Coronary Angiography, Intravascular Ultrasound, and Optical Coherence Tomography for Guiding of Percutaneous Coronary Intervention: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Results from multiple randomized clinical trials comparing outcomes after intravascular ultrasound (IVUS)- and optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) with invasive coronary angiography (ICA)-guided PCI as well as a pivotal trial comparing the 2 intravascular imaging (IVI) techniques have provided mixed results. METHODS: Major electronic databases were searched to identify eligible trials evaluating at least 2 PCI guidance strategies among ICA, IVUS, and OCT. The 2 coprimary outcomes were target lesion revascularization and myocardial infarction. The secondary outcomes included ischemia-driven target lesion revascularization, target vessel myocardial infarction, death, cardiac death, target vessel revascularization, stent thrombosis, and major adverse cardiac events. Frequentist random-effects network meta-analyses were conducted. The results were replicated by Bayesian random-effects models. Pairwise meta-analyses of the direct components, multiple sensitivity analyses, and pairwise meta-analyses IVI versus ICA were supplemented. RESULTS: The results from 24 randomized trials (15 489 patients: IVUS versus ICA, 46.4%, 7189 patients; OCT versus ICA, 32.1%, 4976 patients; OCT versus IVUS, 21.4%, 3324 patients) were included in the network meta-analyses. IVUS was associated with reduced target lesion revascularization compared with ICA (odds ratio [OR], 0.69 [95% CI, 0.54-0.87]), whereas no significant differences were observed between OCT and ICA (OR, 0.83 [95% CI, 0.63-1.09]) and OCT and IVUS (OR, 1.21 [95% CI, 0.88-1.66]). Myocardial infarction did not significantly differ between guidance strategies (IVUS versus ICA: OR, 0.91 [95% CI, 0.70-1.19]; OCT versus ICA: OR, 0.87 [95% CI, 0.68-1.11]; OCT versus IVUS: OR, 0.96 [95% CI, 0.69-1.33]). These results were consistent with the secondary outcomes of ischemia-driven target lesion revascularization, target vessel myocardial infarction, and target vessel revascularization, and sensitivity analyses generally did not reveal inconsistency. OCT was associated with a significant reduction of stent thrombosis compared with ICA (OR, 0.49 [95% CI, 0.26-0.92]) but only in the frequentist analysis. Similarly, the results in terms of survival between IVUS or OCT and ICA were uncertain across analyses. A total of 25 randomized trials (17 128 patients) were included in the pairwise meta-analyses IVI versus ICA where IVI guidance was associated with reduced target lesion revascularization, cardiac death, and stent thrombosis. CONCLUSIONS: IVI-guided PCI was associated with a reduction in ischemia-driven target lesion revascularization compared with ICA-guided PCI, with the difference most evident for IVUS. In contrast, no significant differences in myocardial infarction were observed between guidance strategies.

Aspirin-free antiplatelet strategies after percutaneous coronary interventions.

Dual antiplatelet therapy (DAPT) with aspirin and a platelet P2Y12 receptor inhibitor is the standard antithrombotic treatment after percutaneous coronary interventions (PCI). Several trials have challenged guideline-recommended DAPT after PCI by testing the relative clinical effect of an aspirin-free antiplatelet approach-consisting of P2Y12 inhibitor monotherapy after a short course (mostly 1-3 months) of DAPT-among patients undergoing PCI without a concomitant indication for oral anticoagulation (OAC). Overall, these studies have shown P2Y12 inhibitor monotherapy after short DAPT to be associated with a significant reduction in the risk of bleeding without an increase in thrombotic or ischaemic events compared with continued DAPT. Moreover, the effects of the P2Y12 inhibitor monotherapy without prior DAPT or following a very short course of DAPT after PCI are being investigated in emerging studies, of which one has recently reported unfavourable efficacy results associated with the aspirin-free approach compared with conventional DAPT. Finally, P2Y12 inhibitor alone has been compared with aspirin alone as chronic therapy after DAPT discontinuation, thus challenging the historical role of aspirin as a standard of care for secondary prevention following PCI. A thorough understanding of study designs, populations, treatments, results, and limitations of trials testing P2Y12 inhibitor monotherapy vs. DAPT or vs. aspirin is required to consider adopting this treatment in clinical practice. This review addresses the use of aspirin-free antiplatelet strategies among patients undergoing PCI without a concomitant indication for OAC, providing an overview of clinical evidence, guideline indications, practical implications, ongoing issues, and future perspectives.

Pharmacology and Clinical Development of Factor XI Inhibitors.

Therapeutic anticoagulation is indicated for a variety of circumstances and conditions in several fields of medicine to prevent or treat venous and arterial thromboembolism. According to the different mechanisms of action, the available parenteral and oral anticoagulant drugs share the common principle of hampering or blocking key steps of the coagulation cascade, which unavoidably comes at the price of an increased propensity to bleed. Hemorrhagic complications affect patient prognosis both directly and indirectly (ie, by preventing the adoption of an effective antithrombotic strategy). Inhibition of factor XI (FXI) has emerged as a strategy with the potential to uncouple the pharmacological effect and the adverse events of anticoagulant therapy. This observation is based on the differential contribution of FXI to thrombus amplification, in which it plays a major role, and hemostasis, in which it plays an ancillary role in final clot consolidation. Several agents were developed to inhibit FXI at different stages (ie, suppressing biosynthesis, preventing zymogen activation, or impeding the biological action of the active form), including antisense oligonucleotides, monoclonal antibodies, small synthetic molecules, natural peptides, and aptamers. Phase 2 studies of different classes of FXI inhibitors in orthopedic surgery suggested that dose-dependent reductions in thrombotic complications are not paralleled by dose-dependent increases in bleeding compared with low-molecular-weight heparin. Likewise, the FXI inhibitor asundexian was associated with lower rates of bleeding compared with the activated factor X inhibitor apixaban in patients with atrial fibrillation, although no evidence of a therapeutic effect on stroke prevention is available so far. FXI inhibition could also be appealing for patients with other conditions, including end-stage renal disease, noncardioembolic stroke, or acute myocardial infarction, for which other phase 2 studies have been conducted. The balance between thromboprophylaxis and bleeding achieved by FXI inhibitors needs confirmation in large-scale phase 3 clinical trials powered for clinical end points. Several of such trials are ongoing or planned to define the role of FXI inhibitors in clinical practice and to clarify which FXI inhibitor may be most suited for each clinical indication. This article reviews the rationale, pharmacology, results of medium or small phase 2 studies, and future perspectives of drugs inhibiting FXI.

Biodegradable-Polymer or Durable-Polymer Stents in Patients at High Bleeding Risk: A Randomized, Open-Label Clinical Trial.

BACKGROUND: Limited information is available on the comparative efficacy and safety of different stent platforms in patients at high bleeding risk undergoing an abbreviated dual antiplatelet therapy duration after percutaneous coronary intervention (PCI). The aim of this study was to compare the safety and effectiveness of the biodegradable-polymer sirolimus-eluting stent with the durable-polymer zotarolimus-eluting stent in patients at high bleeding risk receiving 1 month of dual antiplatelet therapy after PCI. METHODS: The Bioflow-DAPT Study is an international, randomized, open-label trial conducted at 52 interventional cardiology hospitals in 18 countries from February 24, 2020, through September 20, 2021. Patients with a clinical indication to PCI because of acute or chronic coronary syndrome who fulfilled 1 or more criteria for high bleeding risk were eligible for enrollment. Patients were randomized to receive either biodegradable-polymer sirolimus-eluting stents or durable-polymer, slow-release zotarolimus-eluting stents after successful lesion preparation, followed by 1 month of dual antiplatelet therapy and thereafter single antiplatelet therapy. The primary outcome was the composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year, and was powered for noninferiority, with an absolute margin of 4.1% at 1-sided 5% alpha. RESULTS: A total of 1948 patients at high bleeding risk were randomly assigned (1:1) to receive biodegradable-polymer sirolimus-eluting stents (969 patients) or durable-polymer zotarolimus-eluting stents (979 patients). At 1 year, the primary outcome was observed in 33 of 969 patients (3.6%) in the biodegradable-polymer sirolimus-eluting stent group and in 32 of 979 patients (3.4%) in the durable-polymer zotarolimus-eluting stent group (risk difference, 0.2 percentage points; upper boundary of the 1-sided 95% CI, 1.8; upper boundary of the 1-sided 97.5% CI, 2.1; P<0.0001 for noninferiority for both tests). CONCLUSIONS: Among patients at high risk for bleeding who received 1 month of dual antiplatelet therapy after PCI, the use of biodegradable-polymer sirolimus-eluting stents was noninferior to the use of durable-polymer zotarolimus-eluting stents with regard to the composite of death from cardiac causes, myocardial infarction, or stent thrombosis. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04137510.

Defining Strategies of Modulation of Antiplatelet Therapy in Patients With Coronary Artery Disease: A Consensus Document from the Academic Research Consortium.

Antiplatelet therapy is the mainstay of pharmacologic treatment to prevent thrombotic or ischemic events in patients with coronary artery disease treated with percutaneous coronary intervention and those treated medically for an acute coronary syndrome. The use of antiplatelet therapy comes at the expense of an increased risk of bleeding complications. Defining the optimal intensity of platelet inhibition according to the clinical presentation of atherosclerotic cardiovascular disease and individual patient factors is a clinical challenge. Modulation of antiplatelet therapy is a medical action that is frequently performed to balance the risk of thrombotic or ischemic events and the risk of bleeding. This aim may be achieved by reducing (ie, de-escalation) or increasing (ie, escalation) the intensity of platelet inhibition by changing the type, dose, or number of antiplatelet drugs. Because de-escalation or escalation can be achieved in different ways, with a number of emerging approaches, confusion arises with terminologies that are often used interchangeably. To address this issue, this Academic Research Consortium collaboration provides an overview and definitions of different strategies of antiplatelet therapy modulation for patients with coronary artery disease, including but not limited to those undergoing percutaneous coronary intervention, and consensus statements on standardized definitions.

Gender equality in medical research: A cardiology-informed examination.

Despite a perceived increase in attention to gender differences in medicine, a comprehensive assessment of gender equality research, particularly in cardiology, remains underexplored. This observational retrospective study, focusing on documents related to "Gender Equality" according to the Sustainable Development Goals, reveals cardiology as a significant area for gender equality research, albeit with a decline in publications post-2018. The analysis highlighted a concentrated effort in the United States and a considerable impact gap between gender-focused and general cardiology research. The global academic community must intensify research into gender disparities, which is essential for achieving professional gender equality and addressing the burden of cardiovascular diseases.

Strategy to optimize PeriproCeduraL AnticOagulation in structural transseptal interventions: Design and rationale of the STOP CLOT trial.

BACKGROUND: Both transcatheter edge-to-edge repair (TEER) of mitral regurgitation or left atrial appendage closure (LAAC) require periprocedural anticoagulation with unfractionated heparin (UFH) that is administered either before or immediately after transseptal puncture (TSP). The optimal timing of UFH administration (before or after TSP) is unknown. The Strategy To Optimize PeriproCeduraL AnticOagulation in Structural Transseptal Interventions trial (STOP CLOT Trial) was designed to determine if early anticoagulation is effective in reducing ischemic complications without increasing the risk of periprocedural bleeding. METHODS: The STOP CLOT trial is a multicenter, prospective, double-blind, placebo-controlled, randomized trial. A total of 410 patients scheduled for TEER or LAAC will be randomized 1:1 either early UFH administration (iv. bolus of 100 units/kg UFH or placebo, given after obtaining femoral vein access and at least 5 minutes prior to the start of the TSP) or late UFH administration (iv. bolus of 100 units/kg UFH or placebo given immediately after TSP). Prespecified preliminary statistical analysis will be performed after complete follow-up of the first 196 randomized subjects. To ensure blinding, a study nurse responsible for randomization and UFH/placebo preparation is not involved in the care of the patients enrolled into the study. The primary study endpoint is a composite of (1) major adverse cardiac and cerebrovascular events (death, stroke, TIA, myocardial infarction, or peripheral embolization) within 30 days post-procedure, (2) intraprocedural fresh thrombus formation in the right or left atrium as assessed with periprocedural transesophageal echocardiography, or (3) occurrence of new ischemic lesions (diameter ≥4 mm) on brain magnetic resonance imaging performed 2 to 5 days after the procedure. The safety endpoint is the occurrence of moderate or severe bleeding complications during the index hospitalization. CONCLUSIONS: Protocols of periprocedural anticoagulation administration during structural interventions have never been tested in a randomized clinical trial. The Stop Clot trial may help reach consensus on the optimal timing of initiation of periprocedural anticoagulation. CLINICAL TRIALS REGISTRATION NUMBER: The study protocol is registered at ClinicalTrials.gov, identifier NCT05305612.

Antithrombotic strategies for preventing graft failure in coronary artery bypass graft.

Coronary artery bypass graft (CABG) procedures face challenges related to graft failure, driven by factors such as acute thrombosis, neointimal hyperplasia, and atherosclerotic plaque formation. Despite extensive efforts over four decades, the optimal antithrombotic strategy to prevent graft occlusion while minimizing bleeding risks remains uncertain, relying heavily on expert opinions rather than definitive guidelines. To address this uncertainty, we conducted a review of randomized clinical trials and meta-analyses of antithrombotic therapy for patients with CABG. These studies examined various antithrombotic regimens in CABG such as single antiplatelet therapy (aspirin or P2Y12 inhibitors), dual antiplatelet therapy, and anticoagulation therapy. We evaluated outcomes including the patency of grafts, major adverse cardiovascular events, and bleeding complications and also explored future perspectives to enhance long-term outcomes for CABG patients. Early studies established aspirin as a key component of antithrombotic pharmacotherapy after CABG. Subsequent randomized controlled trials focused on adding a P2Y12 inhibitor (such as clopidogrel, ticagrelor, or prasugrel) to aspirin, yielding mixed results. This article aims to inform clinical decision-making and guide the selection of antithrombotic strategies after CABG.

Factor XI inhibition in patients with acute coronary syndrome.

A hypercoagulable condition is typical of patients with acute coronary syndrome and is a determining factor in the genesis of recurrent ischaemic events. Modern pharmacological therapies consisting of antiplatelets and anticoagulants derive their rationale for use on the pathophysiological mechanisms most commonly associated with myocardial infarction (MI); they have contributed to reducing the ischaemic risk of these patients, but left ample room for improvement. In particular, trials that have studied the association of an anticoagulant with antiplatelet drugs have provided promising results in terms of efficacy, but highlighted a significant bleeding risk. Evidence derived from experimental animal and epidemiological studies has shown how factor XI (FXI) deficiency is associated with a reduction in thrombotic events but with modest bleeding. These data added to the role that FXI plays in the coagulation cascade constituted an incipit for the pharmacological attempt to decouple thrombosis from haemostasis by means of the inhibition of this factor. The theoretical assumption that FXI inhibitor drugs may be able to reduce the ischaemic risk without significantly increasing the haemorrhagic risk makes these compounds a potential therapeutic aid for patients in secondary prevention after acute MI. To date, on these patients, we only have data from a Phase 2 trial, PACIFIC-AMI (Study to Gather Information About the Proper Dosing and Safety of the Oral FXIa Inhibitor BAY 2 433 334 in Patients Following an Acute Heart Attack). In this study, the primary endpoint-represented by the Bleeding Academic Research Consortium (BARC) composite of Type 2, 3, or 5 bleeding-showed no significant differences between the various doses of asundexian tested (10, 20, and 50 mg quoque die), and between these and placebo (asundexian all doses vs. placebo: hazard ratio, 0.98; 90% confidence interval, 0.71-1.35). The data on efficacy, however, showed neutral results, but it should be noted that the study did not have the adequate statistical power to evaluate this outcome. Valuable information could, therefore, derive in the future from the ongoing Phase 3 trial with milvexian, LIBREXIA-ACS (A Study of Milvexian in Participants After a Recent Acute Coronary Syndrome) and from any future studies that could be started by testing different molecules.

Personalised antiplatelet therapies for coronary artery disease: what the future holds.

Coronary artery disease (CAD) is one of the leading causes of death globally, and antiplatelet therapy is crucial for both its prevention and treatment. Antiplatelet drugs such as aspirin and P2Y12 inhibitors are commonly used to reduce the risk of thrombotic events, including myocardial infarction, stroke, and stent thrombosis. However, the benefits associated with the use of antiplatelet drugs also come with a risk of bleeding complications. The ever-growing understanding of the poor prognostic implications associated with bleeding has set the foundations for defining strategies that can mitigate such safety concern without any trade-off in antithrombotic protection. To this extent, personalised antiplatelet therapy has emerged as a paradigm that optimizes the balance between safety and efficacy by customizing treatment to the individual patient's needs and risk profile. Accurate risk stratification for both bleeding and thrombosis can aid in selecting the optimal antiplatelet therapy and prevent serious and life-threatening outcomes. Risk stratification has traditionally included clinical and demographic characteristics and has expanded to incorporate angiographic features and laboratory findings. The availability of bedside platelet function testing as well as rapid genotyping assays has also allowed for a more individualized selection of antiplatelet therapy. This review provides a comprehensive overview of the current state of the art and future trends in personalised antiplatelet therapy for patients with CAD, with emphasis on those presenting with an acute coronary syndrome and undergoing percutaneous coronary revascularization. The aim is to provide clinicians with a comprehensive understanding of personalised antiplatelet therapy and facilitate informed clinical decision-making.

2022 Joint ESC/EACTS review of the 2018 guideline recommendations on the revascularization of left main coronary artery disease in patients at low surgical risk and anatomy suitable for PCI or CABG.

In October 2021, the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) jointly agreed to establish a Task Force (TF) to review recommendations of the 2018 ESC/EACTS Guidelines on myocardial revascularization as they apply to patients with left main (LM) disease with low-to-intermediate SYNTAX score (0-32). This followed the withdrawal of support by the EACTS in 2019 for the recommendations about the management of LM disease of the previous guideline. The TF was asked to review all new relevant data since the 2018 guidelines including updated aggregated data from the four randomized trials comparing percutaneous coronary intervention (PCI) with drug-eluting stents vs. coronary artery bypass grafting (CABG) in patients with LM disease. This document represents a summary of the work of the TF; suggested updated recommendations for the choice of revascularization modality in patients undergoing myocardial revascularization for LM disease are included. In stable patients with an indication for revascularization for LM disease, with coronary anatomy suitable for both procedures and a low predicted surgical mortality, the TF concludes that both treatment options are clinically reasonable based on patient preference, available expertise, and local operator volumes. The suggested recommendations for revascularization with CABG are Class I, Level of Evidence A. The recommendations for PCI are Class IIa, Level of Evidence A. The TF recognized several important gaps in knowledge related to revascularization in patients with LM disease and recognizes that aggregated data from the four randomized trials were still only large enough to exclude large differences in mortality.

Reversal and removal of oral antithrombotic drugs in patients with active or perceived imminent bleeding.

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.

Overcoming professional barriers encountered by women in interventional cardiology: an EAPCI statement.

Despite the increasing proportion of female medical and nursing students, there is still a significant under-representation of women working as healthcare providers in interventional cardiology, with very few of them reaching senior leadership, academic positions, or acting principal investigators, as well as actively involved in company advisory boards. In this position paper, we will describe the current status of women working in interventional cardiology across Europe. We will also provide an overview of the most relevant determinants of the under-representation of women at each stage of the interventional cardiology career path and offer practical suggestions for overcoming these challenges.

A review of polypills for the prevention of atherosclerotic cardiovascular disease.

Atherosclerotic cardiovascular disease (ASCVD) is a prevalent chronic condition managed through pharmacotherapy targeting modifiable risk factors. However, ASCVD patients often face poor medication adherence due to a high pill burden from multiple oral drugs, contributing to cardiovascular events. Recent evidence indicates that polypills combining antihypertensive and statin medications effectively control risk factors and improve adherence in various ASCVD risk patients. Randomized clinical trials demonstrate polypill efficacy in reducing major cardiovascular events, making them a convenient strategy for both established ASCVD patients and those without ASCVD. These positive results encourage the incorporation of polypills into comprehensive cardiovascular prevention programs, particularly for socio-economically vulnerable populations. Nevertheless, barriers remain, such as unclear regulatory approval pathways and physician hesitancy. Despite challenges, the benefits of fixed-dose combinations are evident and should be encouraged for secondary and primary prevention, especially in high-risk categories. Technological advancements could further support the successful integration of polypills in clinical practice. This review discusses the evidence, challenges, and perspectives of polypills, emphasizing their potential impact on cardiovascular disease management.

Rationale and design of the PARTHENOPE trial: A two-by-two factorial comparison of polymer-free vs biodegradable-polymer drug-eluting stents and personalized vs standard duration of dual antiplatelet therapy in all-comers undergoing PCI.

BACKGROUND: Over the past few decades, percutaneous coronary intervention (PCI) has undergone significant advancements as a result of the combination of device-based and drug-based therapies. These iterations have led to the development of polymer-free drug-eluting stents. However, there is a scarcity of data regarding their clinical performance. Furthermore, while various risk scores have been proposed to determine the optimal duration of dual antiplatelet therapy (DAPT), none of them have undergone prospective validation within the context of randomized trials. DESIGN: The PARTHENOPE trial is a phase IV, prospective, randomized, multicenter, investigator-initiated, assessor-blind study being conducted at 14 centers in Italy (NCT04135989). It includes 2,107 all-comers patients with minimal exclusion criteria, randomly assigned in a 2-by-2 design to receive either the Cre8 amphilimus-eluting stent or the SYNERGY everolimus-eluting stent, along with either a personalized or standard duration of DAPT. Personalized DAPT duration is determined by the DAPT score, which accounts for both bleeding and ischemic risks. Patients with a DAPT score <2 (indicating higher bleeding than ischemic risk) receive DAPT for 3 or 6 months for chronic or acute coronary syndrome, respectively, while patients with a DAPT score ≥2 (indicating higher ischemic than bleeding risk) receive DAPT for 24 months. Patients in the standard DAPT group receive DAPT for 12 months. The trial aims to establish the noninferiority between stents with respect to a device-oriented composite end point of cardiovascular death, target-vessel myocardial infarction, or clinically-driven target-lesion revascularization at 12 months after PCI. Additionally, the trial aims to demonstrate the superiority of personalized DAPT compared to a standard approach with respect to a net clinical composite of all-cause death, any myocardial infarction, stroke, urgent target-vessel revascularization, or type 2 to 5 bleeding according to the Bleeding Academic Research Consortium criteria at 24-months after PCI. SUMMARY: The PARTHENOPE trial is the largest randomized trial investigating the efficacy and safety of a polymer-free DES with a reservoir technology for drug-release and the first trial evaluating a personalized duration of DAPT based on the DAPT score. The study results will provide novel insights into the optimizing the use of drug-eluting stents and DAPT in patients undergoing PCI.

Predictors of target lesion failure after treatment of left main, bifurcation, or chronic total occlusion lesions with ultrathin-strut drug-eluting coronary stents in the ULTRA registry.

BACKGROUND: Data about the long-term performance of new-generation ultrathin-strut drug-eluting stents (DES) in challenging coronary lesions, such as left main (LM), bifurcation, and chronic total occlusion (CTO) lesions are scant. METHODS: The international multicenter retrospective observational ULTRA study included consecutive patients treated from September 2016 to August 2021 with ultrathin-strut (<70 µm) DES in challenging de novo lesions. Primary endpoint was target lesion failure (TLF): composite of cardiac death, target-lesion revascularization (TLR), target-vessel myocardial infarction (TVMI), or definite stent thrombosis (ST). Secondary endpoints included all-cause death, acute myocardial infarction (AMI), target vessel revascularization, and TLF components. TLF predictors were assessed with Cox multivariable analysis. RESULTS: Of 1801 patients (age: 66.6 ± 11.2 years; male: 1410 [78.3%]), 170 (9.4%) experienced TLF during follow-up of 3.1 ± 1.4 years. In patients with LM, CTO, and bifurcation lesions, TLF rates were 13.5%, 9.9%, and 8.9%, respectively. Overall, 160 (8.9%) patients died (74 [4.1%] from cardiac causes). AMI and TVMI rates were 6.0% and 3.2%, respectively. ST occurred in 11 (1.1%) patients while 77 (4.3%) underwent TLR. Multivariable analysis identified the following predictors of TLF: age, STEMI with cardiogenic shock, impaired left ventricular ejection fraction, diabetes, and renal dysfunction. Among the procedural variables, total stent length increased TLF risk (HR: 1.01, 95% CI: 1-1.02 per mm increase), while intracoronary imaging reduced the risk substantially (HR: 0.35, 95% CI: 0.12-0.82). CONCLUSIONS: Ultrathin-strut DES showed high efficacy and satisfactory safety, even in patients with challenging coronary lesions. Yet, despite using contemporary gold-standard DES, the association persisted between established patient- and procedure-related features of risk and impaired 3-year clinical outcome.

Low dose rivaroxaban for the management of atherosclerotic cardiovascular disease.

Atherosclerotic cardiovascular disease is characterized by some risk of major adverse events despite the availability of effective medical therapies for secondary prevention. There is emerging evidence suggesting that thrombin partly contributes to this residual risk. In fact, thrombin (i.e., activated coagulation factor II) triggers not only the conversion of fibrinogen to fibrin but also platelet activation and various pathways responsible for pro-atherogenic and/or pro-inflammatory effects through interaction with protease activated receptors. To reduce the risk associated with thrombin activation, oral anticoagulants antagonists of vitamin K showed promise, but were associated with unacceptable bleeding rates. Direct oral anticoagulants targeting the activated factors X and II carry a lower risk of bleeding than vitamin K antagonists. Rivaroxaban, a direct inhibitor of activated factor X approved at the dose of 20 mg once daily for the prevention of thromboembolic events, has been also investigated at a reduced dose of 2.5 mg twice daily in several alternative scenarios of atherosclerotic cardiovascular disease, in combination with standard of care. Current guidelines recommend that low-dose rivaroxaban is given in an adjunct to standard therapy to patients with stable atherosclerosis and acute coronary syndromes at low bleeding risk. Several studies are underway to evaluate its putative benefits in other clinical settings.

DOACs and rheumatic valvulopathy: always a red light?

Despite the sharp decline in most high-income industrialized countries, rheumatic heart disease (RHD) continues to be highly prevalent in many rural, low- and middle-income countries. RHD most frequently involves the mitral valve, both in the form of isolated regurgitation and in the form of regurgitation associated with mitral stenosis (mitral stenosis, MS). Atrial fibrillation (AF) is a common complication of RHD that is independently associated with an increased risk of death, heart failure, and systemic thromboembolism. Few studies have focused on the issue of the best oral anticoagulation strategy for patients with RHD and AF. Randomized trials establishing the non-inferiority of new direct oral anticoagulants (DOACs) over vitamin K antagonists (VKAs) in the prevention of stroke and systemic embolism excluded AF patients with mechanical valves or with moderate-to-severe MS. Nevertheless, variable proportions of patients with other VHD types were included. Recently, the INVICTUS trial demonstrated that in patients with RHD-related AF, direct oral anticoagulant rivaroxaban is inferior to VKAs in preventing stroke, systemic embolism, myocardial infarction, or death and is similar in bleeding risk. These results confirm and reinforce the recommendations of current international guidelines supporting the use of VKAs in patients with RHD-related AF.

Comparative effects of guided vs. potent P2Y12 inhibitor therapy in acute coronary syndrome: a network meta-analysis of 61 898 patients from 15 randomized trials.

AIMS: Guidelines recommend the use of potent P2Y12 inhibitors over clopidogrel for the reduction of ischaemic events in patients with acute coronary syndrome (ACS). However, this comes at the expense of increased bleeding. A guided selection of P2Y12 inhibiting therapy has the potential to overcome this limitation. We aimed at evaluating the comparative safety and efficacy of guided vs. routine selection of potent P2Y12 inhibiting therapy in patients with ACS. METHODS AND RESULTS: We performed a network meta-analysis of randomized controlled trials (RCTs) comparing different oral P2Y12 inhibitors currently recommended for the treatment of patients with ACS (clopidogrel, prasugrel, and ticagrelor). RCTs including a guided approach (i.e. platelet function or genetic testing) vs. standard selection of P2Y12 inhibitors among patients with ACS were also included. Incidence rate ratios (IRR) and associated 95% confidence intervals (CIs) were estimated. P-scores were used to estimate hierarchies of efficacy and safety. The primary efficacy endpoint was major adverse cardiovascular events (MACE) and the primary safety endpoint was all bleeding. A total of 61 898 patients from 15 RCTs were included. Clopidogrel was used as reference treatment. A guided approach was the only strategy associated with reduced MACE (IRR: 0.80, 95% CI: 0.65-0.98) without any significant trade-off in all bleeding (IRR: 1.22, 95% CI: 0.96-1.55). A guided approach and prasugrel were associated with reduced myocardial infarction. A guided approach, prasugrel, and ticagrelor were associated with reduced stent thrombosis. Ticagrelor was also associated with reduced total and cardiovascular mortality. Prasugrel was associated with increased major bleeding. Prasugrel and ticagrelor were associated with increased minor bleeding. The incidence of stroke did not differ between treatments. CONCLUSION: In patients with an ACS, compared with routine selection of potent P2Y12 inhibiting therapy (prasugrel or ticagrelor), a guided selection of P2Y12 inhibiting therapy is associated with the most favourable balance between safety and efficacy. These findings support a broader adoption of guided approach for the selection of P2Y12 inhibiting therapy in patients with ACS. STUDY REGISTRATION NUMBER: This study is registered in PROSPERO (CRD42021258603). KEY QUESTION: A guided selection of P2Y12 inhibiting therapy using platelet function or genetic testing improves outcomes among patients undergoing percutaneous coronary intervention. Nevertheless, the comparative safety and efficacy of a guided versus routine selection of potent P2Y12-inhibiting therapy in acute coronary syndrome has not been explored. KEY FINDING: In a comprehensive network meta-analysis including the totality of available evidence and using clopidogrel as treatment reference, a guided approach was the only strategy associated with reduced major adverse cardiovascular events without any significant trade-off in bleeding. Prasugrel and ticagrelor increased bleeding and only ticagrelor reduced mortality. TAKE HOME MESSAGE: A guided selection of P2Y12-inhibiting therapy represents the strategy associated with the most favourable balance between safety and efficacy. These findings support a broader adoption of guided P2Y12 inhibiting therapy in patients with acute coronary syndrome.

Antithrombotic Therapy in Patients Undergoing Transcatheter Interventions for Structural Heart Disease.

Contemporary evidence supports device-based transcatheter interventions for the management of patients with structural heart disease. These procedures, which include aortic valve implantation, mitral or tricuspid valve repair/implantation, left atrial appendage occlusion, and patent foramen ovale closure, profoundly differ with respect to clinical indications and procedural aspects. Yet, patients undergoing transcatheter cardiac interventions require antithrombotic therapy before, during, or after the procedure to prevent thromboembolic events. However, these therapies are associated with an increased risk of bleeding complications. To date, challenges and controversies exist regarding balancing the risk of thrombotic and bleeding complications in these patients such that the optimal antithrombotic regimens to adopt in each specific procedure is still unclear. In this review, we summarize current evidence on antithrombotic therapies for device-based transcatheter interventions targeting structural heart disease and emphasize the importance of a tailored approach in these patients.