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Aims: A genotype-guided P2Y12-inhibitor de-escalation strategy, switching acute coronary syndrome (ACS) patients without a CYP2C19 loss-of-function allele from ticagrelor or prasugrel to clopidogrel, has shown to reduce bleeding risk without affecting effectivity of therapy by increasing ischemic risk. We estimated the cost-effectiveness of this personalized approach compared to standard dual antiplatelet therapy (DAPT; aspirin plus ticagrelor/prasugrel) in the Netherlands., Methods and Results: We developed a one-year decision tree based on results of the FORCE-ACS registry, comparing a cohort of ACS patients who underwent genotyping with a cohort of ACS patients treated with standard DAPT. This was followed by a lifelong Markov model to compare lifetime costs, and quality-adjusted life years (QALYs) for a fictional cohort of 1000 patients. The cost-effectiveness analysis was performed from the perspective of the Dutch healthcare system. A genotype-guided de-escalation strategy led to anincrease of 55.30 QALYs and saved €698,286 compared to standard DAPT based on a lifetime horizon. Probabilistic sensitivity analysis showed that the genotype-guided strategy was cost-saving in 93% and increased QALYs in 86% of simulations. The intervention remained cost-effective in the scenario where prices for all P2Y12-inhibitors were equalized. The genotype-guided strategy remained dominant in various other scenario and sensitivity analyses., Conclusion: A genotype-guided de-escalation strategy in patients with ACS was both cost-saving and yielded higher QALYs compared to standard DAPT, highlighting its potential for implementation in clinical practice. Trial registration: ClinicalTrials.gov identifier: NCT03823547., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims:  Patients presenting with acute coronary syndrome (ACS) are frequently treated with the P2Y 12 -inhibitor ticagrelor. Some patients prematurely discontinue ticagrelor, but the incidence of reasons for and clinical implications of treatment modification are relatively unknown., Methods and Results:  Data from 4,278 ACS patients (mean age: 63.6 years, 26.1% women) who were discharged on ticagrelor and enrolled in the FORCE-ACS registry between 2015 and 2020 were used. Treatment modifications were categorized as physician-recommended discontinuation, alteration, interruption, or disruption and occurred in 26.7, 20.1, 2.8, and 3.1% of patients within 12 months of follow-up (VISUAL SUMMARY: ). Underlying reasons for treatment modification differed per type of modification. Overall, the rate of ischemic events defined as all-cause death, myocardial infarction, or stroke was 6.6% at 12 months of follow-up. Cox regression analysis using time-updated modification variables as independent variables showed that treatment interruption (adjusted hazard ratio [HR]: 2.93, 95% confidence interval [CI]: 1.48-5.79, p  < 0.01) and disruption (adjusted HR: 2.33, 95% CI: 1.07-5.07, p  = 0.03) were associated with an increased risk of ischemic events even after adjustment for relevant confounders. Discontinuation and alteration were not associated with increased ischemic risk., Conclusion:  In clinical practice, treatment modifications in ACS patients discharged on ticagrelor are common, although type and reasons for modification are heterogeneous. Treatment interruption and disruption are associated with excess cardiovascular risk., Competing Interests: G.J.V. has received institutional research grants from MicroPort and Ferrer and personal fees from Terumo and AstraZeneca. Y.A. has received an institutional research from the Dutch Heart Foundation. J.P.S.H. has received institutional research grants from Abbott Vascular, AstraZeneca, B. Braun, Getinge, Ferrer, Infraredx, and ZonMw. W.J.K. has received an institutional research grant from AstraZeneca. J.M.T.B. has received institutional research grants from AstraZeneca, Daiichi Sankyo, and ZonMw and personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, CeleCor Therapeutics, Daiichi Sankyo, Eli Lilly, Ferrer, and Idorsia. All other authors have no relationships with industry to disclose., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Background: Acute coronary syndrome (ACS) is frequently accompanied by newly diagnosed atrial fibrillation (AF)., Aims: We aimed to compare the risk of major adverse cardiovascular events (MACE) in ACS patients presenting with known, newly diagnosed, or no AF., Methods: In our multicentre, prospective registry study, we included patients with confirmed ACS. Patients are classified as having known, newly diagnosed or no AF. Newly diagnosed AF is subdivided according to the duration of the episode, time of onset, post-coronary artery bypass graft (CABG) or spontaneous occurrence, and treatment with oral anticoagulants (OAC). The primary endpoint is MACE at 1 year. Key secondary endpoints include ischaemic stroke and bleeding complications., Results: Amongst 4,433 patients with confirmed ACS, 3,598 (81.2%) had no AF, 438 (9.9%) had newly diagnosed AF, and 397 (9.0%) had known AF. The rates of OAC treatment at discharge were 53.4% in patients with newly diagnosed AF and 89.2% in patients with known AF. After adjusting for baseline imbalances, only new AF was independently associated with increased rates of MACE, whereas known AF was not (hazard ratio [HR] 1.52, 95% confidence interval [CI]: 1.19-1.90 and HR 0.93, 95% CI: 0.70-1.23). For ACS patients with newly diagnosed AF, episodes lasting >24 hours were associated with a higher risk of MACE compared to episodes <24 hours (HR 1.99, 95% CI: 1.36-2.93). Episodes of new AF occurring post-CABG had more favourable outcomes compared to spontaneously occurring new AF (HR for MACE 0.52, 95% CI: 0.31-0.86). OAC treatment rates were higher in the new AF subcategories with higher rates of MACE and ischaemic stroke., Conclusions: Newly diagnosed AF in ACS patients was associated with higher rates of MACE and ischaemic stroke compared to ACS patients without or with known AF. Among the ACS patients with new AF, an episode lasting >24 hours was associated with worse outcomes than shorter episodes, while post-CABG occurrence of AF showed relatively better outcomes compared to spontaneously occurring AF. Only 53% of new AF patients were discharged on OAC therapy versus 89% with known AF.

Background: CYP2C19 genotype-guided de-escalation from ticagrelor or prasugrel to clopidogrel may optimize the balance between ischemic and bleeding risk in patients with acute coronary syndrome (ACS)., Objectives: This study sought to compare bleeding and ischemic event rates in genotyped patients vs standard care., Methods: Since 2015, ACS patients in the multicenter FORCE-ACS (Future Optimal Research and Care Evaluation in Patients with Acute Coronary Syndrome) registry received standard dual antiplatelet therapy (DAPT). Since 2021, genotype-guided P2Y 12 inhibitor de-escalation was recommended at a single center, switching noncarriers of the loss-of-function allele CYP2C19∗3 or CYP2C19∗2 from ticagrelor or prasugrel to clopidogrel, whereas loss-of-function carriers remained on ticagrelor or prasugrel. The primary ischemic endpoint, a composite of cardiovascular mortality, myocardial infarction, or stroke, and the primary bleeding endpoint, Bleeding Academic Research Consortium 2, 3, or 5 bleeding, were compared between a genotyped cohort and a cohort treated with standard DAPT after 1 year., Results: Among 5,321 enrolled ACS patients, 406 underwent genotyping compared with 4,915 nongenotyped ACS patients on standard DAPT. In the genotyped cohort, 65.3% (n = 265) were noncarriers, 88.7% (n = 235) of whom were switched to clopidogrel. The primary ischemic endpoint occurred in 5.2% (n = 21) of patients in the genotyped cohort compared to 6.9% (n = 337) in the standard care cohort (adjusted HR: 0.82; 95% CI: 0.53-1.28). The primary bleeding rate was significantly lower in the genotyped cohort compared to the standard care cohort (4.7% vs 9.8%; adjusted HR: 0.47; 95% CI: 0.30-0.76)., Conclusions: The implementation of a CYP2C19 genotype-guided P2Y 12 inhibitor de-escalation strategy in a real-world ACS population resulted in lower bleeding rates without an increase in ischemic events compared to a standard DAPT regimen., Competing Interests: Funding Support and Author Disclosures The FORCE-ACS registry is supported by grants from ZonMw, the St. Antonius Research Fund, and AstraZeneca. The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the manuscript, and its final contents. Dr Vlachojannis has received institutional research grants from MicroPort and Ferrer; and has received personal fees from Terumo and AstraZeneca. Dr Appelman has received an institutional research grant from the Dutch Heart Foundation. Dr Henriques has received institutional research grants from Abbott Vascular, AstraZeneca, B. Braun, Getinge, Ferrer, Infraredx, and ZonMw. Dr Kikkert has received an institutional research grant from AstraZeneca. Dr ten Berg has received institutional research grants from AstraZeneca, Daiichi Sankyo, and ZonMw; and has received personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, CeleCor Therapeutics, Daiichi Sankyo, Eli Lilly, Ferrer, and Idorsia. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Early aspirin withdrawal, also known as P2Y 12 -inhibitor monotherapy, following percutaneous coronary intervention (PCI) for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) can reduce bleeding without a trade-off in efficacy. Still the average daily bleeding risk is highest during the first months and it remains unclear if aspirin can be omitted immediately following PCI., Methods: The LEGACY study is an open-label, multicenter randomized controlled trial evaluating the safety and efficacy of immediate P2Y 12 -inhibitor monotherapy versus dual antiplatelet therapy (DAPT) for 12 months in 3,090 patients. Patients are randomized immediately following successful PCI for NSTE-ACS to 75-100 mg aspirin once daily versus no aspirin. The primary hypothesis is that immediately omitting aspirin is superior to DAPT with respect to major or minor bleeding defined as Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, while maintaining noninferiority for the composite of all-cause mortality, myocardial infarction and stroke compared to DAPT., Conclusions: The LEGACY study is the first randomized study that is specifically designed to evaluate the impact of immediately omitting aspirin, and thus treating patients with P2Y 12 -inhibitor monotherapy, as compared to DAPT for 12 months on bleeding and ischemic events within 12 months following PCI for NSTE-ACS., Competing Interests: Disclosures Dr. Yolande Appelman has received a research grant from the Dutch Heart Foundation. Prof. dr. Jurriën M. ten Berg has received research grants from the ZonMw and speaker fees from Accumetrics, AstraZeneca, Bayer, BMS, Boehringer-Ingelheim, Daiichi Sankyo, Eli Lilly, Ferrer, the Medicines Company and Pfizer. Dr. Peter Damman has received a research grant from AstraZeneca. Dr. Tim P. van de Hoef has received research grants and speaker fees and from Abbott and Philips. Dr. Bimmer E.P.M. Claessen has received speaker fees from Abiomed and consultancy fees from Amgen, Sanofi, Boston Scientific and Philips. Prof. dr. José P.S. Henriques has received research grants from Abbott Vascular, AstraZeneca, B. Braun, Getinge, Ferrer, Infraredx and ZonMw. All other authors have no relationships with industry to disclose., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Graphical AbstractClinical outcomes and treatment adherence during 12 months follow-up. *Second bleeding event in same patient. PCI, percutaneous coronary intervention; TVR, target vessel revascularization., Competing Interests: Conflict of interest: B.E.P.M.C. has received speaker fees from Abiomed and consultancy fees from Amgen, Sanofi, Boston Scientific, and Philips. W.J.K. has received a research grant from AstraZeneca. Y.A. has received a research grant from the Dutch Heart Foundation. J.P.S.H. has received research grants from Abbott Vascular, AstraZeneca, B. Braun, Getinge, Ferrer, Infraredx, and ZonMw. All other authors have no relationships with industry to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: Patients with acute coronary syndrome (ACS) remain at high risk for recurrent ischaemic and bleeding events during follow-up. Our study aimed to quantify and compare the impact of these adverse events on quality of life (QoL)., Methods: Data from patients with ACS prospectively enrolled in the FORCE-ACS registry between January 2015 and December 2019 were used for this study. The primary ischaemic and bleeding events of interest were hospital readmission for ACS and Bleeding Academic Research Consortium type 2 or 3 bleeding during 12 months follow-up. QoL was measured using the EQ-5D Visual Analogue Scale (VAS) score and the 12-item Short Form Survey version 2 derived Physical Component Summary (PCS) and Mental Health Component Summary (MCS) scores at 12 months follow-up., Results: In total, 3339 patients (mean age 66.8 years, 27.9% women) were included. During follow-up, ischaemic events occurred in 202 patients (6.0%) and bleeding events in 565 patients (16.9%). After adjustment for demographic and clinical characteristics, ischaemic events remained independently associated with lower QoL regardless of metric used. Bleeding was also independently associated with lower EQ-5D VAS and PCS scores, but not with a lower MCS score. The QoL decrement associated with ischaemic events was numerically larger than the decrement associated with bleeding., Conclusions: Ischaemic and bleeding events remain prevalent and are independently associated with lower QoL at 12 months follow-up in patients previously admitted for ACS. The incidence and impact of these adverse events should be considered when balancing individual ischaemic and bleeding risks., Competing Interests: Competing interests: WK has received an institutional research grant from AstraZeneca. GJV has received institutional research grants from MicroPort and Ferrer and personal fees from Terumo and AstraZeneca. YA has received an institutional research from the Dutch Heart Foundation. JPSH has received institutional research grants from Abbott Vascular, AstraZeneca, B. Braun, Getinge, Ferrer, Infraredx and ZonMw. JtB has received institutional research grants from AstraZeneca, Daiichi Sankyo and ZonMw and personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, CeleCor Therapeutics, Daiichi Sankyo, Eli Lilly, Ferrer and Idorsia. All other authors have no relationships with industry to disclose., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Early P2Y 12 inhibitor monotherapy has emerged as a promising alternative to 12 months of dual antiplatelet therapy following percutaneous coronary intervention (PCI)., Aims: In this single-arm pilot study, we evaluated the feasibility and safety of ticagrelor or prasugrel monotherapy directly following PCI in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS)., Methods: Patients received a loading dose of ticagrelor or prasugrel before undergoing platelet function testing and subsequent PCI using new-generation drug-eluting stents. The stent result was adjudicated with optical coherence tomography in the first 35 patients. Ticagrelor or prasugrel monotherapy was continued for 12 months. The primary ischaemic endpoint was the composite of all-cause mortality, myocardial infarction, definite or probable stent thrombosis or stroke within 6 months. The primary bleeding endpoint was Bleeding Academic Research Consortium type 2, 3 or 5 bleeding within 6 months., Results: From March 2021 to March 2022, 125 patients were enrolled, of whom 75 ultimately met all in- and exclusion criteria (mean age 64.5 years, 29.3% women). Overall, 70 out of 75 (93.3%) patients were treated with ticagrelor or prasugrel monotherapy directly following PCI. The primary ischaemic endpoint occurred in 3 (4.0%) patients within 6 months. No cases of stent thrombosis or spontaneous myocardial infarction occurred. The primary bleeding endpoint occurred in 7 (9.3%) patients within 6 months., Conclusions: This study provides first-in-human evidence that P2Y 12 inhibitor monotherapy directly following PCI for NSTE-ACS is feasible, without any overt safety concerns, and highlights the need for randomised controlled trials comparing direct P2Y 12 inhibitor monotherapy with the current standard of care.

Aims/hypothesis: Obesity is a major risk factor for type 2 diabetes. However, body composition differs between women and men. In this study we investigate the association between diabetes status and body composition and whether this association is moderated by sex., Methods: In a population-based cohort study (n=7639; age 40-75 years, 50% women, 25% type 2 diabetes), we estimated the sex-specific associations, and differences therein, of prediabetes (i.e. impaired fasting glucose and/or impaired glucose tolerance) and type 2 diabetes (reference: normal glucose metabolism [NGM]) with dual-energy x-ray absorptiometry (DEXA)- and MRI-derived measures of body composition and with hip circumference. Sex differences were analysed using adjusted regression models with interaction terms of sex-by-diabetes status., Results: Compared with their NGM counterparts, both women and men with prediabetes and type 2 diabetes had more fat and lean mass and a greater hip circumference. The differences in subcutaneous adipose tissue, hip circumference and total and peripheral lean mass between type 2 diabetes and NGM were greater in women than men (women minus men [W-M] mean difference [95% CI]: 15.0 cm 2 [1.5, 28.5], 3.2 cm [2.2, 4.1], 690 g [8, 1372] and 443 g [142, 744], respectively). The difference in visceral adipose tissue between type 2 diabetes and NGM was greater in men than women (W-M mean difference [95% CI]: -14.8 cm 2 [-26.4, -3.1]). There was no sex difference in the percentage of liver fat between type 2 diabetes and NGM. The differences in measures of body composition between prediabetes and NGM were generally in the same direction, but were not significantly different between women and men., Conclusions/interpretation: This study indicates that there are sex differences in body composition associated with type 2 diabetes. The pathophysiological significance of these sex-associated differences requires further study., (© 2023. The Author(s).)

Background: Spontaneously depolarizing nodal cells comprise the pacemaker of the heart. Intracellular calcium (Ca 2+ ) plays a critical role in mediating nodal cell automaticity and understanding this so-called Ca 2+ clock is critical to understanding nodal arrhythmias. We previously demonstrated a role for Jph2 (junctophilin 2) in regulating Ca 2+ -signaling through inhibition of RyR2 (ryanodine receptor 2) Ca 2+ leak in cardiac myocytes; however, its role in pacemaker function and nodal arrhythmias remains unknown. We sought to determine whether nodal Jph2 expression silencing causes increased sinoatrial and atrioventricular nodal cell automaticity due to aberrant RyR2 Ca 2+ leak., Methods: A tamoxifen-inducible, nodal tissue-specific, knockdown mouse of Jph2 was achieved using a Cre-recombinase-triggered short RNA hairpin directed against Jph2 (Hcn4:shJph2). In vivo cardiac rhythm was monitored by surface ECG, implantable cardiac telemetry, and intracardiac electrophysiology studies. Intracellular Ca 2+ imaging was performed using confocal-based line scans of isolated nodal cells loaded with fluorescent Ca 2+ reporter Cal-520. Whole cell patch clamp was conducted on isolated nodal cells to determine action potential kinetics and sodium-calcium exchanger function., Results: Hcn4:shJph2 mice demonstrated a 40% reduction in nodal Jph2 expression, resting sinus tachycardia, and impaired heart rate response to pharmacologic stress. In vivo intracardiac electrophysiology studies and ex vivo optical mapping demonstrated accelerated junctional rhythm originating from the atrioventricular node. Hcn4:shJph2 nodal cells demonstrated increased and irregular Ca 2+ transient generation with increased Ca 2+ spark frequency and Ca 2+ leak from the sarcoplasmic reticulum. This was associated with increased nodal cell AP firing rate, faster diastolic repolarization rate, and reduced sodium-calcium exchanger activity during repolarized states compared to control. Phenome-wide association studies of the JPH2 locus identified an association with sinoatrial nodal disease and atrioventricular nodal block., Conclusions: Nodal-specific Jph2 knockdown causes increased nodal automaticity through increased Ca 2+ leak from intracellular stores. Dysregulated intracellular Ca 2+ underlies nodal arrhythmogenesis in this mouse model.

Objectives: To validate the Global Registry of Acute Coronary Events (GRACE) risk score and examine the extent and impact of the risk-treatment paradox in contemporary patients with acute coronary syndrome (ACS)., Methods: Data from 5015 patients with ACS enrolled in the FORCE-ACS registry between January 2015 and December 2019 were used for model validation. The performance of the GRACE risk score for predicting in-hospital and 1-year mortality was evaluated based on indices of model discrimination and calibration. Differences in the delivery of guideline-recommended care among patients who survived hospitalisation (n=4911) per GRACE risk stratum were assessed and the association with postdischarge mortality was examined., Results: Discriminative power of the GRACE risk score was good for predicting in-hospital (c-statistic: 0.86; 95% CI: 0.83 to 0.90) and 1-year mortality (c-statistic: 0.82; 95% CI: 0.79 to 0.84). However, the GRACE risk score overestimated the absolute in-hospital and 1-year mortality risk (Hosmer-Lemeshow goodness-of-fit test p<0.01). Intermediate-risk and high-risk patients were 12% and 29% less likely to receive optimal guideline-recommended care compared with low-risk patients, respectively. Optimal guideline-recommended care was associated with lower mortality in intermediate- and high-risk patients., Conclusions: The GRACE risk score identified patients at higher risk for in-hospital and 1-year mortality, but overestimated absolute risk levels in contemporary patients. Optimal guideline-recommended care was associated with lower mortality in intermediate-risk and high-risk patients, but was less likely to be delivered with increasing mortality risk., Competing Interests: Competing interests: Dr Wouter J Kikkert has received a research grant from AstraZeneca. Dr Georgios J Vlachojannis has research grants from MicroPort and Ferrer and personal fees from Terumo and AstraZeneca. Dr Yolande Appelman has received a research grant from the Dutch Heart Foundation. Professor Dr José PS Henriques has received research grants from Abbott Vascular, AstraZeneca, B. Braun, Getinge, Ferrer, Infraredx and ZonMw. Professor Dr Jurriën M ten Berg has received research grants from AstraZeneca and ZonMw and personal fees from AstraZeneca, Accu-Metrics, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Ferrer, Idorsia, Pfizer and The Medicines Company. All other authors have no relationships with industry to disclose., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Acute coronary syndrome (ACS) mostly arises from so-called vulnerable coronary plaques, particularly prone for rupture. Vulnerable plaques comprise a specific type of plaque, called the thin-cap fibroatheroma (TFCA). A TCFA is characterized by a large lipid-rich necrotic core, a thin fibrous cap, inflammation, neovascularization, intraplaque hemorrhage, microcalcifications or spotty calcifications, and positive remodeling. Vulnerable plaques are often not visible during coronary angiography. However, different plaque features can be visualized with the use of intracoronary imaging techniques, such as intravascular ultrasound (IVUS), potentially with the addition of near-infrared spectroscopy (NIRS), or optical coherence tomography (OCT). Non-invasive imaging techniques, such as computed tomography coronary angiography (CTCA), cardiovascular magnetic resonance (CMR) imaging, and nuclear imaging, can be used as an alternative for these invasive imaging techniques. These invasive and non-invasive imaging modalities can be implemented for screening to guide primary or secondary prevention therapies, leading to a more patient-tailored diagnostic and treatment strategy. Systemic pharmaceutical treatment with lipid-lowering or anti-inflammatory medication leads to plaque stabilization and reduction of cardiovascular events. Additionally, ongoing studies are investigating whether modification of vulnerable plaque features with local invasive treatment options leads to plaque stabilization and subsequent cardiovascular risk reduction.

Acute coronary syndrome mostly arises from rupture or erosion of a vulnerable plaque. Vulnerable plaques typically appear as lipid-rich plaques with a thin cap, called thin-cap fibroatheromas. Various intracoronary imaging techniques can be used to detect vulnerable plaques, such as intravascular ultrasound (IVUS), optical coherence tomography (OCT) and near-infrared spectroscopy (NIRS), each visualizing different high-risk plaque characteristics. IVUS and its post-processing techniques, such as virtual histology IVUS, can primarily be used to identify calcified and soft plaques, while OCT is also able to quantitatively measure the cap thickness. The addition of NIRS allows the exact measurement of lipid content in the plaque. Non-invasive imaging techniques to identify vulnerable plaques, such as computed tomography, are less often used but are evolving and may be of additional diagnostic use, especially when prophylactic treatments for vulnerable plaques are further established. Pharmacological treatment with lipid-lowering or anti-inflammatory medication leads to plaque stabilization and reduction of cardiovascular events. Moreover, the implantation of a stent or scaffold for the local treatment of vulnerable plaques has been found to be safe and to stabilize high-risk plaque features. The use of drug-coated balloons to treat vulnerable plaques is the subject of ongoing research. Future studies should focus on non-invasive imaging techniques to adequately identify vulnerable plaques and further randomized clinical studies are necessary to find the most appropriate treatment strategy for vulnerable plaques., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

Cangrelor is the first and only intravenous P2Y 12 -inhibitor and is indicated when (timely) administration of an oral P2Y 12 inhibitor is not feasible in patients undergoing percutaneous coronary intervention (PCI). Our study evaluated the first years of cangrelor use in two Dutch tertiary care centers. Cangrelor-treated patients were identified using a data-mining algorithm. The cumulative incidences of all-cause death, myocardial infarction, definite stent thrombosis and major bleeding at 48 h and 30 days were assessed using Kaplan-Meier estimates. Predictors of 30-day mortality were identified using uni- and multivariable Cox regression models. Between March 2015 and April 2021, 146 patients (median age 63.7 years, 75.3% men) were treated with cangrelor. Cangrelor was primarily used in ST-segment elevation myocardial infarction (STEMI) patients (84.2%). Approximately half required cardiopulmonary resuscitation (54.8%) or mechanical ventilation (48.6%). The cumulative incidence of all-cause death was 11.0% and 25.3% at 48 h and 30 days, respectively. Two cases (1.7%) of definite stent thrombosis, both resulting in myocardial infarction, occurred within 30 days, but after 48 h. No other cases of recurrent myocardial infarction transpired within 30 days. Major bleeding occurred in 5.6% and 12.5% of patients within 48 h and 30 days, respectively. Cardiac arrest at presentation was an independent predictor of 30-day mortality (adjusted hazard ratio 5.20, 95%-CI: 2.10-12.9, p < 0.01). Conclusively, cangrelor was used almost exclusively in STEMI patients undergoing PCI. Even though cangrelor was used in high-risk patients, its use was associated with a low rate of stent thrombosis.

Dual antiplatelet therapy has long been the standard of care in preventing coronary and cerebrovascular thrombotic events in patients with chronic coronary syndrome and acute coronary syndrome undergoing percutaneous coronary intervention, but choosing the optimal treatment duration and composition has become a major challenge. Numerous studies have shown that certain patients benefit from either shortened or extended treatment duration. Furthermore, trials evaluating novel antithrombotic strategies, such as P2Y12 inhibitor monotherapy, low-dose factor Xa inhibitors on top of antiplatelet therapy, and platelet function- or genotype-guided (de-)escalation of treatment, have shown promising results. Current guidelines recommend risk stratification for tailoring treatment duration and composition. Although several risk stratification methods evaluating ischaemic and bleeding risk are available to clinicians, such as the use of risk scores, platelet function testing , and genotyping, risk stratification has not been broadly adopted in clinical practice. Multiple risk scores have been developed to determine the optimal treatment duration, but external validation studies have yielded conflicting results in terms of calibration and discrimination and there is limited evidence that their adoption improves clinical outcomes. Likewise, platelet function testing and genotyping can provide useful prognostic insights, but trials evaluating treatment strategies guided by these stratification methods have produced mixed results. This review critically appraises the currently available antithrombotic strategies and provides a viewpoint on the use of different risk stratification methods alongside clinical judgement in current clinical practice., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Diagnostic and treatment strategies for acute coronary syndrome have improved dramatically over the past few decades, but mortality and recurrent myocardial infarction rates remain high. An aging population with increasing co-morbidities heralds new clinical challenges. Therefore, in order to evaluate and improve current treatment strategies, detailed information on clinical presentation, treatment and follow-up in real-world patients is needed. The Future Optimal Research and Care Evaluation in patients with Acute Coronary Syndrome (FORCE-ACS) registry (ClinicalTrials.gov Identifier: NCT03823547) is a multi-center, prospective real-world registry of patients admitted with (suspected) acute coronary syndrome. Both non-interventional and interventional cardiac centers in different regions of the Netherlands are currently participating. Patients are treated according to local protocols, enabling the evaluation of different diagnostic and treatment strategies used in daily practice. Data collection is performed using electronic medical records and quality-of-life questionnaires, which are sent 1, 12, 24 and 36 months after initial admission. Major end points are all-cause mortality, myocardial infarction, stent thrombosis, stroke, revascularization and all bleeding requiring medical attention. Invasive therapy, antithrombotic therapy including patient-tailored strategies, such as the use of risk scores, pharmacogenetic guided antiplatelet therapy and patient reported outcome measures are monitored. The FORCE-ACS registry provides insight into numerous aspects of the (quality of) care for acute coronary syndrome patients.