Evolving Concepts in Antithrombotic Therapy: One Size Does Not Fit All

A special issue of Medicina (ISSN 1648-9144).

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 5939

Special Issue Editors


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Guest Editor
1. Department of Translational Medical Sciences, University of Campania Luigi Vanvitelli, 80131 Naples, Italy
2. Vanvitelli Cardiology Unit, Monaldi Hospital, 80131 Naples, Italy
Interests: coagulation cascade; tissue factor; platelet pathophysiology; acute coronary syndrome; atherosclerosis; lipoprotein metabolism
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Guest Editor
Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy
Interests: cardiovascular disease; biomarkers; interventional cardiology; atherothrombosis; atherosclerosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Atherosclerotic disease and its thrombotic complication are the pathophysiological substrate underlying several clinical conditions, such as acute and chronic coronary syndrome (ACS and CCS, respectively), stroke, and peripheral artery disease. Activation of coagulation cascade as well as platelet aggregation are key steps of the thrombotic process. Vessel injury results in exposure of the glycoprotein tissue factor (TF) to the flowing blood. Once exposed, TF binds factor VII/VIIa (FVII/FVIIa), and in presence of calcium ions, it forms a tertiary complex able to activate FX to FXa, FIX to FIXa, and FVIIa itself. The final step is thrombin formation at the site of vessel injury with subsequent platelet activation, fibrinogen to fibrin conversion, and ultimately thrombus formation. Platelets are crucial cells in primary hemostasis. For years, they have been considered only as cell fragments participating in primary hemostasis. However, recent advances in platelet pathophysiology have shown that these cells are able to regulate their gene and protein expression, make de novo protein synthesis, and release different mediators with paracrine effects that may interfere with different cell function. Pharmacological modulation of both components of thrombosis, the coagulation cascade and platelet activation, is of great clinical importance. Several clinical trials have clearly shown the efficacy of anticoagulation and/or antiplatelet aggregation in different thrombotic disorders, even in the context of aortic valve replacement, mitral valve repair through the MITRACLIP system, and left atrial appendix occlusion. However, real world practice has clearly indicated that antithrombotic strategies need to be personalized according to patient characteristics, such as age, concomitant diseases already requiring antithrombotic drugs or at risk for bleeding. In this regard, the combination of multiple antithrombotic drugs represents a challenging scenario and was therefore the focus for multiple recent randomized controlled trials, and more are still to come. As the knowledge about platelets and the coagulation system has substantially evolved within the last few years, so should our approach to antithrombotic treatment. Finally, the ongoing global pandemic of coronavirus disease 2019 (COVID‑19) has also modified our antithrombotic strategies of acute ischemic events.

This issue will focus on current hurdles of antithrombotic treatments in patients with cardiovascular disease, proposing practical solutions to compelling clinical scenarios using a pathophysiology-oriented approach on the basis of current clinical evidence.

Prof. Giovanni Cimmino
Prof. Salvatore De Rosa
Guest Editors

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Keywords

  • Tissue factor
  • Coagulation cascade
  • Platelets
  • Aggregation
  • Thrombosis
  • Acute coronary syndrome
  • Stroke
  • Peripheral artery disease
  • COVID-19 pandemic

Published Papers (2 papers)

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13 pages, 666 KiB  
Article
Peripheral Artery Disease and Abdominal Aortic Aneurysm: The Forgotten Diseases in COVID-19 Pandemic. Results from an Observational Study on Real-World Management
by Francesco Natale, Raffaele Capasso, Alfonso Casalino, Clotilde Crescenzi, Paolo Sangiuolo, Paolo Golino, Francesco S. Loffredo and Giovanni Cimmino
Medicina 2021, 57(7), 672; https://doi.org/10.3390/medicina57070672 - 29 Jun 2021
Cited by 1 | Viewed by 2108
Abstract
Background and Objectives: It is well established that patients with peripheral artery disease (PAD) as well abdominal aortic aneurysm (AAA) have an increased cardiovascular (CV) mortality. Despite this higher risk, PAD and AAA patients are often suboptimality treated. This study assessed the [...] Read more.
Background and Objectives: It is well established that patients with peripheral artery disease (PAD) as well abdominal aortic aneurysm (AAA) have an increased cardiovascular (CV) mortality. Despite this higher risk, PAD and AAA patients are often suboptimality treated. This study assessed the CV profile of PAD and AAA patients, quantifying the survival benefits of target-based risk-factors modification even in light of the COVID-19 pandemic. Materials and Methods: PAD and AAA patients admitted for any reason to the Vascular Unit from January 2019 to February 2020 were retrospectively analyzed. Biochemical and CV profiles as well as ongoing medical therapies were recorded. Benefits of CV risk-factors control were estimated using the SMART-REACH model. A follow-up visit during the year 2020 was scheduled. Results: A total of 669 patients were included. Of these, 190 showed AAA and 479 PAD at any stage. Only 54% of PAD and 41% of AAA patients were on lipid-lowering drugs with non-optimal low-density lipoprotein (LDL) levels for most of them. A better control of all modifiable CV risk-factors based on the current guidelines would offer an absolute risk reduction of the mean 10-year CV risk by 9% in PAD and 14% in AAA. Unfortunately, the follow-up visit was lost because of COVID-19 limitations. Conclusions: Lipid profiles of PAD and AAA patients were far from guideline-based targets, and medical management was suboptimal. In our center, the COVID-19 pandemic impacted on the strict surveillance required in these very high-risk patients. The achievement of guideline-based therapeutic targets would definitively confer additional significant benefits in reducing the CV risk in these patients. Full article
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Review
Percutaneous Left Atrial Appendage Occlusion: An Emerging Option in Patients with Atrial Fibrillation at High Risk of Bleeding
by Giovanni Cimmino, Francesco S. Loffredo, Emanuele Gallinoro, Dario Prozzo, Dario Fabiani, Luigi Cante, Gemma Salerno, Maurizio Cappelli Bigazzi and Paolo Golino
Medicina 2021, 57(5), 444; https://doi.org/10.3390/medicina57050444 - 3 May 2021
Cited by 7 | Viewed by 3285
Abstract
Atrial fibrillation (AF) is a common cardiac arrhythmia with an estimated prevalence of 1% in the general population. It is associated with an increased risk of ischemic stroke, silent cerebral ischemia, and cognitive impairment. Due to the blood flow stasis and morphology, thrombus [...] Read more.
Atrial fibrillation (AF) is a common cardiac arrhythmia with an estimated prevalence of 1% in the general population. It is associated with an increased risk of ischemic stroke, silent cerebral ischemia, and cognitive impairment. Due to the blood flow stasis and morphology, thrombus formation occurs mainly in the left atrial appendage (LAA), particularly in the setting of nonvalvular AF (NVAF). Previous studies have shown that >90% of emboli related to NVAF originate from the LAA, thus prevention of systemic cardioembolism is indicated. According to the current guidelines, anticoagulant therapy with direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs), represents the standard of care in AF patients, in order to prevent ischemic stroke and peripheral embolization. Although these drugs are widely used and DOACs have shown, compared to VKAs, non-inferiority for stroke prevention with significantly fewer bleeding complications, some issues remain a matter of debate, including contraindications, side effects, and adherence. An increasing number of patients, indeed, because of high bleeding risk or after experiencing life-threatening bleedings, must take anticoagulants with extreme caution if not contraindicated. While surgical closure or exclusion of LAA has been historically used in patients with AF with contradictory results, in the recent years, a novel procedure has emerged to prevent the cardioembolic stroke in these patients: The percutaneous left atrial appendage occlusion (LAAO). Different devices have been developed in recent years, though not all of them are approved in Europe and some are still under clinical investigation. Currently available devices have shown a significant decrease in bleeding risk while maintaining efficacy in preventing thromboembolism. The procedure can be performed percutaneously through the femoral vein access, under general anesthesia. A transseptal puncture is required to access left atrium and is guided by transesophageal echocardiography (TEE). Evidence from the current literature indicates that percutaneous LAAO represents a safe alternative for those patients with contraindications for long-term oral anticoagulation. This review summarizes scientific evidences regarding LAAO for stroke prevention including clinical indications and an adequate patient selection. Full article
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