Challenges with oral anticoagulants: bridging before surgery and concomitant use of non-steroidal anti-inflammatory drugs. Focus on revascularization of ischaemic cardiomyopathy and e-cigarettes after percutaneous coronary intervention

For the podcast associated with this article, please visit https://academic.oup.com/eurheartj/pages/Podcasts. Dear colleagues! Welcome to the first 2025 issue of the journal. As we embark on a new year, our unwavering commitment to publishing groundbreaking research continues to drive our mission of reducing the global burden of cardiovascular disease. In the face of numerous challenges, our confidence in the power of scientific discovery inspires optimism for our future. Together, let us advance the boundaries of knowledge and foster innovation to improve lives. This Focus Issue on ischaemic heart disease, thrombosis, and antithrombotic therapies contains the Special Article ‘Intra-operative and post-operative management of conduits for coronary artery bypass grafting: a clinical consensus statement of the European Society of Cardiology Working Group on Cardiovascular Surgery and the European Association for Cardio-Thoracic Surgery Coronary Task Force’ by Sigrid Sandner from the University of Vienna in Austria, and colleagues.1 Coronary artery bypass grafting (CABG) is a pillar in the treatment of ischaemic heart disease.2–8 The authors note that the structural and functional integrity of conduits used for CABG is critical for graft patency. Disruption of endothelial integrity and endothelial dysfunction are incurred during conduit harvesting after mechanical or thermal injury and during conduit storage prior to grafting, leading to acute thrombosis and early graft failure. Late graft failure, for vein grafts, is precipitated by progressive atherogenesis. Intra-operative management includes appropriate selection of conduit-specific harvesting techniques and storage solutions. Arterial grafts are prone to vasospasm after surgical manipulation, and application of intra-operative vasodilatory protocols is critical. Post-operative management includes continuation of oral vasodilator therapy and selection of antithrombotic and lipid-lowering agents to attenuate atherosclerotic disease progression in conduits. In this review, the scientific evidence underlying the key aspects of intra- and post-operative management of conduits for CABG is examined. Clinical consensus statements for best clinical practice are provided, and areas requiring further research are highlighted. In a Viewpoint article entitled ‘Non-vitamin K oral anticoagulants in valvular heart disease before surgery: a tale of bridging vs. no bridging’, Raffaele De Caterina from Pisa University Hospital in Italy, and colleagues indicate that patients needing oral anticoagulants (OACs) because of atrial fibrillation or other thromboembolic conditions, but at one point also scheduled for surgery, have to walk the tight rope between an excess risk of bleeding connected to surgery in the presence of coagulation impairment due to anticoagulation and the risk of thromboembolic events in the case of prolonged anticoagulant interruption.9 When vitamin K antagonists (VKAs) were the only anticoagulants available, with an offset of action of days, there has been a long tradition of bridging VKA interruption with shorter acting parenteral heparins. The authors challenge that notion that bridging should be the default approach in patients on non-vitamin K antagonist oral anticoagulants scheduled for surgery. Circulating proenkephalin (PENK) is a stable endogenous polypeptide with fast response to glomerular dysfunction and tubular damage. In a Fast Track Congress article entitled ‘Proenkephalin improves cardio-renal risk prediction in acute coronary syndromes: the KID-ACS score’, Florian Wenzl from the University of Zurich in Switzerland, and colleagues examined the predictive value of PENK for renal outcomes and mortality in patients with acute coronary syndrome (ACS).10 PENK was measured in plasma in a prospective multicentre ACS cohort from Switzerland (n = 4787) and in validation cohorts from the UK (n = 1141), Czechia (n = 927), and Germany (n = 220). A biomarker-enhanced risk score (KID-ACS score) for simultaneous prediction of in-hospital acute kidney injury (AKI) and 30-day mortality was derived and externally validated. On multivariable adjustment for established risk factors, circulating PENK remained associated with in-hospital AKI (per log2 increase: adjusted odds ratio [aOR] 1.53, P = .007) and 30-day mortality (aOR 2.73, P < .001). The KID-ACS score integrates PENK and showed an area under the receiver operating characteristic curve (AUC) of 0.72 for in-hospital AKI and 0.91 for 30-day mortality in the derivation cohort. Upon external validation, KID-ACS achieved similarly high performance for in-hospital AKI and 30-day mortality, outperforming the contrast-associated AKI score and the GRACE 2.0 score. The authors conclude that circulating PENK offers incremental value for predicting in-hospital AKI and mortality in ACS. The simple six-item KID-ACS risk score integrates PENK and provides a novel tool for simultaneous assessment of renal and mortality risk in patients with ACS. The contribution is accompanied by an Editorial by Luca Crisanti and Christian Mueller from the University of Basel in Switzerland.11 The authors note that these findings extend and corroborate other recent studies on PENK as a more accurate biomarker of renal function. PENK is a widely expressed endogenous polypeptide hormone produced in several organs, which is freely filtered by the kidney. PENK strongly correlates with the measured glomerular filtration rate (GFR), and its levels are not influenced by age or sex. They also note that clear links between specific risk profiles and direct management consequences need to be established. This applies to both the prediction of death and the prediction of AKI. Utimately, large randomized controlled trials would be required to document that those targeted interventions, supported by these biomarkers, can improve patient outcomes. Methods and summary results in the study investigating the bleeding risk associated with NSAID use in patients treated with oral anticoagulants for VTE. CI, confidence interval; NSAID, non-steroidal anti-inflammatory drug; VTE, venous thromboembolism.18 Bleeding risk in patients on OAC needs to be carefully assessed.12–17 In a Clinical Research article entitled ‘Bleeding risk using non-steroidal anti-inflammatory drugs with anticoagulants after venous thromboembolism: a nationwide Danish study’, Søren Riis Petersen from the Aarhus University Hospital in Denmark, and colleagues indicate that the bleeding risk using non-steroidal anti-inflammatory drugs (NSAIDs) in patients treated with OAC for venous thromboembolism (VTE) remains unclear.18 A nationwide cohort study of ∼51 800 VTE patients initiating OAC between 1 January 2012 and 31 December 2022 was conducted. Time-dependent multivariate cause-specific Cox regression was used to compute adjusted hazard ratios (aHRs) between NSAID use and hospital-diagnosed bleeding episodes. Event rates for any bleeding per 100 person-years were 3.5 during periods without NSAID use and 6.3 during periods with NSAID use (number needed to harm = 36 patients treated for 1 year). Compared with non-use, the aHRs for any bleeding associated with NSAID use were 2.09 overall, 1.79 for ibuprofen, 3.30 for diclofenac, and 4.10 for naproxen. Compared with non-use, the aHRs associated with NSAID use were 2.24 for gastrointestinal bleeding, 3.22 for intracranial bleeding, 1.36 for thoracic and respiratory tract bleeding, 1.57 for urinary tract bleeding, and 2.99 for anaemia caused by bleeding (Figure 1). Petersen et al. conclude that patients treated with OAC for VTE have a more than two-fold increased bleeding rate when using NSAIDs. This increased bleeding rate is not restricted to the gastrointestinal tract. This manuscript is accompanied by an Editorial by William Parker and Robert Storey from the University of Sheffield in the UK.19 The authors note that an episode of VTE mandates initiation of anticoagulation, usually an OAC, in all but the rarest of circumstances. However, when doing so, physicians must consider the full context of a patient’s bleeding risk factors, including NSAID use. It is important to appropriately counsel the patient, consider alternatives to NSAIDs, including non-pharmacological therapies, and pursue all possible mitigation strategies to reduce the chance of an adverse outcome. This study assessed long-term mortality outcomes among patients with severe left ventricular systolic dysfunction undergoing revascularization by either coronary artery bypass grafting surgery or percutaneous coronary intervention. LVEF, left ventricular ejection fraction; IPTW, inverse probability of treatment weighting; CABG, coronary artery bypass grafting; PCI, percutaneous coronary intervention.23 The optimal revascularization strategy in patients with ischaemic cardiomyopathy remains unclear, with no contemporary randomized trial data to guide clinical practice.20–22 In a Clinical Research article entitled ‘Coronary artery bypass grafting vs. percutaneous coronary intervention in severe ischaemic cardiomyopathy: long-term survival’ Jason Bloom from the Columbia University Medical Center in New York, NY, USA, and colleagues assessed long-term survival in patients with severe ischaemic cardiomyopathy revascularized by either CABG or percutaneous coronary intervention (PCI).23 Using the Australian and New Zealand Society of Cardiac and Thoracic Surgeons and Melbourne Interventional Group registries (from January 2005 to 2018), patients with severe ischaemic cardiomyopathy (left ventricular ejection fraction [LVEF] < 35%) undergoing PCI or isolated CABG were included in the analysis. Those with ST-elevation myocardial infarction and cardiogenic shock were excluded. The primary outcome was long-term National Death Index-linked mortality up to 10 years following revascularization. Risk adjustment was performed to estimate the average treatment effect using propensity score analysis with inverse probability of treatment weighting (IPTW). A total of ∼2000 patients were included, of whom 1451 patients were treated by CABG and 591 by PCI. IPTW-adjusted demographics, procedural indication, coronary artery disease extent, and LVEF were well balanced between the two patient groups. After risk adjustment, patients treated by CABG compared with those treated by PCI experienced reduced long-term mortality (aHR 0.59, P = .001) over a median follow-up period of 4.0 years. There was no difference between the groups in terms of in-hospital mortality, but there was an increased risk of peri-procedural stroke (aOR 19.6, P < .001) and increased length of hospital stay (P < .001) in patients treated with CABG (Figure 2). Bloom and colleagues conclude that in this multi-centre IPTW analysis, patients with severe ischaemic cardiomyopathy undergoing revascularization by CABG rather than PCI show better long-term survival. The contribution is accompanied by an Editorial by Nathan El Bèze and P. Gabriel Steg from the Université Paris-Cité in France.24 The authors point out that it is important to acknowledge that we are not even certain if the traditional model—where revascularizing viable myocardium leads to recovery of LV function—is valid. With the substantial advances in medical therapy, including the ‘four pillars of heart failure’ and devices such as cardiac resynchronization therapy and implantable cardioverter-defibrillators, medical treatment alone may provide substantially improved outcomes in these patients. This is especially relevant given recent findings, particularly from secondary analyses of the REVIVED-BCIS2 trial, which suggest no clear link between myocardial viability and the benefit of PCI. These developments raise a fundamental question: should we pursue revascularization in patients with ischaemic cardiomyopathy, even when myocardial viability is present? The ideal trial design should include three arms—PCI + optimal medical therapy (OMT), CABG + OMT, and OMT alone—to comprehensively evaluate the relative benefits and risks of each approach. In a Clinical Research article entitled ‘Prognosis after switching to electronic cigarettes following percutaneous coronary intervention: a Korean nationwide study’, Danbee Kang from the Sungkyunkwan University School of Medicine in Seoul, Republic of Korea, and colleagues point out that despite the increasing popularity of electronic cigarettes (e-cigarettes), the prognostic impact of switching to e-cigarettes in smokers with coronary artery disease who have undergone PCI remains unclear.25 Using a nationwide cohort from the Korean National Health Insurance database, ∼18 000 adults (≥20 years) identified as smokers (based on a health screening examination within 3 years before PCI) who underwent health screening within 3 years after PCI were enrolled to determine changes in smoking habits. Patients were classified as continued combustible cigarette users, successful quitters, or switchers to e-cigarettes. The group switching to e-cigarettes was further divided into dual users (using both combustible and e-cigarettes) and those exclusively using e-cigarettes. Primary outcomes included major adverse cardiac events (MACEs), a composite of all-cause death, spontaneous myocardial infarction, and repeat revascularization. Among the total population, 50% continued using combustible cigarettes, 9.4% switched to e-cigarettes, and 41% successfully quit smoking after PCI. During a median follow-up of 2.4 years, the cumulative incidence of MACE was lower among e-cigarette switchers (10%) or quitters (13.4%) than among continued combustible cigarette users (17%). When continued combustible cigarette users were used as the reference, the aHRs for MACE were 0.82 for switchers to e-cigarettes and 0.87 for successful quitters. Compared with dual users, entirely switching to e-cigarettes was associated with a significantly lower MACE risk (HR 0.71). The authors conclude that among smokers who undergo PCI, switching to e-cigarette use (particularly complete transition) or quitting smoking is associated with reduced MACE risk compared with with continued combustible cigarette use. The manuscript is accompanied by an Editorial by Thomas Münzel, Andreas Daiber, and Jürgen Prochaska from the Johannes Gutenberg University University in Mainz, Germany.26 The authors highlight that the study by Kang et al. suggests that switching to e-cigarettes might offer a harm reduction strategy for patients unable to quit smoking entirely. However, uncertainties about the long-term cardiovascular side effects of e-cigarettes necessitate further research to fully understand their safety and efficacy. While quitting smoking is the best way to reduce cardiovascular risk, e-cigarettes may serve as a temporary bridge, but caution is advised due to potential long-term risks. The other side of the coin is that we must safeguard our youth from the dangers of vaping, and immediate action is essential. Young people are being drawn in and ensnared by e-cigarettes at a very early age, potentially leading to lifelong nicotine addiction. Nations worldwide must enforce stringent measures to prevent the uptake of vaping, particularly to protect their children and young people. Future research should focus on the long-term cardiovascular effects of e-cigarettes and developing sustained smoking cessation strategies, especially for those with cardiovascular disease. The issue is also complemented by two Discussion Forum contributions. In a commentary entitled ‘A CHA2DS2-VASc score of 1 is not the same for every patient with atrial fibrillation’ Jolien Neefs from the Amsterdam University Medical Center in the Netherlands and colleagues comment on the recent publication ‘Stroke and bleeding risk in atrial fibrillation with CHA2DS2-VASC risk score of one: the Norwegian AFNOR study’ by Mariam Anjum from the Bærum Hospital in Gjettum, Norway.12,27 Anjum et al. respond in a separate comment.28 The editors hope that this issue of the European Heart Journal will be of interest to its readers. Dr. Crea reports speaker fees from Abbott, Amgen, Astra Zeneca, BMS, Chiesi, Daiichi Sankyo, Menarini outside the submitted work. With thanks to Amelia Meier-Batschelet, Johanna Huggler, and Martin Meyer for help with compilation of this article.