Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation

Background: The use of Warfarin reduces the rate of ischemic stroke in patients with atrial fibrillation but requires frequent monitoring and dose adjustment. Rivaroxaban, an oral factor Xa inhibitor, may provide more consistent and predictable anticoagulant effects than Warfarin.
 Methods: In this Open comparison trial, the researchers compared Rivaroxaban (at a daily dose of 20 mg or 15 mg daily in patient with a creatinine clearance of 30-49 ml/min ) with dose adjusted Warfarin (target INR 2.0 to3.0) in 2,846 patients with nonvalvular atrial fibrillation and CHA2DS2-VASc Score 2 or more. The primary efficacy outcome was stroke or systemic embolism and primary safety outcome was major or minor bleeding. This research was designed to determine whether Rivaroxaban have more efficacy and safety than Warfarin for the primary outcomes.
 Results: Total follow-up period was 6 months. Risk factors and co-morbidities were similar in both groups. Baseline investigations were also similar. Age and sex of both groups were matched. The rate of ischaemic stroke was 1.8% in Rivaroxaban group, as compared with 2.18% in the Warfarin group (p 0.479, nonsignificant). The rate of haemorrhagic stroke was 0.53% in Rivaroxaban group, as compared with 1.36 % in the Warfarin group (p 0.026, significant). Systemic embolism was 0.08% in Rivaroxaban group, as compared with 0.15 % in the Warfarin group (p 0.561, non-significant). The rate of major bleeding was 0.4% in Rivaroxaban group and 0.53 % in the Warfarin group (p 0.361, non-significant). The rate of minor bleeding was 2.10% in Rivaroxaban group, as compared with 2.33% in the Warfarin group (p 0.681, non-significant).
 Conclusions: Rivaroxaban have similar efficacy and better safety profile than Warfarin in patients with nonvalvular atrial fibrillation in Bangladeshi population.
 University Heart Journal Vol. 16, No. 2, Jul 2020; 99-105

Safety and efficacy of rivaroxaban compared to warfarin in patients with atrial fibrillation and advanced stages of chronic kidney disease

BackgroundThe effects of rivaroxaban in patients with atrial fibrillation and a bioprosthetic mitral valve remain uncertain.MethodsIn this randomized trial, we compared rivaroxaban (20 mg once daily) with dose-adjusted warfarin (target international normalized ratio, 2.0 to 3.0) in patients with atrial fibrillation and a bioprosthetic mitral valve. The primary outcome was a composite of death, major cardiovascular events (stroke, transient ischemic attack, systemic embolism, valve thrombosis, or hospitalization for heart failure), or major bleeding at 12 months.ResultsA total of 1005 patients were enrolled at 49 sites in Brazil. A primary-outcome event occurred at a mean of 347.5 days in the rivaroxaban group and 340.1 days in the warfarin group (difference calculated as restricted mean survival time, 7.4 days; 95% confidence interval [CI], −1.4 to 16.3; P<0.001 for noninferiority). Death from cardiovascular causes or thromboembolic events occurred in 17 patients (3.4%) in the rivaroxaban group and in 26 (5.1%) in the warfarin group (hazard ratio, 0.65; 95% CI, 0.35 to 1.20). The incidence of stroke was 0.6% in the rivaroxaban group and 2.4% in the warfarin group (hazard ratio, 0.25; 95% CI, 0.07 to 0.88). Major bleeding occurred in 7 patients (1.4%) in the rivaroxaban group and in 13 (2.6%) in the warfarin group (hazard ratio, 0.54; 95% CI, 0.21 to 1.35). The frequency of other serious adverse events was similar in the two groups.ConclusionsIn patients with atrial fibrillation and a bioprosthetic mitral valve, rivaroxaban was noninferior to warfarin with respect to the mean time until the primary outcome of death, major cardiovascular events, or major bleeding at 12 months. (Funded by PROADI-SUS and Bayer; RIVER ClinicalTrials.gov number, NCT02303795.)

ObjectiveTo compare the clinical benefits of rivaroxaban and warfarin in patients with non-valvular atrial fibrillation (NVAF) with high bleeding risk.MethodsA retrospective study was conducted on patients with high bleeding risk NVAF who were hospitalized at the First Affiliated Hospital of Zhengzhou University between May 31, 2016 and May 31, 2019 and took at least rivaroxaban and warfarin. The clinical benefits of both drugs were assessed by efficacy benefit and safety risk. The primary efficacy benefit was a composite end point for stroke (both ischemic and hemorrhagic) and systemic embolism. The secondary efficacy end points were death and myocardial infarction (MI). The principal safety end point was the composite end point of fatal bleeding and critical organ bleeding.ResultsA total of 1,246 patients with high bleeding risk were enrolled, including 787 patients in the rivaroxaban group and 459 patients in the warfarin group. Results of the primary efficacy benefit endpoint were obtained from 104 patients (13.2%) in the rivaroxaban group and 88 (19.2%) patients in the warfarin group (hazard ratio [HR]: 0.681; 95% confidence interval [CI]: 0.512–0.906; P < 0.001 for non-inferiority). The principal safety end points were observed in 49 (6.23%) patients in the rivaroxaban group and in 55 (11.98%) patients in the warfarin group (HR: 0.469 in the rivaroxaban group; 95% CI: 0.314–0.702; P < 0.001). With respect to secondary efficacy and benefit endpoints, 28 (3.56%) patients in the rivaroxaban group and 22 (4.79%) patients in the warfarin group died, with an HR of 0.760 (95% CI: 0.435–1.329; P = 0.336); 32 (4.07%) patients in the rivaroxaban group; and 26 (5.66%) patients in the warfarin group had MI, with an HR of 1.940 (95% CI: 0.495–1.069, P = 0.254) in the rivaroxaban group.ConclusionsRivaroxaban is non-inferior to warfarin in the prevention of stroke and systemic embolism in patients with high blood NVAF. Rivaroxaban is superior to warfarin in reducing fatal bleeding and bleeding in critical organs.Clinical Trial RegistrationChinese Clinical Trials Registry, identifier ChiCTR2100052454.

AHA 2011 Scientific Sessions highlight key studies

20mg Rivaroxaban is effective and safe in high risk patients with nonvalvular atrial fibrillation in China

<i>Circulation: Cardiovascular Interventions</i> Editors’ Picks

Factors Associated With Major Bleeding Events: Insights From the ROCKET AF Trial (Rivaroxaban Once-daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation)

Rivaroxaban

Background and Aims Patients with chronic kidney disease (CKD) develop bleeding and thromboembolic tendencies, so the indication for the use of anticoagulants for atrial fibrillation (AF) is difficult. AF is the most common chronic cardiac arrhythmia, and thromboembolism and ischemic stroke in particular are the main complications. In recent years, new oral anticoagulants (rivaroxaban) have been developed and have shown superiority over classic anti-vitamin K anticoagulants in preventing the risk of stroke, systemic embolism and bleeding. Aim is to evaluate the safety parameters of rivaroxaban in patients with stage 4 chronic kidney disease (CKD) or a transient sustained decrease in glomerular filtration rate (GFR) to 15–29 ml/min/1,73 m2 in the presence of atrial fibrillation (AF). Method Multicenter prospective randomized study that included patients from cardiology departments in 2019. Of 5448 hospitalized patients, 109 (2%) patients with AF and CKD stage 4 or a sustained decrease in GFR to 15-29 ml/min/1.73 m2 were randomized in a 2:1 ratio to rivaroxaban 15 mg/day (n=73) or warfarin (n=36). Primary endpoint: development of large, small and small clinically significant bleeding according to the BARC (Bleeding Academic Research Consortium) and ISTH (International Society on Thrombosis and Hemostasis) scales. The average follow-up period is 12 months. Results Patients taking warfarin were significantly more likely to develop minor bleeding according to BARC scales (n=26 (72.2%) versus n=31 (42.4%), p&amp;lt;0.01) and ISTH (n=22 (61.1%) versus n=27 (36.9%), p&amp;lt;0.01) and all clinically significant (minor clinically significant and major) bleeding according to the ISTH scale [n=10 (27.7%) versus n=8 (10.9%), p=0.03]. The number of readmissions was 32 (43.8% of patients) in the rivaroxaban group, 17 (47.2% of patients) in the warfarin group (p=0.57), of which 12 (37.5%) and 7 (41.1%) (in the rivaroxaban and warfarin groups, respectively) - for urgent reasons (p=0.96). A significant improvement in the dynamics of creatinine levels, GFR (according to CKD-EPI) in the rivaroxaban group was revealed. Conclusion The study provides evidence of a favorable safety profile for rivaroxaban compared with warfarin in patients with AF and advanced CKD.

IntroductionThe efficacy and safety of antithrombotic strategies remain uncertain in patients with atrial fibrillation undergoing lower-extremity revascularisation.Materials and methodsBetween January 2011 and November 2021, 319 patients with atrial fibrillation after lower-extremity revascularisation received rivaroxaban or warfarin treatment as anticoagulation regimens with different antiplatelet therapy strategies. The primary efficacy outcome was the composite of acute limb ischaemia, major amputation for vascular causes, myocardial infarction, ischaemic stroke, clinically driven target lesion revascularisation, and death from vascular causes. The safety outcomes were major bleeding events according to the International Society on Thrombosis and Haemostasis classification criteria.ResultsA total of 178 and 141 patients received rivaroxaban and warfarin treatments, respectively, after revascularisation with or without antiplatelet regimens. The incidence of the primary efficacy outcome at 36 months in the rivaroxaban group (44 patients, 24.7%) tended to be lower than that in the warfarin group (43 patients, 30.5%) (hazard ratio, 0.870; 95% confidence interval, 0.565–1.339; P = 0.527). The incidence of the secondary efficacy outcomes decreased in the rivaroxaban group (56 patients, 31.6%) compared with that in the warfarin group (61 patients, 43.2%). Major bleeding events occurred in three patients (1.7%) in the rivaroxaban group and five patients (3.5%) in the warfarin group; no significant difference in fatal or intracranial bleeding was observed between the groups.ConclusionThis study describes practical experience regarding the use of rivaroxaban and warfarin in patients with peripheral arterial disease complicated by non-valvular atrial fibrillation following endovascular intervention. The efficacy and safety outcomes do not differ significantly between rivaroxaban and warfarin.

The majority of the patients enrolled in the rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation (J-ROCKET AF) trial had hypertension. In this subgroup analysis, we investigated differences in the safety and efficacy of rivaroxaban and warfarin in subjects with and without hypertension. The baseline blood pressure (BP) measurements of patients with hypertension in the rivaroxaban and warfarin groups were 130/77 mm Hg and 131/77 mm Hg, respectively, whereas those of patients without hypertension were 123/74 mm Hg and 124/73 mm Hg, respectively. The incidence rates of the principal safety outcomes in the rivaroxaban and warfarin groups were 18.39% per year and 16.81% per year, respectively, among patients with baseline hypertension (hazard ratio (HR): 1.10; 95% confidence interval (CI): 0.84-1.45) and 16.71% per year and 15.00% per year, respectively, among patients without hypertension at baseline (HR: 1.14; 95% CI: 0.66-1.97), indicating no significant interaction (P=0.933). The incidence rates of the primary efficacy endpoints in the rivaroxaban group and the warfarin group were 0.54% per year and 2.24% per year, respectively, in patients without baseline hypertension (HR: 0.25; 95% CI: 0.03-2.25), and 1.45% per year and 2.71% per year, respectively, in patients with baseline hypertension (HR: 0.54; 95% CI: 0.25-1.16), indicating no significant interaction (P=0.509). In conclusion, the safety and efficacy profile of rivaroxaban was similar to that of warfarin, independent of baseline hypertensive status.

year; RR 1.5; 95% CI: 1.19-1.89; p<0.001). The warfarin group had 64% in the mean time in therapeutic range and based on the findings, the FDA approved the 150 mg BID dosing regimen. Dabigatran was well tolerated except dyspepsia was more common associated with it versus warfarin (11.3% vs. 5.8% respectively; p <0.001). Note that additionally analysis of RE-LY raised concerns of increased rate of myocardial infarction (MI) was seen with dabigatran compared to warfarin (0.74% per year vs. 0.53% per year; RR 1.38, 95% CI, 1.001.91; p=0.048). Twenty-eight more cases of silent MI were identified during the reanalysis period, that changed the statistically significant difference between dabigatran and warfarin for this outcome (0.81% per year vs. 0.64% per year; RR 1.27; 95% CI, 0.94-1.71; p=0.12) [5,6]. Also, Boehringer Ingelheim confirmed serious cases and potentially life-threatening bleeding associated with dabigatran between March 2008 and October 2011 [7,8]. There were 260 fatal bleeding events worldwide that triggered safety concerns and the need for regular assessment of kidney function and dabigatran use. Rivaroxaban was compared to warfarin in the ROCKET AF trial. The study was a multicentered, randomized, double-blind, doubledummy, event-driven trial, which enrolled 14,264 NAF patients at moderate to high risk for stroke. In contrast to the RE-LY trial, patients who were on warfarin for the ROCKET AF had therapeutic International Normalized Ratio 55% of the time. For the per protocol patient population, rivaroxaban was proven to be noninferior to warfarin in the primary efficacy composite endpoint of stroke and systemic embolism (Hazard Ratio [HR]: 0.79, 95% CI: 0.66-0.96, p<0.001). As for the intention to treat population, rivaroxaban was also noninferior to warfarin, but it fails to show superiority over warfarin (HR: 0.88, 95% CI: 0.74 to 1.03, p<0.001 for noninferiority, and p=0.12 for superiority). Mortality rates were similar between the treatment groups for the as treated population (HR: 0.85, 95% CI: 0.70 to 1.02, p=0.07) and in the intention to treat population (HR: 0.92, 95% CI: 0.82 to 1.03, p=0.15). Patients in the rivaroxaban group had lower rates of critical bleeding, fatal bleedings, and intracranial hemorrhages (p=0.007, p=0.003, p=0.02, respectively) [9]. Advantages of rivaroxaban over dabigatran are that rivaroxaban is the once daily dosing, and can be crushed and mixed with applesauce in patients who are unable to swallow tablets. For patients with nasogastric tube or feeding tube, rivaroxaban can be crushed and suspended in water. In addition to NAF, rivaroxaban is indicated for the treatment and prevention of deep vein thrombosis and pulmonary embolism. One specific dose is approved for each indication so healthcare professionals need to be extremely cautious when prescribing rivaroxaban [10]. The ARISTOTLE compared apixaban with warfarin in a multicentered, randomized, double-blinded, double dummy study. Eighteen-thousand two hundred patients with NAF and at least 1 risk factor for stroke were enrolled. Patients on warfarin had a therapeutic INR 62.2% of the time. Patients in the apixaban group has lower rates of stroke or systemic embolism (HR: 0.79, 95% CI: 0.66 to 0.95, p<0.001 for noninferiority and p=0.01 for superiority), and lower mortality rates (HR: 0.89, 95% CI: 0.80 to 0.99, p=0.047). Additionally, less patients in the apixaban group experienced intracranial bleeding (HR: 0.42, 95% CI: 0.30-0.58, p<0.001) or major or clinically relevant non-major bleeding (HR: 0.68, 95%CI 0.61-0.75, p<0.001) [11]. Advantages of apixaban are that doses do not need to be adjusted unless patients have at least 2 factors: age of 80 years or greater, serum creatinine of 1.5 mg/dl or greater, or body weight less than 60 kg. Disadvantages include the twice daily dosing, not recommended for CLcr<15 mL/min or hemodialysis, and no information available on crush or administration through feeding tube [11]. All of the new anticoagulants have the advantage of having a predictable drug effect, faster onset of action, and less need for monitoring as compared to warfarin. The decision of selecting one anticoagulant over another may be difficult. Although all of the new anticoagulants were noninferior in preventing stroke or systemic embolism, apixaban is the only one proven to be superior as compared to warfarin, and is the only one shown to reduce risk of death from any cause [4,9,12]. While dabigatran does not reduce risks of death, it reduces risks of death from vascular causes (p=0.04). Based on the

P279 Standard dose of rivaroxaban in Asian patients with atrial fibrillation: 20ms vs.15mg? Off label dose reduction of rivaroxaban should be avoided

Rivaroxaban and dabigatran are approved to reduce the risk of stroke in patients with nonvalvular atrial fibrillation (NVAF). However, the clinical benefits of rivaroxaban and dabigatran in people with high bleeding risk are unclear. A retrospective study was conducted on NVAF patients admitted to the First Affiliated Hospital of Zhengzhou University from May 31, 2016 to May 31, 2019. These patients had a high risk of bleeding and were taking at least one study medication. The aim of the study was to evaluate clinical benefits by comparing the efficacy and safety risks of these two medications. A total of 1,301 patients with high bleeding risk were enrolled, including 787 patients in the rivaroxaban group and 514 patients in the dabigatran group. Results of the primary efficacy benefit endpoint were obtained from 104 patients (13.21%) in the rivaroxaban group and 81 (15.76%) patients in the dabigatran group [hazard ratio (HR): 0.860; 95% confidence interval (CI): 0.637-1.162; P = 0.327], this indicates that there was no significant difference between dabigatran and rivaroxaban in preventing stroke and systemic embolism in patients with high bleeding risk NVAF. The principal safety end points were observed in 49 (6.23%) patients in the rivaroxaban group and in 36 (7.00%) patients in the dabigatran group (HR: 0.801 in the rivaroxaban group; 95% CI: 0.512-1.255; P = 0.333), this indicates that there was no a significant difference in reducing fatal bleeding and critical organ bleeding. With respect to secondary efficacy and benefit endpoints, 28 (3.56%) patients in the rivaroxaban group and 26 (5.06%) patients in the dabigatran group died, with an HR of 0.725 (95% CI: 0.425-1.238; P = 0.239); 32 (4.07%) patients in the rivaroxaban group; and 31 (6.03%) patients in the dabigatran group had myocardial infarction (MI), with an HR of 0.668 (95% CI: 0.405-1.102, P = 0.114) in the rivaroxaban group, this indicates that there was no significant difference between dabigatran and rivaroxaban in preventing all-cause death and MI. In NVAF patients with high bleeding risk, there was no significant difference between dabigatran and rivaroxaban in preventing stroke and systemic embolism. There was also no significant difference between dabigatran and rivaroxaban in reducing fatal and critical organ bleeding. Chinese Clinical Trials Registry, identifier ChiCTR2100052454.