Current Pharmaceutical Design - Volume 26, Issue 23, 2020

Background: Anticoagulation in patients with pulmonary embolism. Objective: To identify how non-vitamin K antagonist oral anticoagulants are associated with multiple outcomes in patients with pulmonary embolism. Methods: We performed a systematic search of systematic reviews via multiple electronic databases from inception to August 19th, 2019, without language restriction. Two authors independently extracted data and assessed the methodological quality of the included systematic reviews using the ROBIS tool. Results: We found twelve systematic reviews. Eleven SRs collected their data from randomized clinical trials and one from observational studies. All the included studies were published between 2014 and 2019 in English. The methodological quality of the 12 systematic reviews was low to high. None of the systematic reviews, which are included in our overview of systematic reviews, has evaluated the overall quality of evidence outcome using the Grading of Recommendations Assessments, Development and Evaluation (GRADE) approach. Conclusion: This is the first effort to summarize evidence about non-vitamin K antagonist oral anticoagulants in an overview of systematic reviews focusing exclusively on patients with pulmonary embolism. The evidence suggests that the non-vitamin K antagonist oral anticoagulants seem to be more effective and safer than a dualdrug approach with LMWH- VKA.

Anticoagulation therapy is the cornerstone of treatment in acute vein thrombosis (DVT) and it aims to reduce symptoms, thrombus extension, DVT recurrences, and mortality. The treatment for DVT depends on its anatomical extent, among other factors. Anticoagulation therapy for proximal DVT is clearly recommended (at least for 3 months), while AT for isolated distal DVT should be considered, especially in the presence of high thromboembolic risk factors. The optimal anticoagulant and duration of therapy are determined by the clinical assessment, taking into account the thromboembolic and bleeding risk in each patient in a case-by-case decision making. Non-Vitamin K antagonists oral anticoagulants (NOACs) were a revolution in the anticoagulation management of DVT. Nowadays, NOACs are considered as first-line therapy in the anticoagulation therapy for DVT and are recommended as the preferred anticoagulant agents by most scientific societies. NOACs offer a simple route of administration (oral agents), a rapid onset-offset of their action along with a good efficacy and safety profile in comparison with Vitamin K Antagonists (VKAs). However, there are issues about their efficacy and safety profile in specific populations with high thromboembolic and bleeding risks, such as renal failure patients, active-cancer patients, and pregnant women, in which VKAs and heparins were the standard care of treatment. Since the available data are promising for the use of NOACs in end-stage chronic kidney disease and cancer patients, several ongoing randomized trials are currently trying to solve that issues and give evidence about the safety and efficacy of NOACs in these populations.

Atrial fibrillation is a major cause of debilitating strokes and anticoagulation is an established and indispensable therapy for reducing their rate. Ablation of the arrhythmia has emerged as a putative means of disrupting its natural course by isolating its triggers and modifying its substrate, dependent on the chosen method. An important dilemma lies in the need for continuation of anticoagulation therapy in those previously receiving it following an, apparently, successful intervention, purportedly preventing arrhythmia recurrence with considerably high rates. Current guidance, given scarcity of high-quality data from randomized trials, focuses on established knowledge and recommends anticoagulation continuation based solely on estimated thromboembolic risk. In the present review, it will be attempted to summarize the pathophysiological rationale for maintaining anticoagulation post-successful ablation, along with the latter’s definition, including the two-fold effects of the procedure per se on thrombogenicity. Available evidence pointing to an overall clinical benefit of anticoagulation withdrawal following careful patient assessment will be discussed, including ongoing randomized trials aiming to offer definitive answers. Finally, the proposed mode of post-ablation anticoagulation will be presented, including the emerging, guideline-endorsed, role of direct oral anticoagulants in the field, altering cost/benefit ratio of anticoagulation and potentially affecting the very decision regarding its discontinuation.

Atrial fibrillation (AF) is a common arrhythmia which carries a significant risk of stroke. Secondary prevention, particularly in the acute phase of stroke with anti-thrombotic therapy, has not been validated. The aim of this review is to evaluate the available evidence on the use of antithrombotic therapy in patients with recent stroke who have AF, and suggest a treatment algorithm for the various time points, taking into account both the bleeding and thrombosis risks posed at each stage.

The management of asymptomatic atherosclerotic carotid artery disease and the role of antithrombotic therapy is of increasing importance for stroke prevention. Non-invasive imaging of carotid plaques can identify high-risk plaque features that are associated with the risk of plaque rupture. Carotid plaque necrosis, hemorrhage, fibrous cap thinning, and the presence of foam cells have all been correlated with the risk of rupture and onset of neurological symptoms in patients with carotid stenosis. Antiplatelets are currently recommended for patients with a history of ischemic stroke and/or significant carotid artery stenosis, with aspirin and clopidogrel being the most widely used and studied agents. The role of dual antiplatelet therapy remains controversial. Moreover, there is scarce evidence on the role of newer anticoagulant agents in stable patients with carotid artery stenosis. In this review article, we discuss the pathophysiology of carotid atherosclerosis, the use of non-invasive imaging for detecting the vulnerable carotid plaque and summarize the existing clinical evidence on the use of antiplatelet and antithrombotic agents in carotid artery disease.

Heart failure is a major contributor to global morbidity and mortality burden affecting approximately 1-2% of adults in developed countries, mounting to over 10% in individuals aged >70 years old. Heart failure is characterized by a prothrombotic state and increased rates of stroke and thromboembolism have been reported in heart failure patients compared with the general population. However, the impact of antithrombotic therapy on heart failure remains controversial. Administration of antiplatelet or anticoagulant therapy is the obvious (and well-established) choice in heart failure patients with cardiovascular comorbidity that necessitates their use, such as coronary artery disease or atrial fibrillation. In contrast, antithrombotic therapy has not demonstrated any clear benefit when administered for heart failure per se, i.e. with heart failure being the sole indication. Randomized studies have reported decreased stroke rates with warfarin use in patients with heart failure with reduced left ventricular ejection fraction, but at the expense of excessive bleeding. Non-vitamin K oral anticoagulants have shown a better safety profile in heart failure patients with atrial fibrillation compared with warfarin, however, current evidence about their role in heart failure with sinus rhythm is inconclusive and further research is needed. In the present review, we discuss the role of antithrombotic therapy in heart failure (beyond coronary artery disease), aiming to summarize evidence regarding the thrombotic risk and the role of antiplatelet and anticoagulant agents in patients with heart failure.

Cardiomyopathies are a heterogeneous group of heart muscle diseases and important cause of heart failure with reduced or preserved ejection fraction. Although there is an increasing body of evidence on the incidence, pathophysiology, and natural history of heart failure (HF) in cardiomyopathies, certain aspects of the therapeutic strategies remain unclear. More particularly, there is no consensus if to whether antithrombotic therapy has a favorable risk: benefit ratio in reducing thromboembolic event rate in patients with cardiomyopathies without suffering from primary valvular disease or atrial fibrillation. Although the observational data on increased venous thromboembolic risk are supported by multiple pathophysiological mechanisms, the role of antithrombotic therapy in these patients remains unclear. This review article provides an overview of epidemiologic, pathophysiologic, clinical, and therapeutic data for the prevention of thromboembolism in heart failure due to cardiomyopathies.

Pathologies of the atrial septum include different interatrial communications varying from patent foramen ovale (PFO) to actual defects. Atrial septal defects (ASDs) may be localized within the fossa ovalis such as the secundum type ASD or outside the region of fossa ovalis, such as the ostium primum defect and sinus venosus defect. Over the last decades, the percutaneous closure of interatrial shunts has become a feasible and safe method. During these procedures, the delicate balance between thrombotic risk, device sealing process and bleeding risk is crucial. In this review, we sought to describe current available data on the antiplatelet and antithrombotic management of patients after percutaneous ASD or PFO closure.

Background: Diabetes mellitus (DM) is on the rise globally. Its prevalence has nearly doubled during the last two decades and it is estimated to affect 8.8% of the global population. Cardiovascular disease (CVD) is the leading cause of death in the diabetic population and despite modern anti-inflammatory and cardioprotective therapeutic strategies, diabetic patients have at least a twice fold risk of cardiovascular events. The prothrombotic state in DM is associated with multiple determinants such as platelet alterations, oxidative stress, endothelial changes, circulating mediators. Thus, proper antithrombotic strategies to reduce the risk of CVD in this population are critical. Methods: This article reviews the current antiplatelet and anticoagulant agents in the aspect of primary and secondary prevention of CVD in the diabetic population. Results: The use of aspirin may be considered only at high-risk patients in the absence of contraindications. Cangrelor was not inferior to clopidogrel in preventing the composite outcome of CV death, myocardial infarction and revascularization without increasing major bleeding. Triple therapy in the subpopulation with DM significantly reduced the composite primary outcome of CV death, myocardial infarction or repeat target lesion revascularization. That was not the case for stent thrombosis, which was similar in both groups. Importantly, triple therapy did not result in increased bleeding complications, which were similar in both groups. However, cilostazol is linked to various adverse effects (e.g., headache, palpitations, and gastrointestinal disturbances) that drive many patients to withdrawal. Conclusion: In conclusion, DM is a rapidly growing disease that increases the risk of CVD, AF, and CV mortality. Proper antithrombotic strategies to reduce CVD risk in DM are a necessity. Moreover, new antithrombotic treatments and combination therapies may play a critical role to overcome antiplatelet resistance in DM patients and reduce morbidity and mortality attributed to CVD.

While surgical aortic valve replacement (SAVR) was for years the only available treatment for symptomatic aortic stenosis, the introduction of transcatheter aortic valve implantation (TAVI) in 2002 and the improvement of its technical aspects in the following years, has holistically changed the synchronous therapeutic approach of aortic valve stenosis. Recent evidence has expanded the indication of TAVI from high to lower surgical risk populations with symptomatic aortic stenosis. The administration of antithrombotic therapy periprocedurally and its maintenance after a successful TAVI is crucial for the prevention of complications and affects postprocedural survival. Randomized controlled trials investigating the appropriate combination and the duration of antithrombotic treatment after TAVI are for the moment scarce. This review article sheds light on the underlying pathogenetic mechanisms contributing in periprocedural TAVI thrombotic complications and discuss the efficacy of current antithrombotic policies as evaluated in randomized trials.