rivaroxaban and Myocardial-Ischemia

Antithrombotic treatment is a key component of secondary prevention following acute coronary syndromes (ACS). Although dual antiplatelet therapy is standard therapy post-ACS, duration of treatment is the subject of ongoing debate. Prolonged dual antiplatelet therapy in high-risk patients with history of myocardial infarction reduced the risk of recurrent myocardial infarction, stroke or cardiovascular death. Similarly, in patients with stable coronary artery disease, two-thirds of whom had a history of myocardial infarction, dual antithrombotic therapy with very-low-dose rivaroxaban and aspirin also resulted in improved ischaemic outcomes. In the absence of head-to-head comparison, choosing the most appropriate treatment strategy can be challenging, particularly when it comes to balancing the risks of ischaemia and bleeding. We aim to review the evidence for currently available antithrombotic treatments and provide a practical algorithm to aid the decision-making process.

Topics: Acute Coronary Syndrome; Aged; Algorithms; Aspirin; Cardiovascular Diseases; Coronary Artery Disease; Decision Making; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Risk; Rivaroxaban; Secondary Prevention; Stroke; Ticagrelor

In atrial fibrillation (AF) patients with coronary artery disease (CAD), anticoagulants are commonly used in combination with antiplatelet drugs. However, dual therapy can increase the risk of bleeding, and the potential therapeutic benefits must be weighed against this. Therefore, it is recommended that dual therapy is only used for a limited time, and that monotherapy with anticoagulants should start from 1 year after percutaneous coronary intervention (PCI). However, there is a lack of evidence on the use of monotherapy, in particular with direct oral anticoagulants, in this group of patients.. The AFIRE Study is a multicenter, prospective, randomized, open-label, parallel group study conducted in patients aged ≥20 years with non-valvular AF (NVAF) and CAD. Patients who have undergone PCI or coronary artery bypass graft at least 1 year prior to enrollment, or those without significant coronary lesions requiring PCI (≥50% stenosis), will be included. Approximately 2200 participants will be randomized to receive either rivaroxaban monotherapy or rivaroxaban plus an antiplatelet drug (aspirin, clopidogrel, or prasugrel). The primary efficacy endpoints are the composite of cardiovascular events (stroke, non-central nervous system embolism, myocardial infarction, and unstable angina pectoris requiring revascularizations) and all-cause mortality. The primary safety endpoint is major bleeding as defined by the International Society on Thrombosis and Haemostasis criteria.. This study will be the first to assess the efficacy and safety of rivaroxaban monotherapy in NVAF patients with stable CAD.

Topics: Atrial Fibrillation; Coronary Artery Disease; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Myocardial Ischemia; Platelet Aggregation Inhibitors; Prospective Studies; Rivaroxaban

The article considers modern approaches to the secondary prevention of cardiovascular events in patients with stable ischemic heart disease (IHD) and / or atherosclerosis of peripheral arteries (peripheral artery disease - PAD) with the oral anticoagulant rivaroxaban. The results of the first international prospective phase III study COMPASS for the evaluation of efficacy and safety of rivaroxaban including 27 395 patients with stable IHD or PAD, are discussed. The results of the study were presented at European Congress of Cardiology 2017. Rivaroxaban reduced of the risk of cardiovascular death, stroke and myocardial infarction by 24 %. The results of the study confirm the positive balance of risk / benefit and supplement the previously obtained data on the efficacy of rivaroxaban in patients with cardiovascular diseases.

Topics: Anticoagulants; Humans; Myocardial Infarction; Myocardial Ischemia; Prospective Studies; Rivaroxaban; Stroke

Guidelines recommendations regarding anticoagulant therapy after percutaneous coronary intervention (PCI) among patients with atrial fibrillation (AF) rely on retrospective, nonrandomized observational data. Currently, patients are treated with triple-therapy (dual antiplatelet therapy [DAPT] + oral anticoagulation therapy), but neither the duration of DAPT nor the level of anticoagulation has been studied in a randomized fashion. Recent studies also suggest dual pathway therapy with clopidogrel plus oral anticoagulation therapy may be superior, and other studies suggest that novel oral anticoagulants such as rivaroxaban may further improve patient outcomes.. PIONEER AF-PCI (ClinicalTrials.gov NCT01830543) is an exploratory, open-label, randomized, multicenter clinical study assessing the safety of 2 rivaroxaban treatment strategies and 1 vitamin K antagonist (VKA) treatment strategy in subjects who have paroxysmal, persistent, or permanent nonvalvular AF and have undergone PCI with stent placement. Approximately 2,100 subjects will be randomized in a 1:1:1 ratio to receive either rivaroxaban 15 mg once daily plus clopidogrel 75 mg daily for 12 months (a WOEST trial-like strategy), or rivaroxaban 2.5 mg twice daily (with stratification to a prespecified duration of DAPT 1, 6, or 12 months, an ATLAS trial-like strategy), or dose-adjusted VKA once daily (with stratification to a prespecified duration of DAPT 1, 6, or 12 months, traditional triple therapy). All patients will be followed up for 12 months for the primary composite end point of Thrombolysis in Myocardial Infarction major bleeding, bleeding requiring medical attention, and minor bleeding (collectively, clinically significant bleeding).. The PIONEER AF-PCI study is the first randomized comparison of VKA vs novel oral anticoagulant therapy in patients with NVAF receiving antiplatelet therapy after PCI to assess the relative risks of bleeding complications.

Topics: Administration, Oral; Aged; Atrial Fibrillation; Clopidogrel; Coronary Angiography; Dose-Response Relationship, Drug; Drug Therapy, Combination; Electrocardiography; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Male; Middle Aged; Morpholines; Myocardial Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Retrospective Studies; Rivaroxaban; Thiophenes; Ticlopidine; Treatment Outcome; Vitamin K

Coronary artery disease (CAD) is among the main causes of morbidities and mortalities globally. It is also considered to be an outcome of acute thrombotic events which entail activating platelets as well as coagulation proteins. In particular, rivaroxaban along with aspirin have been considered to reduce thrombotic events. However, they are yet to be evaluated by combining with or putting them against each other in patients experiencing CAD. This study intends to carry out an evaluation of whether combining rivaroxaben with aspirin will be effective and safe in treating patients experiencing chronic CAD.. We intend to search information from the following databases: MEDLINE, EMBASE, Web of Science, Cochrane library, WanFang, and China National Knowledge Infrastructure. In the search, we intend to regard randomized control trials written in either English or Chinese and only those published until December 2021, as well as only those that have assessed the effectiveness and safety of combining rivaroxaban and aspirin in treating patients suffering from chronic CAD. We intend to accompany the study identification with searching or relevant reference lists as well as citations. We will also contact respective authors to provide additional information or data were needful. From the search, we will collate all citations identified and remove all duplicates. Similarly, 2 independent authors will screen all the titles and abstracts and assess them against the inclusion criteria for the study. Only selected studies will be included for critical appraisal, extraction of data, and synthesis. We will then conduct statistical analyses by utilizing a random-effect model.. This study does not require ethical approval as the findings will be published in a peer-review journal.. 10.17605/OSF.IO/WBGE4.

Topics: Aspirin; Coronary Artery Disease; Humans; Meta-Analysis as Topic; Myocardial Ischemia; Research Design; Rivaroxaban; Systematic Reviews as Topic; Treatment Outcome

Aim      To evaluate the effect of low-dose rivaroxaban on quality of life of patients and clinical manifestations of functional class (FC) II-III stable angina.Material and methods  26 patients with ischemic heart disease (IHD) with FC II-III stable angina, who were newly prescribed rivaroxaban 2.5 mg twice a day in combination with acetylsalicylic acid 75-100 mg, were followed for 10 weeks. During the first (before the beginning of treatment) and the last weeks of study, patients kept diaries, in which they reported angina attacks and short-acting nitrate intake, filled in an angina questionnaire (SAQ), and underwent electrocardiogram (ECG) Holter monitoring (HM).Results The treatment was associated with decreases in the frequency of angina attacks (by 19.5 %; р=0.027) and the number of taken short-acting nitrate pills (by 17.1 %; р=0.021) and an improvement of quality of life according to stability scales (р=0.042). Data from ECG HM showed decreases in the number and duration of ischemic episodes (p≤0.05).Conclusion      The treatment of IHD patients with rivaroxaban 2.5 mg twice a day in combination with acetylsalicylic acid 75-100 mg for 2 mos. was associated with decreased frequency of angina attacks, reduced requirement for short-acting nitrate, and with improvement of quality of life.

Topics: Angina, Stable; Humans; Myocardial Ischemia; Quality of Life; Rivaroxaban; Surveys and Questionnaires

We describe the case of an 86-year-old man with a background of severe left ventricular dysfunction and ischaemic cardiomyopathy who, having been optimised for heart failure therapy in hospital, unexpectedly deteriorated again with hypotension and progressive renal failure over the course of 2 days. Common causes of decompensation were ruled out and a bedside echocardiogram unexpectedly diagnosed new pericardial effusion with tamponade physiology. The patient underwent urgent pericardiocentesis and 890 mL of haemorrhagic fluid was drained. Common causes for haemopericardium were ruled out, and the spontaneous haemopericardium was thought to be related to introduction of rivaroxaban anticoagulation. The patient made a full recovery and was well 2 months following discharge. This case highlights the challenges of diagnosing cardiac tamponade in the presence of more common disorders that share similar non-specific clinical features. In addition, this case adds to growing evidence that therapy with direct oral anticoagulants can be complicated by spontaneous haemopericardium, especially when coadministered with other agents that affect clotting, renal dysfunction and cytochrome P3A5 inhibitors.

Topics: Acute Kidney Injury; Aged, 80 and over; Anticoagulants; Cardiac Tamponade; Cytochrome P-450 CYP3A Inhibitors; Diagnosis, Differential; Drainage; Echocardiography; Heart Failure; Humans; Hypotension; Male; Myocardial Ischemia; Pericardial Effusion; Rivaroxaban; Ventricular Dysfunction, Left

Acute myocardial infarction is a leading cause of death worldwide. Though highly beneficial, reperfusion of myocardium is associated with reperfusion injury. While indirect inhibition of Factor Xa has been shown to attenuate myocardial ischemia-reperfusion (I/R) injury, the underlying mechanism remains unclear. Our study sought to evaluate the effect of rivaroxaban (RIV), a direct inhibitor of Factor Xa, on myocardial I/R injury and determine its cellular targets.. We used a rat model of 40-min coronary ligation followed by reperfusion. RIV (3 mg/kg) was given per os 1 h before reperfusion. Infarct size and myocardial proteic expression of survival pathways were assessed at 120 and 30 min of reperfusion, respectively. Plasmatic levels of P-selectin and von Willebrand factor were measured at 60 min of reperfusion. Cellular RIV effects were assessed using hypoxia-reoxygenation (H/R) models on human umbilical vein endothelial cells and on rat cardiomyoblasts (H9c2 cell line).. RIV decreased infarct size by 21% (42.9% vs. 54.2% in RIV-treated rats and controls respectively, P < 0.05) at blood concentrations similar to human therapeutic (387.7 ± 152.3 ng/mL) levels. RIV had no effect on H/R-induced modulation of endothelial phenotype, nor did it alter myocardial activation of reperfusion injury salvage kinase and survivor activating factor enhancement pathways at 30 min after reperfusion. However, RIV exerted a cytoprotective effect on H9c2 cells submitted to H/R.. RIV decreased myocardial I/R injury in rats at concentrations similar to human therapeutic ones. This protection was not associated with endothelial phenotype modulation but rather with potential direct cytoprotection on cardiomyocytes.

Topics: Animals; Cardiotonic Agents; Factor Xa; Factor Xa Inhibitors; Human Umbilical Vein Endothelial Cells; Humans; Male; Myocardial Ischemia; Myocardial Reperfusion; Myocardial Reperfusion Injury; Myocytes, Cardiac; P-Selectin; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Rivaroxaban; von Willebrand Factor

The recent publication of the PEGASUS and COMPASS studies could have a great influence on the clinical management of patients with stable ischemic heart disease. In the presence of possible eligibility for both approaches, a practical tool based on inclusion/exclusion criteria of the two studies could be useful for clinical decision of ideal treatment for suitable patients. We therefore report a simple nomogram helpful in identifying the treatment indicated on the base of patient's characteristics.

Topics: Aspirin; Cerebrovascular Disorders; Clinical Decision-Making; Clinical Protocols; Drug Administration Schedule; Drug Therapy, Combination; Factor Xa Inhibitors; Humans; Myocardial Infarction; Myocardial Ischemia; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Registries; Risk; Rivaroxaban; Ticagrelor

A direct oral anti-coagulant, FXa inhibitor, has been applied to the clinical treatment of myocardial infarction (MI). Experimental studies in mice indicated that FXa inhibitors reduced atherosclerosis and prevented cardiac dysfunction after coronary ligation. These studies suggested that protease-activated receptor (PAR) 2, a major receptor of activated FX, may play an important role in atherosclerosis and cardiac remodeling.. The effects of a FXa inhibitor, rivaroxaban, were investigated in a new murine model of ischemic cardiomyopathy (ICM) using SR-BI KO/ApoeR61. Hypo E mice were fed rivaroxaban-containing (n=49) or control chow diets (n=126) after the induction of MI. The survival curve of the rivaroxaban-treated group 2 weeks after the induction of MI was improved significantly as compared with the non-treatment group (survival rate: 75.5% vs. 47.4%, respectively, p=0.0012). Echocardiography and the expression of BNP showed that rivaroxaban attenuated heart failure. Histological analyses revealed that rivaroxaban reduced aortic atherosclerosis and coronary occlusion, and markedly attenuated cardiac fibrosis. Rivaroxaban treatment decreased cardiac PAR2 levels and pro-inflammatory genes. In vitro, rivaroxaban application demonstrated the increase of cell viability against hypoxia in cardiac myocytes and the reduction of hypoxia-induced inflammation and fibrosis-related molecules in cardiac fibroblasts. The effects of the PAR2 antagonist against hypoxia-induced inflammation were comparable to rivaroxaban in cardiac fibroblasts.. Rivaroxaban treatment just after MI in Hypo E mice prevented the progression of ICM by attenuating cardiac remodeling, partially through the suppression of the PAR2-mediated inflammatory pathway.

Topics: Animals; Cardiomyopathies; Diet; Disease Models, Animal; Disease Progression; Factor Xa Inhibitors; Male; Mice; Mice, Knockout; Mice, Knockout, ApoE; Myocardial Infarction; Myocardial Ischemia; Rivaroxaban; Scavenger Receptors, Class B

The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial found clinical benefit of low-dose rivaroxaban plus aspirin, but at the expense of increased bleeding risk in patients with stable vascular disease.. This study evaluated the balance of ischemic and bleeding risks according to the presence of ≥1 enrichment criteria in "COMPASS-eligible" patients.. Key COMPASS selection criteria were applied to identify a COMPASS-eligible population (n = 16,875) from the REACH (REduction of Atherothrombosis for Continued Health) Registry of stable atherothrombotic patients. Ischemic outcome was the composite of cardiovascular death, myocardial infarction, or stroke. Bleeding outcome was serious bleeding (hemorrhagic stroke, hospitalization for bleeding, transfusion).. Patients were categorized according to the enrichment criteria: age >65 years (81.5%), diabetes (41.0%), moderate renal failure (40.2%), peripheral artery disease (33.7%), current smoker (13.8%), heart failure (13.3%), ischemic stroke (11.1%), and asymptomatic carotid stenosis (8.7%). Each criterion was associated with a consistent increase in ischemic and bleeding events, but no individual subgroup derived a more favorable trade-off. Patients with multiple criteria had a dramatic increase in ischemic risk (7.0% [95% confidence interval (CI): 5.6% to 8.7%], 12.5% [95% CI: 11.1% to 14.1%], 16.6% [95% CI: 14.7% to 18.6%], and 21.8% [95% CI: 19.9% to 23.9%] with 1, 2, 3, and ≥4 enrichment criteria, respectively), but a more modest absolute increase in bleeding risk (1.5% [95% CI: 0.9% to 2.1%], 1.8% [95% CI: 1.3% to 2.2%], 2.0% [95% CI: 1.5% to 2.6%], 3.2% [95% CI: 2.6% to 3.9%]).. In a population of stable vascular patients at high risk of atherothrombotic events, the subset with multiple enrichment criteria had a greater absolute increase in ischemic than in bleeding risk and may be good candidates for low-dose rivaroxaban in addition to aspirin.

Topics: Aged; Aspirin; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Hemorrhage; Humans; Ischemia; Male; Myocardial Ischemia; Prospective Studies; Registries; Risk Assessment; Rivaroxaban

In the clinical practice a physician quite often is at a loss due to "freedom of choice" granted by availability of direct oral anticoagulants (DOAC). If a patient with nonvalvular atrial fibrillation (AF) has indications for therapy with anticoagulants which DOAC should be preferred? What are benefits for a patient with ischemic heart disease and AF when definite NOAC is chosen and what are risks inherent of this choice? Answers to such questions are given in this paper.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Myocardial Ischemia; Pyridones; Rivaroxaban; Stroke; Warfarin

New oral anticoagulants (NOAC) have been introduced in Swedish health care as first line treatment of atrial fibrillation and venous thromboembolism. NOAC have also been studied in combination with platelet antiaggregation in both patients with coronary and peripheral arterial disease, and reduced doses will presumably emerge as routine treatment also in these conditions.

Topics: Acute Coronary Syndrome; Anticoagulants; Antithrombins; Cardiovascular Diseases; Coronary Artery Disease; Dabigatran; Drug Therapy, Combination; Factor Xa Inhibitors; Humans; Myocardial Infarction; Myocardial Ischemia; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Sweden; Thiazoles

Direct oral anticoagulants (DOACs) have been promoted in patients with nonvalvular atrial fibrillation (nv-AF) as a more convenient alternative to vitamin K antagonists. We estimated 1-year dabigatran and rivaroxaban adherence rates in nv-AF patients and assessed associations between baseline patient characteristics and nonadherence.. This cohort study included OAC-naive nv-AF patients with no contraindications to OAC, who initiated dabigatran and rivaroxaban, using nationwide data from French national health care databases. One-year adherence was defined by the proportion of days covered of 80% or more over a fixed 1-year period after treatment initiation. Associations between nonadherence and baseline patient characteristics were assessed using multivariate logistic regression models.. The population was composed of 11 141 dabigatran (women: 48%; mean age: 74 ± 10.7 y; ≥80 y: 34.9%) and 11 126 rivaroxaban (46.5%; 74 ± 10.9 y; 34.8%) new users. One-year adherence was 53.3% in dabigatran-treated and 59.9% in rivaroxaban-treated patients, consistent with numerous subgroup analyses. A switch to vitamin K antagonist was observed in 14.5% of dabigatran and 11.7% of rivaroxaban patients; 10.2% and 5.9% of patients switched to another DOAC, respectively; and 4.3% of patients died in the 2 cohorts. In patients who did not die or switch during the follow-up, 1-year adherence was 69.6% in dabigatran-treated and 72.3% in rivaroxaban-treated patients. Having concomitant ischemic heart diseases was associated with an increased risk of nonadherence in the 2 cohorts.. In this real-life study, 1-year adherence to DOAC is poor in nv-AF new users. Despite the introduction of DOAC, adherence to OACs may remain a significant challenge in AF patients.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Comorbidity; Dabigatran; Databases, Factual; Female; France; Health Care Surveys; Humans; Male; Medication Adherence; Middle Aged; Myocardial Ischemia; Rivaroxaban; Stroke; Vitamin K

Non-vitamin K antagonist oral anticoagulation (NOAC) agents have been approved for stroke prophylaxis in atrial fibrillation (AF). We investigated 'real-world' information on how these drugs are being adopted.. Using Danish nationwide administrative registers, we identified all oral anticoagulation-naïve AF patients initiating oral anticoagulation from 22 August 2011 through 31 October 2013. Using logistic regression analysis, baseline characteristics and temporal utilization trends were compared between initiators of warfarin vs. one of the N OACs: dabigatran, rivaroxaban, or apixaban. We identified 18 611 oral anticoagulation-naïve AF patients of which 9902 (53%) initiated warfarin treatment, 7128 (38%) dabigatran, 1303 (7%) rivaroxaban, and 278 (1%) apixaban. Overall, 40% of newly initiated patients were started on dabigatran within the first 4 months of when the drug came on market. By October, 2013, 40% were being started on warfarin and dabigatran, respectively, and another 20% were started on either rivaroxaban or apixaban. Rivaroxaban and apixaban users generally had a higher predicted risk of stroke and bleeding compared with warfarin and dabigatran users. Older age, female gender, and prior stroke were some of the factors associated with NOAC use vs. warfarin, whereas chronic kidney disease, myocardial infarction, and heart failure showed the opposite association.. Among oral anticoagulation-naïve AF patients initiated on oral anticoagulation in Denmark, warfarin initiation has declined since the introduction of dabigatran in August 2011. Dabigatran is the most frequently used alternative option to warfarin; however, use of rivaroxaban and apixaban is increasing. Patients initiated with rivaroxaban or apixaban in general have a higher predicted stroke and bleeding risks compared with warfarin or dabigatran initiators.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Comorbidity; Dabigatran; Denmark; Female; Heart Failure; Humans; Male; Middle Aged; Morpholines; Myocardial Infarction; Myocardial Ischemia; Practice Patterns, Physicians'; Pyrazoles; Pyridones; Registries; Renal Insufficiency, Chronic; Rivaroxaban; Sex Factors; Stroke; Thiophenes; Warfarin