Cardiovascular & Haematological Disorders - Drug Targets - Volume 15, Issue 2, 2015

The development of new or direct oral anticoagulants was triggered by the disadvantages of classic oral anticoagulation, which was isolated in Link’s laboratory in 1940. Some of these limitations are the individual variation in response to these drugs, drug interaction and the need for regular laboratory monitoring. With increasing comorbidity and life expectancy in populations these limitations led to interruption of treatment or even underuse of treatment in light of potential side effects. With the introduction of novel oral anticoagulants some of these drawbacks are targeted whereas even these drugs also have some limitations and should be given with cautions and not to all patients having an indication for anticoagulation.

Thrombo-embolism of the venous system consisting of deep vein thrombosis (DVT) and pulmonary embolism (PE) is common and associated with high morbidity and mortality. Symptomatic venous thrombembolism (VTE) manifests in about 1/3 of cases as PE and 2/3 as DVT. There is a strongly compound between early mortality after venous VTE and PE, age, malignancies and cardiovascular diseases. Anticoagulation therapy is the main therapeutic approach for the treatment of acute VTE and to prevent recurrent VTE events. For decade’s classic anticoagulants like heparin, low-molecular-weight heparins (LMWHs), fondaparinux, and vitamin K antagonists have been the gold standards in therapy and are widely used. Novel oral anticoagulants (NOAC) like the direct thrombin inhibitor (dabigatran etexilate) and the direct factor Xa inhibitors (e.g. rivaroxaban, apixaban, and edoxaban) have been introduced to overcome the drawbacks of vitamin K antagonists. The efficacy and safety of these NOAC have been investigated in several randomized trials. Here we want to give an overview about the NOACS in the treatment of acute and chronic VTE and their use for primary prevention of acute VTE.

Atrial fibrillation is known to be associated with an increased risk of ischaemic stroke and systemic embolism. After stratification using various risk calculation scores, patients were traditionally prescribed anticoagulants in the form of Aspirin or the traditional Vitamin K Antagonists. The use of Warfarin has proven to reduce incidents of ischaemic stroke; however its use has several limitations. The necessity for strict anticoagulation monitoring so as to maintain the narrow therapeutic range as measured by the international normalized ratio (INR) between 2 and 3 is one of these. In clinical practice, patients are within the therapeutic range lesser than two-thirds of the time and furthermore, its use is associated with a significant risk of major bleeding. The advent of Novel oral Anticoagulants marks a new era in anticoagulant therapy. The use of direct thrombin inhibitors and Factor Xa inhibitors has documented a favorable bleeding profile while being similarly or more efficacious when compared to VKA. Early studies indicate a significant reduction in the composite of stroke or systemic embolism and lowering of all-cause mortality. In this review we discuss the evidence for the clinical benefit and safety of the novel anticoagulants versus warfarin among patients with atrial fibrillation and probationary guidelines towards their use.

The implementation of therapeutic anticoagulation influences the severity and outcome of patients with coronary artery disease (CAD). This review aims to summarize the current guidelinebased recommendations about the use of new oral anticoagulants (NOACs) in patients with stable CAD (SCAD), acute coronary syndromes (ACS), percutaneous coronary interventions (PCI) and in patients with concomitant atrial fibrillation (AF). The implications of the use of specific NOACs, such as the direct factor Xa inhibitors apixaban and rivaroxaban as well as the direct thrombin inhibitor dabigatran are outlined and compared to the benefits of vitamin k antagonists and antiplatelet agents such as thienopyridines in these settings.

Antithrombotic treatment after heart valve surgery is of utmost importance depending on the type of used valve. Since in the early 1960s, oral anticoagulation with vitamin K antagonist are the gold-standard for prevention of thromboembolism at replaced heart valves. The introduction of new oral anticoagulation has dramatically changed treatment strategy in patients with atrial fibrillation and in patients with venous thromboembolism like deep vein thrombosis and pulmonary embolism. However, to date, the use of these newer drugs is contraindicated after implantation of mechanical heart valves for prevention of thromboembolism. Large trial revealed significantly higher rates of thromboembolism and bleeding events as compared to oral anticoagulation. Further studies are required to evaluate the several newer oral anticoagulations in patients with mechanical heart valve.

Atrial fibrillation is an age-dependent disease with symptomatic and prognostic implications. Treatment options include rhythm as well as rate control. However, there is a need for anticoagulation depending on calculated individual annual risk. Treatment options include antiplatelet therapy, oral anticoagulation and the use of novel oral anticoagulation (NOACs). To date, the safety and efficacy of NOACs in atrial fibrillation is established in large mega-trials. However, there is still concern on the use of NOACs in invasive procedures such as coronary angiography, electrophysiological procedures, and general surgical procedures. This review will give an overview about current data of NAOCs in procedures for rhythm control (pulmonary vein isolation and current cardioversion).

The use of novel oral anticoagulation (NOACs) has emerged as an alternative for oral anticoagulation with vitamin-K antagonists in different clinical settings. However, despite the several advantages of these new drugs, there are also several limitations and cautious is recommended in different clinical settings in patients with a high comorbidity index. This review article will describe the current evidence of treatment monitoring, possible drug interaction, and will give an overview about treatment options in case of complications.

New oral anticoagulants (NOACs) are becoming available as alternatives to vitamin K antagonists (VKAs) to prevent systemic embolism in patients with non-valvular atrial fibrillation for the prevention and treatment of venous thromboembolism and pulmonary embolism. A comprehensive understanding of the basic concepts of hemostaseology, the underlying pharmacology, drug interactions and management of potential complications is essential for the selection of suitable patients to receive NOACs, for correct prescription and for optimal patient treatment. Furthermore, the use of NOACs in a perioperative setting is crucial, as it requires knowledge of time and dose of last intake of drug, current renal function and the planned procedure in order to assess the overall risk of bleeding. Although no antidote exists to reverse the effects of these novel drugs, selective substitution of coagulation factors and dialysis may be necessary. Therefore, choosing the most beneficial alternative to VKAs on an individual basis can be challenging for physicians. In conclusion, the recent introduction of NOACs represents an opportunity for anticoagulative treatment regimes, while the benefits, risks and limitations should be reflected carefully. The purpose of this systematic review is to highlight features and to provide practical guidance of NOACs in comparison with VKAs that should be considered in a multifaceted decision making process to improve efficacy and safety.

The state-of-the-art of oxygen-ozone therapy is now clarified and all the mechanisms of action of medical ozone are within classical biochemistry and molecular biology. The outcomes of standard treatments in peripheral arterial occlusive disease (PAOD) and dry-form of age-related macular degeneration (AMD) have been compared with the documented therapeutic results achieved with ozonated autohemotherapy (O-AHT). On the other hand, the clinical data of O-AHT on stroke remain indicative. As the cost of O-AHT is almost irrelevant, its application in all public hospitals, especially those of poor Countries, would allow two advantages: the first is for the patient, who will improve her/his conditions, and the second is for Health Authorities burdened with increasing costs. The aim of this paper is to report to clinical scientists that O-AHT is a scientific-based therapeutic approach without side effects. The integration of O-AHT with effective approved drugs is likely to yield the best clinical results in several chronic inflammatory diseases.

Several new oral anticoagulants (NOAC) have been recently studied and approved for the prevention and treatment of venous thromboembolism (VTE) which includes deep vein thrombosis and pulmonary embolism. Although, NOACs possess several advantages when compared to traditional therapy each has its own limitations; especially in the elderly and in patients with low body weight, renal impairment and in those with high risk of bleeding. Apixaban is a factor Xa inhibitor recently approved for the treatment and prevention of VTE in the United States. The purpose of this manuscript is to review describes the pharmacological properties of NAOC’s and to discuss clinical trial results and clinical applications of these agents in the prevention and treatment of VTE with special emphasis on the role of apixaban.

Background: Myelodysplastic Syndromes (MDS) are a group of clonal hematopoietic stem cell disorders with significant heterogeneity in their clinical presentation and the prognosis of the patients. Several attempts have been made to incorporate flow cytometry (FC) findings into the diagnostic and/or prognostic criteria of dysplasia, but bone marrow (BM) aspirate morphology evaluation remains the gold-standard for diagnosis. The purpose of this study was to provide a diagnostic tool for MDS that relies on BM immunophenotyping and objectifies the interpretation of FC analysis and to validate its capacity to discriminate MDS from other causes of cytopenias. Methods: To that purpose, a mathematical formula was developed which incorporates granulocytic maturation markers and the percentage of selected myeloid populations and translates them into a single parameter that quantifies the maturation and differentiation defects of BM granulocytes, named Dysmyelopoiesis Index (DMI). Bone marrow samples from 84 MDS patients and 47 non-MDS cytopenic patients were analyzed with FC and DMI was calculated for every patient. Results: DMI detected clonal dysplasia with 84.5% sensitivity and 93.6% specificity, identified as MDS 77.2% of low grade patients and revealed multilineage dysplasia for a number of RA and RARS cases. It discriminated prognostic subgroups of MDS patients (P< .005) and negatively correlated with IPSS (r= - .472, P= .000), WPSS (r= - .481, P= .000) and IPSS-R (r= -.395, P= .000). Conclusions: DMI represents an accurate quantification of dysmyelopoiesis and an effective stand-alone diagnostic test for MDS, facilitating FC analysis and daily clinical practice.