ROCKET AF Study Research Articles

XaMINA: A Real-World, Prospective, Observational Study of Treatment-Naïve Patients Treated with Rivaroxaban for Stroke Prevention in Atrial Fibrillation in Asia.

The efficacy and safety of rivaroxaban for the prevention of stroke and systemic embolism have been demonstrated in Asian and non-Asian patients with non-valvular atrial fibrillation (NVAF) in multiple studies. However, limited published data exist on its use specifically in treatment-naïve patients from the Asia region. Patients in South Korea and Taiwan can now receive rivaroxaban as first-line therapy, allowing for data generation in this patient group. XaMINA was a prospective, real-world, multicenter, single-arm, observational cohort study of patients with NVAF in South Korea and Taiwan naïve to anticoagulation and initiating rivaroxaban. The primary outcome was major bleeding; secondary outcomes included all-cause mortality, symptomatic thromboembolic events, and treatment persistence. In total, 1094 patients were included and the follow-up was 1year. The baseline mean CHADS2 score was 1.63±0.98, mean CHA2DS2-VASc score was 2.92±1.42, and mean HAS-BLED score was 1.00±0.75. The primary outcome occurred in 20 (1.8%) patients [incidence rate 2.1 events per 100 patient-years (95% CI 1.35-3.25)]. Thromboembolic events occurred in 9 (0.8%) patients, of whom 5 (0.5%) had stroke, 3 (0.3%) myocardial infarction, and 1 (0.1%) a transient ischemic attack. There were no cases of non-central nervous system systemic embolism, and 735 (67.2%) patients persisted with rivaroxaban treatment for 1year. XaMINA demonstrated low incidence rates of major bleeding events and thromboembolic events in patients with NVAF newly initiating rivaroxaban in South Korea and Taiwan, consistent with previous real-world studies reconfirming the results of the ROCKET AF study. The trial was registered on ClinicalTrials.gov (identifier NCT03284762) on 15 September 2017.

Atrial fibrillation in elderly patients. Features of using rivaroxaban

The problem of anticoagulant treatment of elderly patients with atrial fibrillation (AF) is very topical for everyday medical practice because, on the one hand, the proportion of elderly patients among those who have AF is constantly increasing, and, on the other hand, there is no doubt that treatment of elderly patients involves many problems associated with a large number of complications. This material reviews the choice of optimal anticoagulant therapy for older AF patients and focuses on the use of rivaroxaban. Clinical research data show that rivaroxaban is one of the optimal drugs of choice for older patients. Thus, a comparative meta-analysis of the safety of various non-vitamin-K oral anticoagulants (NOAC) in patients of ≥75 years of age (in AF and deep vein thrombosis) showed that administration of rivaroxaban in comparison with warfarin was associated with an almost twofold significantly lower frequency of fatal bleedings (HR 0.53; 95% Cl 0.30-0.93; p = 0.03). According to the ROCKET-AF study, intake of rivaroxaban in elderly patients was comparable in efficiency and safety profile to warfarin. Since renal dysfunction is common in older patients with AF, safety issues are very important. In a ROCKET-AF study, the use of rivaroxaban in patients with moderate renal dysfunction was known to be associated with a lower frequency of fatal bleeding (0.28 vs. 0.74 per 100 patients/ year; HR 0.39; 95% CI 0.15-0.99; p = 0.047) than that of warfarin. Given the high probability of development of exacerbation of IHD in elderly patients with AF, they need an anticoagulant that maximally protects them from acute coronary complications. In the meta-analysis of 28 randomized trials with NOAC, only rivaroxaban was associated with a significant reduction by 22% in the risk of myocardial infarction and acute coronary syndrome compared to other control drugs. In conclusion, it can be stated that rivaroxaban may be a good choice for anticoagulant treatment specifically for elderly patients with AF, especially given its efficacy and safety profile and the adherence of patients to therapy.

Discussion

Discussion

Elderly Patients with Atrial Fibrillation: Focus on Comorbidity and Safety of Anticoagulant Therapy

The article discusses issues related to the prescription of anticoagulant therapy to elderly patients with atrial fibrillation (AF), especially those over 70 and 80 years of age. The relevance of the issue is primarily due to the prevalence of AF in this cohort of patients, and the second is due to the higher incidence of comorbidity. The presented material demonstrates the peculiarities of anticoagulant therapy application in groups of patients older than 75, based on the data of randomized clinical trials, and also presents extrapolation of the results of RCTs to the real clinical practice (data of registers and cohort trials). The use of unreasonably low doses of oral anticoagulants in elderly patients is debated. It often leads to a decrease in the efficacy of anticoagulant therapy without improving the drugs safety profile. A new validated scale (ABH) for evaluating of anticoagulant therapy safety is presented in the article. The ABH scale can be used before prescribing to patients exactly direct oral anticoagulants. This scale is simpler and more practical than the HAS-BLED scale. The data for the ABH scale are validated based on direct oral anticoagulants in 21,248 patients from the Norwegian register. The presented results demonstrate a favorable efficiency and safety profile of rivaroxaban in comparison with warfarin in patients 75 years and older. Thus, the overall benefit for the use of rivaroxaban against warfarin in patients > 75 years of age in the subanalysis of the ROCKET-AF study was statistically significantly greater than in younger patients with AF. Data on 11121 patients with AF who were treated with rivaroxaban for the prevention of stroke and systemic embolism are included in the combined analysis of the XANTUS, XANAP and XANTUS-EL registers. 96% of patients in the study did not have serious thromboembolic events. The amount of major bleeding was 1.7 per 100 patient-years, and gastrointestinal bleeding was 0.7 per 100 patient-years. This turned out to be less than in some other registry studies. In addition, patients showed good adherence to rivaroxaban treatment: after a year, 77.4% of patients continued to take the drug.

Rivaroxaban for Stroke Prevention in Patients with Non-Valvular Atrial Fibrillation and Active Cancer

BACKGROUNDThe link between aging, cancer and atrial fibrillation is well known and the appropriate anticoagulation management of non-valvular atrial fibrillation (NVAF) in patients with active cancer is of growing clinical concern. Rivaroxaban has been broadly used for the primary prevention of stroke and systemic embolism in the general population of patients with NVAF. However, individuals with a serious concomitant illness associated with a life expectancy of less than 2 years were excluded from pivotal trials including the ROCKET-AF study, limiting the generalizability of results to patients with active cancer. There is little published evidence on the safety and efficacy of rivaroxaban for NVAF in this specific subgroup. OBJECTIVESThe aim of this study was to assess the safety and efficacy of rivaroxaban in patients with active cancer and NVAF. METHODSThe use of rivaroxaban in cancer patients at Memorial Sloan Kettering Cancer Center (MSKCC) was monitored in the setting of a Quality Assessment Initiative. Patients with active cancer and NVAF treated with rivaroxaban from 1/1/2014 through 3/31/2016 are included in this analysis. Endpoints of interest were defined a priori and include stroke, systemic embolism, major bleeding and clinically-relevant non-major bleeding leading to discontinuation of rivaroxaban for at least 7 days (CRNMB). Clinical events were assessed through text searches of medical records. The analysis was performed respecting different times on previous anticoagulation, considering the first 90 days as the acute phase of treatment and contrasting it with the subsequent chronic phase. RESULTSA total of 163 evaluable patients were included in the analysis, with a median age of 72.0 years (interquartile range=67.0-77.5 years) and 56% of these individuals being men. The majority had a solid tumor (85%), with stage IV disease reported in 50% of cases. The mean CHA2DS2-Vasc score was 3.2 (standard deviation=1.5) and 64% of patients were already in the chronic phase of anticoagulation. Results for the acute, chronic and combined phases of anticoagulation are presented in the Table and plotted in the Figure. The estimated cumulative incidence of ischemic stroke, major bleeding, and CRNMB at 1 year were 1.4% (95% CI=0-3.4%), 1.2% (95% CI=0-2.9%) and 14.0% (95% CI=4.2-22.7%) respectively, after adjusting for competing risks. Interestingly, the cumulative incidence of major bleeding in our cohort is lower than the value reported for the ORBIT-AF registry of cancer patients on dabigatran or a vitamin K antagonist for NVAF, in which the estimated rate of this complication was 5.1/100 patient-years. Lastly, the 1-year cumulative incidence of mortality was 22.6% (95% CI=12.2-31.7%). This high risk of death was present throughout the observation period and reflects the cancer population. One patient died after developing an acute ischemic cerebrovascular insult and a myocardial infarction. There were no deaths related to bleeding and no recorded systemic embolism episodes. CONCLUSIONSThe safety and efficacy profile of rivaroxaban treatment for NVAF in patients with active cancer seems comparable to what was observed for the general population in the ROCKET-AF study, but ideally a prospective study would be required to confirm these findings. [Display omitted] [Display omitted] DisclosuresYu:Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Soff:Janssen Scientific Affairs, LLC: Consultancy, Research Funding. Mantha:Janssen Scientific Affairs, LLC: Research Funding.

De los ensayos clínicos a la práctica clínica. Evidencias con rivaroxaban en el tratamiento anticoagulante del paciente con fibrilación auricular no valvular

Despite the information provided by clinical trials is important, there are relevant clinical differences between those patients included in clinical trials and data of daily outpatient clinics. As a result, in some cases, the results of randomized clinical trials could not be directly applied to clinical practice. In this context, to perform «real-life» registries is mandatory.In the ROCKET-AF study, rivaroxaban, a once-daily direct oral anticoagulant, was at least as effective as warfarin for preventing stroke or systemic embolism, with similar rates of major bleeding, but with a lesser risk of intracranial, critical and fatal bleedings. In the last years, different large registries have confirmed that rivaroxaban is effective and even safer in real-life patients than in ROCKET-AF.The aim of this review is to update the current evidence about the efficacy, effectiveness and safety of rivaroxaban in real-life patients.

Rivaroxaban in non valvular atrial fibrillation: subgroups analysis

After the ROCKET AF study main paper several subgroups analysis were recently published. These studies are useful to better evaluate the rivaroxaban efficacy and safety in different clinical conditions. Here the subgroup analysis of patients with moderate renal failure, heart failure and diabetes are presented. Post hoc data on patients who underwent an electrical or pharmacological cardioversion during ROKET AF follow up were available and here we analyze also the results of the first randomized study on electrical cardioversion in patients treated with new oral anticolagulants: the X-VeRT trial. A metanalysis of all the studies with rivaroxaban (one on stroke prevention in atrial fibrillation, two on acute coronary syndromes, four on deep venous thrombosis prophylaxis and two on pulmonary embolism treatment) with respect to the risk of myocardial infarction is examined.

Response to Letter Regarding Article, “Renal Dysfunction as a Predictor of Stroke and Systemic Embolism in Patients With Nonvalvular Atrial Fibrillation: Validation of the R 2 CHADS 2 Index in the ROCKET AF (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) and ATRIA (Anticoagulation and Risk

Response to Letter Regarding Article, “Renal Dysfunction as a Predictor of Stroke and Systemic Embolism in Patients With Nonvalvular Atrial Fibrillation: Validation of the R ₂ CHADS ₂ Index in the ROCKET AF (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) and ATRIA (Anticoagulation and Risk

Stroke prediction with an adjusted R-CHA2DS2VASc score in a cohort of patients with a Myocardial Infarction

A new risk stratification scheme incorporating the original CHADS2 score and renal function, entitled R(2)CHADS(2), was validated in the ROCKET-AF and ATRIA study cohorts. Adjusting and validating a modified R-CHA2DS2VASc score as a predictor of ischaemic stroke and all-cause mortality in patients discharged following admission for a Myocardial Infarction (MI). Observational retrospective single-centre cohort study including 1711 patients admitted with MI and discharged alive. We tested the prognostic performance of R-CHA2DS2VASc, based on the original CHA2DS2VASc score with few modifications (addition of renal function parameters [glomerular filtration rate and urea], performance of a revascularization procedure and history of atrial fibrillation). R-CHA2DS2VASc was evaluated for its discriminative performance and calibration in the prediction of ischaemic stroke (primary endpoint), all-cause mortality and a composite endpoint of ischemic stroke plus all-cause mortality (secondary outcomes) during follow-up. R-CHA2DS2VASc score's areas under the curve (AUC) for the occurrence of primary and secondary outcomes were: Ischaemic stroke: AUC 0.717 ± 0.031, p<0.001 (vs. 0.681 ± 0.043 for CHA2DS2VASc, p=0.290); all-cause mortality during follow-up: AUC 0.811 ± 0.014, p<0.001 (vs. 0.782 ± 0.019 for GRACE, p=0.245); composite endpoint: AUC 0.803 ± 0.014, p<0.001. The integrated discrimination improvement index (IDI) and relative IDI for the primary endpoint were 0.015 and 28.2%, respectively, while the IDI and relative IDI for all-cause mortality were 0.13 and 72.1%, suggesting a large improvement in risk stratification. An R-CHA2DS2VASc score below 3 had a negative predictive value of 98.6% for the occurrence of ischaemic stroke. The modified R-CHA2DS2VASc score has shown good calibration and high discriminative performance in the prediction of post-discharge ischaemic stroke and all-cause mortality. The inclusion of renal function in thromboembolic risk predicting schemes seems warranted.

New oral anticoagulant drugs: real-world data.

Oral anticoagulants or ‘blood thinners’ were proposed in 400 BC during the time of Hippocrates [1]. The first paper entitled ‘Coumadin (warfarin) sodium – a new anticoagulant’ was published in 1956 [2]. Despite its limitations, coumadin stood the test of time. Ximelagatran, a very potent oral thrombin inhibitor, licensed in Europe for a short time, was later withdrawn in 2006 for concerns of causing hepatotoxicity [3].

Comparison of Cost-Effectiveness of Anticoagulation with Dabigatran, Rivaroxaban and Apixaban in Patients with Non-Valvular Atrial Fibrillation Across Countries

AbstractAbstract 1164The three new oral anticoagulants (NOAC) dabigatran 110mg bid and 150mg bid, investigated in the RE-LY trial, rivaroxaban 20mg od of the ROCKET trial, and apixaban 5mg bid of the ARISTOTLE trial showed equivalent or superior efficacy and safety compared to warfarin in these patients. We performed a cost-effectiveness analysis for these NOACs in Germany and compared the quality of life (QALY), incremental cost effectiveness ratios (ICER), and total costs across those countries form where these data are published.The base case population was a hypothetical cohort of patients 65 years or older with AF who were at increased risk for stroke (CHADS2-score >1) and had no contraindications to anticoagulation. The time horizon was based on the life expectancy of the German population. The QALYs, health insurance costs, and ICER for the NOACs compared with warfarin were calculated for each study. The sensitivity analysis was performed for different base case prices. The Markov decision model was adopted using the TreeAge Pro 2011 program. The data of the outcomes of ischemic stroke and cerebral embolism, major and intracerebral haemorrhage, myocardial infarction, and mortality were taken from the 3 studies comparing the NOAC with INR-adjusted warfarin. Prices for clinical events and for outpatient care were taken from the institute for payment regulations in German hospitals (InEK).The base-case analysis of a 65 years old person with a >2 CHADS2 score using the data from the RE-LY study resulted in 11.41 QALYs for warfarin, 11.53 QALYs for dabigatran 110mg bid, 11.66 QALYs for dabigatran 150 mg bid. ICERs per QALY were 49640€ for dabigatran 110 mg bid and 49590€ for dabigatran 150 mg bid versus warfarin. The same base-case analysis using the data from the ROCKET AF study resulted in 10.79 QALYs for warfarin versus 11.05 QALYs for rivaroxaban. ICERs per QALY were 48980€ for rivaroxaban versus warfarin. The base-case analysis using the data from the ARISTOTLE study resulted and 11.04 QALYs for warfarin versus 11.38 QALYs for apixaban. ICERs per QALY were 49720€ for apixaban versus warfarin. According the Markov Model the daily value based daily prices were 1.25€ for dabigatran 110 mg bid, 2.50€ for dabigatran 150 mg bid, 2.60€ for rivaroxaban, and 3.10€ for apixaban in Germany. The model was highly sensitive to the daily costs for the NOACs but relatively insensitive to other model inputs. Calculating the range of NOAC prices from 0.2 to 10 Euro versus the ICERs dabigatran 110 mg bid produced the highest increase of ICERs over this range of daily costs (Tukey-Kramer test, p<0.05) Comparing these data across countries using the published data shows that the willingness to pay per QALY as well as differences in treatment costs between substantially influences the daily prices of the NOACs.The data demonstrate the necessity to analyse the cost-effectiveness separately for every study due to differences in the INR-adjusted warfarin treated control group. The better the outcome during treatment with warfarin the lower is the benefit of the NOAC. The tendency of the cost-effectiveness calculated by the Markov model is comparable across countries. Disclosures:No relevant conflicts of interest to declare.

Rivaroxaban for Stroke Prevention in Atrial Fibrillation and Secondary Prevention in Patients With a Recent Acute Coronary Syndrome

The occurrence of disabling stroke, the major fatal consequence of atrial fibrillation, can be reduced by almost two-thirds with warfarin oral anticoagulation. Recent estimates on the prevalence of atrial fibrillation in the USA suggest that approximately 3 million people suffer from this common cardiac arrhythmia, therefore, the socioeconomic impact of adequate oral anticoagulation is enormous. Rivaroxaban, a direct orally available factor Xa inhibitor, is the first of a new class of drugs that target a central factor of the coagulation cascade upstream of thrombin. In the ROCKET AF clinical trial, rivaroxaban demonstrated noninferiority compared with warfarin for stroke prevention in patients with atrial fibrillation, while intracranial and fatal bleeding occurred less frequently with rivaroxaban treatment. Rivaroxban has recently been approved for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation by the US FDA and EMA. Very recently, rivaroxaban in addition to dual antiplatelet therapy, was shown to reduce mortality in patients with a recent acute coronary syndrome in the ATLAS ACS 2-TIMI 51 clinical trial. The clinical evaluation of rivaroxaban in cardiovascular disease and the results of the ROCKET AF study, the landmark clinical trial of rivaroxaban for stroke prevention, are discussed along with the unique pharmacological profile of rivaroxaban.

RIVAROXABAN IN THE PREVENTION OF THROMBOEMBOLIC COMPLICATIONS IN PATIENTS WITH ATRIAL FIBRILLATION

The possibilities of antithrombotic therapy in atrial fibrillation are highlighted. The alternative antithrombotic agents, including rivaroxaban presented along with the traditional drugs (acetyl-salicylic acid, warfarin). Efficacy and safety of rivaroxaban is considered on the basis of the results of the ROCKET-AF study.

New anticoagulants for the prevention of stroke in atrial fibrillation

Oral anticoagulation in atrial fibrillation is obligatory to lower the risk of spontaneous cerebrovascular and systemic thromboembolism. For this purpose, vitamin K antagonists (coumarins) have been recommended as the most effective drugs for a long time. However, problems with the practical use of these agents, e.g. the need for frequent and regular coagulation controls, the inter-individual differences in maintaining a stable therapeutic range, as well as drug or food interactions, have led to the search and investigation of alternative compounds characterized by a more simple use (e.g. without regular controls of therapeutic levels), high efficacy, as well as low risk of bleeding. The direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban and apixaban have recently been investigated to prove whether they fulfill the high expectancy of an ideal anticoagulant with respect to a more favorable efficacy/safety profile and without the need for coagulation controls, thereby improving quality of life. Dabigatran (RE-LY) achieved an impressive reduction in stroke and non-central nervous system (non-CNS) embolism (110 mg: 1.5%/year; 150 mg: 1.1%/year) in contrast to warfarin (1.7%/year; P = 0.34 and P < 0.001) with a favorable action on bleeding hazards. The results of rivaroxaban which were obtained in the ROCKET AF study (on treatment analysis: stroke and non-CNS embolism: 1.7%/year vs. 2.15%/year with warfarin; P = 0.015; primary safety endpoint major and minor bleeding: 14.91 vs. 14.52%; P = 0.442) point in the same direction. And finally, compared to aspirin, apixaban reduced the combined primary efficacy endpoint by 52% with comparable rates of bleeding (AVERROES). This review gives a summary of the current knowledge about these agents and their potential future importance.