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Aim: To assess the value of the thrombotic risk criteria proposed in the 2023 guidelines of the European Society of Cardiology (ESC) for the management of acute coronary syndrome (ACS) to predict the ischaemic risk after percutaneous coronary intervention (PCI)., Methods and Results: Consecutive patients with acute or chronic coronary syndrome undergoing PCI at a large tertiary-care center from 2014 to 2019 were included. Patients were stratified into low, moderate, or high thrombotic risk based on the ESC criteria. The primary endpoint was major adverse cardiovascular events (MACEs) at 1 year, a composite of all-cause death, myocardial infarction (MI), and stroke. Secondary endpoints included major bleeding. Among 11 787 patients, 2641 (22.4%) were at low-risk, 5286 (44.8%) at moderate risk, and 3860 (32.7%) at high-risk. There was an incremental risk of MACE at 1 year in patients at moderate (hazard ratios (HR) 2.53, 95% confidence interval (CI) 1.78-3.58) and high-risk (HR 3.39, 95% CI 2.39-4.80) as compared to those at low-risk, due to higher rates of all-cause death and MI. Major bleeding rates were increased in high-risk patients (HR 1.59, 95% CI 1.25-2.02), but similar between the moderate and low-risk group. The Harrell's C-index for MACE was 0.60., Conclusion: The thrombotic risk criteria of the 2023 ESC guidelines for ACS enable to stratify patients undergoing PCI in categories with an incremental 1 year risk of MACE; however, their overall predictive ability for MACE is modest. Future studies should confirm the value of these criteria to identify patients benefiting from an extended treatment with a second antithrombotic agent., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Based on recent clinical data, the 2020 ESC guidelines on non-ST-elevation acute coronary syndrome (NSTE-ACS) suggest to tailor antithrombotic strategy on individual thrombotic risk. Nonetheless, prevalence and prognostic impact of the high thrombotic risk (HTR) criteria proposed are yet to be described. In this analysis from the PROMETHEUS registry, we assessed prevalence and prognostic impact of HTR, defined according to the 2020 ESC NSTE-ACS guidelines, and if the benefits associated with prasugrel vs. clopidogrel vary with thrombotic risk., Methods and Results: PROMETHEUS was a multicentre prospective study comparing prasugrel vs. clopidogrel in ACS patients undergoing percutaneous coronary intervention (PCI). Patients were at HTR if presenting with one clinical plus one procedural risk feature. The primary endpoint was major adverse cardiac events (MACE), composite of death, myocardial infarction, stroke, or unplanned revascularization, at 1 year. Adjusted hazard ratio (adjHR) and 95% confidence intervals (CIs) were calculated with propensity score stratification and multivariable Cox regression. Among 16 065 patients, 4293 (26.7%) were at HTR and 11 772 (73.3%) at low-to-moderate thrombotic risk. The HTR conferred increased incidence of MACE (23.3 vs. 13.6%, HR 1.85, 95% CI 1.71-2.00, P < 0.001) and its single components. Prasugrel was prescribed in patients with less comorbidities and risk factors and was associated with reduced risk of MACE (HTR: adjHR 0.83, 95% CI 0.68-1.02; low-to-moderate risk: adjHR 0.75, 95% CI 0.64-0.88; pinteraction = 0.32)., Conclusion: High thrombotic risk, as defined by the 2020 ESC NSTE-ACS guidelines, is highly prevalent among ACS patients undergoing PCI. The HTR definition had a strong prognostic impact, as it successfully identified patients at increased 1 year risk of ischaemic events., Competing Interests: Conflict of interest: M.B.E. receives a pension from and has equity in Eli Lilly and Company. G.S. reports a research grant from Boston Scientific and speaker or consulting fees from B. Braun, Biosensors, and Boston Scientific. T.H. has received research grant support from Eli Lilly and Daiichi Sankyo. S.S. has received from Abbott Vascular, Boston Scientific, and Cardiovascular Systems, Inc. U.B. has received honoraria from Amgen, AstraZeneca, Abbott, and Boston Scientific. G.D. has received consulting fees and advisory board fees from AstraZeneca, consulting fees from Biosensors, and previously holding stock in Medtronic. R.M. reports grants from Abbott Laboratories, AstraZeneca, Bayer, Beth Israel Deaconess, Bristol Myers Squibb, CSL Behring, DSI, Medtronic, Novartis Pharmaceuticals, and OrbusNeich; personal fees from Abbott Laboratories, Boston Scientific, Medscape/WebMD, Siemens Medical Solutions, PLx Opco Inc/dba PLx Pharma Inc., Roivant Sciences, Sanofi, and Medtelligence (Janssen Scientific Affairs); other from Abbott laboratories, other from Abiomed, other from Bristol Myers Squibb, other from Claret Medical, other from Elixir Medical, other from The Medicines eCompany, other from Spectranetics/Philips/Volcano Corp., and other from Watermark Research Partners; and non-financial support and other from Regeneron Pharmaceuticals, and Idorsia Pharmaceuticals Ltd. The other authors report no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: The aim of this study was to assess the effect of ticagrelor monotherapy among high-risk patients with anaemia undergoing percutaneous coronary intervention (PCI)., Methods and Results: In the TWILIGHT (Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial, after 3 months of ticagrelor plus aspirin, high-risk patients were maintained on ticagrelor and randomized to aspirin or placebo for 1 year. Anaemia was defined as haemoglobin <13 g/dL for men and <12 g/dL for women. The primary endpoint was Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. The key secondary endpoint was a composite of all-cause death, myocardial infarction, or stroke.Out of 6828 patients, 1329 (19.5%) had anaemia and were more likely to have comorbidities, multivessel disease, and to experience bleeding or ischaemic complications than non-anaemic patients. Among anaemic patients, BARC 2, 3, or 5 bleeding occurred less frequently with ticagrelor monotherapy than with ticagrelor plus aspirin [6.4% vs. 10.7%; hazard ratio (HR) 0.60; 95% confidence interval (CI) 0.41-0.88; P = 0.009]; the rate of the key secondary endpoint was similar in the two arms (5.2% vs. 4.8%; HR 1.07; 95% CI 0.66-1.74; P = 0.779). These effects were consistent in patients without anaemia (interaction P values 0.671 and 0.835, respectively)., Conclusion: In high-risk patients undergoing PCI, ticagrelor monotherapy after 3 months of ticagrelor-based dual antiplatelet therapy was associated with a reduced risk of clinically relevant bleeding without any increase in ischaemic events irrespective of anaemia status (TWILIGHT: NCT02270242)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Remarkable progress has been made in the pharmacological management of patients with cardiovascular disease, including the frequent use of antithrombotic agents. Nonetheless, bleeding complications remain frequent and potentially life-threatening. Therapeutic interventions relying on prompt antithrombotic drug reversal or removal have been developed to assist clinicians in treating patients with active bleeding or an imminent threat of major bleeding due to urgent surgery or invasive procedures. Early phase studies on these novel strategies have shown promising results using surrogate pharmacodynamic endpoints. However, the benefit of reversing/removing antiplatelet or anticoagulant drugs should always be weighed against the possible prothrombotic effects associated with withdrawal of antithrombotic protection, bleeding, and surgical trauma. Understanding the ischemic-bleeding risk tradeoff of antithrombotic drug reversal and removal strategies in the context of urgent high-risk settings requires dedicated clinical investigations, but challenges in trial design remain, with relevant practical, financial, and ethical implications., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Complex percutaneous coronary intervention (C-PCI) is associated with an increased risk of ischaemic and bleeding complications. We aimed to assess the safety and efficacy of a 1-3-month dual antiplatelet therapy (DAPT) regimen followed by P2Y12 inhibitor monotherapy after C-PCI., Methods and Results: We conducted a meta-analysis of randomized trials comparing a 1-3-month DAPT regimen followed by P2Y12 inhibitor monotherapy with standard (≥12 months) DAPT in patients undergoing C-PCI. C-PCI criteria and the co-primary bleeding and ischaemic outcomes were determined according to each trial. Secondary outcomes included major bleeding, all-cause death, myocardial infarction, and stent thrombosis. All outcomes were evaluated at 12 months after randomization. We used hazard ratios (HRs) and 95% confidence interval (CI) as a metric of choice for treatment effects with random-effects models. Among 8299 screened studies, five randomized trials fulfilled the eligibility criteria. In the pooled population of 34 615 patients, 8818 (25.5%) underwent C-PCI. As compared with standard DAPT, a 1-3-month DAPT regimen followed by P2Y12 inhibitor monotherapy reduced the bleeding risk in C-PCI (HR:0.66, 95% CI:0.44-0.98) and non-C-PCI (HR:0.60, 95% CI:0.45-0.79) patients (P-interaction = 0.735). Furthermore, the risk for the primary ischaemic endpoint was similar in patients randomized to either arm, with significant effect modification by PCI complexity showing an enhanced benefit of 1-3-month DAPT in patients undergoing C-PCI (C-PCI, HR:0.69, 95% CI:0.48-1.00; non-C-PCI, HR:1.04, 95% CI:0.84-1.30; P-interaction = 0.028)., Conclusion: As compared with a standard DAPT, a 1-3-month DAPT regimen followed by P2Y12 inhibitor monotherapy reduced bleeding complications after C-PCI without increasing the risk of ischaemic events.PROSPERO-registered (CRD42021259271)., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients at high bleeding risk (HBR) is still debated. The current study, using the totality of existing evidence, evaluated the impact of an abbreviated DAPT regimen in HBR patients., Methods and Results: A systematic review and meta-analysis was performed to search randomized clinical trials comparing abbreviated [i.e. very-short (1 month) or short (3 months)] with standard (≥6 months) DAPT in HBR patients without indication for oral anticoagulation. A total of 11 trials, including 9006 HBR patients, were included. Abbreviated DAPT reduced major or clinically relevant non-major bleeding [risk ratio (RR): 0.76, 95% confidence interval (CI): 0.61-0.94; I2 = 28%], major bleeding (RR: 0.80, 95% CI: 0.64-0.99, I2 = 0%), and cardiovascular mortality (RR: 0.79, 95% CI: 0.65-0.95, I2 = 0%) compared with standard DAPT. No difference in all-cause mortality, major adverse cardiovascular events, myocardial infarction, or stent thrombosis was observed. Results were consistent, irrespective of HBR definition and clinical presentation., Conclusion: In HBR patients undergoing PCI, a 1- or 3-month abbreviated DAPT regimen was associated with lower bleeding and cardiovascular mortality, without increasing ischaemic events, compared with a ≥6-month DAPT regimen., Study Registration: PROSPERO registration number CRD42021284004., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: To evaluate the impact of perioperative P2Y12 receptor inhibitor therapy among patients undergoing cardiac surgery within 1 year of percutaneous coronary intervention (PCI)., Methods and Results: Patients undergoing cardiac surgery in the year post-PCI at three tertiary care centres between 2011 and 2018 were stratified into those who had received at least one dose of P2Y12 inhibitor prior to surgery (within 5 days for clopidogrel or prasugrel, or within 3 days for ticagrelor) and those who had not. The outcomes of interest were major adverse cardiac and cerebrovascular events (MACCEs) and bleeding. Among 20 279 PCI patients, 359 (1.8%) underwent cardiac surgery in the ensuing year, 76.3% of whom received coronary artery bypass grafts. Overall, 33 (9.2%) MACCEs and 85 (23.7%) bleeding events occurred within 30 days post-cardiac surgery. Perioperative P2Y12 inhibition (N = 133, 37%) was not associated with the risk of MACCEs or bleeding, despite numerically lower rates of myocardial infarction or stent thrombosis (0.0% vs. 2.6%; P = 0.089). Patients who continued the P2Y12 inhibitor until the day of surgery (N = 60, 17%) had significantly higher bleeding risk [adjusted odds ratio 2.93, 95% confidence interval 1.53-5.59)]. Predictors of MACCEs included a time interval from PCI to cardiac surgery of ≤30 days and reduced ejection fraction, whereas urgent/emergent surgery predicted bleeding. Chronic kidney disease and myocardial infarction as indication for PCI predicted both MACCEs and bleeding., Conclusion: Among patients undergoing cardiac surgery in the year after PCI, the perioperative risk of ischaemic and bleeding events might be influenced by P2Y12 inhibitor therapy in addition to other risk parameters, including the timing and urgency of the procedure., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: We aimed to evaluate the treatment effects of ticagrelor monotherapy in the very high risk cohort of patients with concomitant diabetes mellitus (DM) and chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI)., Methods and Results: In the TWILIGHT (Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial, after 3-month dual antiplatelet therapy with ticagrelor and aspirin post-PCI, event-free patients were randomized to either aspirin or placebo in addition to ticagrelor for 12 months. Those with available information on DM and CKD status were included in this subanalysis and were stratified by the presence or absence of either condition: 3391 (54.1%) had neither DM nor CKD (DM-/CKD-), 1822 (29.0%) had DM only (DM+/CKD-), 561 (8.9%) had CKD only (DM-/CKD+), and 8.0% had both DM and CKD (DM+/CKD+). The incidence of the primary endpoint of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding did not differ according to DM/CKD status (P-trend = 0.13), but there was a significant increase in BARC 3 or 5 bleeding (P-trend &lt; 0.001) as well as the key secondary endpoint of death, myocardial infarction, or stroke (P-trend &lt; 0.001). Ticagrelor plus placebo reduced bleeding events compared with ticagrelor plus aspirin across all four groups, including DM+/CKD+ patients with respect to BARC 2-5 [4.5% vs. 8.7%; hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.24-1.01] as well as BARC 3-5 (0.8% vs. 5.3%; HR 0.15, 95% CI 0.03-0.53) bleeding, with no evidence of heterogeneity. The risk of death, myocardial infarction, or stroke was similar between treatment arms across all groups., Conclusion: Irrespective of the presence of DM, CKD, and their combination, ticagrelor monotherapy reduced the risk of bleeding without a significant increase in ischaemic events compared with ticagrelor plus aspirin., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have cardiovascular (CV) benefits in patients with heart failure with reduced ejection fraction (HFrEF). Whether these medications improve CV outcomes irrespective of heart failure history or left ventricular ejection fraction (LVEF) in HFrEF remains unknown., Methods and Results: All randomized, placebo-controlled trials of SGLT-2 inhibitors reporting similar CV outcomes were searched in PubMed from 1 January 2010 to 1 October 2021. The primary outcome was the composite of hospitalization for heart failure or CV death. Secondary outcomes included all-cause mortality. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were used as effect estimates and calculated with a random-effects model. Data from 11 trials and a total of 66 957 patients (n = 36 758 SGLT-2 group, n = 30 199 placebo group) were included. SGLT-2 inhibitors reduced the risk of hospitalization for heart failure or CV death in patients with (HR 0.76, 95% CI 0.71-0.80) and without (HR 0.76, 95% CI 0.68-0.86; Pinteraction = 0.69) heart failure. Patients with (HR 0.87, 95% CI 0.80-0.95) and without (HR 0.84, 95% CI 0.73-0.95; Pinteraction = 0.67) heart failure treated with SGLT-2 inhibitors had a reduction in all-cause mortality. Reduction in the primary outcome was consistently observed in HFrEF patients with (HR 0.68, 95% CI 0.59-0.78) and without (HR 0.84, 95% CI 0.71-0.99; Pinteraction = 0.13) severely reduced LVEF, and in heart failure with preserved ejection fraction patients (HR 0.80, 95% CI 0.70-0.92; Pinteraction = 0.65)., Conclusion: SGLT-2 inhibitors improved CV outcomes irrespective of heart failure history or type, and severity of LVEF reduction., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aim: Optimal dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) intends to balance ischemic and bleeding risks. Various DAPT de-escalation strategies, defined as switching from a full-dose potent to a reduced dose or less potent P2Y12 inhibitor, have been evaluated in several ACS-PCI trials. We aimed to compare DAPT de-escalation to standard DAPT with full-dose potent P2Y12 inhibitors in ACS patients who underwent PCI., Methods and Results: PubMed, Google Scholar, and Cochrane Central Register of Controlled Trials were searched for eligible randomized controlled trials. Aspirin monotherapy trials were excluded. Five randomized trials (n = 10 779 patients) that assigned DAPT de-escalation (genetically guided to clopidogrel n = 1242; platelet function guided to clopidogrel n = 1304; unguided to clopidogrel n = 1672; unguided to lower dose n = 1170) vs. standard DAPT (control group n = 5391) were included in this analysis. DAPT de-escalation was associated with a significant reduction in Bleeding Academic Research Consortium ≥2 bleeding (HR 0.57, 95% CI 0.42-0.78; I2 = 77%) as well as major adverse cardiac events, represented in most trials by the composite of cardiovascular mortality, myocardial infarction, stent thrombosis, and stroke (HR 0.77, 95% CI 0.62-0.96; I2 = 0%). Notwithstanding the limited power, consistency was noted across various de-escalation strategies., Conclusion: De-escalation of DAPT after PCI for ACS, both unguided and guided by genetic or platelet function testing (PFT), was associated with lower rates of clinically relevant bleeding and ischemic events as compared to standard DAPT with potent P2Y12 inhibitors based on five open-label RCTs reviewed., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: The aim of this study was to assess the impact of chronic kidney disease (CKD) on the safety and efficacy of ticagrelor monotherapy among patients undergoing percutaneous coronary intervention (PCI)., Methods and Results: In this prespecified subanalysis of the TWILIGHT trial, we evaluated the treatment effects of ticagrelor with or without aspirin according to renal function. The trial enrolled patients undergoing drug-eluting stent implantation who fulfilled at least one clinical and one angiographic high-risk criterion. Chronic kidney disease, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, was a clinical study entry criterion. Following a 3-month period of ticagrelor plus aspirin, event-free patients were randomly assigned to aspirin or placebo on top of ticagrelor for an additional 12 months. Of the 6835 patients randomized and with available eGFR at baseline, 1111 (16.3%) had CKD. Ticagrelor plus placebo reduced the primary endpoint of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding as compared with ticagrelor plus aspirin in both patients with [4.6% vs. 9.0%; hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.31-0.80] and without (4.0% vs. 6.7%; HR 0.59, 95% CI 0.47-0.75; Pinteraction = 0.508) CKD, but the absolute risk reduction was greater in the former group. Rates of death, myocardial infarction, or stroke were not significantly different between the two randomized groups irrespective of the presence (7.9% vs. 5.7%; HR 1.40, 95% CI 0.88-2.22) or absence of (3.2% vs. 3.6%; HR 0.90, 95% CI 0.68-1.20; Pinteraction = 0.111) CKD., Conclusion: Among CKD patients undergoing PCI, ticagrelor monotherapy reduced the risk of bleeding without a significant increase in ischaemic events as compared with ticagrelor plus aspirin., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Aims: Patients at high bleeding risk (HBR) represent a prevalent subgroup among those undergoing percutaneous coronary intervention (PCI). Early aspirin discontinuation after a short course of dual antiplatelet therapy (DAPT) has emerged as a bleeding avoidance strategy. The aim of this study was to assess the effects of ticagrelor monotherapy after 3-month DAPT in a contemporary HBR population., Methods and Results: This prespecified analysis of the TWILIGHT trial evaluated the treatment effects of early aspirin withdrawal followed by ticagrelor monotherapy in HBR patients undergoing PCI with drug-eluting stents. After 3 months of ticagrelor plus aspirin, event-free patients were randomized to 12 months of aspirin or placebo in addition to ticagrelor. A total of 1064 (17.2%) met the Academic Research Consortium definition for HBR. Ticagrelor monotherapy reduced the incidence of the primary endpoint of Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding compared with ticagrelor plus aspirin in HBR (6.3% vs. 11.4%; hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.35-0.82) and non-HBR patients (3.5% vs. 5.9%; HR 0.59, 95% CI 0.46-0.77) with similar relative (Pinteraction = 0.67) but a trend towards greater absolute risk reduction in the former [-5.1% vs. -2.3%; difference in absolute risk differences (ARDs) -2.8%, 95% CI -6.4% to 0.8%, P = 0.130]. A similar pattern was observed for more severe BARC 3 or 5 bleeding with a larger absolute risk reduction in HBR patients (-3.5% vs. -0.5%; difference in ARDs -3.0%, 95% CI -5.2% to -0.8%, P = 0.008). There was no significant difference in the key secondary endpoint of death, myocardial infarction, or stroke between treatment arms, irrespective of HBR status., Conclusions: Among HBR patients undergoing PCI who completed 3-month DAPT without experiencing major adverse events, aspirin discontinuation followed by ticagrelor monotherapy significantly reduced bleeding without increasing ischaemic events, compared with ticagrelor plus aspirin. The absolute risk reduction in major bleeding was larger in HBR than non-HBR patients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Aims: To evaluate the acute and chronic patterns of myocardial injury among patients with coronavirus disease-2019 (COVID-19), and their mid-term outcomes., Methods and Results: Patients with laboratory-confirmed COVID-19 who had a hospital encounter within the Mount Sinai Health System (New York City) between 27 February 2020 and 15 October 2020 were evaluated for inclusion. Troponin levels assessed between 72 h before and 48 h after the COVID-19 diagnosis were used to stratify the study population by the presence of acute and chronic myocardial injury, as defined by the Fourth Universal Definition of Myocardial Infarction. Among 4695 patients, those with chronic myocardial injury (n = 319, 6.8%) had more comorbidities, including chronic kidney disease and heart failure, while acute myocardial injury (n = 1168, 24.9%) was more associated with increased levels of inflammatory markers. Both types of myocardial injury were strongly associated with impaired survival at 6 months [chronic: hazard ratio (HR) 4.17, 95% confidence interval (CI) 3.44-5.06; acute: HR 4.72, 95% CI 4.14-5.36], even after excluding events occurring in the first 30 days (chronic: HR 3.97, 95% CI 2.15-7.33; acute: HR 4.13, 95% CI 2.75-6.21). The mortality risk was not significantly different in patients with acute as compared with chronic myocardial injury (HR 1.13, 95% CI 0.94-1.36), except for a worse prognostic impact of acute myocardial injury in patients <65 years of age (P-interaction = 0.043) and in those without coronary artery disease (P-interaction = 0.041)., Conclusion: Chronic and acute myocardial injury represent two distinctive patterns of cardiac involvement among COVID-19 patients. While both types of myocardial injury are associated with impaired survival at 6 months, mortality rates peak in the early phase of the infection but remain elevated even beyond 30 days during the convalescent phase., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Since its introduction in 1977, percutaneous coronary intervention has become one of the most commonly performed therapeutic procedures worldwide. Such widespread diffusion, however, would have not been possible without a concomitant evolution of the pharmacotherapies associated with this intervention. Antithrombotic agents are fundamental throughout the management of patients undergoing coronary stent implantation, starting from the procedure itself to the long-term prevention of cardiovascular events. The last 40 years of interventional cardiology have seen remarkable improvements in both drug therapies and device technologies, which largely reflected a progressive understanding of the pathophysiological mechanisms of coronary artery disease, as well as procedure- and device-related adverse events. The purpose of this article is to provide an overview of the important milestones in antithrombotic pharmacology that have shaped clinical practice of today while also providing insights into knowledge gaps and future directions., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aim: The aim of this study was to evaluate whether coronary artery disease (CAD) severity exerts a gradient of risk in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI)., Methods and Results: A total of 445 patients with severe AS undergoing TAVI were included into a prospective registry between 2007 and 2012. The preoperative SYNTAX score (SS) was determined from baseline coronary angiograms. In case of revascularization prior to TAVI, residual SS (rSS) was also determined. Clinical outcomes were compared between patients without CAD (n = 158), patients with low SS (0-22, n = 207), and patients with high SS (SS > 22, n = 80). The pre-specified primary endpoint was the composite of cardiovascular death, stroke, or myocardial infarction (MI). At 1 year, CAD severity was associated with higher rates of the primary endpoint (no CAD: 12.5%, low SS: 16.1%, high SS: 29.6%; P = 0.016). This was driven by differences in cardiovascular mortality (no CAD: 8.6%, low SS: 13.6%, high SS: 20.4%; P = 0.029), whereas the risk of stroke (no CAD: 5.1%, low SS: 3.3%, high SS: 6.7%; P = 0.79) and MI (no CAD: 1.5%, low SS: 1.1%, high SS: 4.0%; P = 0.54) was similar across the three groups. Patients with high SS received less complete revascularization as indicated by a higher rSS (21.2 ± 12.0 vs. 4.0 ± 4.4, P < 0.001) compared with patients with low SS. High rSS tertile (> 14) was associated with higher rates of the primary endpoint at 1 year (no CAD:12.5%, low rSS: 16.5%, high rSS: 26.3%, P = 0.043)., Conclusions: Severity of CAD appears to be associated with impaired clinical outcomes at 1 year after TAVI. Patients with SS > 22 receive less complete revascularization and have a higher risk of cardiovascular death, stroke, or MI than patients without CAD or low SS., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)