference-delivered MBCT approach is of interest. Suggestions for adapting MBCT to target the needs of ACS patients are discussed., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Many countries have published clinical practice guidelines for appropriate clinical decisions, optimal treatment, and improved clinical outcomes in patients with acute coronary syndrome. Developing guidelines that are specifically tailored to the Korean environment is crucial, considering the treatment system, available medications and medical devices, racial differences, and level of language communication. In 2017, the Korean Society of Myocardial Infarction established a guideline development committee. However, at that time, it was not feasible to develop guidelines, owing to the lack of knowledge and experience in guideline development and the absence of methodology experts. In 2022, the National Evidence-Based Healthcare Collaborating Agency collaborated with a relevant academic association to develop internationally reliable guidelines, with strict adherence to the methodology for evidence-based guideline development. The first Korean acute coronary syndrome guideline starts from the 9 key questions for pharmacotherapy., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2024. The Korean Society of Cardiology.)

Background and Purpose: DT-678 is a novel antiplatelet prodrug, capable of releasing the antiplatelet active metabolite of clopidogrel (AM) upon exposure to glutathione. In this study, we investigated factors responsible for clopidogrel high on-treatment platelet reactivity (HTPR) in acute coronary syndrome (ACS) patients and evaluated the capacity of DT-678 to overcome HTPR., Experimental Approach: A total of 300 consecutive ACS patients naive to P2Y 12 receptor inhibitors were recruited and genotyped for CYP2C19 alleles. Blood samples were drawn before and after administration of 600-mg clopidogrel. Platelet reactivity index (PRI) and plasma AM concentrations were determined and grouped according to their CYP2C19 genotypes. DT-678 was applied ex vivo to whole blood samples to examine its inhibitory effects. To further examine the antiplatelet effectiveness of DT-678 in vivo, 20 healthy human subjects were recruited in a Phase I clinical trial, and each received a single dose of either 3-mg DT-678 or 75-mg clopidogrel. The pharmacokinetics and pharmacodynamics in different CYP2C19 genotype groups were compared., Key Results: Statistical analyses revealed that CYP2C19 genotype, body mass index, hyperuricaemia, and baseline PRI were significantly associated with a higher risk of clopidogrel HTPR in ACS patients. The addition of DT-678 ex vivo decreased baseline PRI regardless of CYP2C19 genotypes, overcoming clopidogrel HTPR. This observation was further confirmed in healthy volunteers receiving 3 mg of DT-678., Conclusion and Implications: These results suggest that DT-678 effectively overcomes clopidogrel HTPR resulting from genetic and/or clinical factors in Chinese ACS patients, demonstrating its potential to improve antiplatelet therapy., (© 2024 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Acute coronary syndrome continues to be a significant cardiovascular issue. Statins are commonly acknowledged as medications that reduce LDL-C levels and stabilize plaques. Nevertheless, their efficacy is limited. Presently, PCSK9 inhibitors are suggested to be advantageous in patients who are already receiving statin treatment. The study seeks to assess the safety and effectiveness of PCSK9 inhibitors in individuals who have been treated with statins after experiencing acute coronary syndrome (ACS), as well as investigate the impact on the characteristics of coronary plaque., Methods: Articles were identified from PubMed, Cochrane Central Register of Controlled Trials, and ProQuest. Our analysis comprised trials and observational studies that compared the plaque phenotype, lipid profile, and safety outcomes between PCSK9 inhibitors and a control group in patients with acute coronary syndrome who were already being treated with statins. The random-effect model was used to measure the pooled effect, which was presented in terms of mean difference, standardized mean difference, and risk ratio., Results: Acquired 12 studies that fulfilled our criteria. The addition of PCSK9 inhibitors ameliorates the plaque phenotype significantly in terms of percent atheroma volume (P = 0.02), total atheroma volume (P < 0.010), fibrous cap thickness (P < 0.00001), lipid arc (P < 0.00001), quantitative flow ratio (P = 0.003), and diameter of stenosis (P = 0.0003) but not in lipid/lesion length (P = 0.17). The administration of PCSK9 inhibitors led to a considerable improvement in all lipid profiles (P < 0.00001). Regarding safety analysis, there is no substantial disparity in the likelihood of non-serious side events (RR 1.21; P = 0.2), however, a significant reduction in the risk of serious adverse effects (RR 0.77; P = 0.04) in the PCSK9 inhibitor group., Conclusions: The addition of PCSK9 inhibitors compared to statin-only treatment led to a majority of patients experiencing significant benefits in terms of safety and efficacy following ACS., (© 2024. The Author(s).)