rivaroxaban and Myocardial-Infarction

Heart failure (HF) is a major public health issue associated with significantly increased risk of stroke. It remains uncertain whether oral anticoagulation (OAC) in patients with heart failure and sinus rhythm (HF-SR) could improve prognosis.. We performed a systematic search of PubMed and Embase databases for randomized controlled clinical trials assessing oral anticoagulants versus antiplatelets or placebo in patients with HF or ventricular dysfunction/cardiomyopathy without clinical HF and SR. The outcomes assessed were stroke/systemic embolism, major bleeding, myocardial infarction, all-cause mortality, and HF hospitalization.. Seven trials of 15,794 patients were eligible for our analyses. The overall follow-up duration was 32,367 patient-years corresponding to a mean follow-up of 2.05 years per patient. Four trials included patients treated with warfarin and three included patients treated with rivaroxaban. OAC was associated with reduced rate of stroke or systemic embolism compared to control (odds ratio (OR): 0.57, 95% confidence interval (CI): 0.44, 0.73, number needed to treat (NNT): 71.9) but higher rate of major bleeding (OR: 1.92, 95% CI: 1.47, 2.50, number needed to harm (NNH): 57.1). In the subgroup analysis according to the type of OAC, rivaroxaban was associated with significantly reduced rate of stroke or systemic embolism (1.24 vs 1.97 events per 100 patient-years, respectively, OR: 0.63, 95% CI: 0.45, 0.88, NNT: 82) and higher risk of major bleeding (OR: 1.66, 95% CI: 1.26, 2.20) compared to antiplatelets or placebo. There was no significant differences between groups for the outcomes of myocardial infarction, all-cause mortality, and HF hospitalization.. This analysis shows that any benefit of OAC for stroke prevention may be offset by an increased risk of major bleeding in HF-SR patients. A well-designed randomized controlled trial of newer safer OACs is needed in this population.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Heart Failure; Hemorrhage; Humans; Myocardial Infarction; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Vitamins

The aim of this study was to evaluate the efficacy and safety of antithrombotic regimens and their combinations in preventing thrombotic incidents in patients with stable atherosclerotic cardiovascular disease (S-ASCVD).. A systematic literature search was conducted in the PubMed, Embase, Cochrane Library, Scopus, and Google Scholar databases. The primary comprehensive endpoint was a major adverse cardiovascular event (MACE) composite of cardiovascular death, stroke, or myocardial infarction, while the secondary endpoints were cardiovascular death, all-cause stroke, ischemic stroke, myocardial infarction, and all-cause death. The safety endpoint was major bleeding. Bayesian network meta-regression analysis in R software was used to calculate the final effect size and to correct for the effect of follow-up time on the outcome effect size.. Twelve studies reporting 122,190 patients with eight antithrombotic regimens were included in this systematic review. For the primary composite endpoint, low-dose aspirin plus clopidogrel 75 mg (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.33-0.87) and low-dose aspirin plus rivaroxaban 2.5 mg twice daily (HR 0.53, 95% CI 0.34-0.82) showed significantly better efficacy than clopidogrel monotherapy, and the efficacy was comparable among the first two regimens. Unfortunately, none of the active regimens significantly decreased all-cause death, cardiovascular death branch, and all-cause stroke as part of the secondary endpoints. Low-dose aspirin plus ticagrelor 90 mg twice daily (HR 0.81, 95% CI 0.69-0.94) and low-dose aspirin plus ticagrelor 60 mg twice daily (HR 0.84, 95% CI 0.74-0.95) had a significant advantage in myocardial infarction compared with low-dose aspirin monotherapy, while low-dose aspirin plus 2.5 mg rivaroxaban twice daily (HR 0.62, 95% CI 0.41-0.94) was better than low-dose aspirin in the treatment of ischemic stroke. In the major bleeding branch, low-dose aspirin plus ticagrelor 90 mg twice daily (HR 2.2, 95% CI 1.70-2.90), low-dose aspirin plus ticagrelor 60 mg twice daily (HR 2.1, 95% CI 1.70-2.60), low-dose aspirin plus rivaroxaban 2.5 mg twice daily (HR 1.7, 95% CI 1.30-2.00), and rivaroxaban 5 mg twice daily (HR 1.5, 95% CI 1.20-1.90) showed higher major bleeding risk compared with low-dose aspirin.. Considering MACEs, myocardial infarction, all kinds of stroke, ischemic stroke, and major bleeding, low-dose aspirin plus rivaroxaban 2.5 mg twice daily should be considered the preferred regimen for S-ASCVD patients with low bleeding risk.

Topics: Aspirin; Atherosclerosis; Bayes Theorem; Cardiovascular Diseases; Clopidogrel; Drug Therapy, Combination; Fibrinolytic Agents; Hemorrhage; Humans; Ischemic Stroke; Myocardial Infarction; Network Meta-Analysis; Platelet Aggregation Inhibitors; Regression Analysis; Rivaroxaban; Stroke; Ticagrelor

A systematic review and network meta-analysis (NMA) were conducted to explore the efficacy and safety of different antiplatelet or anticoagulation drugs in chronic coronary syndromes patients.. Electronic databases (Pubmed, Embase and Cochrane databases) were systematically searched to identify randomized controlled trials evaluating different antiplatelet or anticoagulation drugs (aspirin, aspirin + clopidogrel, aspirin + clopidogrel + cilostazol, clopidogrel/prasugrel + aspirin, aspirin + rivaoxaban 2.5 mg, aspirin + ticagrelor 60 mg, aspirin + ticagrelor 90 mg, clopidogrel or rivroxaban 5 mg) versus placebo for treatment chronic coronary syndromes patients. Outcomes included major adverse cardiovascular events, all cause death, major bleeding and myocardial infarction. A random-effect Bayesian NMA was conducted for outcomes of interest, and results were presented as odds ratios (ORs) and 95% credible intervals. The NMA was performed using R Software with a GeMTC package. A Bayesian NMA was performed and relative ranking of agents was assessed using surface under the cumulative ranking probabilities.. Ten randomized controlled trials met criteria for inclusion and finally included in this NMA. In head-to-head comparison, no significant difference was observed between all antithrombotic treatment strategies with respect to primary endpoint of major adverse cardiovascular events. In head-to-head comparison, no significant difference was observed between all antithrombotic treatment strategies with respect to all cause death. Clopidogrel/prasugrel + aspirin (OR = 3.8, 95% credible intervals [CrI]: 1.3-12.0, P < .05) and aspirin + rivaroxaban 2.5 mg (OR = 3.1, 95%CrI: 1.1-9.5, P < .05) was associated with an increase of the major bleeding. Compared with aspirin alone, aspirin + clopidogrel (OR = 0.42, 95%CrI: 0.22-0.76, P < .05) and aspirin + ticagrelor 90 mg (OR = 0.42, 95%CrI: 0.17-0.95, P < .05) was associated with a decrease of the myocardial infarction.. Myocardial infarction was significantly lower when adding clopidogrel or ticagrelor 90 mg to aspirin than those in the aspirin alone group. However, clopidogrel/prasugrel and rivaroxaban 2.5 mg was associated with an increase of the major bleeding than aspirin alone.

Topics: Acute Coronary Syndrome; Anticoagulants; Aspirin; Bayes Theorem; Clopidogrel; Fibrinolytic Agents; Hemorrhage; Humans; Myocardial Infarction; Network Meta-Analysis; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Rivaroxaban; Ticagrelor; Treatment Outcome

This meta-analysis was conducted to compare the efficacy and safety of rivaroxaban with warfarin in patients with atrial fibrillation (AF) and diabetes mellitus.. PubMed, Embase, Cochrane Library, and Web of Science databases were systematically searched from the establishment of databases up to 15 October 2019. Studies on efficacy and safety outcomes of rivaroxaban and warfarin were included. Efficacy and safety outcomes, including stroke, ischemic stroke, stroke or systemic embolism, myocardial infarction, major adverse cardiac events, major bleeding, intracranial hemorrhage, and major gastrointestinal bleeding were collected for meta-analysis.. Compared with warfarin, rivaroxaban could significantly reduce stroke (risk ratio [RR] 0.77; 95% confidence interval [CI] 0.63-0.95; P = 0.01), ischemic stroke (RR 0.74; 95% CI 0.63-0.87; P = 0.0004), stroke or systemic embolism (RR 0.73; 95% CI 0.60-0.89; P = 0.002), myocardial infarction (RR 0.68; 95% CI 0.56-0.82; P < 0.0001), and major adverse cardiac events (RR 0.71; 95% CI 0.53-0.94; P = 0.02) in patients with AF and diabetes. Moreover, rivaroxaban was associated with a lower risk of major bleeding (RR 0.79; 95% CI 0.65-0.96; P = 0.02), intracranial hemorrhage (RR 0.52; 95% CI 0.39-0.69; P < 0.00001), and major gastrointestinal bleeding (RR 0.74; 95% CI 0.56-0.98; P = 0.04). Similar results were obtained in stratified meta-analysis of cohort studies.. Our study suggests a favorable risk-benefit profile of rivaroxaban, with superior efficacy and safety over warfarin in patients with AF and diabetes.

Topics: Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Diabetes Mellitus; Hemorrhage; Humans; Myocardial Infarction; Rivaroxaban; Stroke; Warfarin

Rivaroxaban is a factor Xa inhibitor oral anticoagulant first approved for use in the United States in 2011. Under the drug class commonly termed direct oral anticoagulants, rivaroxaban is approved for the most indications within its class, 7 indications, which are: (1) reduction of risk of stroke and systemic embolism (SE) in nonvalvular atrial fibrillation, (2) treatment of deep vein thrombosis (DVT), (3) treatment of pulmonary embolism (PE), (4) reduction in the risk of recurrence of DVT and/or PE, (5) prophylaxis of DVT following hip or knee replacement surgery, (6) prophylaxis of venous thromboembolism in acutely ill medical patients at risk for thromboembolic complications not at high risk of bleeding, and (7) reduction of risk of major cardiovascular events in patients with chronic coronary artery disease or peripheral artery disease. Considering the relationship between cardiovascular disease, renal impairment, and the use of oral anticoagulants, the following targeted review was created. This review reports the results of the primary pharmacology, pharmacokinetic modeling, clinical safety and efficacy, and real-world postmarketing effectiveness and safety of rivaroxaban in patients with various degrees of renal impairment. Based on these data, rivaroxaban is a viable option for when anticoagulation is needed in patients who have both cardiovascular disease and renal impairment. However, as with any therapy, the benefits and risks of intervention should be carefully assessed and balanced. Patients treated with rivaroxaban for several of its approved indications should have their kidney function assessed prior to and during continued therapy to ensure consistency with the drug label.

Topics: Anticoagulants; Area Under Curve; Humans; Myocardial Infarction; Patient Acuity; Product Surveillance, Postmarketing; Randomized Controlled Trials as Topic; Renal Insufficiency; Rivaroxaban; Stroke; Thrombosis

The objective was to assess the real-world cost-effectiveness of rivaroxaban, versus vitamin K antagonists (VKAs), for stroke prevention in patients with atrial fibrillation (AF) from a French national health insurance perspective.. A Markov model was developed with a lifetime horizon and cycle length of 3 months. All inputs were drawn from real-world evidence (RWE) studies: data on baseline patient characteristics at model entry were obtained from a French RWE study, clinical event rates as well as persistence rates for the VKA treatment arm were estimated from a variety of RWE studies, and a meta-analysis provided comparative effectiveness for rivaroxaban compared to VKA. Model outcomes included costs (drug costs, clinical event costs, and VKA monitoring costs), quality-adjusted life-years (QALY) and life-years (LY) gained, incremental cost per QALY, and incremental cost per LY. Sensitivity analyses were performed to test the robustness of the model and to better understand the results drivers.. In the base-case analysis, the incremental total cost was €714 and the total incremental QALYs and LYs were 0.12 and 0.16, respectively. The resulting incremental cost/QALY and incremental cost/LY were €6,006 and €4,586, respectively. The results were more sensitive to the inclusion of treatment-specific utility decrements and clinical event rates.. Although there is no official willingness-to-pay threshold in France, these results suggest that rivaroxaban is likely to be cost-effective compared to VKA in French patients with AF from a national insurance perspective.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Female; France; Humans; Male; Markov Chains; Middle Aged; Myocardial Infarction; Quality-Adjusted Life Years; Rivaroxaban; Stroke; Vitamin K; Warfarin

As the management of acute coronary syndrome (ACS) continues to evolve, many old practices proved to be of a little benefit and other approaches established the new pillars of modern medicine. Treating ACS patients with dual antiplatelet therapy (DAPT) for a year by combining aspirin and a P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel) has resulted in better outcomes and is currently the standard of therapy. However, owing to the persistent activation of the coagulation cascade, patients may continue to experience recurrent ischemia and high mortality rates despite compliance with the dual antiplatelet therapy. Research is underway to establish new treatment modalities for secondary prevention post-ACS, including the use of the novel direct oral anticoagulants (DOACs).. Multiple trials have been conducted to evaluate the use of DOACs for the secondary prevention after ACS. Recent emerging data showed that the addition of rivaroxaban in a very low dose of 2.5 mg twice daily to the regular DAPT regimen after ACS is beneficial in the reduction of major cardiovascular events, including recurrent myocardial infarction (MI) and strokes. On the other hand, other DOACs, including apixaban, did not show similar efficacy and did not improve the cardiovascular outcomes. Patients who experience an ACS continue to suffer long-term consequences and thromboembolic complications. Many studies have shown that after the initial ACS event, patients remain in a hypercoagulable state and are more prone to recurrent ischemic attacks including stroke, recurrent MI, or unstable angina (UA). With the objective of seeking better outcomes, it is imperative to explore more aggressive anticoagulation strategies in ACS patients. In this article, we discuss the progress that was made and the limitations we face regarding the role of different anticoagulants in this setting.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Rivaroxaban; Secondary Prevention; Stroke

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

Left ventricular (LV) thrombus is commonly seen in patients with extensive anterior ST-elevation myocardial infarction. The standard of care for LV thrombus is anticoagulation with warfarin. However, there has been an increasing trend of case reports using non-vitamin K antagonist oral anticoagulants (NOAC) for the treatment of LV thrombus. This study aimed to perform a meta-summary of the literature to characterise and evaluate the safety and feasibility of using NOAC in patients with LV thrombus. We searched for articles published in four electronic databases: PubMed, EMBASE, Scopus and Google Scholar using an appropriate keyword/MeSH term search strategy. Twenty-four studies comprising 36 patients were included in the analysis. Rivaroxaban was used in majority of patients (47.2%), whilst Apixaban and Dabigatran were prescribed in 25.0% and 27.8% of patients respectively. The most commonly associated risk factor found was post-acute myocardial infarction in 15 patients (41.7%). LV thrombus resolution was met by most patients (87.9%), and the median duration of treatment to resolution was 30.0 days (IQR = 22.5-47.0). One non-fatal bleeding event (3.0%) and no embolic events were reported. The use of NOAC may have a role in the treatment of LV thrombus in selected patients. Further randomized controlled trials are needed to evaluate this treatment strategy.

Topics: Administration, Oral; Anticoagulants; Dabigatran; Hemorrhage; Humans; Myocardial Infarction; Pyrazoles; Pyridones; Rivaroxaban; Thrombosis; Ventricular Dysfunction, Left

The optimal anti-thrombotic therapy for secondary prevention after an acute coronary syndrome is still a matter of debate. While current guidelines recommend dual anti-platelet therapy with aspirin and a P2Y12 inhibitor over 12 months especially in patients with stent implantation, the value of prolonged anticoagulation is still controversial. In the ATLAS-TIMI 52 trial, a low-dose direct factor Xa inhibition with rivaroxaban compared with placebo reduced the combined primary endpoint of cardiovascular mortality, myocardial infraction and stroke with an increase in major bleeding complications. This article discusses the value and problems of adding low-dose rivaroxaban to anti-platelet therapy as secondary prevention measure after an acute myocardial infarction. It will describe the pros and cons of intensified anti-platelet therapy versus dual pathway inhibition and give recommendations for different patient groups in clinical practice.

Topics: Acute Coronary Syndrome; Acute Disease; Anticoagulants; Aspirin; Clinical Trials as Topic; Drug Therapy, Combination; Factor Xa Inhibitors; Humans; Myocardial Infarction; Practice Guidelines as Topic; Purinergic P2Y Receptor Antagonists; Rivaroxaban

Topics: Anticoagulants; Aspirin; Clopidogrel; Drug Synergism; Drug Therapy, Combination; Factor Xa Inhibitors; Hemorrhage; Humans; Mortality; Multicenter Studies as Topic; Myocardial Infarction; Platelet Aggregation Inhibitors; Postoperative Complications; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Rivaroxaban; Stents; Stroke; Thrombophilia; Ticlopidine

Evidence from the real-world setting complements evidence coming from randomized controlled trials. We aimed to summarize all available evidence from high-quality real-world observational studies about efficacy and safety of nonvitamin-K oral anticoagulants compared with vitamin-K antagonists in patients with atrial fibrillation.. We searched PubMed and Web of Science until January 7, 2017 for observational nationwide or health insurance databases reporting matched or adjusted results comparing nonvitamin-K oral anticoagulants versus vitamin-K antagonists in patients with atrial fibrillation. Outcomes assessed included ischemic stroke, ischemic stroke or systemic embolism, any stroke or systemic embolism, myocardial infarction, intracranial hemorrhage, major hemorrhage, gastrointestinal hemorrhage, and death.. In 28 included studies of dabigatran, rivaroxaban, and apixaban compared with vitamin-K antagonists, all 3 nonvitamin-K oral anticoagulants were associated with a large reduction of intracranial hemorrhage (apixaban hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.31-0.63; dabigatran HR, 0.42; 95% CI, 0.37-0.49; rivaroxaban HR, 0.64; 95% CI, 0.47-0.86); similar rates of ischemic stroke and ischemic stroke or systemic embolism (apixaban HR, 1.05; 95% CI, 0.75-1.19 and HR, 1.08; 95% CI, 0.95-1.22 / dabigatran HR, 0.96; 95% CI, 0.80-1.16 and HR, 1.17; 95% CI, 0.92-1.50 / rivaroxaban HR, 0.89; 95% CI, 0.76-1.04 and HR, 0.73; 95% CI, 0.52-1.04, respectively); apixaban and dabigatran with lower mortality (HR, 0.65; 95% CI, 0.56-0.75 and HR, 0.63; 95% CI, 0.53-0.75, respectively); apixaban with fewer gastrointestinal (HR, 0.63; 95% CI, 0.42-0.95) and major hemorrhages (HR, 0.55; 95% CI, 0.48-0.63); dabigatran and rivaroxaban with more gastrointestinal hemorrhages (HR, 1.20; 95% CI, 1.06-1.36 and HR, 1.24; 95% CI, 1.08-1.41, respectively); dabigatran and rivaroxaban with similar rate of myocardial infarction (HR, 0.96; 95% CI, 0.77-1.21 and HR, 1.02; 95% CI, 0.54-1.89, respectively).. This meta-analysis confirms the main findings of the randomized controlled trials of dabigatran, rivaroxaban, and apixaban in the real-world setting and, hence, strengthens their validity.

Topics: Anticoagulants; Atrial Fibrillation; Brain Ischemia; Dabigatran; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Myocardial Infarction; Proportional Hazards Models; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Warfarin

Currently, little evidence is available on the length and type of anticoagulation used for extended treatment for prevention of recurrent venous thromboembolism (VTE) in patients with unprovoked VTE who have completed initial oral anticoagulation therapy.. To compare the efficacy and safety of available oral therapeutic options (aspirin, warfarin, direct oral anticoagulants (DOACs)) for extended thromboprophylaxis in adults with a first unprovoked VTE, to prevent VTE recurrence after completion of an acceptable initial oral anticoagulant treatment period, as defined in individual studies.. For this review, the Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (March 2017) as well as the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2). We also searched trials registries (March 2017) and reference lists of relevant articles.. We included randomised controlled trials in which patients with a first, symptomatic, objectively confirmed, unprovoked VTE, who had been initially treated with anticoagulants, were randomised to extended prophylaxis (vitamin K antagonists (VKAs), antiplatelet agents, or DOACs) versus no prophylaxis or placebo. We also included trials that compared one type of extended prophylaxis versus another type of extended prophylaxis.. Two review authors independently selected studies, assessed quality, and extracted data. We resolved disagreements by discussion.. Six studies with a combined total of 3436 participants met the inclusion criteria. Five studies compared extended prophylaxis versus placebo: three compared warfarin versus placebo, and two compared aspirin versus placebo. One study compared one type of extended prophylaxis (rivaroxaban) versus another type of extended prophylaxis (aspirin). For extended prophylaxis versus placebo, we downgraded the quality of the evidence for recurrent VTE and all-cause mortality to moderate owing to concerns arising from risks of selection and performance bias in individual studies. For all other outcomes in this review, we downgraded the quality of the evidence to low owing to concerns arising from risk of bias for the studies stated above, combined with concerns over imprecision. For extended prophylaxis versus other extended prophylaxis, we downgraded the quality of the evidence for recurrent VTE and major bleeding to moderate owing to concerns over imprecision. Risk of bias in the individual study was low.Meta-analysis showed that extended prophylaxis was no more effective than placebo in preventing VTE-related mortality (odds ratio (OR) 0.98, 95% confidence interval (CI) 0.14 to 6.98; 1862 participants; 4 studies; P = 0.98; low-quality evidence), recurrent VTE (OR 0.63, 95% CI 0.38 to 1.03; 2043 participants; 5 studies; P = 0.07; moderate-quality evidence), major bleeding (OR 1.84, 95% CI 0.87 to 3.85; 2043 participants; 5 studies; P = 0.86; low-quality evidence), all-cause mortality (OR 1.00, 95% CI 0.63 to 1.57; 2043 participants; 5 studies; P = 0.99; moderate-quality evidence), clinically relevant non-major bleeding (OR 1.78, 95% CI 0.59 to 5.33; 1672 participants; 4 studies; P = 0.30; low-quality evidence), stroke (OR 1.15, 95% CI 0.39 to 3.46; 1224 participants; 2 studies; P = 0.80; low-quality evidence), or myocardial infarction (OR 1.00, 95% CI 0.35 to 2.87; 1495 participants; 3 studies; P = 1.00; low-quality evidence).One study showed that the novel oral anticoagulant rivaroxaban was associated with fewer recurrent VTEs than aspirin (OR 0.28, 95% CI 0.15 to 0.54; 1389 participants; P = 0.0001; moderate-quality evidence). Data show no clear differences in the incidence of major bleeding between rivaroxaban and aspirin (OR 3.06, 95% CI 0.37 to 25.51; 1389 participants; P = 0.30; moderate-quality evidence) nor in the incidence of clinically relevant non-major bleeding (OR 0.84, 95% CI 0.37 to 1.94; 1389 participants; 1 study; P = 0.69; moderate-quality evidenc. Evidence is currently insufficient to permit definitive conclusions concerning the effectiveness and safety of extended thromboprophylaxis in prevention of recurrent VTE after initial oral anticoagulation therapy among participants with unprovoked VTE. Additional good-quality large-scale randomised controlled trials are required before firm conclusions can be reached.

Topics: Administration, Oral; Anticoagulants; Aspirin; Hemorrhage; Humans; Myocardial Infarction; Randomized Controlled Trials as Topic; Recurrence; Rivaroxaban; Secondary Prevention; Stroke; Venous Thromboembolism; Warfarin

Atrial fibrillation (AF) ranks the most prevailing type of cardiac rhythm disorder and AF patients are associated with a significantly increased risk of stroke compared to others. This study is designed to assess the relative efficacy of several clinical events prevention anticoagulants in patients with AF. Conventional pairwise meta-analysis was performed with fixed-effect model initially, then network meta-analysis was performed with random-effects model within results illustrated by cumulative odds ratios (ORs) and corresponding 95% credible interval (CrI). The rank probabilities of each treatment outcomes were summarized by the surface under the cumulative ranking curve (SUCRA). We conducted a systematic review and collected key clinical data from 37 studies with respect to 5 anticoagulant treatments for AF. Patients treated with rivaroxaban and apixaban are associated with a reduced risk of stroke compared to those treated with warfarin (OR 0.72, 95% CrI 0.53 to 0.88; OR 0.68, 95% CrI 0.48 to 0.91). Rivaroxaban (SUCRA = 0.712) appears to be the most preferable one with respect to vascular events, and both apixaban (SUCRA = 0.720) and rivaroxaban (SUCRA = 0.678) are preferable to others with respect to stroke. Dabigatran outperforms others with respect to the outcome of mortality (SUCRA = 0.695), hemorrhage events (SUCRA = 0.747), and myocardial infarction (SUCRA = 0.620). In conclusion, dabigatran has a noticeable and comprehensive advantage compared to others with respect to preventing several complications including hemorrhage events, myocardial infarction, and mortality. In addition, apixaban may be the best choice of preventing stroke, and rivaroxaban is more preferable to others with respect to preventing vascular events.

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Hemorrhage; Humans; Mortality; Myocardial Infarction; Network Meta-Analysis; Odds Ratio; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Warfarin

The incidence of post-operative arterial thrombosis (AT) (acute myocardial infarction [AMI] and ischaemic stroke) is increased in patients undergoing total hip replacement (THR) or total knee replacement (TKR). We compared the incidence of post-operative AT in non-vitamin K antagonist oral anticoagulants (NOACs)-treated and enoxaparin-treated patients, performing a systematic review of phase III randomised controlled trials (RCTs) of venous thromboembolism (VTE) prophylaxis in THR and TKR. Studies were identified by electronic search of MEDLINE and EMBASE database until July 2014. Differences between NOACs and enoxaparin groups in the efficacy and safety outcomes were expressed as odds ratios (ORs) with pertinent 95 % confidence intervals (95 % CI). Statistical heterogeneity was assessed with the I² statistic. Eleven phase III RCTs for a total of 31,319 patients were included. Patients underwent TKR in six studies and THR in five studies. The NOACs under study were dabigatran (four studies), apixaban (three studies) and rivaroxaban (four studies). AT occurred in 0.23 % of patients on NOACs and in 0.27 % of patients on enoxaparin: the OR at fixed-effect model was 0.86 (95 % CI 0.53-1.40; I² 11 %). No differences in AT incidence among the three NOACs were observed. The incidence of major and clinically relevant bleeding was similar in NOACs and enoxaparin groups (OR 1.03, 95 % CI 0.92-1.15; I² 38 %). In conclusion, in RCTs of pharmacological VTE prophylaxis in patients undergoing THR or TKR, there was no difference in the incidence of post-operative AT among patients treated with NOACs, compared to those treated with enoxaparin.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Brain Ischemia; Clinical Trials, Phase III as Topic; Dabigatran; Enoxaparin; Factor Xa Inhibitors; Female; Humans; Incidence; Male; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; Postoperative Complications; Postoperative Hemorrhage; Prothrombin; Pulmonary Embolism; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Treatment Outcome

This study was designed to compare efficacy and safety among novel oral anticoagulants (NOACs), which have not been directly compared in randomized control trials to date.. We performed network meta-analyses of randomized control trials in preventing thromboembolic events and major bleeding in patients with atrial fibrillation. PubMed, Embase, and the Cochrane Database of Systematic Reviews for published studies and various registries of clinical trials for unpublished studies were searched for 2002-2013. All phase III randomized controlled trials (RCTs) of NOACs (apixaban, edoxaban, dabigatran, rivaroxaban), idraparinux, and ximelagatran were reviewed.. A systematic literature search identified nine phase III RCTs for primary analyses. The efficacy of each NOAC was similar with respect to our primary composite endpoint following adjustment for open label designs [odds ratios (ORs) versus vitamin K antagonists: apixaban 0.79; dabigatran 150mg 0.77; edoxaban 60mg 0.87; rivaroxaban 0.86] except for dabigatran 110mg and edoxaban 30mg. Apixaban and edoxaban 30mg and 60mg had significantly fewer major bleeding events than dabigatran 150mg, ricvaroxaban, and vitamin K antagonists. All NOACs were similar in reducing secondary endpoints with the exception of dabigatran 110mg and 150mg which were associated with a significantly greater incidence of myocardial infarction compared to apixaban, edoxaban 60mg, and rivaroxaban.. Our indirect comparison with adjustment for study design suggests that the efficacy of the examined NOACs is similar across drugs, but that some differences in safety and risk of myocardial infarction exist, and that open label study designs appear to overestimate safety and treatment efficacy. Differences in study design should be taken into account in the interpretation of results from RCTs of NOACs.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Azetidines; Benzylamines; Dabigatran; Hemorrhage; Humans; Myocardial Infarction; Odds Ratio; Oligosaccharides; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Thiazoles; Thromboembolism; Treatment Outcome; Vitamin K

Secondary prevention of atherothrombotic events is the domain of antiplatelet therapy and according to present risk is used one drug strategy or combination of acetylsalicylic acid with ADP receptor blockers. The importance of the combination of dual antiplatelet therapy together with xabans or dabigatran was investigated in 6 clinical trials. Only one of them (ATLAS ACS 2-TIMI 51) indicated that treatment with small dose of rivaroxaban (2 × 2.5 mg) may be added to dual strategy of acetylsalicylic acid and clopidogrel. The risk of major bleeding event is increased and net clinical benefit is only about 0.5 % per year. Dual therapy with aspirin and prasugrel or tikagrelor is beneficial. In the second part of the review is discussed higher incidence of myocardial infarction in controlled group in the trial comparing treatment of dabigatran with warfarin. This relationship has not been resolved, however, in patients with higher risk of coronary events and indication of anticoagulant treatment with direct oral anticoagulants it is recommended to choose from xabans (apixaban and rivaroxaban).

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Aspirin; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Clopidogrel; Dabigatran; Hemorrhage; Humans; Morpholines; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Pyrazoles; Pyridones; Rivaroxaban; Secondary Prevention; Thiophenes; Ticlopidine; Warfarin

To evaluate the risk of myocardial infarction (MI) associated with the use of rivaroxaban.. We searched PubMed, CINAHL, Cochrane CENTRAL, Scopus, and the Web of Science for randomized controlled trials of rivaroxaban that reported on MI as clinical outcomes. We express the associations as odds ratios and their 95% confidence intervals. A trial sequential analysis was carried out to ensure validity of our findings.. Nine trials were selected (N=53 827), including one study on stroke prophylaxis in atrial fibrillation, two in acute coronary syndrome, four of short-term prophylaxis of deep venous thrombosis, and two for treatment of deep venous thrombosis/pulmonary embolism. Control arms included warfarin, enoxaparin, or placebo administration. Rivaroxaban was associated with a significantly lower risk of MI compared with the agents used in the control group (odds ratio, 0.82; 95% confidence interval, 0.72-0.94; P=0.004). No heterogeneity was noted in the risk (I=0%; P=0.55); trial sequential analysis reinforced the validity of our findings.. Rivaroxaban is associated with a significantly lower risk of MI in a broad spectrum of patients when tested against different controls.

Topics: Anticoagulants; Chi-Square Distribution; Humans; Morpholines; Myocardial Infarction; Odds Ratio; Patient Selection; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Rivaroxaban; Thiophenes; Time Factors

Arterial and venous thrombotic states, including myocardial infarction (MI), stroke and deep vein thrombosis with subsequent pulmonary embolism, are a significant cause of cardiovascular mortality and morbidity. Factor Xa (FXa) plays a pivotal role in thrombus formation. Its inhibition following acute coronary syndromes (ACS) blocks amplification of thrombin generation and subsequent clot formation, resulting in a risk reduction in recurrent MI, stroke and death. For this reason, a predictable form of oral anticoagulation continues to be an ongoing need. Rivaroxaban , the first oral FXa inhibitor, acts by direct inhibition of FXa and does not require an antithrombin cofactor for its activity.. This paper describes the pharmacokinetics (PK) of low-dose rivaroxaban tested in patients with ACS. Age, gender, renal function and body weight have no clinically significant effects on the PK of the drug in treatment of ACS. Caution should be maintained during co-administration of strong CYP3A4 inducers and inhibitors. Among patients with moderate and severe hepatic impairment and in those with associated coagulopathies, rivaroxaban however is contraindicated.. The mortality benefit with low-dose rivaroxaban in ACS patients was first demonstrated in ATLAS ACS2 TIMI-51 trial. With its rapid oral bioavailability, predictable PK, low drug-drug interaction and no need for monitoring, the use of low-dose rivaroxaban in addition to dual antiplatelet therapy offers an appealing new option in improving outcomes following ACS in the modern era of novel oral FXa inhibitors.

Topics: Acute Coronary Syndrome; Administration, Oral; Blood Coagulation Tests; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drug Evaluation, Preclinical; Drug Interactions; Factor Xa; Factor Xa Inhibitors; Half-Life; Humans; Morpholines; Myocardial Infarction; Pulmonary Embolism; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Thiophenes; Thrombin; Thrombosis

A network meta-analysis of the three new oral anticoagulants was performed from the three trials comparing dabigatran, rivaroxaban and apixaban with warfarin in patients with atrial fibrillation.. Data were extracted of the RE-LY study of dabigatran 110 mg bid and dabigatran 150 mg bid, the ROCKET AF trial of rivaroxaban and the ARISTOTLE trial of apixaban for the composite outcome of ischemic stroke and systemic embolism, for major bleeding, intracerebral bleeding, mortality and myocardial infarction.. Dabigatran (150 mg bid) showed superior efficacy in preventing ischemic stroke plus systemic embolism to dabigatran (110 mg bid, P=0.0364) and rivaroxaban (P=0.0388). Apixaban had equivalent efficacy with rivaroxaban and dabigatran (either dose). Apixaban was safer (less major bleeding) than dabigatran (150 mg bid, P=0.036) or rivaroxaban (P=0.0002). Intracerebral hemorrhage occurred with equal frequency for all agents except for rivaroxaban (higher risk than dabigatran 110 mg bid, P=0.0070). Myocardial infarction occurred less frequently with rivaroxaban and apixaban compared to either dose of dabigatran (all P<0.05).. All-cause mortality was not different for any agent or regimen. In the absence of head-to-head comparisons, this network meta-analysis suggests that apixaban and dabigatran 110 mg bid may offer the best benefit-risk balance for stroke prevention in non-valvular atrial fibrillation. Dabigatran 150 mg bid may be preferred for patients with a high risk for embolism.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Cerebral Hemorrhage; Chi-Square Distribution; Dabigatran; Embolism; Female; Humans; Male; Middle Aged; Morpholines; Myocardial Infarction; Odds Ratio; Pyrazoles; Pyridones; Risk Assessment; Risk Factors; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Angiotensin II Type 2 Receptor Blockers; Anticoagulants; Atrial Fibrillation; Cardiology; Coronary Disease; Drug-Eluting Stents; Heart Diseases; Humans; Morpholines; Myocardial Infarction; Rivaroxaban; Thiophenes; Thrombosis; Vitamin K

Topics: Angina, Unstable; Anticoagulants; Azetidines; Benzimidazoles; Benzylamines; Brain Ischemia; Clinical Trials as Topic; Coumarins; Dabigatran; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Forecasting; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Morpholines; Myocardial Infarction; Peptide Fragments; Polysaccharides; Prothrombin; Pyrazoles; Pyridines; Pyridones; Recombinant Proteins; Rivaroxaban; Thiophenes; Thrombin; Thrombophilia; Thrombosis; Warfarin

Patients with peripheral artery disease (PAD) requiring lower extremity revascularization (LER) have a high risk of adverse limb and cardiovascular events. The results from the VOYAGER PAD (efficacy and safety of rivaroxaban in reducing the risk of major thrombotic vascular events in subjects with symptomatic peripheral artery disease undergoing peripheral revascularization procedures of the lower extremities) trial have demonstrated that rivaroxaban significantly reduced this risk with an overall favorable net benefit for patients undergoing surgical revascularization. However, the efficacy and safety for those treated by surgical bypass, including stratification by bypass conduit (venous or prosthetic), has not yet been described.. In the VOYAGER PAD trial, patients who had undergone surgical and endovascular infrainguinal LER to treat PAD were randomized to rivaroxaban 2.5 mg twice daily or placebo on top of background antiplatelet therapy (aspirin 100 mg to be used in all and clopidogrel in some at the treating physician's discretion) and followed up for a median of 28 months. The primary end point was a composite of acute limb ischemia, major amputation of vascular etiology, myocardial infarction, ischemic stroke, and cardiovascular death. The principal safety outcome was major bleeding using the TIMI (thrombolysis in myocardial infarction) scale. The index procedure details, including conduit type (venous vs prosthetic), were collected at baseline.. Among 6564 randomized patients, 2185 (33%) had undergone surgical LER. Of these 2185 patients, surgical bypass had been performed for 1448 (66%), using a prosthetic conduit for 773 patients (53%) and venous conduit for 646 patients (45%). Adjusting for the baseline differences and anatomic factors, the risk of unplanned limb revascularization in the placebo arm was 2.5-fold higher for those receiving a prosthetic conduit vs a venous conduit (adjusted hazard ratio [HR], 2.53; 95% confidence interval [CI], 1.65-3.90; P < .001), and the risk of acute limb ischemia was three times greater (adjusted HR, 3.07; 95% CI, 1.84-5.11; P < .001). The use of rivaroxaban reduced the primary outcome for the patients treated with bypass surgery (HR, 0.78; 95% CI, 0.62-0.98), with consistent benefits for those receiving venous (HR, 0.66; 95% CI, 0.49-0.96) and prosthetic (HR, 0.87; 95% CI, 0.66-1.15) conduits (P. Surgical bypass with a prosthetic conduit was associated with significantly higher rates of major adverse limb events relative to venous conduits even after adjustment for patient and anatomic characteristics. Adding rivaroxaban 2.5 mg twice daily to aspirin or dual antiplatelet therapy significantly reduced this risk, with an increase in the bleeding risk, but had a favorable benefit risk for patients treated with bypass surgery, regardless of conduit type. Rivaroxaban should be considered after lower extremity bypass for symptomatic PAD to reduce ischemic complications of the heart, limb, and brain.

Topics: Aspirin; Hemorrhage; Humans; Ischemia; Lower Extremity; Myocardial Infarction; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Treatment Outcome

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y. The study is a prospective, single-center, randomized controlled trial. A total of 1020 patients with CHD and GID undergoing PCI will be enrolled. Patients are randomized (1:1) to receive either rivaroxaban 10 mg plus clopidogrel 75 mg daily or aspirin 100 mg plus clopidogrel 75 mg daily; both treatments will last 6 months. The primary endpoint is Bleeding Academic Research Consortium (BARC) type 2-5 bleeding requiring medical intervention. The secondary endpoint is a composite of major adverse cardiovascular and cerebrovascular events (MACCE), including all-cause death, cardiac death, nonfatal myocardial infarction, stent thrombosis, ischemia-driven target vessel revascularization, and stroke.. The objective of this study is to evaluate the efficacy and safety of rivaroxaban plus clopidogrel versus aspirin plus clopidogrel in patients with CHD and GID undergoing PCI. We aim to explore an optimized antithrombotic strategy, which achieves the same anti-ischemic effect as standard DAPT without increasing the risk of GIB, for patients with CHD and GID undergoing PCI.. This protocol is registered at the Chinese Clinical Trial Registry under the number ChiCTR2100044319. And this publication is based on version 1.4 of the trial protocol dated Sep 6, 2021.

Topics: Aspirin; Clopidogrel; Coronary Artery Disease; Drug Therapy, Combination; Gastrointestinal Diseases; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Randomized Controlled Trials as Topic; Rivaroxaban; Treatment Outcome

COMMANDER-HF was a randomised trial comparing rivaroxaban 2.5 mg two times a day to placebo, in addition to antiplatelet therapy, in patients hospitalised for worsening heart failure with coronary artery disease and sinus rhythm. Patients with diabetes are at increased risk of cardiovascular events and therefore have more to gain.. In this post-hoc analysis, we evaluated the efficacy and safety of rivaroxaban in patients with (n=2052) and without diabetes (n=2970). The primary outcome was the composite of cardiovascular death, myocardial infarction (MI) or ischaemic stroke. HRs and 95% CIs with interaction analyses were used to describe event-rates and treatment effects. Patients with diabetes had a higher prevalence of cardiovascular comorbidities (eg, hypertension, obesity) and increased incidence of cardiovascular events. Adjusted HRs for events in people with versus without diabetes were 1.34 (95% CI 1.19 to 1.50) for the primary outcome, 1.21 (95% CI 0.84 to 1.75) for stroke, 1.51 (95% CI 1.14 to 1.99) for MI, 1.17 (95% CI 1.05 to 1.31) for heart failure hospitalisation and 1.06 (95% CI 0.56 to 2.01) for major bleeding. Rivaroxaban had no significant effect on event-rates in patients with and without diabetes (all interaction p values >0.05). Low-dose rivaroxaban was associated with an overall reduction in ischaemic stroke (HR 0.66; 95% CI 0.47 to 0.95), with no apparent subgroup interaction according to diabetes status (p-int=0.93).. In COMMANDER-HF a diagnosis of diabetes conferred higher rates of cardiovascular events that, with exception of ischaemic stroke, was not substantially reduced by rivaroxaban. Rivaroxaban was associated with reduced risk of ischaemic stroke for patients with and without diabetes.. NCT01877915; Post-results.

Topics: Brain Ischemia; Cohort Studies; Coronary Artery Disease; Diabetes Mellitus; Factor Xa Inhibitors; Heart Failure; Humans; Ischemic Stroke; Myocardial Infarction; Retrospective Studies; Rivaroxaban; Stroke

Anterior acute myocardial infarction (AMI) is associated with an increased risk of left ventricular (LV) thrombus formation. We hypothesized that adding low-dose oral rivaroxaban to the usual antiplatelet regimen would reduce the risk of LV thrombus in patients with large AMI.. APERITIF is an investigator-initiated, multicenter randomized open-label, blinded end-point (PROBE) trial, nested in the ongoing "FRENCHIE" registry, a French multicenter prospective observational study, in which all consecutive patients admitted within 48 hours of symptom onset in a cardiac Intensive Care Unit (ICU) for AMI are included (NCT04050956). Among them, patients with anterior ST-elevation-myocardial infarction (STEMI) or very high-risk non- ST-elevation-myocardial infarction (NSTEMI) patients with involvement of the left anterior descending artery are randomized into 2 groups: Dual Antiplatelet Therapy (DAPT) alone or DAPT plus rivaroxaban 2.5mg twice daily for 4 weeks, started as soon as possible after completion of the initial percutaneous coronary intervention/angiography procedure. The primary endpoint is the presence of LV thrombus at 1 month, as detected by contrast enhanced CMR (CE-CMR). Secondary endpoints include LV thrombus dimension (greatest diameter), the rate of major bleedings and major cardiovascular events at 1 month. Based on estimated event rates, a sample size of 560 patients is needed to show superiority of DAPT plus rivaroxaban therapy versus DAPT alone, with 80% power.. The APERITIF trial will determine whether, in patients with large AMIs, the use of rivaroxaban 2.5mg twice daily in addition to DAPT reduces LV thrombus formation, compared with DAPT alone.. gov Identifier: NCT05077683.

Topics: Anterior Wall Myocardial Infarction; Anticoagulants; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Rivaroxaban; ST Elevation Myocardial Infarction; Thrombosis; Treatment Outcome

To describe outcomes of patients with chronic coronary artery disease (CAD) and/or peripheral artery disease (PAD) enrolled in the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) randomized trial who were treated with the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily during long-term open-label extension (LTOLE).. Of the 27 395 patients enrolled in COMPASS, 12 964 (mean age at baseline 67.2 years) from 455 sites in 32 countries were enrolled in LTOLE and treated with the combination of rivaroxaban and aspirin for a median of 374 additional days (range 1-1191 days). During LTOLE, the incident events per 100 patient years were as follows: for the primary outcome [cardiovascular death, stroke, or myocardial infarction (MI)] 2.35 [95% confidence interval (CI) 2.11-2.61], mortality 1.87 (1.65-2.10), stroke 0.62 (0.50-0.76), and MI 1.02 (0.86-1.19), with CIs that overlapped those seen during the randomized treatment phase with the combination of rivaroxaban and aspirin. The incidence rates for major and minor bleeding were 1.01 (0.86-1.19) and 2.49 (2.24-2.75), compared with 1.67 (1.48-1.87) and 5.11 (95% CI 4.77-5.47), respectively, during the randomized treatment phase with the combination.. In patients with chronic CAD and/or PAD, extended combination treatment for a median of 1 year and a maximum of 3 years was associated with incidence rates for efficacy and bleeding that were similar to or lower than those seen during the randomized treatment phase, without any new safety signals.

Topics: Aspirin; Drug Therapy, Combination; Humans; Infant; Myocardial Infarction; Peripheral Arterial Disease; Rivaroxaban; Stroke

The Clopidogrel and Acetylsalicylic Acid in Bypass Surgery for Peripheral Arterial Disease (CASPAR) trial is the only large, double-blind, placebo-controlled trial of dual antiplatelet therapy (DAPT) versus aspirin in patients with peripheral artery disease (PAD) after lower extremity revascularization (LER). The trial was neutral for index-graft occlusion/revascularization, amputation or death (hazard ratio [HR] 0.98, 95% confidence interval [CI] 0.78-1.23, p = .87) with an excess of global utilization of streptokinase and tissue plasminogen activator for occluded coronary arteries moderate or severe bleeding (HR 2.84, 95% CI 1.32-6.08, p = .007).. VOYAGER-PAD demonstrated that rivaroxaban significantly reduces acute limb ischemia (ALI), major amputation, myocardial infarction (MI), stroke and CV death but increased bleeding. The relative efficacy and safety of rivaroxaban in a CASPAR like population and for similar outcomes is unknown. The current analysis is a post-hoc exploratory analysis of a "CASPAR like" composite of ALI, unplanned index limb revascularization (UILR), amputation or CV death in surgical patients.. In the 2185 who underwent surgical LER, rivaroxaban reduced the CASPAR endpoint at 1 (HR 0.76, 95% CI 0.62-0.95, p = .0133) and 3 years (HR 0.84, 95% CI 0.71-1.00, p = .0461, Figure). There were similar reductions in composites of ALI, amputation or CV death (HR 0.79, p = .0228) and ALI, UILR, amputation, MI, IS or CV death (HR 0.85, p = .0410).. The combination of rivaroxaban and aspirin significantly reduces ischemic outcomes in patients with PAD after LER. Although no formal head-to-head comparison exists, in a similar population and for similar outcomes, this regimen demonstrated benefit where trials of DAPT were neutral. These data suggest that factor Xa inhibition may provide specific benefits in this population and that DAPT should not be considered a proven substitution.

Topics: Aspirin; Drug Therapy, Combination; Hemorrhage; Humans; Ischemia; Lower Extremity; Myocardial Infarction; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Tissue Plasminogen Activator; Treatment Outcome

In the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial, there was a significant reduction in the adjudicated primary outcome among patients with stable atherosclerotic vascular disease randomized to dual pathway inhibition (rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily) vs aspirin monotherapy, but not with rivaroxaban 5 mg twice daily vs aspirin monotherapy. Whether the results are similar without adjudication is unknown.. To examine the impact of dual pathway inhibition (with rivaroxaban plus aspirin) or rivaroxaban monotherapy compared with aspirin monotherapy on investigator-reported CV events and to understand the extent of concordance between investigator-reported and centrally adjudicated clinical events.. This is a secondary analysis of the COMPASS trial, an international, double-blind, double-dummy, randomized clinical trial with a 3-by-2 partial factorial design that evaluated participants with stable atherosclerotic vascular disease receiving rivaroxaban plus aspirin, rivaroxaban monotherapy, or aspirin monotherapy. End points were collected by blinded site investigators and adjudicated by a blinded clinical end point committee. Data were analyzed from March 2013 through February 2017.. Participants received dual inhibition pathway (2.5 mg rivaroxaban twice daily plus 100 mg aspirin once daily), rivaroxaban monotherapy (5 mg twice daily), or aspirin monotherapy (100 mg once daily).. The primary efficacy outcome was a composite of cardiovascular (CV) death, stroke, or myocardial infarction (MI). Adjudicated and investigator-reported end points were compared.. A total of 27 395 patients (mean [SD] age, 68.2 [7.9] years; 78.0% men) were assessed, including 9152 patients randomized to dual pathway inhibition, 9117 patients randomized to rivaroxaban monotherapy, and 9126 patients randomized to aspirin monotherapy. Adjudication reduced the number of events by 10% to 15% for most end points. Among investigator-reported end points, dual pathway inhibition significantly reduced the rate of the primary efficacy outcome compared with aspirin alone (411 patients [4.5%] vs 542 patients [5.9%]; hazard ratio [HR], 0.75 [95% CI, 0.66-0.85]; P < .001), with similar reduction in adjudicated end points, (379 patients [4.1%] vs 496 patients [5.4%]; HR, 0.76 [95% CI, 0.66-0.86]; P < .001). Likewise, effects on ischemic end points were highly concordant (κ statistic = 0.94 [95% CI, 0.93-0.95] for the primary composite end point). Unlike with adjudicated outcomes, there was a significant reduction in the primary end point with rivaroxaban monotherapy vs aspirin monotherapy using investigator-reported events (477 patients [5.2%] vs 542 patients [5.9%]; HR, 0.88 [95% CI, 0.78-0.99]; P = .04) compared with adjudicated events (448 patients [4.9%] vs 496 patients [5.4%]; HR, 0.90 [95% CI, 0.79-1.03]; P = .12).. This secondary analysis of the COMPASS trial found that whether assessed by blinded site investigators or adjudicators, dual pathway inhibition significantly reduced CV events among patients with stable atherosclerotic disease compared with aspirin plus placebo. These findings suggest that using investigator-reported events in blinded clinical trials may be a more efficient alternative to adjudication.. ClinicalTrials.gov Identifier: NCT01776424.

Topics: Aged; Aspirin; Atherosclerosis; Drug Therapy, Combination; Female; Humans; Male; Myocardial Infarction; Rivaroxaban; Stroke

The COMPASS trial demonstrated that the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily compared with aspirin 100 mg once daily reduced major adverse cardiovascular events (MACE) in patients with chronic coronary artery disease or peripheral artery disease by 24% during a mean follow-up of 23 months. We explored whether this effect varies by sex.. The effects were examined in women and men using log-rank tests and Kaplan-Meier curve. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were obtained from stratified Cox proportional hazards models to explore subgroup effects including subgroup of women and men according to baseline modified REACH risk score. Of 27 395 patients randomized, 18 278 were allocated to receive rivaroxaban plus aspirin (n = 9152) or aspirin alone (n = 9126), and of these, 22.1% were women. Women compared with men had similar incidence rates for MACE and major bleeding but borderline lower rates for myocardial infarction (1.7% vs. 2.2%, P = 0.05). The effect of combination therapy compared with aspirin in women and men was consistent for MACE (women: 3.8% vs. 5.2%, HR 0.72, 95% CI 0.54-0.97; men: 4.2% vs. 5.5%, HR 0.76, 95% CI 0.66-0.89; P interaction 0.75) and major bleeding (women: 3.1% vs. 1.4%, HR 2.22, 95% CI 1.42-3.46; men: 3.2% vs. 2.0%, HR 1.60, 95% CI 1.29-1.97; P interaction 0.19). There was no significant interaction between randomized treatment and baseline modified REACH score above or below the median for MACE or major bleeding.. In patients with stable coronary artery disease or peripheral artery disease, the combination of rivaroxaban (2.5 mg twice daily) and aspirin compared with aspirin alone appears to produce consistent benefits in women and men, independent of baseline cardiovascular risk.

Topics: Aged; Aged, 80 and over; Aspirin; Comorbidity; Coronary Artery Disease; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Health Status Disparities; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Risk Assessment; Risk Factors; Rivaroxaban; Sex Factors; Stroke; Time Factors; Treatment Outcome

Patients with symptomatic lower extremity peripheral artery disease (LE-PAD) experience an increased risk of major vascular events. There is limited information on what clinical features of symptomatic LE-PAD prognosticate major vascular events and whether patients at high risk have a greater absolute benefit from low-dose rivaroxaban and aspirin.. To quantify the risk of major vascular events and investigate the response to treatment with low-dose rivaroxaban and aspirin among patients with symptomatic LE-PAD based on clinical presentation and comorbidities.. This is a subanalysis of a previously reported subgroup of patients with symptomatic LE-PAD who were enrolled in a large, double-blind, placebo-controlled randomized clinical trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies [COMPASS]) in 602 centers in 33 countries from March 2013 to January 2020. Data analysis was completed from May 2016 to June 2020.. A combination of low-dose rivaroxaban and aspirin compared with aspirin alone.. Thirty-month incidence risk of myocardial infarction, stroke and cardiovascular death (MACE), major adverse limb events (MALE) including major vascular amputation, and bleeding.. The COMPASS trial enrolled 4129 patients with symptomatic LE-PAD (mean [SD] age, 66.8 [8.8] years; 2932 men [71.0%]). The 30-month Kaplan-Meier incidence risk of MACE or MALE, including major amputation, was 22.6% in those with prior amputation (this outcome was observed in 54 patients), 17.6% (n = 15) in those with Fontaine III or IV symptoms, and 11.8% (n = 142) in those with previous peripheral artery revascularization, classifying these features as high-risk limb presentations. The 30-month incidence risk of MACE or MALE, including major amputation, was 14.1% (n = 118) in those with kidney dysfunction, 13.5% (n = 67) in those with heart failure, 13.4% (n = 199) in those with diabetes, and 12.8% (n = 222) in those with polyvascular disease, classifying these features as high-risk comorbidities. Among patients with either high-risk limb presentations or high-risk comorbidities, treatment with rivaroxaban and aspirin compared with aspirin alone was associated with an estimated 4.2% (95% CI, 1.9%-6.2%) absolute risk reduction for MACE or MALE, including major amputation, at 30 months. Although the estimated absolute risk increase of major bleeding was higher with rivaroxaban and aspirin in combination than aspirin alone (2.0% [95% CI, 0.5%-3.9%]) for patients with either high-risk limb presentation or high-risk comorbidity, the estimated absolute risk increase of fatal or critical organ bleeding was low in this high-risk group (0.4% [95% CI, 0.2%-1.8%]), such that the net clinical benefit was estimated to be 3.2% (95% CI, 0.6%-5.3%).. Patients with LE-PAD with high-risk limb presentations or high-risk comorbidities had a high incidence of major vascular events. For these patients, treatment with rivaroxaban and aspirin in combination compared with aspirin alone led to a large absolute reduction in vascular risk.

Topics: Aged; Amputation, Surgical; Aspirin; Cardiovascular Diseases; Comorbidity; Diabetes Mellitus; Double-Blind Method; Factor Xa Inhibitors; Female; Heart Failure; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Prognosis; Renal Insufficiency; Rivaroxaban; Severity of Illness Index; Stroke

COVID-19 is associated with both venous and arterial thrombotic complications. While prophylactic anticoagulation is now widely recommended for hospitalized patients with COVID-19, the effectiveness and safety of thromboprophylaxis in outpatients with COVID-19 has not been established.. PREVENT-HD is a double-blind, placebo-controlled, pragmatic, event-driven phase 3 trial to evaluate the efficacy and safety of rivaroxaban in symptomatic outpatients with laboratory-confirmed COVID-19 at risk for thrombotic events, hospitalization, and death. Several challenges posed by the pandemic have necessitated innovative approaches to clinical trial design, start-up, and conduct. Participants are randomized in a 1:1 ratio, stratified by time from COVID-19 confirmation, to either rivaroxaban 10 mg once daily or placebo for 35 days. The primary efficacy end point is a composite of symptomatic venous thromboembolism, myocardial infarction, ischemic stroke, acute limb ischemia, non-central nervous system systemic embolization, all-cause hospitalization, and all-cause mortality. The primary safety end point is fatal and critical site bleeding according to the International Society on Thrombosis and Haemostasis definition. Enrollment began in August 2020 and is expected to enroll approximately 4,000 participants to yield the required number of end point events.. PREVENT-HD is a pragmatic trial evaluating the efficacy and safety of the direct oral anticoagulant rivaroxaban in the outpatient setting to reduce major venous and arterial thrombotic events, hospitalization, and mortality associated with COVID-19.

Topics: Adult; Cause of Death; COVID-19; Double-Blind Method; Extremities; Factor Xa Inhibitors; Female; Hemorrhage; Hospital Mortality; Hospitalization; Humans; Ischemia; Ischemic Stroke; Male; Middle Aged; Myocardial Infarction; Outpatients; Placebos; Rivaroxaban; Thrombosis; Venous Thromboembolism

In patients with chronic coronary or peripheral artery disease enrolled in the Cardiovascular Outcomes for People Using Anticoagulation Strategies trial, randomised antithrombotic treatments were stopped after a median follow-up of 23 months because of benefits of the combination of rivaroxaban 2.5 mg two times per day and aspirin 100 mg once daily compared with aspirin 100 mg once daily. We assessed the effect of switching to non-study aspirin at the time of early stopping.. Incident composite of myocardial infarction, stroke or cardiovascular death was estimated per 100 person-years (py) during randomised treatment (n=18 278) and after study treatment discontinuation to non-study aspirin (n=14 068).. During randomised treatment, the combination compared with aspirin reduced the composite (2.2 vs 2.9/100 py, HR: 0.76, 95% CI 0.66 to 0.86), stroke (0.5 vs 0.8/100 py, HR: 0.58, 95% CI 0.44 to 0.76) and cardiovascular death (0.9 vs 1.2/100 py, HR: 0.78, 95% CI 0.64 to 0.96). During 1.02 years after early stopping, participants originally randomised to the combination compared with those randomised to aspirin had similar rates of the composite (2.1 vs 2.0/100 py, HR: 1.08, 95% CI 0.84 to 1.39) and cardiovascular death (1.0 vs 0.8/100 py, HR: 1.26, 95% CI 0.85 to 1.86) but higher stroke rate (0.7 vs 0.4/100 py, HR: 1.74, 95% CI 1.05 to 2.87) including a significant increase in ischaemic stroke during the first 6 months after switching to non-study aspirin.. Discontinuing study rivaroxaban and aspirin to non-study aspirin was associated with the loss of cardiovascular benefits and a stroke excess.. NCT01776424.

Topics: Aged; Aspirin; Coronary Disease; Drug Monitoring; Drug Substitution; Drug Therapy, Combination; Duration of Therapy; Female; Fibrinolytic Agents; Humans; Ischemic Stroke; Male; Mortality; Myocardial Infarction; Outcome and Process Assessment, Health Care; Peripheral Arterial Disease; Rivaroxaban; Withholding Treatment

Stroke is often a devastating event among patients with heart failure with reduced ejection (HFrEF). In COMMANDER HF, rivaroxaban 2.5 mg b.i.d. did not reduce the composite of first occurrence of death, stroke, or myocardial infarction compared with placebo in patients with HFrEF, coronary artery disease (CAD), and sinus rhythm. We now examine the incidence, timing, type, severity, and predictors of stroke or a transient ischaemic attack (TIA), and seek to establish the net clinical benefit of treatment with low-dose rivaroxaban.. In this double-blind, randomized trial, 5022 patients who had HFrEF(≤40%), elevated natriuretic peptides, CAD, and who were in sinus rhythm were treated with rivaroxaban 2.5 mg b.i.d. or placebo in addition to antiplatelet therapy, after an episode of worsening HF. The primary neurological outcome for this post hoc analysis was time to first event of any stroke or TIA. Over a median follow-up of 20.5 (25th-75th percentiles 20.0-20.9) months, 150 all-cause stroke (127) or TIA (23) events occurred (ischaemic stroke in 82% and haemorrhagic stroke in 11% of stroke events). Overall, 47.5% of first-time strokes were either disabling (16.5%) or fatal (31%). Prior stroke, low body mass index, geographic region, and the CHA2DS2-VASc score were predictors of stroke/TIA. Rivaroxaban significantly reduced the primary neurological endpoint of all-cause stroke or TIA compared with placebo by 32% (1.29 events vs. 1.90 events per 100 patient-years), adjusted for the time from index HF event to randomization and stratified by geographic region (adjusted hazard ratio 0.68, 95% confidence interval 0.49-0.94), with a number needed to treat of 164 patients per year to prevent one stroke/TIA event. The principal safety endpoint of fatal bleeding or bleeding into a critical space, occurred at a similar rate on rivaroxaban and placebo (0.44 events vs. 0.55 events per 100 patient-years).. Patients with HFrEF and CAD are at risk for stroke or TIA in the period following an episode of worsening heart failure in the absence of atrial fibrillation. Most strokes are of ischaemic origin and nearly half are either disabling or fatal. Rivaroxaban at a dose of 2.5 mg b.i.d. reduced rates of stroke or TIA compared with placebo in this population.. COMMANDER HF (A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants with Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure); ClinicalTrials.gov NCT01877915.

Topics: Aged; Brain Ischemia; Case-Control Studies; Coronary Artery Disease; Double-Blind Method; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Heart Failure; Hemorrhage; Humans; Incidence; Ischemic Attack, Transient; Male; Middle Aged; Myocardial Infarction; Placebos; Platelet Aggregation Inhibitors; Rivaroxaban; Stroke; Stroke Volume

Adding rivaroxaban to aspirin in patients with stable atherosclerotic disease reduces the recurrence of cardiovascular disease (CVD) but increases the risk of major bleeding. The aim of this study was to estimate the individual lifetime treatment benefit and harm of adding low-dose rivaroxaban to aspirin in patients with stable cardiovascular disease.. Patients with established CVD from the COMPASS trial (n = 27 390) and SMART prospective cohort study (n = 8139) were used. Using the pre-existing lifetime SMART-REACH model for recurrent CVD, and a newly developed Fine and Gray competing risk-adjusted lifetime model for major bleeding, individual treatment effects from adding low-dose rivaroxaban to aspirin in patients with stable CVD were estimated, expressed in terms of (i) life-years free of stroke or myocardial infarction (MI) gained; and (ii) life-years free from major bleeding lost. Calibration of the SMART-REACH model for prediction of recurrent CVD events in the COMPASS study was good. The major bleeding risk model as derived in the COMPASS trial showed good external calibration in the SMART cohort. Predicted individual gain in life expectancy free of stroke or MI from added low-dose rivaroxaban had a median of 16 months (range 1-48 months), while predicted individualized lifetime lost in terms of major bleeding had a median of 2 months (range 0-20 months).. There is a wide distribution in lifetime gain and harm from adding low-dose rivaroxaban to aspirin in individual patients with stable CVD. Using these lifetime models, benefits and bleeding risk can be weighed for each individual patient, which could facilitate treatment decisions in clinical practice.

Topics: Aged; Aspirin; Cardiovascular Diseases; Double-Blind Method; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Risk Assessment; Rivaroxaban; Stroke

Patients treated with antithrombotic drugs are at risk of bleeding. Bleeding may be the first manifestation of underlying cancer.. We examined new cancers diagnosed in relation to gastrointestinal or genitourinary bleeding among patients enrolled in the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies) and determined the hazard of new cancer diagnosis after bleeding at these sites.. Of 27 395 patients enrolled (mean age, 68 years; women, 21%), 2678 (9.8%) experienced any (major or minor) bleeding, 713 (2.6%) experienced major bleeding, and 1084 (4.0%) were diagnosed with cancer during a mean follow-up of 23 months. Among 2678 who experienced bleeding, 257 (9.9%) were subsequently diagnosed with cancer. Gastrointestinal bleeding was associated with a 20-fold higher hazard of new gastrointestinal cancer diagnosis (7.4% versus 0.5%; hazard ratio [HR], 20.6 [95% CI, 15.2-27.8]) and 1.7-fold higher hazard of new nongastrointestinal cancer diagnosis (3.8% versus 3.1%; HR, 1.70 [95% CI, 1.20-2.40]). Genitourinary bleeding was associated with a 32-fold higher hazard of new genitourinary cancer diagnosis (15.8% versus 0.8%; HR, 32.5 [95% CI, 24.7-42.9]), and urinary bleeding was associated with a 98-fold higher hazard of new urinary cancer diagnosis (14.2% versus 0.2%; HR, 98.5; 95% CI, 68.0-142.7). Nongastrointestinal, nongenitourinary bleeding was associated with a 3-fold higher hazard of nongastrointestinal, nongenitourinary cancers (4.4% versus 1.9%; HR, 3.02 [95% CI, 2.32-3.91]).. In patients with atherosclerosis treated with antithrombotic drugs, any gastrointestinal or genitourinary bleeding was associated with higher rates of new cancer diagnosis. Any gastrointestinal or genitourinary bleeding should prompt investigation for cancers at these sites.. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01776424.

Topics: Aged; Aspirin; Atherosclerosis; Coronary Artery Disease; Drug Therapy, Combination; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Neoplasms; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Stroke

The COMPASS trial assessed the impact of adding low dose rivaroxaban to aspirin in selected patients (pts). After an acute myocardial infarction (MI), when dual antiplatelet treatment is no longer needed, patients might be eligible for aspirin/rivaroxaban co-therapy. The characteristics and risks of such a population are unclear.. Data were extracted from the FAST-MI 2005, 2010 and 2015 nationwide French registries. Characteristics and long-term mortality were compared according to COMPASS eligibility and between registry and trial populations.. Among 9954 patients alive and free of events at one year, 4402 (44%) were classified as COMPASS-Like (i.e. meeting COMPASS inclusion and without exclusion criteria), 1720 (17%) COMPASS-Excluded (i.e. meeting any exclusion criterion) and 3832 (39%) Non-COMPASS (i.e. meeting neither COMPASS inclusion nor exclusion criteria). COMPASS-Like patients were at higher risk and had higher 5-year mortality compared with Non-COMPASS patients. COMPASS-Excluded patients had the highest mortality. COMPASS enrichment criteria defined a population at increased risk of death: eligible pts. had 40% higher 5-year adjusted mortality (Hazard Ratio = 1.40 [1.15; 1.70]), while excluded pts. had 57% higher risk (Hazard Ratio = 1.57 [1.25; 1.97]). Patients meeting the COMPASS criteria one year after MI differed from those included in the randomized trial.. Based on the population included in the French FAST-MI registries, enrichment criteria used in COMPASS defined a population representing 44% of the overall population of MI patients surviving to one year, and these patients are at high risk of 5-year mortality. They were at higher risk compared to chronic stable vascular patients enrolled in the trial. Registered with Clinicaltrials.gov under the number: NCT00673036.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Cohort Studies; Female; Follow-Up Studies; France; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Population Surveillance; Registries; Rivaroxaban

Although acetylsalicylic acid is of proven benefit for secondary prevention in patients with cardiovascular disease, the risk of recurrent ischemic events remains high. Intensification of antithrombotic therapy with more potent antiplatelet drugs, dual antiplatelet therapy, or vitamin K antagonists further reduces the risk of major adverse cardiovascular events compared with acetylsalicylic acid alone but increases the risk of bleeding without reducing mortality. In patients with prior coronary artery disease or peripheral arterial disease the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial revealed that compared with acetylsalicylic acid alone, dual pathway inhibition with low-dose rivaroxaban (2.5 mg twice-daily), an oral factor Xa inhibitor, plus acetylsalicylic acid reduced major adverse cardiovascular event by 24%, major adverse limb events by 47%, and mortality by 18%. Major bleeding was increased by 70%, but there was no increase in fatal or intracranial bleeding. This article (1) reviews the results of the COMPASS trial, (2) explains why dual pathway inhibition is superior to antiplatelet or anticoagulant therapy alone, (3) compares the results with rivaroxaban plus aspirin with those with other antithrombotic regimens, and (4) provides insight into how best to apply the COMPASS results into practice.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cardiovascular Diseases; Chronic Disease; Coronary Artery Disease; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Recurrence; Research Design; Rivaroxaban; Secondary Prevention; Stroke

Whether anticoagulation benefits patients with heart failure (HF) in sinus rhythm is uncertain. The COMMANDER HF randomized clinical trial evaluated the effects of adding low-dose rivaroxaban to antiplatelet therapy in patients with recent worsening of chronic HF with reduced ejection fraction, coronary artery disease (CAD), and sinus rhythm. Although the primary end point of all-cause mortality, myocardial infarction, or stroke did not differ between rivaroxaban and placebo, there were numerical advantages favoring rivaroxaban for myocardial infarction and stroke.. To examine whether low-dose rivaroxaban was associated with reduced thromboembolic events in patients enrolled in the COMMANDER HF trial.. Post hoc analysis of the COMMANDER HF multicenter, randomized, double-blind, placebo-controlled trial in patients with CAD and worsening HF. The trial randomized 5022 patients postdischarge from a hospital or outpatient clinic after treatment for worsening HF between September 2013 and October 2017. Patients were required to be receiving standard care for HF and CAD and were excluded for a medical condition requiring anticoagulation or a bleeding history. Patients were randomized in a 1:1 ratio. Analysis was conducted from June 2018 and January 2019.. Patients were randomly assigned to receive 2.5 mg of rivaroxaban given orally twice daily or placebo in addition to their standard therapy.. For this post hoc analysis, a thromboembolic composite was defined as either (1) myocardial infarction, ischemic stroke, sudden/unwitnessed death, symptomatic pulmonary embolism, or symptomatic deep venous thrombosis or (2) all of the previous components except sudden/unwitnessed deaths because not all of these are caused by thromboembolic events.. Of 5022 patients, 3872 (77.1%) were men, and the overall mean (SD) age was 66.4 (10.2) years. Over a median (interquartile range) follow-up of 19.6 (11.7-30.8) months, fewer patients assigned to rivaroxaban compared with placebo had a thromboembolic event including sudden/unwitnessed deaths: 328 (13.1%) vs 390 (15.5%) (hazard ratio, 0.83; 95% CI, 0.72-0.96; P = .01). When sudden/unwitnessed deaths were excluded, the results analyzing thromboembolic events were similar: 153 (6.1%) vs 190 patients (7.6%) with an event (hazard ratio, 0.80; 95% CI, 0.64-0.98; P = .04).. In this study, thromboembolic events occurred frequently in patients with HF, CAD, and sinus rhythm. Rivaroxaban may reduce the risk of thromboembolic events in this population, but these events are not the major cause of morbidity and mortality in patients with recent worsening of HF for which rivaroxaban had no effect. While consistent with other studies, these results require confirmation in prospective randomized clinical trials.. ClinicalTrials.gov identifier: NCT01877915.

Topics: Aged; Aspirin; Chronic Disease; Coronary Artery Disease; Death, Sudden; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Heart Failure; Humans; Male; Middle Aged; Mortality; Myocardial Infarction; Platelet Aggregation Inhibitors; Proportional Hazards Models; Pulmonary Embolism; Rivaroxaban; Stroke; Stroke Volume; Thienopyridines; Thromboembolism; Venous Thrombosis

Chronic kidney disease is associated with an increased risk of both bleeding and ischemic cardiovascular events.. The purpose of this study was to determine the balance of risks and benefits from the dual pathway antithrombotic regimen (rivaroxaban 2.5 mg twice daily [bd] plus aspirin, compared with aspirin) in vascular patients with or without moderate renal dysfunction.. This was a secondary analysis of the COMPASS (Cardiovascular OutcoMes for People using Anticoagulation StrategieS) trial involving 27,395 patients with chronic coronary or peripheral artery disease.. In COMPASS, 21,111 patients had an estimated glomerular filtration rate (GFR) at baseline of ≥60 ml/min, 6,276 had a GRF of <60 ml/min. Both the primary efficacy outcome (cardiovascular death, myocardial infarction, or stroke) and major bleeding were more frequent in those with renal dysfunction, and the frequency of these outcome events was inversely related to GFR. However, the primary outcome was consistently reduced with rivaroxaban 2.5 mg bd plus aspirin, irrespective of GFR category (GFR ≥60 ml/min, 3.5% rivaroxaban plus aspirin, 4.5% aspirin alone, hazard ratio [HR]: 0.76, 95% confidence interval [CI]: 0.64 to 0.90; GFR <60 ml/min, 6.4% rivaroxaban plus aspirin, 8.4% aspirin alone, HR: 0.75; 95% CI: 0.60 to 0.94). Major bleeding was more frequent with rivaroxaban 2.5 mg plus aspirin versus aspirin alone in those with GFR ≥60 ml/min (2.9% rivaroxaban plus aspirin, 1.6% aspirin alone, HR: 1.81; 95% CI: 1.44 to 2.28) and similarly in those with GFR <60 ml/min (3.9% rivaroxaban plus aspirin, 2.7% aspirin alone, HR: 1.47, 95% CI: 1.05 to 2.07).. The benefits of the dual pathway COMPASS regimen (rivaroxaban 2.5 mg bd plus aspirin), versus aspirin alone, are preserved in patients with moderate renal dysfunction without evidence of an excess hazard of bleeding.

Topics: Aged; Aspirin; Coronary Artery Disease; Correlation of Data; Double-Blind Method; Drug Therapy, Combination; Female; Fibrinolytic Agents; Glomerular Filtration Rate; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Outcome and Process Assessment, Health Care; Peripheral Arterial Disease; Renal Insufficiency, Chronic; Risk Adjustment; Rivaroxaban

Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease.. In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.. Between March 12, 2013, and May 10, 2016, 27 395 patients were enrolled to the COMPASS trial, of whom 24 824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, p<0·0001). By comparison, treatment with rivaroxaban alone did not significantly improve the primary outcome when compared with treatment with aspirin alone (411 [5%] of 8250 vs 460 [6%] of 8261; HR 0·89, 95% CI 0·78-1·02, p=0·094). Combined rivaroxaban plus aspirin treatment resulted in more major bleeds than treatment with aspirin alone (263 [3%] of 8313 vs 158 [2%] of 8261; HR 1·66, 95% CI 1·37-2·03, p<0·0001), and similarly, more bleeds were seen in the rivaroxaban alone group than in the aspirin alone group (236 [3%] of 8250 vs 158 [2%] of 8261; HR 1·51, 95% CI 1·23-1·84, p<0·0001). The most common site of major bleeding was gastrointestinal, occurring in 130 [2%] patients who received combined rivaroxaban plus aspirin, in 84 [1%] patients who received rivaroxaban alone, and in 61 [1%] patients who received aspirin alone. Rivaroxaban plus aspirin reduced mortality when compared with aspirin alone (262 [3%] of 8313 vs 339 [4%] of 8261; HR 0·77, 95% CI 0·65-0·90, p=0·0012).. In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide.. Bayer AG.

Topics: Aged; Aspirin; Cardiovascular Diseases; Coronary Artery Disease; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Morbidity; Myocardial Infarction; Platelet Aggregation Inhibitors; Rivaroxaban; Stroke

Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications.. This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.. Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043).. Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding.. Bayer AG.

Topics: Aged; Amputation, Surgical; Aspirin; Cardiovascular Diseases; Carotid Artery Diseases; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Incidence; Lower Extremity; Male; Middle Aged; Morbidity; Myocardial Infarction; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Stroke

This study sought to assess whether there were significant interactions of procedural access strategies and lesion characteristics with bleeding and ischemic events among atrial fibrillation (AF) patients anticoagulated with rivaroxaban or warfarin following a percutaneous coronary intervention.. Among stented AF patients, the impact of procedural access strategies or lesion characteristics on antithrombotic safety and efficacy outcomes is unclear.. In the PIONEER AF-PCI (An Open-label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention) trial, 2,124 patients were randomized to 3 groups and followed for 12 months: 1) rivaroxaban 15 mg once daily plus a P2Y. Compared with warfarin, both rivaroxaban regimens consistently reduced clinically significant bleeding across subgroups of radial versus femoral arterial access and by vascular closure device use. Treatment effect of rivaroxaban on major adverse cardiovascular events did not vary when stratified by ischemia-driven revascularization, urgency of revascularization, location of culprit artery, presence of bifurcation lesion, presence of thrombus, type, and length of stent or number of stents (interaction p > 0.05 for all subgroups).. Among stented AF patients requiring long-term oral anticoagulation, there was no effect modification by procedure or lesion characteristics of either clinically significant bleeding or major adverse cardiovascular events. Rivaroxaban-based therapy was superior to warfarin plus DAPT in bleeding outcomes regardless of the type of stent or arterial access during the index coronary revascularization. (A Study Exploring Two Strategies of Rivaroxaban [JNJ39039039; BAY-59-7939] and One of Oral Vitamin K Antagonist in Patients With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention [PIONEER AF-PCI]; NCT01830543).

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Drug Administration Schedule; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Factors; Rivaroxaban; Stents; Stroke; Time Factors; Treatment Outcome; Warfarin

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

Heart failure is associated with activation of thrombin-related pathways, which predicts a poor prognosis. We hypothesized that treatment with rivaroxaban, a factor Xa inhibitor, could reduce thrombin generation and improve outcomes for patients with worsening chronic heart failure and underlying coronary artery disease.. In this double-blind, randomized trial, 5022 patients who had chronic heart failure, a left ventricular ejection fraction of 40% or less, coronary artery disease, and elevated plasma concentrations of natriuretic peptides and who did not have atrial fibrillation were randomly assigned to receive rivaroxaban at a dose of 2.5 mg twice daily or placebo in addition to standard care after treatment for an episode of worsening heart failure. The primary efficacy outcome was the composite of death from any cause, myocardial infarction, or stroke. The principal safety outcome was fatal bleeding or bleeding into a critical space with a potential for causing permanent disability.. Over a median follow-up period of 21.1 months, the primary end point occurred in 626 (25.0%) of 2507 patients assigned to rivaroxaban and in 658 (26.2%) of 2515 patients assigned to placebo (hazard ratio, 0.94; 95% confidence interval [CI], 0.84 to 1.05; P=0.27). No significant difference in all-cause mortality was noted between the rivaroxaban group and the placebo group (21.8% and 22.1%, respectively; hazard ratio, 0.98; 95% CI, 0.87 to 1.10). The principal safety outcome occurred in 18 patients who took rivaroxaban and in 23 who took placebo (hazard ratio, 0.80; 95% CI, 0.43 to 1.49; P=0.48).. Rivaroxaban at a dose of 2.5 mg twice daily was not associated with a significantly lower rate of death, myocardial infarction, or stroke than placebo among patients with worsening chronic heart failure, reduced left ventricular ejection fraction, coronary artery disease, and no atrial fibrillation. (Funded by Janssen Research and Development; COMMANDER HF ClinicalTrials.gov number, NCT01877915 .).

Topics: Aged; Coronary Artery Disease; Double-Blind Method; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Follow-Up Studies; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Patient Readmission; Platelet Aggregation Inhibitors; Rivaroxaban; Stroke; Stroke Volume; Treatment Failure

D-dimer has been used as both a diagnostic and prognostic biomarker in the assessment of patients with venous thromboembolism, but its prognostic value in the setting of arterial acute coronary syndromes (ACS) and the ability of pharmacotherapy to reduce D-dimer in ACS is less well characterized. It was hypothesized that elevated baseline D-dimer would be associated with poor clinical outcomes in ACS, and that Factor Xa inhibition with Rivaroxaban would reduce D-dimer acutely and chronically. The ATLAS ACS TIMI-46 trial assessed the safety and efficacy of rivaroxaban compared with placebo in ACS patients. A subset of subjects had a D-dimer measured at baseline (n = 1,834, 52.5%). A univariate and multivariable logistic regression assessed the relation between baseline D-dimer and a composite end point of cardiovascular death, myocardial infarction, or stroke through 6 months. The Wilcoxon rank sum test was used to compare change in D-dimer level between the treatment groups from baseline. Baseline D-dimer was associated with the composite efficacy outcome in a univariate logistic regression (odds ratio 1.15, 95% confidence interval 1.03 to 1.29, p = 0.015) and a multivariable logistic regression (odds ratio 1.13, 95% confidence interval 1.00 to 1.28, p = 0.048). Rivaroxaban administration lowered D-dimer levels compared wth placebo after administration of the first dose of study drug (p = 0.026), at day 30 (p < 0.001) and day 180 (p < 0.001). In conclusion, elevated baseline D-dimer was associated with an increased risk of the composite outcome within 6 months of the ACS event and administration of the Factor Xa inhibitor rivaroxaban was associated with lower D-dimer levels compared with placebo after the first dose, at day 30 and day 180.

Topics: Acute Coronary Syndrome; Biomarkers; Factor Xa Inhibitors; Female; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Myocardial Infarction; Risk; Rivaroxaban; Stroke

Dual antiplatelet therapy (DAPT), aspirin plus a P2Y12 inhibitor, is the standard antithrombotic treatment following acute coronary syndromes. The factor Xa inhibitor rivaroxaban reduced mortality and ischaemic events when added to DAPT, but caused increased bleeding. The safety of a dual pathway antithrombotic therapy approach combining low-dose rivaroxaban (in place of aspirin) with a P2Y12 inhibitor has not been assesssed in acute coronary syndromes. We aimed to assess rivaroxaban 2·5 mg twice daily versus aspirin 100 mg daily, in addition to clopidogrel or ticagrelor (chosen at investigator discretion before randomisation), for patients with acute coronary syndromes started within 10 days after presentation and continued for 6-12 months.. In this double-blind, multicentre, randomised trial (GEMINI-ACS-1) done at 371 clinical centres in 21 countries, eligible patients were older than 18 years with unstable angina, non-ST segment elevation myocardial infarction (NSTEMI) or ST segment elevation myocardial infarction (STEMI), with positive cardiac biomarkers and either ischaemic electrocardiographic changes or an atherosclerotic culprit lesion identified during angiography. Participants were randomly assigned (1:1) within 10 days after admission for the index acute coronary syndromes event to either aspirin or rivaroxaban based on a computer-generated randomisation schedule. Randomisation was balanced by using randomly permuted blocks with size of four and was stratified based on the background P2Y12 inhibitor (clopidogrel or ticagrelor) intended to be used at the time of randomisation. Investigators and patients were masked to treatment assignment. Patients received a minimum of 180 days of double-blind treatment with rivaroxaban 2·5 mg twice daily or aspirin 100 mg daily. The choice of clopidogrel or ticagrelor during trial conduct was not randomised and was based on investigator preference. The primary endpoint was thrombolysis in myocardial infarction (TIMI) clinically significant bleeding not related to coronary artery bypass grafting (CABG; major, minor, or requiring medical attention) up to day 390. Primary analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02293395.. Between April 22, 2015, and Oct 14, 2016, 3037 patients with acute coronary syndromes were randomly assigned; 1518 to receive aspirin and 1519 to receive rivaroxaban. 1704 patients (56%) were in the ticagrelor and 1333 (44%) in the clopidogrel strata. Median duration of treatment was 291 days (IQR 239-354). TIMI non-CABG clinically significant bleeding was similar with rivaroxaban versus aspirin therapy (total 154 patients [5%]; 80 participants [5%] of 1519 vs 74 participants [5%] of 1518; HR 1·09 [95% CI 0·80-1·50]; p=0·5840).. A dual pathway antithrombotic therapy approach combining low-dose rivaroxaban with a P2Y12 inhibitor for the treatment of patients with acute coronary syndromes had similar risk of clinically significant bleeding as aspirin and a P2Y12 inhibitor. A larger, adequately powered trial would be required to definitively assess the efficacy and safety of this approach.. Janssen Research & Development and Bayer AG.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Aspirin; Clopidogrel; Coronary Angiography; Double-Blind Method; Drug Therapy, Combination; Electrocardiography; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Rivaroxaban; Thrombolytic Therapy; Ticagrelor; Ticlopidine; Treatment Outcome

Optimal antithrombotic treatment after transcatheter aortic valve replacement (TAVR) is unknown and determined empirically. The direct factor Xa inhibitor rivaroxaban may potentially reduce TAVR-related thrombotic complications and premature valve failure.. GALILEO is an international, randomized, open-label, event-driven, phase III trial in more than 1,520 patients without an indication for oral anticoagulation who underwent a successful TAVR (ClinicalTrials.govNCT02556203). Patients are randomized (1:1 ratio), 1 to 7days after a successful TAVR, to either a rivaroxaban-based strategy or an antiplatelet-based strategy. In the experimental arm, subjects receive rivaroxaban (10mg once daily [OD]) plus acetylsalicylic acid (ASA, 75-100mg OD) for 90days followed by rivaroxaban alone. In the control arm, subjects receive clopidogrel (75mg OD) plus ASA (as above) for 90days followed by ASA alone. In case new-onset atrial fibrillation occurs after randomization, full oral anticoagulation will be implemented with maintenance of the original treatment assignment. The primary efficacy end point is the composite of all-cause death, stroke, myocardial infarction, symptomatic valve thrombosis, pulmonary embolism, deep venous thrombosis, and systemic embolism. The primary safety end point is the composite of life-threatening, disabling, and major bleeding, according to the Valve Academic Research Consortium definitions.. GALILEO will test the hypothesis that a rivaroxaban-based antithrombotic strategy reduces the risk of thromboembolic complications post-TAVR with an acceptable risk of bleeding compared with the currently recommended antiplatelet therapy-based strategy in subjects without need of chronic oral anticoagulation.

Topics: Aortic Valve Stenosis; Aspirin; Cardiovascular Diseases; Cause of Death; Clopidogrel; Drug Therapy, Combination; Embolism; Factor Xa Inhibitors; Heart Valve Diseases; Humans; Mortality; Myocardial Infarction; Platelet Aggregation Inhibitors; Postoperative Care; Pulmonary Embolism; Rivaroxaban; Stroke; Thrombosis; Ticlopidine; Transcatheter Aortic Valve Replacement; Venous Thrombosis

Rivaroxaban reduces cardiovascular death, myocardial infarction (MI), or stroke in patients following acute coronary syndrome (ACS). We aimed to characterize the specific effects of rivaroxaban on the size and type of MI.. The Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 51 (ATLAS ACS 2-TIMI 51) study randomized 15,526 patients with a recent ACS to rivaroxaban 2.5 mg BID, rivaroxaban 5 mg BID, or placebo. An independent clinical events committee adjudicated each MI that occurred during the study and further classified them based on type. Data are presented as two-year Kaplan-Meier event rates and hazard ratios (HRs) and 95% confidence intervals (CI).. In total, 665 patients experienced a post-randomization MI. The majority (n=535, 80.5%) were spontaneous (Type 1) events. Rivaroxaban reduced spontaneous MI when compared with placebo (4.4% vs 5.7%, HR 0.80, 95% 0.67-0.95, p=0.01), and there were directionally consistent reductions with both the 2.5 mg BID (4.7% vs 5.7%, HR 0.84, 95% 0.68-1.02, p=0.08) and 5 mg BID doses (4.1% vs 5.7%, HR 0.77, 95% 0.62-0.94, p=0.01) as compared with placebo. Rivaroxaban reduced MI with large elevations in troponin or creatine kinase-MB (CK-MB) fraction (1.8% vs 2.4%, HR 0.73, 95% CI 0.56-0.96, p=0.03) and STEMI events (1.7% vs 2.5%, HR 0.74, 95% CI 0.56-0.99, p=0.04).. In patients stabilized and followed after ACS, the majority of MIs that occur are spontaneous and rivaroxaban significantly reduced the incidence of these events. Notably, rivaroxaban reduced MIs with extensive biomarker release and ST-segment elevation.

Topics: Acute Coronary Syndrome; Biomarkers; Creatine Kinase, MB Form; Drug Administration Schedule; Factor Xa Inhibitors; Humans; Middle Aged; Myocardial Infarction; Rivaroxaban; Secondary Prevention; Thrombolytic Therapy; Treatment Outcome; Troponin

Thrombin is a critical element of crosstalk between pathways contributing to worsening of established heart failure (HF). The aim of this study is to explore the efficacy and safety of rivaroxaban 2.5 mg bid compared with placebo (with standard care) after an exacerbation of HF in patients with reduced ejection fraction (HF-rEF) and documented coronary artery disease.. This is an international prospective, multicentre, randomized, double-blind, placebo-controlled, event-driven study of approximately 5000 patients for a targeted 984 events. Patients must have a recent symptomatic exacerbation of HF, increased plasma concentrations of natriuretic peptides (B-type natriuretic peptide ≥200 pg/mL or N-terminal pro-B-type natriuretic peptide ≥800 pg/mL), with left ventricular ejection fraction ≤40% and coronary artery disease. Patients requiring anticoagulation for atrial fibrillation or other conditions will be excluded. After an index event (overnight hospitalization, emergency department or observation unit admission, or unscheduled outpatient parenteral treatment for worsening HF), patients will be randomized 1:1 to rivaroxaban or placebo (with standard of care). The primary efficacy outcome event is a composite of all-cause mortality, myocardial infarction or stroke. The principal safety outcome events are the composite of fatal bleeding or bleeding into a critical space with potential permanent disability, bleeding events requiring hospitalization and major bleeding events according to International Society on Thrombosis and Haemostasis bleeding criteria.. COMMANDER HF is the first prospective study of a target-specific oral antithrombotic agent in HF. It will provide important information regarding rivaroxaban use following an HF event in an HF-rEF patient population with coronary artery disease.

Topics: Administration, Oral; Coronary Artery Disease; Double-Blind Method; Factor Xa Inhibitors; Heart Failure; Humans; Myocardial Infarction; Prospective Studies; Research Design; Risk Factors; Rivaroxaban; Stroke; Survival Rate

Atherogenesis is a complex inflammatory process stemming from the accumulation and oxidation of low density lipoproteins (LDL). IgM autoantibodies against phosphorylcholine (anti-PC) bind to the PC epitope on oxidized LDL (OxLDL), inhibiting the uptake of oxLDL by macrophages in atherosclerotic lesions. Anti-PC autoantibodies have been reported to be protective against atherothrombosis. We investigated the relationship of anti-PC concentrations with cardiovascular outcomes in patients with acute coronary syndromes (ACS). We measured anti-PC levels within 7 days of an ACS in 3,356 patients enrolled in the ATLAS ACS-TIMI 46 trial, a randomized dose ranging study of rivaroxaban versus placebo. The primary endpoint was death, myocardial infarction (MI), stroke, or severe recurrent ischemia (SRI) requiring revascularization during 6 months. The median baseline anti-PC concentration was 40.9 U/mL (25th, 75th percentiles: 25.4, 67.4). There was no significant association between anti-PC levels and the primary endpoint (Q1: 6.8 %, Q2: 4.2 %, Q3: 7.8 %, Q4: 5.4 %, p-trend = 0.87), all-cause mortality (Q1: 1.4 %, Q2: 0.7 %, Q3: 2.4 %, Q4: 0.9 %, p-trend = 0. 96), or any of the other individual endpoint components (MI: p-trend = 0.87, Stroke: p-trend = 0.43, SRI: p-trend = 0.66). Using the previously reported anti-PC cutpoint of 17 U/mL did not reveal a significant relationship between anti-PC concentrations and cardiovascular outcomes (<17 U/mL: 8.1 % vs. ≥17 U/mL: 5.8 %; p = 0.11). Similarly, evaluation of anti-PC as a continuous variable did not reveal a significant association (p = 0.30). In this study of patients early after ACS undergoing intensive secondary preventive therapy, IgM anti-PC titers did not exhibit a significant relationship with cardiovascular outcomes.

Topics: Acute Coronary Syndrome; Aged; Antibodies, Antiphospholipid; Factor Xa Inhibitors; Female; Humans; Immunoglobulin M; Male; Middle Aged; Morpholines; Myocardial Infarction; Phosphorylcholine; Rivaroxaban; Stroke; Thiophenes

We investigated the prevalence of prior myocardial infarction (MI) and incidence of ischaemic cardiovascular (CV) events among atrial fibrillation (AF) patients.. In ROCKET AF, 14 264 patients with nonvalvular AF were randomized to rivaroxaban or warfarin. The key efficacy outcome for these analyses was CV death, MI, and unstable angina (UA). This pre-specified analysis was performed on patients while on treatment. Rates are per 100 patient-years. Overall, 2468 (17%) patients had prior MI at enrollment. Compared with patients without prior MI, these patients were more likely to be male (75 vs. 57%), on aspirin at baseline (47 vs. 34%), have prior congestive heart failure (78 vs. 59%), diabetes (47 vs. 39%), hypertension (94 vs. 90%), higher mean CHADS2 score (3.64 vs. 3.43), and fewer prior strokes or transient ischaemic attacks (46 vs. 54%). CV death, MI, or UA rates tended to be lower in patients assigned rivaroxaban compared with warfarin [2.70 vs. 3.15; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.73-1.00; P = 0.0509]. CV death, MI, or UA rates were higher in those with prior MI compared with no prior MI (6.68 vs. 2.19; HR 3.04, 95% CI 2.59-3.56) with consistent results for CV death, MI, or UA for rivaroxaban compared with warfarin in prior MI compared with no prior MI (P interaction = 0.10).. Prior MI was common and associated with substantial risk for subsequent cardiac events. Patients with prior MI assigned rivaroxaban compared with warfarin had a non-significant 14% reduction of ischaemic cardiac events.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Double-Blind Method; Embolism; Female; Humans; Kaplan-Meier Estimate; Male; Morpholines; Myocardial Infarction; Platelet Aggregation Inhibitors; Pyridines; Rivaroxaban; Stroke; Thiophenes; Ticlopidine; Treatment Outcome; Warfarin

The present analysis reports on the pre-specified subgroup of ST-elevation myocardial infarction (STEMI) patients, in whom anticoagulant therapy has been of particular interest.. In ATLAS ACS-2-TIMI-51 (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction-51), rivaroxaban reduced cardiovascular events across the spectrum of acute coronary syndrome (ACS).. Seven thousand eight hundred seventeen patients in ATLAS ACS-2-TIMI 51 presented with a STEMI. After being stabilized (1 to 7 days), they underwent randomization to twice daily rivaroxaban 2.5 mg, rivaroxaban 5 mg, or placebo. Data are presented as 2-year Kaplan-Meier rates, and for intention-to-treat (ITT) and modified ITT (mITT) analyses.. Among STEMI patients, rivaroxaban reduced the primary efficacy endpoint of cardiovascular death, myocardial infarction, or stroke, compared with placebo (ITT: 8.4% vs. 10.6%, hazards ratio [HR]: 0.81, 95% confidence interval [CI]: 0.67 to 0.97, p = 0.019; mITT: 8.3% vs. 9.7%, HR: 0.85, 95% CI: 0.70 to 1.03, p = 0.09). This reduction emerged by 30 days (ITT and mITT: 1.7% vs. 2.3%, p = 0.042) and was evident in analyses that included events while patients received background dual antiplatelet therapies (ITT: 7.9% vs. 11.9%, p = 0.010; mITT: 7.7% vs. 10.1%, p = 0.061). In terms of the individual doses, rivaroxaban 2.5 mg reduced cardiovascular death (ITT: 2.5% vs. 4.2%, p = 0.006; mITT: 2.2% vs. 3.9%, p = 0.006), which was not seen with 5 mg of rivaroxaban. Rivaroxaban versus placebo increased non-coronary artery bypass grafting Thrombolysis In Myocardial Infarction major bleeding (2.2% vs. 0.6%, p < 0.001) and intracranial hemorrhage (0.6% vs. 0.1%, p = 0.015) without a significant increase in fatal bleeding (0.2% vs. 0.1%, p = 0.51).. In patients with a recent STEMI, rivaroxaban reduced cardiovascular events. This benefit emerged early and persisted during continued treatment with background antiplatelet therapies. Rivaroxaban compared with placebo increased the rate of major bleeding, but there was no significant increase in fatal bleeding. (An Efficacy and Safety Study for Rivaroxaban in Patients With Acute Coronary Syndrome; NCT00809965).

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Male; Middle Aged; Morpholines; Myocardial Infarction; Prospective Studies; Rivaroxaban; Thiophenes; Thrombolytic Therapy; Treatment Outcome

Rivaroxaban is a factor Xa inhibitor that was recently reviewed by the Food and Drug Administration as a potential therapy to reduce the risk of recurrent atherothrombotic events in patients with acute coronary syndromes. Approval of this drug would represent a paradigm shift away from dual antiplatelet therapy toward long-term triple antithrombotic therapy. However, to date, no other experimental anticoagulant agent has demonstrated a favorable risk-benefit profile in this population, in part because of the expected increased risk in major bleeding by combining aspirin, a P2Y12 receptor inhibitor, and an anticoagulant. Approvability of rivaroxaban was considered largely on the basis of the ATLAS ACS 2-TIMI 51 (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects With Acute Coronary Syndrome ACS 2-Thrombolysis In Myocardial Infarction 51) trial, which demonstrated a significant reduction in a composite of cardiovascular death, myocardial infarction, and stroke. Although the primary efficacy endpoint was met, a substantial amount of missing data was observed. We discuss the impact of missing data in this trial, its implications for informative censoring of safety events (major bleeding), and implications for future cardiovascular outcomes trials.

Topics: Acute Coronary Syndrome; Anticoagulants; Coronary Thrombosis; Double-Blind Method; Factor Xa; Factor Xa Inhibitors; Humans; Morpholines; Myocardial Infarction; Randomized Controlled Trials as Topic; Reproducibility of Results; Rivaroxaban; Thiophenes; Treatment Outcome; United States; United States Food and Drug Administration

Although therapy with aspirin or aspirin plus a thienopyridine reduces the incidence of long-term adverse cardiovascular events among patients with acute coronary syndrome (ACS), there remains a significant residual risk of cardiovascular death, recurrent myocardial infarction (MI), and stroke. In a phase 2 trial (ClinicalTrials.gov NCT00402597) in which the addition of the factor Xa inhibitor rivaroxaban was compared with placebo, among ACS patients receiving either aspirin alone or dual-antiplatelet therapy with aspirin and a thienopyridine, the end point of death, MI, or stroke compared with placebo was reduced (87/2331 [3.9%] vs 62/1160 [5.5%]; hazard ratio 0.69, [95% CI 0.50-0.96], P = .027). Two candidate doses of rivaroxaban were selected for further evaluation in a pivotal phase 3.. The second ATLAS-ACS 2 TIMI 51 Trial is an international, randomized, double-blind, event-driven (n = 983) phase 3 trial involving more than 15,570 patients hospitalized with ACS (ClinicalTrials.gov NCT00809965). All patients are treated with a background of standard therapy including low-dose aspirin, and patients are stratified by the administration of a thienopyridine (clopidogrel or ticlopidine; stratum 2) or not (stratum 1). Within each stratum, patients are randomly assigned in a 1:1:1 ratio to receive rivaroxaban 2.5 mg twice daily, or rivaroxaban 5 mg twice daily, or placebo twice daily. The primary efficacy end point is the composite of cardiovascular death, MI, or stroke. The primary safety end point is thrombolysis in MI major bleeding not associated with coronary artery bypass graft surgery.. The ATLAS-ACS 2 TIMI 51 is testing the hypothesis that anticoagulation with the oral factor Xa inhibitor rivaroxaban reduces cardiovascular death, MI, and stroke among patients with ACS treated with guideline-based therapies for ACS.

Topics: Acute Coronary Syndrome; Adolescent; Adult; Anticoagulants; Coronary Angiography; Double-Blind Method; Electrocardiography; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Male; Middle Aged; Morpholines; Myocardial Infarction; Prospective Studies; Rivaroxaban; Thiophenes; Thrombolytic Therapy; Treatment Outcome; Young Adult

Rivaroxaban is an oral direct factor Xa inhibitor that has been effective in prevention of venous thromboembolism in patients undergoing elective orthopaedic surgery. However, its use after acute coronary syndromes has not been investigated. In this setting, we assessed the safety and efficacy of rivaroxaban and aimed to select the most favourable dose and dosing regimen.. In this double-blind, dose-escalation, phase II study, undertaken at 297 sites in 27 countries, 3491 patients stabilised after an acute coronary syndrome were stratified on the basis of investigator decision to use aspirin only (stratum 1, n=761) or aspirin plus a thienopyridine (stratum 2, n=2730). Participants were randomised within each strata and dose tier with a block randomisation method at 1:1:1 to receive either placebo or rivaroxaban (at doses 5-20 mg) given once daily or the same total daily dose given twice daily. The primary safety endpoint was clinically significant bleeding (TIMI major, TIMI minor, or requiring medical attention); the primary efficacy endpoint was death, myocardial infarction, stroke, or severe recurrent ischaemia requiring revascularisation during 6 months. Safety analyses included all participants who received at least one dose of study drug; efficacy analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00402597.. Three patients in stratum 1 and 26 in stratum 2 never received the study drug. The risk of clinically significant bleeding with rivaroxaban versus placebo increased in a dose-dependent manner (hazard ratios [HRs] 2.21 [95% CI 1.25-3.91] for 5 mg, 3.35 [2.31-4.87] for 10 mg, 3.60 [2.32-5.58] for 15 mg, and 5.06 [3.45-7.42] for 20 mg doses; p<0.0001). Rates of the primary efficacy endpoint were 5.6% (126/2331) for rivaroxaban versus 7.0% (79/1160) for placebo (HR 0.79 [0.60-1.05], p=0.10). Rivaroxaban reduced the main secondary efficacy endpoint of death, myocardial infarction, or stroke compared with placebo (87/2331 [3.9%] vs 62/1160 [5.5%]; HR 0.69, [95% CI 0.50-0.96], p=0.0270). The most common adverse event in both groups was chest pain (248/2309 [10.7%] vs 118/1153 [10.2%]).. The use of an oral factor Xa inhibitor in patients stabilised after an acute coronary syndrome increases bleeding in a dose-dependent manner and might reduce major ischaemic outcomes. On the basis of these observations, a phase III study of low-dose rivaroxaban as adjunctive therapy in these patients is underway.. Johnson & Johnson Pharmaceutical Research & Development and Bayer Healthcare AG.

Topics: Acute Coronary Syndrome; Administration, Oral; Aspirin; Chest Pain; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Morpholines; Myocardial Infarction; Proportional Hazards Models; Pyridines; Recurrence; Risk Reduction Behavior; Rivaroxaban; Safety; Statistics, Nonparametric; Stroke; Thiophenes; Treatment Outcome

Topics: Antibodies, Monoclonal, Humanized; Humans; Myocardial Infarction; Rivaroxaban; Treatment Outcome

In the pivotal randomized controlled trials (RCTs) for patients with atrial fibrillation, direct oral anticoagulants (DOACs) had similar or even superior efficacy and safety compared with warfarin. However, RCTs comparing different DOACs are nonexistent and previous observational studies have yielded conflicting results. In this nationwide cohort study, rates of any stroke or systemic embolism (stroke/SE) and major bleeding were compared among new users of apixaban, dabigatran, and rivaroxaban with atrial fibrillation from 2014 to 2019. Inverse probability weighting was used to yield balanced study groups, and outcomes were compared using Cox regression. Stroke/SE rates were similar in patients receiving apixaban, dabigatran, and rivaroxaban. Dabigatran was associated with twofold higher rates of myocardial infarction (MI) than rivaroxaban (1.4 events/100 person-years (py) vs 0.7 events/100-py, hazard ratio [HR] 2.21, 95% confidence interval [CI], 1.00-4.90) and apixaban (1.4 events/100-py vs 0.7 events/100-py, HR 2.26, 95% CI, 0.90-5.67), although the second comparison included the possibility of a null effect. Rivaroxaban was associated with higher major bleeding rates compared with apixaban (2.9 events/100-py vs 1.8 events/100-py, HR 1.64, 95% CI, 1.13-2.37) and dabigatran (2.9 events/100-py vs 1.4 events/100-py, HR 2.18, 95% CI, 1.21-3.93). Specifically, rivaroxaban had higher rates of major gastrointestinal bleeding and other major bleeding than apixaban. In conclusion, although stroke/SE rates were similar for DOACs, rivaroxaban was associated with higher rates of major bleeding than other DOACs and lower rates of MI than dabigatran. These results may help guide oral anticoagulant selection, especially in patients at high risk of bleeding or MI.

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Hemorrhage; Humans; Myocardial Infarction; Propensity Score; Rivaroxaban; Stroke

In clinical trials, event adjudication is a process to review and confirm the accuracy of outcomes reported by site investigators. Despite efforts to automate the communication between a clinical-data-and-coordination center and an event adjudication committee, the review and confirmation of outcomes, as the core function of the process, still fully rely on human labor. To address this issue, we present an automated event adjudication system and its application in two randomized controlled trials.. Centrally executed by a clinical-data-and-coordination center, the automated event adjudication system automatedly assessed and classified outcomes in a clinical data management system. By checking clinically predefined criteria, the automated event adjudication system either confirmed or unconfirmed an outcome and automatedly updated its status in the database. It also served as a management tool to assist staff to oversee the process of event adjudication. The system has been applied in: (1) the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial and (2) the New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source (NAVIGATE ESUS) trial. The automated event adjudication system first screened outcomes reported on a case report form and confirmed those with data matched to preset definitions. For selected primary efficacy, secondary, and safety outcomes, the unconfirmed cases were referred to a human event adjudication committee for a final decision. In the New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source (NAVIGATE ESUS) trial, human adjudicators were given priority to review cases, while the automated event adjudication system took the lead in the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial.. Outcomes that were adjudicated in a hybrid model are discussed here. The COMPASS automated event adjudication system adjudicated 3283 primary efficacy outcomes and confirmed 1652 (50.3%): 132 (21.1%) strokes, 522 (53%) myocardial infarctions, and 998 (59.7%) causes of deaths. The NAVIGATE ESUS one adjudicated 737 cases of selected outcomes and confirmed 383 (52%): 219 (51.5%) strokes, 34 (42.5%) myocardial infarctions, 73 (54.9%) causes of deaths, and 57 (57.6%) major bleedings. After one deducts the time needed for migrating the system to a new study, the automated event adjudication system helped to reduce the time required for human review from approximately 1303 to 716.5 h for the Cardiovascular Outcomes for People Using Anticoagulation Strategies trial and from 387 to 196 h for the New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source trial.. The automated event adjudication system in combination with human adjudicators provides a streamlined and efficient approach to event adjudication in clinical trials. To immediately apply automated event adjudication, one can first consider the automated event adjudication system and involve human assistance for cases unconfirmed by the former.

Topics: Aspirin; Double-Blind Method; Embolic Stroke; Embolism; Factor Xa; Factor Xa Inhibitors; Humans; Myocardial Infarction; Rivaroxaban; Stroke

To appraise all available antithrombotic treatments within or after 12 months following coronary revascularization and/or acute coronary syndrome in two network meta-analyses.. Forty-three (N = 189 261 patients) trials within 12 months and 19 (N = 139 086 patients) trials beyond 12 months were included for efficacy/safety endpoints appraisal. Within 12 months, ticagrelor 90 mg bis in die (b.i.d.) [hazard ratio (HR), 0.66; 95% confidence interval (CI), 0.49-0.88], aspirin and ticagrelor 90 mg (HR, 0.85; 95% CI, 0.76-0.95), or aspirin, clopidogrel and rivaroxaban 2.5 mg b.i.d. (HR, 0.66; 95% CI, 0.51-0.86) were the only treatments associated with lower cardiovascular mortality, compared with aspirin and clopidogrel, without or with greater bleeding risk for the first and the other treatment options, respectively. Beyond 12 months, no strategy lowered mortality; compared with aspirin; the greatest reductions of myocardial infarction (MI) were found with aspirin and clopidogrel (HR, 0.68; 95% CI, 0.55-0.85) or P2Y12 inhibitor monotherapy (HR, 0.76; 95% CI: 0.61-0.95), especially ticagrelor 90 mg (HR, 0.54; 95% CI, 0.32-0.92), and of stroke with VKA (HR, 0.56; 95% CI, 0.44-0.76) or aspirin and rivaroxaban 2.5 mg (HR, 0.58; 95% CI, 0.44-0.76). All treatments increased bleeding except P2Y12 monotherapy, compared with aspirin.. Within 12 months, ticagrelor 90 mg monotherapy was the only treatment associated with lower mortality, without bleeding risk trade-off compared with aspirin and clopidogrel. Beyond 12 months, P2Y12 monotherapy, especially ticagrelor 90 mg, was associated with lower MI without bleeding trade-off; aspirin and rivaroxaban 2.5 mg most effectively reduced stroke, with a more acceptable bleeding risk than VKA, compared with aspirin.Registration URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifiers: CRD42021243985 and CRD42021252398.

Topics: Aspirin; Cardiology; Clopidogrel; Coronary Artery Disease; Fibrinolytic Agents; Hemorrhage; Humans; Myocardial Infarction; Network Meta-Analysis; Purinergic P2Y Receptor Antagonists; Rivaroxaban; Stroke; Ticagrelor

Antiphospholipid syndrome (APS) can affect different organ systems, including the heart and adrenal glands. Despite being known for its prothrombotic characteristics, APS can have serious bleeding complications. Occasionally, thrombotic and bleeding episodes can present simultaneously in an APS patient. Whenever these events co-occur, resuming anticoagulation becomes a topic of debate. As such, we present the case of a 43-year-old male with triple positive antiphospholipid antibodies, indicating APS, who presented with chest pain. Anticoagulants were switched one month before presentation from warfarin to a direct oral anticoagulant, rivaroxaban. Non-ST elevation myocardial infarction, as well as new-onset left-sided adrenal hemorrhage, were diagnosed. The patient developed adrenal insufficiency; therefore, corticosteroids were administered, and warfarin was resumed to prevent further thrombotic episodes.

Topics: Adult; Antiphospholipid Syndrome; Hemorrhage; Humans; Male; Myocardial Infarction; Rivaroxaban; Warfarin

Factor Xa (FXa) not only plays an active role in the coagulation cascade but also exerts non-hemostatic signaling through the protease-activated receptors (PARs). This study aimed to investigate whether the FXa inhibitor, Rivaroxaban (RIV), attenuates adverse cardiac remodeling in rats with myocardial infarction (MI) and to identify the underlying molecular mechanisms it uses.. An MI model was induced in eight-week-old, male Wistar rats, by permanent ligation of the left anterior descending coronary artery. MI rats were randomly assigned to receive RIV or protease-activated receptors 2-antagonist (PAR-2 antagonist, FSLLRY) treatment for four weeks. Histological staining, echocardiography and hemodynamics were used to assess the cardioprotective effects of RIV. Meanwhile, pharmacological approaches of agonist and inhibitor were used to observe the potential pathways in which RIV exerts antifibrotic effects in neonatal rat cardiac fibroblasts (CFs). In addition, real-time PCR and western blot analysis were performed to examine the associated signaling pathways.. Our findings demonstrate that RIV attenuates MI-induced cardiac remodeling and improves heart function, partly by inhibiting the activation of the PAR-2 and TGF-β1 signaling pathways.

Topics: Animals; Factor Xa; Fibrosis; Male; Myocardial Infarction; Rats; Rats, Wistar; Receptors, Proteinase-Activated; Rivaroxaban; Signal Transduction; Transforming Growth Factor beta1; Ventricular Remodeling

Prospectively collected data comparing the safety and effectiveness of individual non-vitamin K antagonists (NOACs) are lacking. Our objective was to directly compare the effectiveness and safety of NOACs in patients with newly diagnosed atrial fibrillation (AF).. In GLORIA-AF, a large, prospective, global registry program, consecutive patients with newly diagnosed AF were followed for 3 years. The comparative analyses for (1) dabigatran vs rivaroxaban or apixaban and (2) rivaroxaban vs apixaban were performed on propensity score (PS)-matched patient sets. Proportional hazards regression was used to estimate hazard ratios (HRs) for outcomes of interest.. The GLORIA-AF Phase III registry enrolled 21,300 patients between January 2014 and December 2016. Of these, 3839 were prescribed dabigatran, 4015 rivaroxaban and 4505 apixaban, with median ages of 71.0, 71.0, and 73.0 years, respectively. In the PS-matched set, the adjusted HRs and 95% confidence intervals (CIs) for dabigatran vs rivaroxaban were, for stroke: 1.27 (0.79-2.03), major bleeding 0.59 (0.40-0.88), myocardial infarction 0.68 (0.40-1.16), and all-cause death 0.86 (0.67-1.10). For the comparison of dabigatran vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 1.16 (0.76-1.78), myocardial infarction 0.84 (0.48-1.46), major bleeding 0.98 (0.63-1.52) and all-cause death 1.01 (0.79-1.29). For the comparison of rivaroxaban vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 0.78 (0.52-1.19), myocardial infarction 0.96 (0.63-1.45), major bleeding 1.54 (1.14-2.08), and all-cause death 0.97 (0.80-1.19).. Patients treated with dabigatran had a 41% lower risk of major bleeding compared with rivaroxaban, but similar risks of stroke, MI, and death. Relative to apixaban, patients treated with dabigatran had similar risks of stroke, major bleeding, MI, and death. Rivaroxaban relative to apixaban had increased risk for major bleeding, but similar risks for stroke, MI, and death.. URL: https://www.. gov . Unique identifiers: NCT01468701, NCT01671007. Date of registration: September 2013.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Dabigatran; Hemorrhage; Humans; Myocardial Infarction; Prospective Studies; Pyridones; Registries; Rivaroxaban; Stroke

The aim of this study was to analyze the clinical characteristics of fatal adverse events (AEs) of rivaroxaban combined with aspirin and to underline the importance of the rational use of drugs.. The WHO global database of reported potential side effects of medicinal products (VigiBase) was searched for fatal AEs in the combined use of rivaroxaban and aspirin, and the clinical characteristics of those cases with sufficient information (vigiGrade completeness score ≥ 0.80) were analyzed.. By January 19, 2020, 2309 fatal adverse event reports of rivaroxaban combined with aspirin from 21 countries were entered in VigiBase. One hundred and twenty cases contained further information, of which 42 were female (35%) and 78 were male (65%). The median age was 75 (range 34 to 93) years, and 109 cases (91%) were elderly patients (≥ 65 years). The AEs listed in the fatal case reports included bleeding in 114 cases (mainly intracranial hemorrhage and gastrointestinal hemorrhage, 59 and 46 respectively, accounting for 88%) and ischemic events in six cases (ischemic stroke in three, acute myocardial infarction in two, myocardial infarction combined with acute liver failure in one). Among the patients with bleeding events, 108 (95%) had existing risk factors for bleeding or for interacting with aspirin or rivaroxaban. These may be divided into the following: diseases (hypertension, renal impairment, history of stroke, peptic ulcer, or previous bleeding), drugs (high dose aspirin, antiplatelet drugs, anticoagulants, P-gp inhibitors/CYP3A4 inhibitors, non-steroidal anti-inflammatory drugs, steroids, and selective serotonin reuptake inhibitors), or other factors (e.g., elderly, low body weight, or excessive intake of ginger, fish oil, or alcohol). There were 45 cases with two or more of these risk factors in addition to rivaroxaban and aspirin. Patients with ischemic events are often in very high-risk groups of atherosclerotic cardiovascular disease (ASCVD) or self-discontinuation of treated drugs. Medication errors occurred in 24 patients (20%): excessive treatment in 17 cases, contraindication in three, frequency error in two, excessive treatment combined with contraindication in one, and self-discontinuation in one.. Fatal AEs related to rivaroxaban combined with aspirin, including bleeding and ischemic events, have been reported mostly in the elderly, and sometimes involved medication errors. The fatal AEs mainly manifested as serious bleeding, and most of them occurred in patients with concurrent multiple risk factors. Monitoring coagulation during rivaroxaban treatment is recommended in very high-risk ASCVD populations, and attention should be paid to prevention of medication errors.

Topics: Aspirin; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Ischemia; Male; Myocardial Infarction; Platelet Aggregation Inhibitors; Rivaroxaban

Secondary prevention of cardiovascular events among patients with diagnosed cardiovascular disease and high ischemic risk poses a significant challenge in clinical practice. The combinations of aspirin with low-dose (LD) ticagrelor or LD rivaroxaban have shown superiority in preventing major adverse cardiovascular events (MACE) compared with aspirin treatment alone. The comparative value for money of these two regimens remains unexplored.. We analyzed each regimen's annual cost needed to treat (CNT) by multiplying the annualized number needed to treat (aNNT) by the annual cost of each drug. The aNNTs were based on outcome data from PEGASUS TIMI-54 and COMPASS trials. Scenario analyses were performed to overcome variances in terms of population risk. Costs were calculated as 75% of US National Average Drug Acquisition Cost (NADAC), extracted in January 2022. The primary outcome was defined as CNT to prevent one MACE across the two regimens. Secondary value analysis was performed for myocardial infarction (MI), stroke, and cardiovascular death as separate outcomes.. The aNNTs to prevent MACE with LD ticagrelor and with LD rivaroxaban were 229 [95% confidence interval (CI) 141-734] and 147 (95% CI 104-252), respectively. At an annual cost of US$3726 versus US$4533, the corresponding CNTs were US$853,254 (95% CI 525,366-2,734,884) with LD ticagrelor and US$666,351 (95% CI 471,432-1,142,316) with LD rivaroxaban.. Combining aspirin with LD rivaroxaban provides better value for money than with LD ticagrelor for secondary prevention of MACE.

Topics: Adenosine; Aspirin; Drug Therapy, Combination; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Rivaroxaban; Secondary Prevention; Ticagrelor; Treatment Outcome

To compare real-world effectiveness and safety of direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation (AFib) for prevention of stroke.. A comparative cohort study in UK general practice data from The Health Improvement Network database.. Before matching, 5655 patients ≥18 years with nonvalvular AFib who initiated at least one DOAC between 1 July 2014 and 31 December 2020 were included. DOACs of interest included apixaban, rivaroxaban, edoxaban and dabigatran, with the primary comparison between apixaban and rivaroxaban. Initiators of DOACs were defined as new users with no record of prescription for any DOAC during 12 months before index date.. The primary outcome was stroke (ischaemic or haemorrhagic). Secondary outcomes included the occurrence of all-cause mortality, myocardial infarction (MI), transient ischaemic attacks (TIA), major bleeding events and a composite angina/MI/stroke (AMS) endpoint.. Compared with rivaroxaban, patients initiating apixaban showed similar rates of stroke (HR: 0.93; 95% CI 0.64 to 1.34), all-cause mortality (HR: 1.03; 95% CI 0.87 to 1.22), MI (HR: 0.95; 95% CI 0.54 to 1.68), TIA (HR: 1.03; 95% CI 0.61 to 1.72) and AMS (HR: 0.96; 95% CI 0.72 to 1.27). Apixaban initiators showed lower rates of major bleeding events (HR: 0.60; 95% CI 0.47 to 0.75).. Among patients with nonvalvular AFib, apixaban was as effective as rivaroxaban in reducing rate of stroke and safer in terms of major bleeding episodes. This head-to-head comparison supports conclusions drawn from indirect comparisons of DOAC trials against warfarin and demonstrates the potential for real-world evidence to fill evidence gaps and reduce uncertainty in both health technology assessment decision-making and clinical guideline development.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Hemorrhage; Humans; Ischemic Attack, Transient; Myocardial Infarction; Primary Health Care; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; United Kingdom; Warfarin

Low-dose direct oral anticoagulant (DOAC) use is quite prevalent in clinical practice, but evidence of its effectiveness and safety compared with high-dose DOAC in patients with atrial fibrillation (AF) remains limited. We aimed to assess the effectiveness and safety of low-dose and high-dose DOACs in patients with AF with similar baseline characteristics.. We used a cohort of hospitalized patients with a primary or secondary diagnosis of AF after discharge to the community, whose data were stored in the Quebec administrative databases, from 2011 to 2017. Older adults with AF newly prescribed with rivaroxaban (15 or 20 mg) or apixaban (2.5 mg or 5 mg) were classified as under treatment (UT) and intent to treat (ITT). We used an inverse probability treatment weighting study of new users of rivaroxaban and apixaban to address confounding by indication. The primary effectiveness outcome was ischemic stroke/systemic embolism (SE), while the primary safety outcome was major bleeding (MB). We used Cox proportional models to estimate the marginal hazard ratios (HRs).. A total of 1,722 and 4,639 patients used low-dose and standard-dose rivaroxaban, respectively, while 3,833 and 6,773 patients used low-dose and standard-dose apixaban, respectively. No significant difference was observed in the incidence of comparative stroke/SE and MB between low-dose and standard-dose rivaroxaban, except for the risk of acute myocardial infarction (AMI), which was increased with the low dose in the UT analysis. For apixaban, no difference was found in the bleeding rates, but the risk of stroke/SE (HR: 1.95; 95% confidence interval (CI): 1.38-2.76) and death (HR: 1.99; 95% CI: 1.46-2.70) were greater in the low-dose group than in the standard-dose group in the UT analysis. Similar results were observed for the ITT analysis.. No significant differences were observed in the effectiveness or safety outcome between low-dose and standard-dose rivaroxaban, except for AMI. However, low-dose apixaban was associated with a greater risk of stroke/SE and death without a reduction in the bleeding rates.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Humans; Myocardial Infarction; Pyridones; Rivaroxaban; Stroke

Topics: Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Rivaroxaban; Stroke; Treatment Outcome

The aim: To increase the treatment effectiveness of CHF patients after MI with stenting by using magnesium and potassium salts of gluconic acid, eplerenone, and rivaroxaban in complex therapy.. Materials and methods: The research was performed at the premises of Ivano-Frankivsk Regional Clinical Cardiology Centre, Ukraine. 84 patients with CHF after past MI were examined.. Results and conclusions: A more pronounced anti-ischemic effect has been linked to the use of combination therapy with rivaroxaban on the background of basic therapy (BT) in patients with CHF after MI, compared with the use of magnesium and potassium salts of gluconic acid or eplerenone. The use of eplerenone in the complex treatment of these patients on the background of BT has been proven to provide a pronounced reverse remodeling of the left myocardium in the postinfarction period.

Topics: Eplerenone; Gluconates; Heart Failure; Humans; Magnesium; Mineralocorticoid Receptor Antagonists; Myocardial Infarction; Myocardium; Potassium; Rivaroxaban; Salts; Spironolactone

Recently, the cardiovascular outcomes for people using anticoagulation strategies (COMPASS) trial demonstrated that dual therapy reduced cardiovascular outcomes compared with aspirin alone in patients with stable atherosclerotic disease.. We sought to assess the proportion of patients eligible for the COMPASS trial and to compare the epidemiology and outcome of these patients with those without COMPASS inclusion or with any exclusion criteria in a contemporary, nationwide cohort of patients with stable coronary artery disease. Among the 4068 patients with detailed information allowing evaluation of eligibility, 1416 (34.8%) did not fulfil the inclusion criteria (COMPASS-Not-Included), 841 (20.7%) had exclusion criteria (COMPASS-Excluded), and the remaining 1811 (44.5%) were classified as COMPASS-Like. At 1 year, the incidence of major adverse cardiovascular event (MACE), a composite of cardiovascular death, myocardial infarction, and stroke, was 0.9% in the COMPASS-Not-Included and 2.0% in the COMPASS-Like (P = 0.01), and 5.0% in the COMPASS-Excluded group (P < 0.0001 for all comparisons). Among the COMPASS-Like population, patients with multiple COMPASS enrichment criteria presented a significant increase in the risk of MACE (from 1.0% to 3.3% in those with 1 and ≥3 criteria, respectively; P = 0.012), and a modest absolute increase in major bleeding risk (from 0.2% to 0.4%, respectively; P = 0.46).. In a contemporary real-world cohort registry of stable coronary artery disease, most patients resulted as eligible for the COMPASS. These patients presented a considerable annual risk of MACE that consistently increases in the presence of multiple risk factors.

Topics: Aspirin; Coronary Artery Disease; Humans; Myocardial Infarction; Registries; Rivaroxaban

To determine the association between direct oral anticoagulant (DOAC) use and risk of major adverse cardiac events (MACEs) in patients with atrial fibrillation (AF).. This study is a single-center prospective observational cohort study including 2366 outpatients with non-valvular AF on treatment with DOACs or vitamin K antagonists (VKAs) from February 2008 for patients on VKA and September 2013 for patients on novel oral anticoagulants. The primary endpoint was the incidence of MACE including fatal and non-fatal myocardial infarction (MI), cardiac revascularization, and cardiovascular death.. The mean age was 75.1±9.0 years; 44.7% were women. During a mean follow-up of 33.3±21.9 months (6567 patients/years) 133 MACEs occurred (2.03%/year): 79 MI/cardiac revascularization and 54 cardiovascular deaths. Of these, 101 were on VKAs (2.42%/year) and 32 on DOACs (1.34%/year; log-rank test P=.040). This difference was evident also considering MI alone (1.53%/year and 0.63%/year in the VKA and DOAC group, respectively, log-rank test P=.009). At multivariable Cox proportional hazard regression analysis, use of DOACs was associated with a lower risk of MACE (hazard ratio, 0.636; 95% CI, 0.417 to 0.970; P=.036) and MI (hazard ratio, 0.497; 95% CI, 0.276 to 0.896; p=.020). Sensitivity analysis showed that this association was consistent in younger patients (<75 years), in patients with anemia, and in those without chronic obstructive pulmonary disease and heart failure. We also found that both dabigatran and apixaban/rivaroxaban were associated with a lower rate of MACE, with similar efficacy between full and low doses.. DOACs are associated with a lower risk of MACE in patients with AF independently from dosage.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Female; Heart Failure; Humans; Male; Medication Adherence; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Prospective Studies; Rivaroxaban

To address literature gaps on treatment with real-world evidence, this study compared effectiveness, safety, and cost outcomes in NVAF patients with coronary or peripheral artery disease (CAD, PAD) prescribed apixaban versus other oral anticoagulants. NVAF patients aged ≥65 years co-diagnosed with CAD/PAD initiating warfarin, apixaban, dabigatran, or rivaroxaban were selected from the US Medicare population (January 1, 2013 to September 30, 2015). Propensity score matching was used to match apixaban versus warfarin, dabigatran, and rivaroxaban cohorts. Cox models were used to evaluate the risk of stroke/systemic embolism (SE), major bleeding (MB), all-cause mortality, and a composite of stroke/myocardial infarction/all-cause mortality. Generalized linear and two-part models were used to compare stroke/SE, MB, and all-cause costs between cohorts. A total of 33,269 warfarin-apixaban, 9,335 dabigatran-apixaban, and 33,633 rivaroxaban-apixaban pairs were identified after matching. Compared with apixaban, stroke/SE risk was higher in warfarin (hazard ratio [HR]: 1.93; 95% confidence interval [CI]: 1.61 to 2.31), dabigatran (HR: 1.69; 95% CI: 1.18 to 2.43), and rivaroxaban (HR: 1.24; 95% CI: 1.01 to 1.51) patients. MB risk was higher in warfarin (HR: 1.67; 95% CI: 1.52 to 1.83), dabigatran (HR: 1.37; 95% CI: 1.13 to 1.68), and rivaroxaban (HR: 1.87; 95% CI: 1.71 to 2.05) patients vs apixaban. Stroke/SE- and MB-related medical costs per-patient per-month were higher in warfarin, dabigatran, and rivaroxaban patients versus apixaban. Total all-cause health care costs were higher in warfarin and rivaroxaban patients compared with apixaban patients. In conclusion, compared with apixaban, patients on dabigatran, rivaroxaban, or warfarin had a higher risk of stroke/SE, MB, and event-related costs.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cause of Death; Coronary Artery Disease; Dabigatran; Embolism; Female; Health Care Costs; Hemorrhage; Humans; Male; Mortality; Myocardial Infarction; Peripheral Arterial Disease; Propensity Score; Proportional Hazards Models; Pyrazoles; Pyridones; Rivaroxaban; Stroke; United States; Warfarin

The goal of this study was to assess the differences between an ex ante and an ex post cost-effectiveness analysis of Dabigatran etexilate vs VKAs for the prevention of thromboembolic events in non-valvular atrial fibrillation patients and to draw lessons on the design and use of real-world data for decision making.. The same model was used to calculate the cost-effectiveness ratio using two sets of parameters. One set included the efficacy and safety outcomes data from RE-LY, the pivotal trial comparing Dabigatran to warfarin; cost data came from an ex ante publication. Outcomes data for the second set came from real-world data studies. Cost data were a mix of real-world data and other sources. Two treatment strategies were compared: treatment initiation by either Dabigatran or VKAs, followed by either VKAs or Dabigatran. A crude comparison of results was performed; the impact of data differences was then assessed. Probabilistic sensitivity results of the two analyses were compared.. With real-world evidence, Dabigatran at both dosages was more effective for the prevention of ischemic strokes, intra-cranial haemorrhages, with less major extra-cranial haemorrhages and a similar risk of myocardial infarction. Using clinical trial data, Dabigatran150 mg (resp. Dabigatran110 mg) as a first-line treatment vs VKAs yielded an ICER of € 8077/QALY (resp. € 13,116/QALY). Real-world evidence scenarios were cost-saving and more effective for both dosages.. The reassessment of outcomes and cost data had an impact on results, improving the efficiency of Dabigatran. We identify methodological issues which should be discussed if post-launch RWE based cost-effectiveness data become a standard in HTA decision making.

Topics: Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Dabigatran; France; Hemorrhage; Humans; Myocardial Infarction; Quality-Adjusted Life Years; Rivaroxaban; Stroke; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Embolism; Health Expenditures; Humans; Ischemic Stroke; Japan; Models, Econometric; Myocardial Infarction; Quality-Adjusted Life Years; Rivaroxaban; Warfarin

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Body Mass Index; Comorbidity; Factor Xa Inhibitors; Female; Heart Disease Risk Factors; Hemorrhage; Humans; Incidence; Japan; Male; Middle Aged; Myocardial Infarction; Obesity; Product Surveillance, Postmarketing; Prospective Studies; Risk Assessment; Rivaroxaban; Stroke; Thinness; Thromboembolism; Time Factors; Treatment Outcome

Evidence for the efficacy of direct oral anticoagulants (DOACs) to prevent cardiovascular (CV) events and mortality in older individuals with a low estimated glomerular filtration rate (eGFR) is lacking. We sought to characterize the association of oral anticoagulant use with CV morbidity in elderly patients with or without reductions in eGFRs, comparing DOACs with vitamin K antagonists (VKAs).. Population-based retrospective cohort study.. All individuals 66 years or older with an initial prescription for oral anticoagulants dispensed in Ontario, Canada, from 2009 to 2016.. DOACs (apixaban, dabigatran, and rivaroxaban) compared with VKAs by eGFR group (≥60, 30-59, and<30mL/min/1.73m. The primary outcome was a composite of a CV event (myocardial infarction, revascularization, or ischemic stroke) or mortality. Secondary outcomes were CV events alone, mortality, and hemorrhage requiring hospitalization.. High-dimensional propensity score matching of DOAC to VKA users and Cox proportional hazards regression.. 27,552 new DOAC users were matched to 27,552 new VKA users (median age, 78 years; 49% women). There was significantly lower risk for CV events or mortality among DOAC users compared with VKA users (event rates of 79.78 vs 99.77 per 1,000 person-years, respectively; HR, 0.82 [95% CI, 0.75-0.90]) and lower risk for hemorrhage (event rates of 10.35 vs 16.77 per 1,000 person-years, respectively; HR, 0.73 [95% CI, 0.58-0.91]). There was an interaction between eGFR and the association of anticoagulant class with the primary composite outcome (P<0.02): HRs of 1.01 [95% CI, 0.92-1.12], 0.83 [95% CI, 0.75-0.93], and 0.75 [95% CI, 0.51-1.10] for eGFRs of≥60, 30 to 59, and<30mL/min/1.73m. Retrospective observational study design limits causal inference; dosages of DOACs and international normalized ratio values were not available; low event rates in some subgroups limited statistical power.. DOACs compared with VKAs were associated with lower risk for the composite of CV events or mortality, an association for which the strength was most apparent among those with reduced eGFRs. The therapeutic implications of these findings await further study.

Topics: Aged; Aged, 80 and over; Antithrombins; Brain Ischemia; Cause of Death; Comorbidity; Dabigatran; Female; Glomerular Filtration Rate; Hemorrhage; Humans; Male; Mortality; Myocardial Infarction; Myocardial Revascularization; Ontario; Procedures and Techniques Utilization; Propensity Score; Proportional Hazards Models; Pyrazoles; Pyridones; Renal Insufficiency, Chronic; Retrospective Studies; Rivaroxaban; Thrombophilia; Vitamin K

Following the publication of the COMPASS trial, the European Medicines Agency has approved a regimen of combination of rivaroxaban 2.5mg twice daily and a daily dose of 75-100mg acetylsalicylic acid (ASA) for patients with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) at high risk of ischemic events. However, the applicability of such a therapeutic strategy in France is currently unknown.. To describe the proportion of patients eligible to COMPASS in France, their baseline clinical characteristics and the rate of major adverse cardiovascular events, using the REACH registry.. From the the REduction of Atherothrombosis for Continued Health (REACH) registry database, a large international registry of patients with, or at risk, of atherothrombosis, we analyzed patients included in France with either established CAD and/or PAD and fulfilling the inclusion and exclusion criteria of the COMPASS trial. The ischemic outcome was a composite of cardiovascular (CV) death, myocardial infarction (MI), or stroke, and serious bleeding were defined as haemorrhagic stroke or bleeding leading to hospitalization or transfusion.. Among more than 65000 patients enrolled in REACH, 2.012 patients were evaluable and enrolled in France. Among them, 1194 patients (59.3%) were eligible to COMPASS. The main reasons for exclusion of the COMPASS trial, were high bleeding risk (59.1%), anticoagulant use (43.4%), requirement for dual antiplatelet therapy within 1 year of an ACS or PCI (24.7%). In the "COMPASS eligible population", the rate of MACE (CV, MI and stroke) at 4 years follow-up was 13.4% [11.3-15.8], and serious bleeding was 2.5% at 4 years [1.6-3.4]. Patients with polyvascular disease (n=219) had the highest rate of MACE, compared with patients with CAD only and PAD only (19.1% [13.9-26.1] vs. 11.6% [9.1-14.8] vs 13.2% [9.2-18.8], P<0.0001, respectively).. The COMPASS therapeutic strategy in France appears to be applicable to more than half of CAD or PAD patients. This population appears at high residual risk of atherothrombotic events, and patients with polyvascular disease experienced the highest rate of events.

Topics: Aged; Analysis of Variance; Anticoagulants; Aspirin; Atherosclerosis; Coronary Artery Disease; Drug Administration Schedule; Female; Follow-Up Studies; France; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Patient Selection; Percutaneous Coronary Intervention; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Prospective Studies; Registries; Risk Factors; Rivaroxaban; Stroke; Thrombosis; Time Factors; Treatment Outcome

Topics: Amputation, Surgical; Aspirin; Brain Ischemia; Chocolate; Cysts; Humans; Ischemia; Ischemic Stroke; Magnetic Resonance Imaging; Myocardial Infarction; Peripheral Arterial Disease; Rivaroxaban; Stroke

There is little data on management and outcomes of atrial fibrillation (AF) patients on direct oral anticoagulants (DOAC) undergoing general surgery.We retrospectively assessed 98 surgeries in 85 nonvalvular AF patients aged 73 ± 8 (59 men) receiving DOACs. Cardiac, emergency, and minimally invasive surgeries were excluded.The CHA

Topics: Aged; Aged, 80 and over; Antithrombins; Atrial Fibrillation; Blood Loss, Surgical; Carotid Artery Diseases; Cerebral Infarction; Dabigatran; Digestive System Surgical Procedures; Elective Surgical Procedures; Embolism; Endoscopy; Factor Xa Inhibitors; Female; Humans; Male; Myocardial Infarction; Orthopedic Procedures; Perioperative Care; Postoperative Complications; Postoperative Hemorrhage; Pyrazoles; Pyridines; Pyridones; Retrospective Studies; Rivaroxaban; Thiazoles; Thromboembolism; Urologic Surgical Procedures; Vascular Surgical Procedures

Antiplatelet therapy (APT) use in combination with oral anticoagulation is common among patients with atrial fibrillation, but there is scarce information regarding its effect on outcomes in patients on non-vitamin K antagonist oral anticoagulants (NOAC). We aimed to evaluate the safety and efficacy of APT use in a 'real-world' cohort of nonvalvular atrial fibrillation (NVAF) patients initiating NOAC.. We conducted a retrospective multicentre study including 2361 consecutive NVAF patients initiating NOAC between January 2013 and December 2016. Patients with an acute ischaemic event within the last 12 months (acute coronary syndrome, stroke or revascularization) were excluded. Patients were followed up, and all clinical events were recorded at 3 months. The primary outcome of the study was major bleeding, and the secondary outcomes were stroke, nonfatal myocardial infarction, intracranial bleeding and death.. One hundred forty-five (6.1%) patients received concomitant APT, and aspirin was the more common (79%). At 3 months, 25 (1.1%) patients had major bleeding, 8 (0.3%) had nonfatal myocardial infarction, 7 (0.3%) had ischaemic stroke, and 40 (1.7%) died. After multivariate adjustment, concomitant APT was associated with higher risk for major bleeding (HR = 3.62, 95% CI 1.32-9.89; P = .012), but was not associated with a higher risk of other clinical outcomes.. Concomitant APT use is uncommon among these patients and does not seem to be associated with lower rates of ischaemic events or death. However, there are signals for an increased risk of bleeding, which reinforces current guideline recommendations.

Topics: Aged; Aged, 80 and over; Antithrombins; Aspirin; Atrial Fibrillation; Dabigatran; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Mortality; Myocardial Infarction; Platelet Aggregation Inhibitors; Proportional Hazards Models; Purinergic P2Y Receptor Antagonists; Pyrazoles; Pyridines; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Thiazoles

Topics: Blood Coagulation; Clinical Trials as Topic; Disease Progression; Factor Xa Inhibitors; Heart Failure; Hemorrhage; Humans; Myocardial Infarction; Patient Readmission; Platelet Aggregation Inhibitors; Risk Factors; Rivaroxaban; Stroke; Thromboembolism; Treatment Outcome

Topics: Acute Disease; Anemia, Iron-Deficiency; Anticoagulants; Cardiotonic Agents; Case-Control Studies; Diuretics; Factor Xa Inhibitors; Heart Aneurysm; Heart Failure; Humans; Hypertension; Iron; Myocardial Infarction; Pacemaker, Artificial; Percutaneous Coronary Intervention; Placebos; Portraits as Topic; Rivaroxaban; Stroke; Stroke Volume; Thrombosis; Urea

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

Topics: Aspirin; Atherosclerosis; Chronic Disease; Clinical Trials as Topic; Death; Drug Therapy, Combination; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Rivaroxaban; Secondary Prevention; Stroke; Thrombosis; Vascular Diseases

Topics: Adult; Aged; Diagnosis, Differential; Echocardiography; Factor Xa Inhibitors; Female; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Infarction; Rivaroxaban; Thrombosis

Direct oral anticoagulants are commonly used instead of vitamin K antagonists in patients needing long-term anticoagulant treatment. As their use has become more popular, there is an increase possibility to perform a major surgery on an urgent or emergency basis on patients under nonvitamin-K antagonist oral anticoagulants.. We report a case of a ruptured abdominal aortic aneurysm on a male patient under rivaroxaban and clopidogrel. Emergency open repair of the aneurysm was performed. No anti-Xa antidote was administered. The patient had an uneventful recovery.. An open repair of a ruptured abdominal aortic aneurysm under rivaroxaban is feasible. However, an antidote should be available in cases of uncontrolled diffused bleeding. To the best of our knowledge, this is the first reported case of successful open repair of a ruptured abdominal aortic aneurysm on a patient under rivaroxaban and clopidogrel.

Topics: Aortic Aneurysm, Abdominal; Aortic Rupture; Aortography; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Clopidogrel; Computed Tomography Angiography; Drug Administration Schedule; Emergencies; Factor Xa Inhibitors; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Rivaroxaban; Treatment Outcome

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

In the COMPASS trial, combined aspirin and rivaroxaban treatment reduced ischaemic events in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD). We estimated the proportion of COMPASS eligible patients among unselected patients undergoing coronary angiography (CAG) and compared outcome rates among COMPASS eligible and non-eligible patients.. We applied the COMPASS study criteria on patients undergoing CAG in Western Denmark (2004-11). Both COMPASS eligible and non-eligible patients had CAD/PAD and met no exclusion criteria, but only COMPASS eligible patients met the inclusion criteria. We assessed the COMPASS primary endpoint of cardiovascular death, ischaemic stroke, haemorrhagic stroke, or myocardial infarction (MI). We computed event rates and adjusted incidence rate ratios (aIRRs). Of 80 071 patients undergoing CAG, 27 939 did not have CAD or PAD and were not considered. Of the 52 132 patients remaining, 11 930 were COMPASS eligible. Rates of the primary endpoint were 4.8 (95% confidence interval 4.6-5.0) events per 100 person-years among COMPASS eligible patients and 2.3 (2.2-2.4) among COMPASS non-eligible patients [aIRR 1.7 (1.6-1.9)]. COMPASS eligible patients also had higher risks of cardiovascular death [aIRR 2.5 (2.1-3.0)], ischaemic stroke [aIRR 1.4 (1.2-1.6)], and MI [aIRR 1.9 (1.7-2.1)].. In this all-comers CAG cohort, 15% were eligible for combined aspirin and rivaroxaban treatment. COMPASS eligible patients had up to 2.5-fold higher rates of cardiovascular events than non-eligible patients. The higher incidence of ischaemic events in COMPASS eligible patients highlights an unmet need for additional preventive measures.

Topics: Aged; Aspirin; Cerebrovascular Disorders; Clinical Decision-Making; Coronary Angiography; Coronary Artery Disease; Denmark; Drug Therapy, Combination; Eligibility Determination; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Patient Selection; Peripheral Arterial Disease; Randomized Controlled Trials as Topic; Registries; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome

The aim of this study was to compare effectiveness and safety of low-strength and high-strength direct oral anticoagulants (DOACs) with warfarin in the Australian Veteran population.. Sequential cohort study using inverse probability of treatment weighting (IPTW) and propensity score matching. Initiators of high-strength (apixaban 5 mg, dabigatran 150 mg, rivaroxaban 20 mg) and low-strength DOACS (apixaban 2.5 mg, dabigatran 110 mg, rivaroxaban 15 mg) were compared with warfarin initiators.. Australian Government Department of Veterans' Affairs claims database.. 4836 patients who initiated oral anticoagulants (45.8%, 26.0% and 28.2% on low-strength, high-strength DOACs and warfarin, respectively) between August 2013 and March 2015. Mean age was 85, 75 and 83 years for low-strength, high-strength DOACs and warfarin initiators, respectively.. One-year risk of hospitalisation for ischaemic stroke, any bleeding event or haemorrhagic stroke. Secondary outcomes were 1-year risk of hospitalisation for myocardial infarction and death.. Using the IPTW method, no difference in risk of ischaemic stroke or bleeding was found with low-strength DOACs compared with warfarin. As a class, no increased risk of myocardial infarction was found for low-strength DOACs, however, risk was elevated for apixaban (HR 2.25, 95% CI 1.23 to 4.13). For high-strength DOACs, no difference was found for ischaemic stroke compared with warfarin, however, there was a significant reduction in risk of bleeding events (HR 0.63, 95% CI 0.44 to 0.89) and death (HR 0.40, 95% CI 0.28 to 0.58). Propensity score matching showed no difference in risk of ischaemic stroke or bleeding.. We found that in the practice setting both DOAC formulations were similar to warfarin with regard to effectiveness and had no increased risk of bleeding.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Australia; Comparative Effectiveness Research; Dabigatran; Databases, Factual; Female; Hemorrhage; Humans; Logistic Models; Male; Myocardial Infarction; Propensity Score; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Veterans; Warfarin

Rivaroxaban is a direct oral anticoagulant administered to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF). The Xarelto Post-Authorization Safety and Effectiveness Study in Japanese Patients with Atrial Fibrillation (XAPASS) was a prospective, observational, post-marketing surveillance study that examined the safety and effectiveness of rivaroxaban in routine clinical practice. This sub-analysis of the XAPASS investigated the outcomes of patients with worsening renal function (WRF).. The XAPASS included 11,308 patients with NVAF who began treatment with rivaroxaban. Of 9578 patients who completed 1-year follow-up, the 7509 patients, for whom the change in creatinine clearance could be assessed, were included in the present analysis. Patients with WRF were those with a decrease in creatinine clearance of ≥20% from enrollment to any time point; patients with stable renal function (SRF) were those without such a decrease. Outcomes in patients with WRF versus SRF were compared at 1 year.. No association between WRF and occurrence of any bleeding, major bleeding, and stroke/systemic embolism/myocardial infarction was observed in patients with AF on rivaroxaban treatment during 1-year follow-up in real-world clinical practice. Clinicaltrials.gov: NCT01582737.

Topics: Aged; Atrial Fibrillation; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Incidence; Japan; Male; Middle Aged; Myocardial Infarction; Product Surveillance, Postmarketing; Proportional Hazards Models; Prospective Studies; Renal Insufficiency; Rivaroxaban; Stroke; Treatment Outcome

The occurrence of distal coronary lesions causing simultaneous occlusion of two coronary arteries in the setting of ST elevation myocardial infarction is a rare occurrence. This can occur due to simultaneous plaque rupture at more than one site or embolisation in coronary arteries. We describe a case of a middle-aged man who presented with acute inferoposterior lateral wall ST elevation myocardial infarction with simultaneous occlusion of distal left anterior descending artery and distal left circumflex artery on angiogram. The patient was treated with intracoronary streptokinase, followed by glycoprotein (GP) IIb/IIIa inhibitor and Factor X inhibitor (Rivaroxaban) with full resolution of flow in the distal vessels. Thus, coronary lesions, not amenable to stenting, can be dealt percutaneously, using a combination of old and newer pharmacological agents without stenting.

Topics: Coronary Angiography; Coronary Disease; Coronary Occlusion; Electrocardiography; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Glycoprotein GPIIb-IIIa Complex; Rivaroxaban; Streptokinase; Treatment Outcome

Direct oral anticoagulants (DOAC) are at least non-inferior to warfarin in efficacy and safety among patients with nonvalvular atrial fibrillation. Limited evidence is available regarding outcomes for nonvalvular atrial fibrillation patients with coronary/peripheral artery disease.. Non-valvular atrial fibrillation patients aged ≥65 years diagnosed with coronary/peripheral artery disease in the US Medicare population, newly initiating DOACs (apixaban, rivaroxaban, dabigatran) or warfarin were selected from January 1, 2013 to September 30, 2015. Propensity score matching was used to compare DOACs vs warfarin. Cox proportional hazards models were used to estimate the risk of stroke/systemic embolism, major bleeding, and composite of stroke/myocardial infarction/all-cause mortality.. There were 15,527 apixaban-warfarin, 6,962 dabigatran-warfarin, and 25,903 rivaroxaban-warfarin-matched pairs, with a mean follow-up of 5-6 months. Compared with warfarin, apixaban was associated with lower rates of stroke/systemic embolism (hazard ratio [HR] 0.48; 95% confidence interval [CI], 0.37-0.62), major bleeding (HR 0.66; 95% CI, 0.58-0.75), and stroke/myocardial infarction/all-cause mortality (HR 0.63; 95% CI, 0.58-0.69); dabigatran and rivaroxaban were associated with lower rates of stroke/myocardial infarction/all-cause mortality (HR 0.79; 95% CI, 0.70-0.90 and HR 0.87; 95% CI, 0.81-0.92, respectively). Rivaroxaban was associated with a lower rate of stroke/systemic embolism (HR 0.72; 95% CI, 0.60-0.89) and a higher rate of major bleeding (HR 1.14; 95% CI, 1.05-1.23) vs warfarin.. All DOACs were associated with lower stroke/myocardial infarction/all-cause mortality rates compared with warfarin; differences were observed in rates of stroke/systemic embolism and major bleeding. Findings from this observational analysis provide important insights about oral anticoagulation therapy among non-valvular atrial fibrillation patients with coronary/peripheral artery disease and may help physicians in the decision-making process when treating this high-risk group of patients.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Dabigatran; Embolism; Female; Hemorrhage; Humans; Male; Medicare; Myocardial Infarction; Peripheral Arterial Disease; Proportional Hazards Models; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; United States; Warfarin

Rivaroxaban selectively inhibits factor Xa (FXa), which plays a central role in blood coagulation. In addition, FXa activates protease-activated receptor-2 (PAR-2). We have shown that PAR-2. Wild-type (WT) and PAR-2. Rivaroxaban increased the prothrombin time and inhibited the formation of intravascular thrombi in mice subjected to LAD ligation. WT mice receiving rivaroxaban immediately after surgery had similar infarct sizes at day 1 as controls but exhibited significantly less impairment of cardiac function at day 3 and beyond compared to the placebo group. Rivaroxaban also inhibited the expansion of the infarct at day 28. Rivaroxaban did not significantly affect the expression of inflammatory mediators or a neutrophil marker at day 2 after LAD ligation. Delaying the start of rivaroxaban administration until 3 days after surgery failed to preserve cardiac function. In addition, rivaroxaban did not reduce cardiac dysfunction in PAR-2. Early administration of rivaroxaban preserves cardiac function in mice after LAD ligation.

Topics: Animals; Disease Models, Animal; Factor Xa Inhibitors; Heart Diseases; Humans; Mice; Myocardial Infarction; Rivaroxaban

Left ventricular (LV) thrombus is a major complication of acute systolic cardiomyopathy especially after a large anterior myocardial infarction (AMI), and it poses a significant embolic risk, up to five times higher than the general population. Current guidelines for LV thrombi recommend vitamin K antagonist for anticoagulation in contrast to novel oral anticoagulants (NOACs) which have not been studied well in cases of LV thrombus. We present a case of patient with AMI, who was noted to have severe systolic dysfunction and a large LV thrombus which was successfully treated with rivaroxaban therapy with complete resolution of LV thrombus on two months follow-up.

Topics: Administration, Oral; Anticoagulants; Heart Diseases; Humans; Myocardial Infarction; Rivaroxaban; Thrombosis; Time Factors

Thromboembolic and bleeding risk are elevated in older patients with atrial fibrillation and prior stroke. We compared dabigatran with rivaroxaban for secondary prevention in a national population after skilled nursing facility (SNF) discharge.. Medicare fee-for-service beneficiaries aged ≥ 65 years with atrial fibrillation hospitalized for ischemic stroke (November 2011-October 2013) and subsequently admitted to an SNF were studied. Dabigatran (n = 332) and rivaroxaban users (n = 378) were compared in a retrospective, active comparator, new-user cohort. The index medication claim occurred within 120 days after hospital discharge and exposure continued until a 14-day treatment gap ('as treated'). The primary net clinical benefit outcome was the time to recurrent stroke, transient ischemic attack, intracranial hemorrhage, extracranial bleed, myocardial infarction, venous thromboembolism, or death. All-cause mortality was evaluated separately as a secondary outcome. Multivariable adjusted Cox models stratified by dosage estimated hazard ratios (aHR).. Among those receiving low dosages, the crude composite event rate was 40.4/100 person-years among dabigatran users and 33.7/100 person-years among rivaroxaban users. The composite outcome [aHR 1.48; 95% confidence interval (CI) 0.87-2.51] and all-cause mortality (aHR 1.67; 95% CI 0.84-3.31) rates were higher among low-dose dabigatran users. For those receiving standard doses, the crude composite event rates were 19.5/100 person-years for dabigatran users and 37.1/100 person-years for rivaroxaban users. Although no difference in mortality was observed, the composite outcome rate was lower among standard-dose dabigatran users (aHR 0.65; 95% CI 0.36-1.15).. In older adults treated with direct-acting oral anticoagulants after ischemic stroke, outcome rates varied considerably by drug and dosage.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Female; Hemorrhage; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Male; Medicare; Myocardial Infarction; Proportional Hazards Models; Retrospective Studies; Rivaroxaban; Secondary Prevention; Skilled Nursing Facilities; Stroke; Thromboembolism; United States

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-acting oral anticoagulants (DOACs) have become available for the prevention of stroke in patients with atrial fibrillation (AF). Conflicting results have been published on the risk of acute myocardial infarction (AMI) with the use of DOACs in comparison with vitamin K antagonists (VKAs). The objective of the present study was to evaluate the risk of AMI in patients with AF who are exposed to either VKAs, DOACs or low-dose (< 325 mg) aspirin.. We conducted a population-based cohort study using data from the Clinical Practice Research Datalink (2008-2014). The study population (n = 30 146) consisted of all patients ≥18 years with a diagnosis of AF who were new users of VKAs, DOACs (rivaroxaban and dabigatran) or aspirin. Cox proportional hazards models were used to estimate the hazard ratio (HR) of AMI for users of DOACs or aspirin vs. VKA. Adjustments were made for age, gender, lifestyle, risk factors, comorbidity and other drugs.. The risk of AMI was doubled when we compared current use of DOACs with current use of VKAs [adjusted HR 2.11; 95% confidence interval (CI) 1.08, 4.12] and for current users of aspirin vs. current VKA users (adjusted HR 1.91; 95% CI 1.45, 2.51).. There is a twofold increase in the risk of AMI for users of DOACs, in comparison with VKAs, in AF therapy. In addition, the results suggested that in patients with AF, the incidence of AMI is higher during aspirin monotherapy than during the use of VKAs.

Topics: Administration, Oral; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Dabigatran; Female; Fibrinolytic Agents; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Factors; Rivaroxaban; Stroke; Vitamin K

We aimed to examine the comparative effectiveness and safety between dabigatran and rivaroxaban in atrial fibrillation patients.. We conducted a population-based, retrospective, new-user cohort study based on the National Health Insurance claims database in Taiwan. Adult atrial fibrillation patients who initiated dabigatran (N=10 625) or rivaroxaban (N=4609) between June 1, 2012 and May 31, 2014 were identified as the overall population. A propensity score was derived using logistic regression to model the probability of receipt of rivaroxaban as a function of potential confounders. Altogether, 4600 dabigatran users were matched with 4600 rivaroxaban users to create a propensity score-matched population. The marginal proportional hazards model was applied among the propensity score-matched population as the primary analysis, and the proportional hazards model with adjustment of the quintiles of the propensity score among the overall population was used as the secondary analysis. Rivaroxaban users had a higher risk of all-cause death than dabigatran users (hazard ratio 1.44, 95%CI 1.17-1.78 in the primary analysis and hazard ratio 1.47, 95%CI 1.23-1.75 in the secondary analysis). Rivaroxaban users also possessed a higher risk of gastrointestinal hemorrhage needing transfusion than dabigatran users in the primary analysis (hazard ratio 1.41, 95%CI 1.02-1.95), but the difference diminished in the secondary analysis (hazard ratio 1.20, 95%CI 0.92-1.56). The risks of ischemic stroke, acute myocardial infarction, arterial embolism/thrombosis, and intracranial hemorrhage were similar between the 2 groups.. Rivaroxaban therapy was associated with a statistically significant increase in all-cause death compared with dabigatran therapy in atrial fibrillation patients.

Topics: Aged; Aged, 80 and over; Antithrombins; Atrial Fibrillation; Blood Transfusion; Cause of Death; Comparative Effectiveness Research; Dabigatran; Embolism; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Logistic Models; Male; Mortality; Myocardial Infarction; Propensity Score; Proportional Hazards Models; Retrospective Studies; Rivaroxaban; Stroke

Sex-specific effectiveness of rivaroxaban (RIVA), dabigatran (DABI), and warfarin in reducing myocardial infarction (MI), heart failure (HF), and all-cause mortality among patients with atrial fibrillation are not known. We assessed sex-specific associations of RIVA, DABI, or warfarin use with the risk of MI, HF, and all-cause mortality among patients with atrial fibrillation.. Medicare beneficiaries (men: 65 734 [44.8%], women: 81 135 [55.2%]) with atrial fibrillation who initiated oral anticoagulants formed the study cohort. Inpatient admissions for MI, HF, and all-cause mortality were compared between the 3 drugs separately for men and women using 3-way propensity-matched samples. In men, RIVA use was associated with a reduced risk of MI admissions compared with warfarin use (hazard ratio [95% confidence interval (CI): 0.59 [0.38-0.91]), with a trend towards reduced risk compared with DABI use (0.67 [0.44-1.01]). In women, there were no significant differences in the risk of MI admissions across all 3 anticoagulants. In both sexes, RIVA use and DABI use were associated with reduced risk of HF admissions (men: RIVA; 0.75 [0.63-0.89], DABI; 0.81 [0.69-0.96]) (women: RIVA; 0.64 [0.56-0.74], DABI; 0.73 [0.63-0.83]) and all-cause mortality (men: RIVA; 0.66 [0.53-0.81], DABI; 0.75 [0.61-0.93]) (women: RIVA; 0.76 [0.63-0.91], DABI; 0.77 [0.64-0.93]) compared with warfarin use.. RIVA use and DABI use when compared with warfarin use was associated with a reduced risk of HF admissions and all-cause mortality in both sexes. However, reduced risk of MI admissions noted with RIVA use appears to be limited to men.

Topics: Administration, Oral; Administrative Claims, Healthcare; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cause of Death; Chi-Square Distribution; Dabigatran; Databases, Factual; Female; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Medicare; Multivariate Analysis; Myocardial Infarction; Patient Admission; Propensity Score; Proportional Hazards Models; Retrospective Studies; Risk Factors; Rivaroxaban; Sex Factors; Time Factors; Treatment Outcome; United States; Warfarin

Effectiveness data on novel oral anticoagulants (NOACs) versus warfarin for stroke prevention in non-valvular atrial fibrillation (NVAF) by prior warfarin use are limited.. We used data from the US MarketScan databases from 2009 to 2012. NVAF patients initiating dabigatran or rivaroxaban were matched with up to 5 warfarin users. Propensity score-adjusted Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for relevant endpoints in NOACs versus warfarin users. Separate analyses were conducted to compare anticoagulant-naïve users of NOACs and those switching from warfarin.. Among 32,918 dabigatran, 3301 rivaroxaban, and 109,447 warfarin users with NVAF, 225 intracranial bleeds, 1035 ischemic strokes, 958 myocardial infarctions, and 1842 gastrointestinal bleeds were identified. Compared to warfarin users, patients initiating NOACs had similar ischemic stroke rates and lower intracranial bleeding rates, while the gastrointestinal bleeding rate was higher in dabigatran users than warfarin users. Associations of dabigatran with ischemic stroke risk differed between anticoagulant-naïve initiators and patients switching from warfarin; dabigatran was associated with lower ischemic stroke rates in naïve users (HR 0.65, 95% CI 0.52-0.82) but not in switchers (HR 1.20, 95% CI 0.95-1.51), compared to warfarin. Risk of stroke and bleeding was not different between rivaroxaban and warfarin users.. Real-world effectiveness of NOACs (compared to warfarin) for diverse outcomes was comparable to efficacy reported in published clinical trials. However, harms and benefits of switching from warfarin to dabigatran need to be evaluated.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Rivaroxaban; Warfarin

The potential impact of missing data on the results of clinical trials has received heightened attention recently. A National Research Council study provides recommendations for limiting missing data in clinical trial design and conduct, and principles for analysis, including the need for sensitivity analyses to assess robustness of findings to alternative assumptions about the missing data. A Food and Drug Administration advisory committee raised missing data as a serious concern in their review of results from the ATLAS ACS 2 TIMI 51 study, a large clinical trial that assessed rivaroxaban for its ability to reduce the risk of cardiovascular death, myocardial infarction or stroke in patients with acute coronary syndrome. This case study describes a variety of measures that were taken to address concerns about the missing data.. A range of analyses are described to assess the potential impact of missing data on conclusions. In particular, measures of the amount of missing data are discussed, and the fraction of missing information from multiple imputation is proposed as an alternative measure. The sensitivity analysis in the National Research Council study is modified in the context of survival analysis where some individuals are lost to follow-up. The impact of deviations from ignorable censoring is assessed by differentially increasing the hazard of the primary outcome in the treatment groups and multiply imputing events between dropout and the end of the study. Tipping-point analyses are described, where the deviation from ignorable censoring that results in a reversal of significance of the treatment effect is determined. A study to determine the vital status of participants lost to follow-up was also conducted, and the results of including this additional information are assessed.. Sensitivity analyses suggest that findings of the ATLAS ACS 2 TIMI 51 study are robust to missing data; this robustness is reinforced by the follow-up study, since inclusion of data from this study had little impact on the study conclusions.. Missing data are a serious problem in clinical trials. The methods presented here, namely, the sensitivity analyses, the follow-up study to determine survival of missing cases, and the proposed measurement of missing data via the fraction of missing information, have potential application in other studies involving survival analysis where missing data are a concern.

Topics: Acute Coronary Syndrome; Cardiovascular Diseases; Double-Blind Method; Factor Xa Inhibitors; Humans; Lost to Follow-Up; Multicenter Studies as Topic; Myocardial Infarction; Patient Dropouts; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Survival Analysis

We report the case of a 65--year-old woman admitted for inferior ST-segment elevation myocardial infarction complicated by complete atrioventricular block. The patient was under treatment with a novel oral anticoagulant (NOAC, rivaroxaban) because of a history of recurrent idiopathic pulmonary embolism. Emergency angiography showed complete acute thrombotic occlusion of the right coronary artery. After manual thrombectomy, there was no angiographic evidence of underlying atherosclerosis, therefore no further percutaneous coronary intervention was performed. Subsequent clinical course was uneventful. Laboratory tests demonstrated the presence of a heterozygous mutation of the factor II gene (G20210A), confirming the clinical evidence of a thrombophilic state. As rivaroxaban seemed to be ineffective in preventing spontaneous coronary thrombosis in this patient, antithrombotic therapy was shifted to warfarin plus low-dose aspirin. No further ischemic events occurred during the 1-year follow-up. It can be hypothesized that factor Xa inhibition by NOACs, such as rivaroxaban, could be insufficient in case of a thrombophilic state due to thrombin mutation. A brief review of the current literature on use of NOACs in acute coronary syndromes is also reported.

Topics: Aged; Anticoagulants; Female; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Rivaroxaban; ST Elevation Myocardial Infarction; Thrombophilia; Treatment Outcome

We aimed to investigate the relationship between aspirin use and clinical outcomes in patients enrolled in Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), in particular, those with known coronary artery disease (CAD).. Patients in ROCKET AF, comparing rivaroxaban and warfarin, were analyzed. Aspirin use was assessed at baseline. Stroke and systemic embolism, myocardial infarction, death, and major or nonmajor clinically relevant (NMCR) bleeding were compared between groups. Multivariable modeling was done adjusting for baseline risk factors.. A total of 5,205 (36.5%) patients were receiving aspirin at baseline (mean dose 99.2mg); 30.6% of those had known CAD. Patients receiving aspirin were more likely to have prior myocardial infarction (22% vs 14%; P<.001) and heart failure (68% vs 59%; P<.001). Relative efficacy of rivaroxaban versus warfarin was similar with and without aspirin use for both stroke/systemic embolism (P=.95 for interaction), and major or NMCR bleeding (P=.76 for interaction). After adjustment, aspirin use was associated with similar rates of stroke/systemic embolism (hazard ratio [HR] 1.16, 95% CI 0.98-1.37; P=.094) but higher rates of all-cause death (HR 1.27, 95% CI 1.13-1.42; P<.0001) and major or NMCR bleeding (HR 1.32, 95% CI 1.21-1.43; P<.0001). There was a significant interaction between no CAD at baseline and aspirin for all-cause death (P=.009).. Aspirin use at baseline was associated with an increased risk for bleeding and all-cause death in ROCKET AF, a risk most pronounced in patients without known CAD. Although these findings may reflect unmeasured clinical factors, further investigation is warranted to determine optimal aspirin use in patients with AF.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Comorbidity; Drug Therapy, Combination; Embolism; Factor Xa Inhibitors; Female; Heart Failure; Hemorrhage; Humans; Male; Middle Aged; Mortality; Myocardial Infarction; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk Factors; Rivaroxaban; Stroke; Warfarin

Contemporary rates of oral anticoagulant (OAC) therapy and associated outcomes among patients undergoing percutaneous coronary intervention (PCI) have been poorly described.. Using data from an integrated health care system from 2009 to 2014, we identified patients on OACs within 30 days of PCI. Outcomes included in-hospital bleeding and mortality. Of 9566 PCIs, 837 patients (8.8%) were on OACs, and of these, 7.9% used non-vitamin K antagonist agents. OAC use remained stable during the study (8.1% in 2009, 9.0% in 2014; P=0.11), whereas use of non-vitamin K antagonist agents in those on OACs increased (0% in 2009, 16% in 2014; P<0.01). Following PCI, OAC-treated patients had higher crude rates of major bleeding (11% versus 6.5%; P<0.01), access-site bleeding (2.3% versus 1.3%; P=0.017), and non-access-site bleeding (8.2% versus 5.2%; P<0.01) but similar crude rates of in-hospital stent thrombosis (0.4% versus 0.3%; P=0.85), myocardial infarction (2.5% versus 3.0%; P=0.40), and stroke (0.48% versus 0.52%; P=0.88). In addition, prior to adjustment, OAC-treated patients had longer hospitalizations (3.9±5.5 versus 2.8±4.6 days; P<0.01), more transfusions (7.2% versus 4.2%; P<0.01), and higher 90-day readmission rates (22.1% versus 13.1%; P<0.01). In adjusted models, OAC use was associated with increased risks of in-hospital bleeding (odds ratio 1.50; P<0.01), 90-day readmission (odds ratio 1.40; P<0.01), and long-term mortality (hazard ratio 1.36; P<0.01).. Chronic OAC therapy is frequent among contemporary patients undergoing PCI. After adjustment for potential confounders, OAC-treated patients experienced greater in-hospital bleeding, more readmissions, and decreased long-term survival following PCI. Efforts are needed to reduce the occurrence of adverse events in this population.

Topics: Aged; Aged, 80 and over; Angina Pectoris; Anticoagulants; Atrial Fibrillation; Comorbidity; Dabigatran; Databases, Factual; Female; Hospital Mortality; Humans; Kaplan-Meier Estimate; Length of Stay; Logistic Models; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Patient Readmission; Percutaneous Coronary Intervention; Postoperative Hemorrhage; Propensity Score; Proportional Hazards Models; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Stents; Stroke; Thrombosis; Venous Thromboembolism; Warfarin

Left ventricular (LV) thrombus is usually seen in situations with reduced LV function, and is mostly seen in patients with large anterior ST-elevation myocardial infarction (MI). Most embolic events, in patients with LV thrombus formation, occur within the first 3-4 months, thus the recommendations regarding the duration of anticoagulant therapy. According to guidelines, an oral vitamin K antagonist, warfarin, is being used as an anticoagulant for this period. Novel oral anticoagulants were found to be either non-inferior or superior compared with warfarin in prevention of thromboembolism in patients with non-valvular atrial fibrillation. However, the data about their role in the management of LV thrombus are limited to case reports. Here, we report on the dissolution of LV apical thrombus in 3 patients with anterior ST-elevation MI receiving dual antiplatelet therapy and rivaroxaban on a reduced dose for 3 months.

Topics: Aged; Combined Modality Therapy; Coronary Angiography; Coronary Thrombosis; Diagnosis, Differential; Echocardiography; Factor Xa Inhibitors; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Rivaroxaban; Stents; Ventricular Dysfunction, Left

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

Medical costs that may be avoided when any of the four new oral anticoagulants (NOACs), dabigatran, rivaroxaban, apixaban, and edoxaban, are used instead of warfarin for the treatment of non-valvular atrial fibrillation (NVAF) were estimated and compared. Additionally, the overall differences in medical costs were estimated for NVAF and venous thromboembolism (VTE) patient populations combined.. Medical cost differences associated with NOAC use vs warfarin or placebo among NVAF and VTE patients were estimated based on clinical event rates obtained from the published trial data. The clinical event rates were calculated as the percentage of patients with each of the clinical events during the trial periods. Univariate and multivariate sensitivity analyses were conducted for the medical-cost differences determined for NVAF patients. A hypothetical health plan population of 1 million members was used to estimate and compare the combined medical-cost differences of the NVAF and VTE populations and were projected in the years 2015-2018.. In a year, the medical-cost differences associated with NOAC use instead of warfarin were estimated at -$204, -$140, -$495, and -$340 per patient for dabigatran, rivaroxaban, apixaban, and edoxaban, respectively. In 2014, among the hypothetical population, the medical-cost differences were -$3.7, -$4.2, -$11.5, and -$6.6 million for NVAF and acute VTE patients treated with dabigatran, rivaroxaban, apixaban, and edoxaban, respectively. In 2014, for the combined NVAF, acute VTE, and extended VTE patient populations, medical-cost differences were -$10.0, -$10.9, -$21.0, and -$21.0 million for dabigatran, rivaroxaban, 2.5 mg apixaban, and 5 mg apixaban, respectively. Medical-cost differences associated with use of NOACs were projected to steadily increase from 2014 to 2018.. Medical costs are reduced when NOACs are used instead of warfarin/placebo for the treatment of NVAF or VTE, with apixaban being associated with the greatest reduction in medical costs.

Topics: Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Costs and Cost Analysis; Dabigatran; Health Expenditures; Hemorrhage; Humans; Models, Econometric; Myocardial Infarction; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; United States; Venous Thromboembolism; Warfarin

Topics: Coronary Artery Disease; Factor Xa Inhibitors; Heart Failure; Humans; Myocardial Infarction; Research Design; Rivaroxaban; Stroke

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Electric Countershock; Embolism; Factor Xa Inhibitors; Heart Diseases; Hemorrhage; Humans; International Normalized Ratio; Middle Aged; Morpholines; Multicenter Studies as Topic; Myocardial Infarction; Prospective Studies; Randomized Controlled Trials as Topic; Research Design; Risk; Rivaroxaban; Stroke; Thiophenes; Thrombophilia; Time Factors; Treatment Outcome; Vitamin K; Warfarin

Large Phase 3 clinical trials for stroke prevention in atrial fibrillation (AF) have compared non-vitamin K antagonist oral anticoagulants (NOACs) against warfarin, with the edoxaban trial only recently reported. In the absence of head to head trials directly comparing these NOACs against each other, we compared the efficacy and safety of edoxaban to other agents by an indirect comparison analysis. We performed an indirect comparison analysis of edoxaban (2 dose strategies) against apixaban (1 dose), dabigatran etexilate (2 doses) and rivaroxaban (1 dose), for their relative efficacy and safety against each other. For high-dose edoxaban vs apixaban, there were no significant differences in efficacy endpoints, mortality, myocardial infarction and major bleeding. Apixaban was associated with less major or clinically relevant non-major bleeding (hazard ratio [HR] 0.79; 95% confidence interval [CI] 0.70-0.90) and gastrointestinal bleeding (HR 0.72; 95% CI 0.53-0.99). For dabigatran 110 mg twice daily, there were no significant differences in the main efficacy or safety endpoints. Dabigatran 150 mg bid was associated with lower stroke/systemic embolism (SE) (HR 0.75; 95% CI 0.56-0.99), stroke (HR 0.73; 95% CI 0.55-0.96) and haemorrhagic stroke (HR 0.48; 95% CI 0.23-0.99). There were no significant differences between high-dose edoxaban vs rivaroxaban for efficacy endpoints or mortality, but rivaroxaban had more major and/or clinically relevant non-major bleeding. When compared to low-dose edoxaban, apixaban was associated with lower stroke/SE (HR 0.70; 95% CI 0.55-0.89), stroke (HR 0.70; 95% CI 0.55-0.92) and ischaemic stroke (HR 0.65; 95% CI 0.50-0.89), but more major bleeding (HR 1.47; 95% CI 1.20-1.80). For dabigatran 110 mg bid, there were no significant differences in the efficacy endpoints, but dabigatran 110 mg bid had higher major (and gastrointestinal) bleeding. Dabigatran 150 mg bid and rivaroxaban were associated with lower stroke/SE and ischaemic stroke, but higher bleeding rates. In the present analysis, we have provided for the first time, comparisons of efficacy and safety of edoxaban against other NOACs. Notwithstanding the significant limitations of an indirect comparison analysis, some differential effects are evident with the NOACs for stroke prevention, allowing us to allow the prescriber a 'choice' to be able to fit the drug to the patient clinical profile (and vice versa).

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Clinical Trials, Phase III as Topic; Dabigatran; Female; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Myocardial Infarction; Precision Medicine; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Survival Analysis; Thiazoles; Thiophenes; Treatment Outcome

Atrial fibrillation is associated with development of thromboembolic events. New oral anticoagulants (apixaban, rivaroxaban and dabigatran) are recommended for antithrombotic therapy in patients with non-valvular atrial fibrillation (NVAF) with moderate and high risk of stroke.. The objective of this study was to evaluate the cost-effectiveness ratio of apixaban compared to dabigatran and rivaroxaban in patients with NVAF from the Russian Federation national health care system perspective.. This analysis used a Markov model that allowed estimation of the incremental cost-effectiveness ratio (ICER) for apixaban compared to rivaroxaban and dabigatran 110 mg and 150 mg over lifetime horizon for patients with NVAF. The model enclosed cardiovascular event rates based on the results of the indirect treatment comparison that combined data from the randomized clinical trials comparing clinical effectiveness and safety of apixaban, rivaroxaban and dabigatran with warfarin (ARISTOTLE, ROCKET-AF, RE-LY). The following cardiovascular events were considered: ischemic and hemorrhagic stroke, systemic embolism, intracranial hemorrhage, other major bleeds, clinically relevant non-major bleeds and myocardial infarction. Direct medical costs were determined based on the rates of the compulsory national medical insurance system. The price of the new oral anticoagulants was taken as a weighted average tender price for the year 2013. In the model both costs and benefits (quality-adjusted life years and life-years) were discounted at 3.5%. Cost-effectiveness threshold was set at 1.4 million rubles per quality-adjusted life year (QALY) gained and corresponded to the three times GDP per capita in 2013 in the Russian Federation.. In the base case analysis it was demonstrated that apixaban compared to dabigatran 110 mg and 150 mg and rivaroxaban provided additional 0.101, 0.060 and 0.072 life years as well as additional 0.063; 0.038 and 0.041 QALYs respectively. Over lifetime horizon apixaban compared to dabigatran 110 mg and 150 mg and rivaroxaban required additional treatment costs equal to 22.78; 31.18 and 6.70 thousands rubles, respectively. With that estimated incremental cost-effectiveness ratio for apixaban compared to dabigatran 110 mg and 150 mg and rivaroxaban was 362.60, 805.54 and 162.45 thousands rubles per QALY correspondingly.. Apixaban provided increased life expectancy compared to other new anticoagulants and may be considered as a cost-effective alternative to dabigatran 110 mg and 150 mg and rivaroxaban from the Russian Federation national health care system perspective.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Blood Coagulation; Cost-Benefit Analysis; Dabigatran; Drug Monitoring; Hemorrhage; Humans; Models, Statistical; Morpholines; Myocardial Infarction; Prognosis; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Russia; Stroke; Thiophenes; Warfarin

Topics: Acute Coronary Syndrome; Altitude; Blood Coagulation Disorders; Coffee; Factor Xa Inhibitors; Heparin; Humans; Lipoproteins; Lymphatic Diseases; Morpholines; Myocardial Infarction; Platelet Aggregation Inhibitors; Rivaroxaban; Thiophenes; Thrombocytopenia; Thrombosis; Troponin; Venous Thrombosis; von Willebrand Diseases

Topics: Acute Coronary Syndrome; Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Electrocardiography; Expert Testimony; Humans; Morpholines; Myocardial Infarction; Practice Guidelines as Topic; Rivaroxaban; Stroke; Survival Analysis; Thiophenes; Treatment Outcome

Topics: Anticoagulants; Controlled Clinical Trials as Topic; Coronary Thrombosis; Dose-Response Relationship, Drug; Humans; Morpholines; Myocardial Infarction; Risk Assessment; Rivaroxaban; Secondary Prevention; Survival Rate; Thiophenes