0
selected
-
1.
Antithrombotic Therapy in Acute Coronary Syndromes: Current Evidence and Ongoing Issues Regarding Early and Late Management.
Guedeney, P, Collet, JP
Thrombosis and haemostasis. 2021;(7):854-866
Abstract
A few decades ago, the understanding of the pathophysiological processes involved in the coronary artery thrombus formation has placed anticoagulant and antiplatelet agents at the core of the management of acute coronary syndrome (ACS). Increasingly potent antithrombotic agents have since been evaluated, in various association, timing, or dosage, in numerous randomized controlled trials to interrupt the initial thrombus formation, prevent ischemic complications, and ultimately improve survival. Primary percutaneous coronary intervention, initial parenteral anticoagulation, and dual antiplatelet therapy with potent P2Y12 inhibitors have become the hallmark of ACS management revolutionizing its prognosis. Despite these many improvements, much more remains to be done to optimize the onset of action of the various antithrombotic therapies, for further treating and preventing thrombotic events without exposing the patients to an unbearable hemorrhagic risk. The availability of various potent P2Y12 inhibitors has opened the door for individualized therapeutic strategies based on the clinical setting as well as the ischemic and bleeding risk of the patients, while the added value of aspirin has been recently challenged. The strategy of dual-pathway inhibition with P2Y12 inhibitors and low-dose non-vitamin K antagonist oral anticoagulant has brought promising results for the early and late management of patients presenting with ACS with and without indication for oral anticoagulation. In this updated review, we aimed at describing the evidence supporting the current gold standard of antithrombotic management of ACS. More importantly, we provide an overview of some of the ongoing issues and promising therapeutic strategies of this ever-evolving topic.
-
2.
Guidelines for mono, double and triple antithrombotic therapy.
van Uden, RCAE, Houtenbos, I, Griffioen-Keijzer, A, Odekerken, DAM, van den Bemt, PMLA, Becker, ML
Postgraduate medical journal. 2021;(1153):730-737
Abstract
Guidelines for antithrombotic therapy are complex, especially if a patient has several indications that require antithrombotic therapy. In general, no patient should receive lifelong double or triple antithrombotic therapy. In this overview, we outline the most common indications for mono, double and triple antithrombotic therapy; the preferred antithrombotic therapy and the recommended duration of therapy. Both antiplatelet therapy and therapeutic anticoagulation therapy with vitamin K antagonists or direct oral anticoagulants were included. European guidelines were used or, if no European guidelines were available, the Dutch guidelines were used.
-
3.
Antiplatelet Effects of Bioactive Compounds Present in Tomato Pomace.
Fuentes, E, Trostchansky, A, Reguengo, LM, Junior, MRM, Palomo, I
Current drug targets. 2021;(15):1716-1724
Abstract
Cardiovascular diseases (CVD) currently account for nearly half of non-communicable diseases. Epidemiological studies have demonstrated the cardiovascular protective role of a diet rich in vegetables and fruits. In this context, our research outcomes have demonstrated the antiplatelet activities of fruits and vegetable extracts widely consumed, among which tomato was highlighted in our lab work. Tomato pomace, a major byproduct of tomato paste production, consists of skin and seeds and is a rich source of bioactive compounds. Tomato pomace has potent antithrombotic effects, even greater than the tomato. Given the large volumes of an industrial generation of tomato pomace, there is an opportunity to use this by-product to obtain a functional product with antiaggregant and antithrombotic properties that could be useful as an additive in health foods and thus prevent CVD. This review will focus on the platelet as the target for the antithrombotic actions exerted by the different bioactive compounds present in tomato pomace.
-
4.
Molecular Basis of the Therapeutical Potential of Clove (Syzygium aromaticum L.) and Clues to Its Anti-COVID-19 Utility.
Vicidomini, C, Roviello, V, Roviello, GN
Molecules (Basel, Switzerland). 2021;(7)
Abstract
The current COronaVIrus Disease 19 (COVID-19) pandemic caused by SARS-CoV-2 infection is enormously affecting the worldwide health and economy. In the wait for an effective global immunization, the development of a specific therapeutic protocol to treat COVID-19 patients is clearly necessary as a short-term solution of the problem. Drug repurposing and herbal medicine represent two of the most explored strategies for an anti-COVID-19 drug discovery. Clove (Syzygium aromaticum L.) is a well-known culinary spice that has been used for centuries in folk medicine in many disorders. Interestingly, traditional medicines have used clove since ancient times to treat respiratory ailments, whilst clove ingredients show antiviral and anti-inflammatory properties. Other interesting features are the clove antithrombotic, immunostimulatory, and antibacterial effects. Thus, in this review, we discuss the potential role of clove in the frame of anti-COVID-19 therapy, focusing on the antiviral, anti-inflammatory, and antithrombotic effects of clove and its molecular constituents described in the scientific literature.
-
5.
Rationale for the Role of Heparin and Related GAG Antithrombotics in COVID-19 Infection.
Magnani, HN
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2021;:1076029620977702
Abstract
The SARS-CoV-2 pandemic has focused attention on prevention, restriction and treatment methods that are acceptable worldwide. This means that they should be simple and inexpensive. This review examines the possible role of glycosaminoglycan (GAG) antithrombotics in the treatment of COVID-19. The pathophysiology of this disease reveals a complex interplay between the hemostatic and immune systems that can be readily disrupted by SARS-CoV-2. Some of the GAG antithrombotics also possess immune-modulatory actions and since they are relatively inexpensive they could play an important role in the management of COVID-19 and its complications.
-
6.
Emerging agents for the treatment and prevention of stroke: progress in clinical trials.
Safouris, A, Magoufis, G, Tsivgoulis, G
Expert opinion on investigational drugs. 2021;(10):1025-1035
Abstract
INTRODUCTION Recent years have witnessed unprecedented progress in stroke care, but unmet needs persist regarding the efficacy of acute treatment and secondary prevention. Novel approaches are being tested to enhance the efficacy of thrombolysis or provide neuroprotection in non-thrombolized patients. AREAS COVERED The current review highlights pharmaceutical agents under evaluation in clinical trials concerning the acute, subacute, and chronic phase post-stroke. We examine the evidence in favor of tenecteplase as an alternative thrombolytic drug to alteplase, nerinetide as a promising neuroprotective agent, and glibenclamide for reducing edema in malignant hemispheric infarction. We discuss the use of ticagrelor and the promising novel category of factor XI inhibitors in the subacute phase after stroke. We offer our insights on combined rivaroxaban and antiplatelet therapy, PCSK-9 inhibitors, and other non-statin hypolipidemic agents, as well as novel antidiabetic agents that have been shown to reduce cardiovascular events in the long-term. EXPERT OPINION Current approaches in stroke treatment and stroke prevention have already transformed stroke care from a linear one-for-all treatment paradigm to a more individualized approach that targets specific patient subgroups with novel pharmaceutical agents. This tendency enriches the therapeutic armamentarium with novel agents developed for specific stroke subgroups. ABBREVIATIONS IVT: intravenous thrombolysis; RCTs: randomized-controlled clinical trials; TNK: Tenecteplase; COVID-19: Coronavirus 2019 Disease; EXTEND-IA TNK The Tenecteplase versus Alteplase Before Endovascular Therapy for Ischemic Stroke trial; AIS: acute ischemic stroke; NNT: number needed to treat; MT: mechanical thrombectomy; sICH: symptomatic intracranial hemorrhage; mRS: modified Rankin Scale; AHA/ASA: American Heart Association/American Stroke Association; ESO: European Stroke Organization; NA-1: Nerinetide; ENACT Evaluating Neuroprotection in Aneurysm Coiling Therapy; CTA: CT angiography; TIA: transient ischemic attack; CHANCE Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events; LOF: loss-of-function; PRINCE Platelet Reactivity in Acute Nondisabling Cerebrovascular Events; THALES Acute Stroke or Transient Ischemic Attack Treated with Ticagrelor and ASA [acetylsalicylic acid] for Prevention of Stroke and Death; CHANCE-2: Clopidogrel With Aspirin in High-risk Patients With Acute Non-disabling Cerebrovascular Events II; FXI: Factor XI; PACIFIC-STROKE Program of Anticoagulation via Inhibition of FXIa by the Oral Compound BAY 2433334-NonCardioembolic Stroke study; COMPASS Cardiovascular Outcomes for People Using Anticoagulation Strategies; CANTOS-ICAD: Combination Antithrombotic Treatment for Prevention of Recurrent Ischemic Stroke in Intracranial Atherosclerotic Disease; SAMMPRIS Stenting and Aggressive Medical Therapy for Preventing Recurrent Stroke in Intracranial Stenosis; WASID Warfarin-Aspirin Symptomatic Intracranial Disease; SPARCL Stroke Prevention by Aggressive Reduction in Cholesterol Levels; LDL-C: low-density lipoprotein cholesterol; TST: Treat Stroke to Target; IMPROVE-IT: Improved Reduction of Outcomes: Vytorin Efficacy International Trial; PCSK9: proprotein convertase subtilisin-kexin type 9; FOURIER Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk; CLEAR Cholesterol Lowering via Bempedoic acid, an ACL-inhibiting Regimen; REDUCE-IT: Reduction of Cardiovascular Events With EPA Intervention Trial; STRENGTH Outcomes Study to Assess STatin Residual Risk Reduction With EpaNova in HiGh CV Risk PatienTs With Hypertriglyceridemia; ACCORD Action to Control Cardiovascular Risk in Diabetes; ADVANCE Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation; VADT Veterans Affairs Diabetes Trial; GLP-1R: Glucagon-like peptide-1 receptor; SGLT2: sodium-glucose cotransporter 2; CONVINCE COlchicine for preventioN of Vascular Inflammation in Non-CardioEmbolic stroke; PROBE Prospective Randomized Open-label Blinded Endpoint assessment.
-
7.
Meta-analysis Comparing Direct Oral Anticoagulants Versus Vitamin K Antagonists After Transcatheter Aortic Valve Implantation.
Ueyama, H, Kuno, T, Ando, T, Briasoulis, A, Fox, J, Hayashida, K, Takagi, H
The American journal of cardiology. 2020;(7):1102-1107
Abstract
Atrial fibrillation (AF) is a common co-morbidity in patients undergoing transcatheter aortic valve implantation (TAVI), but whether direct oral anticoagulants (DOACs) confer similar safety and efficacy compared with vitamin K antagonist (VKA) remains unclear in this population. The aim of our study was to investigate the safety and efficacy of DOACs compared with VKA in patients undergoing TAVI with concomitant indication of oral anticoagulation. PUBMED and EMBASE were searched through October 2019 for studies comparing DOACs versus VKA in patients undergoing TAVI with indication of oral anticoagulation. The main efficacy outcomes were all-cause mortality and stroke whereas the main safety outcome was major and/or life-threatening bleeding. Our search identified 5 eligible studies including 2,569 patients. Majority of patients had atrial fibrillation as indication of anticoagulation. There were no significant differences in all-cause mortality, major and/or life-threatening bleeding, and stroke in patients treated with DOACs versus VKA (odds ratio [OR] 1.07, 95% confidence interval [CI] [0.73 to 1.57], p = 0.72, OR = 0.85, 95% CI [0.64 to 1.12], p = 0.24, OR 1.52, 95% CI [0.93 to 2.48], p = 0.09, respectively). In conclusion, in patients undergoing TAVI with concomitant indication for oral anticoagulation, all-cause mortality, major and/or life-threatening bleeding, and stroke were similar between DOACs and VKA. Further large scale randomized controlled trials are needed to search the optimal oral anticoagulation regimen in this population.
-
8.
Management of anticoagulant-refractory thrombotic antiphospholipid syndrome.
Cohen, H, Sayar, Z, Efthymiou, M, Gaspar, P, Richards, T, Isenberg, D
The Lancet. Haematology. 2020;(8):e613-e623
Abstract
Lifelong anticoagulation with warfarin or alternative vitamin K antagonist is the standard anticoagulant treatment for thrombotic antiphospholipid syndrome. Anticoagulant-refractory thrombotic antiphospholipid syndrome can be broadly defined as breakthrough thrombosis while on standard oral anticoagulation treatment and its management is a major challenge given the serious nature of the thrombotic disease observed, which has become refractory to oral anticoagulation. The factors (genetic and cellular) that cause anticoagulant-refractory thrombotic antiphospholipid syndrome are now better understood. However, efforts to use this greater understanding have not yet transformed the capacity to treat it successfully in many patients. In this Viewpoint, we review the factors that are likely to be contributing to the cause of this syndrome and consider how they might be modified or inhibited. We also discuss management, including general strategies to minimise thrombotic risk, intensification of anticoagulation, addition of an antiplatelet agent, adjunctive treatment for thrombosis, immunomodulatory therapy, complement inhibition, vascular options, and future potential therapeutic targets.
-
9.
A critical evaluation of caplacizumab for the treatment of acquired thrombotic thrombocytopenic purpura.
Gómez-Seguí, I, Fernández-Zarzoso, M, de la Rubia, J
Expert review of hematology. 2020;(11):1153-1164
Abstract
Introduction: Acquired thrombotic thrombocytopenic purpura (aTTP) is a thrombotic microangiopathy caused by inhibitory autoantibodies against ADAMTS13 protein. Until recently, the combination of plasma exchange (PEX) and immunosuppression has been the standard front-line treatment in this disorder. However, aTTP-related mortality, refractoriness, and relapse are still a matter of concern. Areas covered: The better understanding of the pathophysiological mechanisms of aTTP has allowed substantial improvements in the diagnosis and treatment of this disease. Recently, the novel anti-VWF nanobody caplacizumab has been approved for acute episodes of aTTP. Caplacizumab is capable to block the adhesion of platelets to VWF, therefore inhibiting microthrombi formation in the ADAMTS13-deficient circulation. In this review, the characteristics of caplacizumab together with the available data of its efficacy and safety in the clinical setting will be analyzed. Besides, the current scenario of aTTP treatment will be provided, including the role of other innovative drugs. Expert opinion: With no doubt, caplacizumab is going to change the way we treat aTTP. In combination with standard treatment, caplacizumab can help to significantly reduce aTTP-related mortality and morbidity and could spare potential long-term consequences by minimizing the risk of exacerbation.
-
10.
Tinzaparin Sodium Pharmacokinetics in Patients with Chronic Kidney Disease: Practical Implications.
Helfer, H, Siguret, V, Mahé, I
American journal of cardiovascular drugs : drugs, devices, and other interventions. 2020;(3):223-228
-
-
Free full text
-
Abstract
Low-molecular-weight heparins (LMWHs) are the mainstay of the prophylaxis and treatment of venous thromboembolism (VTE). Due to their renal elimination, the risk of accumulation with the related bleeding risk may represent a limitation for the use of LMWHs in patients with chronic kidney disease (CKD) as the risk of major bleeding is increased in patients with creatinine clearance (CrCl) < 30 mL/min, especially in patients with cancer. LMWH structure and molecular weight (MW) are heterogeneous among available agents. The elimination of tinzaparin, which has the highest mean MW among LMWHs, is less dependent on renal function as it is also metabolized through the reticuloendothelial system. A subcutaneous therapeutic dose of tinzaparin (175 IU/kg) once daily has been shown to cause no accumulation of anti-factor Xa activity in patients with CrCl ≥ 20 mL/min. Clinical experience from randomized controlled studies has shown no significant impact of CKD on bleeding risk in cancer patients receiving treatment doses of tinzaparin. This suggests that in these patients the use of treatment doses of tinzaparin does not require anticoagulation monitoring or dose adjustment.