Future of factor XI inhibitors in cardiovascular practice.

Anticoagulation is indicated for treatment and prevention of arterial and venous thrombosis. Targeting different steps of the coagulation process, currently available anticoagulants entail an increased risk of bleeding, which detrimentally impacts on prognosis and hinders the administration of an effective antithrombotic regimen. Factor XI (FXI) inhibition has emerged as a strategy to uncouple prevention of thrombosis from bleeding. Indeed, while FXI is crucial for the amplification phase in pathological thrombosis, it is ancillary in physiological hemostasis. A comprehensive search in several scientific databases has been performed to identify relevant studies in the field. In addition, ongoing trials have been searched for in proper datasets to provide an updated and comprehensive assessment of the current state of investigations on FXI inhibition. Many compounds have been tested to inhibit FXI at different stages (i.e., synthesis, activation, or interactions with target molecules and coagulation factors). These include antisense oligonucleotides, monoclonal antibodies, small molecules, natural peptides and aptamers. In phase 2 studies, FXI inhibitors reduced thrombotic complications without any corresponding increase in bleeding. FXI inhibitors were noninferior and potentially superior to low-molecular-weight heparin in orthopedic surgery and reduced bleeding compared to apixaban in patients with atrial fibrillation. FXI inhibition is also under testing in other conditions, including end-stage renal disease, cancer, or noncardioembolic stroke. FXI inhibition represents a promising and rapidly emerging approach for a number of clinical indications. This article reviews the rationale, evidence, pharmacology, and future applications of FXI inhibition.

Percutaneous interventions for pulmonary embolism.

Pulmonary embolism (PE) ranks as a leading cause of in-hospital mortality and the third most common cause of cardiovascular death. The spectrum of PE manifestations varies widely, making it difficult to determine the best treatment approach for specific patients. Conventional treatment options include anticoagulation, thrombolysis, or surgery, but emerging percutaneous interventional procedures are being investigated for their potential benefits in heterogeneous PE populations. These novel interventional techniques encompass catheter-directed thrombolysis, mechanical thrombectomy, and hybrid approaches combining different mechanisms. Furthermore, inferior vena cava filters are also available as an option for PE prevention. Such interventions may offer faster improvements in right ventricular function, as well as in pulmonary and systemic haemodynamics, in individual patients. Moreover, percutaneous treatment may be a valid alternative to traditional therapies in high bleeding risk patients and could potentially reduce the burden of mortality related to major bleeds, such as that of haemorrhagic strokes. Nevertheless, the safety and efficacy of these techniques compared to conservative therapies have not been conclusively established. This review offers a comprehensive evaluation of the current evidence for percutaneous interventions in PE and provides guidance for selecting appropriate patients and treatments. It serves as a valuable resource for future researchers and clinicians seeking to advance this field. Additionally, we explore future perspectives, proposing "percutaneous primary pulmonary intervention" as a potential paradigm shift in the field.

Exploring the impact of cardiologists expertise on publication metrics.

BACKGROUND: In the field of academic cardiology, the assessment of an author's scholarly impact and professional progression heavily relies on publications and citations. This study investigates whether specific cardiology expertise correlates with accelerated professional growth. METHODS: Using data from the 2023 European Society of Cardiology congress, 948 faculty attendees with an h-index of 30 or higher were analyzed. Expertises were categorized into six groups, and their association with publications and citations peaks was explored. RESULTS: Interventional cardiologists exhibited the highest annual publication peak, followed by imaging and electrophysiology experts. However, no significant differences were observed in citation peaks among expertise groups. While imaging experts initially appeared to reach citation peaks faster, this effect diminished after statistical adjustments. Additionally, holding multiple expertise areas prolonged the time to reach publication and citation peaks by approximately six years. CONCLUSION: This study underscores the influence of expertise in interventional cardiology on publication peaks but suggests that citation peaks and career progression velocity remain unaffected by expertise type. Furthermore, it highlights that holding multiple areas of expertise slowers the attainment of career peak for scholarly authors.

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.

Pharmacological and clinical appraisal of factor XI inhibitor drugs.

The evolution of anticoagulation therapy, from vitamin K antagonists to the advent of direct oral anticoagulants (DOACs) almost two decades ago, marks significant progress. Despite improved safety demonstrated in pivotal trials and post-marketing observations, persistent concerns exist, particularly regarding bleeding risk and the absence of therapeutic indications in specific subgroups or clinical contexts. Factor XI (FXI) has recently emerged as a pivotal contributor to intraluminal thrombus formation and growth, playing a limited role in sealing vessel wall injuries. Inhibiting FXI presents an opportunity to decouple thrombosis from haemostasis, addressing concerns related to bleeding events while safeguarding against thromboembolic events. Notably, FXI inhibition holds promise for patients with end-stage renal disease or cancer, where clear indications for DOACs are currently lacking. Various compounds have undergone design, testing, and progression to phase 2 clinical trials, demonstrating a generally favourable safety and tolerability profile. However, validation through large-scale phase 3 trials with sufficient power to assess both safety and efficacy outcomes is needed. This review comprehensively examines FXI inhibitors, delving into individual classes, exploring their pharmacological properties, evaluating the latest evidence from randomized trials, and offering insights into future perspectives.

PCSK9 inhibitors: current status and emerging frontiers in lipid control.

INTRODUCTION: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of global mortality, imposing substantial healthcare economic burdens. Among the modifiable risk factors, hypercholesterolemia, especially elevated low-density lipoprotein cholesterol (LDL-C), plays a pivotal role in ASCVD development. Novel therapies such as PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9) inhibitors are emerging to address this concern. These inhibitors offer the potential to reduce ASCVD risk by directly targeting LDL-C levels. AREAS COVERED: The article reviews the structural and functional aspects of PCSK9, highlighting its role in LDL receptor regulation. The pharmacological strategies for PCSK9 inhibition, including monoclonal antibodies, binding peptides, gene silencing, and active immunization, are explored. Clinical evidence from various trials underscores the safety and efficacy of PCSK9 inhibitors in reducing LDL-C levels and potentially improving cardiovascular outcomes. Despite these promising results, challenges such as cost-effectiveness and long-term safety considerations are addressed. EXPERT OPINION: Among PCSK9 inhibitors, monoclonal antibodies represent a cornerstone. Many trials have showed their efficacy in reducing LDL-C and the risk for major adverse clinical events, revealing long-lasting effects, with special benefits particularly for statin-intolerant and familial hypercholesterolemia patients. However, long-term impacts, high costs, and patient selection necessitate further research.

Association of trial characteristics with simultaneous publication and its impact on citations and mentions: a cross-sectional study.

INTRODUCTION AND OBJECTIVES: Randomized trials are often presented at medical conferences and published simultaneously or later. Predictors of simultaneous publication and its consequences are undetermined. Our aim was to characterize the practice of simultaneous publication, identify its predictors, and evaluate its impact. METHODS: In this cross-sectional study, we included randomized trials presented at late-breaking science sessions of major cardiovascular conferences from 2015 to 2021. The association of trial characteristics with the timing of publication was analyzed. The impact of simultaneous vs nonsimultaneous publication was investigated on the number of 1-year citations and 1-month mentions, and the total citations and mentions at the longest observation follow-up. RESULTS: Of 478 trials included in the analysis, 48.7% were published simultaneously. Simultaneous publications were more likely to be presented in the main conference room (OR, 6.09; 95%CI, 1.34-36.92; P=.029) and were characterized by a shorter review time (OR, 0.95; 95%CI, 0.91-0.96; P<.001). Simultaneous publications were associated with higher 1-year citations (R2, 43.81; 95%CI, 23.89-63.73; P<.001), 1-month mentions (R2, 132.32; 95%CI, 85.42-179.22; P<.001) and total citations (R2, 222.89; 95%CI, 127.98-317.80; P<.001). CONCLUSIONS: Randomized trials presented in the main conference room and with shorter review time were more likely to be published simultaneously. Simultaneous publications were associated with more citations and mentions than nonsimultaneous publications.

Navigating the Course of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention: A Review of Guided Approaches.

Dual antiplatelet therapy (DAPT) is the standard approach to prevent thrombotic events in patients undergoing percutaneous coronary intervention and presenting with chronic or acute coronary syndromes. However, a sizeable proportion of patients presents with an impaired or unwarranted response to DAPT depending on genetic polymorphisms or variability in platelet response. Therefore, the concept of changing the type or dose of antiplatelet drugs based on the result of platelet function or genotype tests (ie, guided DAPT) has been introduced. The goal of guided DAPT is to intensify the antiplatelet potency in patients at high risk of thrombotic events (ie, escalation) and to decrease the antiplatelet potency in patients at high risk of bleeding (ie, de-escalation). This review aims to present an up-to-date and comprehensive overview of the latest research findings on DAPT modulation guided by either platelet function or genetic testing, discussing its current indications and future directions.

Antithrombotic Therapy for Primary and Secondary Prevention of Ischemic Stroke: JACC State-of-the-Art Review.

Stroke is a devastating condition with significant morbidity and mortality worldwide. Antithrombotic therapy plays a crucial role in both primary and secondary prevention of stroke events. Single or dual antiplatelet therapy is generally preferred in cases of large-artery atherosclerosis and small-vessel disease, whereas anticoagulation is recommended in conditions of blood stasis or hypercoagulable states that mostly result in red thrombi. However, the benefit of antithrombotic therapies must be weighed against the increased risk of bleeding, which can pose significant challenges in the pharmacological management of this condition. This review provides a comprehensive summary of the currently available evidence on antithrombotic therapy for ischemic stroke and outlines an updated therapeutic algorithm to support physicians in tailoring the strategy to the individual patient and the underlying mechanism of stroke.

Eligibility to Intensified Antithrombotic Regimens for Secondary Prevention in Patients Who Underwent Percutaneous Coronary Intervention.

Single antiplatelet therapy (SAPT) and intensified antithrombotic regimens (prolonged dual antiplatelet therapy [DAPT] or dual pathway inhibition [DPI]) are recommended for secondary prevention in patients who underwent percutaneous coronary intervention (PCI) after initial DAPT. We aimed to characterize eligibility to such strategies and to explore to what extent guidelines are applied in clinical practice. Patients who underwent PCI for acute or chronic coronary syndrome who completed initial DAPT were analyzed from a prospective registry. Patients were categorized into SAPT, prolonged DAPT/DPI, or DPI groups as per guideline indication by using a risk stratification algorithm. Predictors of receiving intensified regimens and the divergency of practice from guidelines were investigated. Between October 2019 and September 2021, a total of 819 patients were included. Based on the guidelines, 83.7% of patients qualified for SAPT, 9.6% for any intensified regimen (i.e., prolonged DAPT or DPI), and 6.7% for DPI only. At multivariable analysis, patients were more likely to receive an intensified regimen if they had diabetes, dyslipidemia, peripheral artery disease, multivessel disease, or previous myocardial infarction. Conversely, they were less likely to receive an intensified regimen if they had atrial fibrillation, chronic kidney disease, or previous stroke. Guidelines were not followed in 18.3% of cases. In particular, only 14.3% of candidates to intensified regimens were treated accordingly. In conclusion, although the majority of patients who underwent PCI after the initial period of DAPT were eligible for SAPT, 1 out of 6 had an indication to intensified regimens. However, such intensified regimens were underused among eligible patients.