Treatment Effect Of Rivaroxaban Research Articles

The treatment effect of rivaroxaban on clot characteristics in patients who present acutely with first time deep vein thrombosis.

The acute vascular disease deep vein thrombosis (DVT) requires oral anticoagulants to prevent progression. Monitoring therapeutic efficacy of direct oral anticoagulants (DOAC), including rivaroxaban, is problematic as no reliable test is available. Advances in rheometry have led to the development of a functional coagulation biomarker using Gel Point (GP) analysis which assesses clot structure formation. The biomarker measures incipient clot formation time (TGP) and quantifies fibrin clot structure in terms of fractal dimension (df). This study aimed to investigate clot structure formation in first time DVT and the effect of rivaroxaban treatment. This prospective observational cohort study measured the GP and standard laboratory markers at three sample points: pre-treatment and at 20 and 60 days following 15 mg BD and 20 mg OD rivaroxaban respectively. Forty DVT patients (mean age 64 years [SD±14.8]; 23 males, 17 female) were recruited. The results show that DVT vs non-DVT patients did not have a significantly different GP profile (df: 1.72±0.06 vs 1.70±0.06 and TGP: 267±68 sec vs 262±73 sec) with both within the defined healthy index. In addition, rivaroxaban therapy increased TGP to 392 s (±135 s) after 20 days, and subsequently increased to 395 s (±194 s) at 60 days but did not significantly increase df (from 1.69±0.05 to 1.71±0.06). The results indicate in this cohort of DVT patients there was no underlying hypercoagulable effect as determined by gel point analysis. Furthermore, the anticoagulant effect of rivaroxaban prolonged clotting, suggesting a protective effect against clot formation, without significantly reducing clot microstructural properties.

Risk factors and clinical outcomes in chronic coronary and peripheral artery disease: An analysis of the randomized, double-blind COMPASS trial.

Secondary prevention in patients with coronary artery disease and peripheral artery disease involves antithrombotic therapy and optimal control of cardiovascular risk factors. In the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) study, adding low-dose rivaroxaban on top of aspirin lowered cardiovascular events, but there is limited data about risk factor control in secondary prevention. We studied the association between risk factor status and outcomes, and the impact of risk factor status on the treatment effect of rivaroxaban, in a large contemporary population of patients with coronary artery disease or peripheral artery disease. We reported ischemic events (cardiovascular death, stroke, or myocardial infarction) in participants from the randomized, double-blind COMPASS study by individual risk factor (blood pressure, smoking status, cholesterol level, presence of diabetes, body mass index, and level of physical activity), and by number of risk factors. We compared rates and hazard ratios of patients treated with rivaroxaban plus aspirin vs aspirin alone within each risk factor category and tested for interaction between risk factor status and antithrombotic regimen. Complete baseline risk factor status was available in 27,117 (99%) patients. Status and number of risk factors were both associated with increased risk of ischemic events. Rates of ischemic events (hazard ratio 2.2; 95% confidence interval 1.8-2.6) and cardiovascular death (hazard ratio 2.0; 1.5-2.7) were more than twofold higher in patients with 4-6 compared with 0-1 risk factors (p < 0.0001 for both). Rivaroxaban reduced event rates independently of the number of risk factors (p interaction 0.93), with the largest absolute benefit in patients with the highest number of risk factors. More favorable risk factor status and low-dose rivaroxaban were independently associated with lower risk of cardiovascular events.

4112Risk factors and clinical outcomes in chronic CAD and PAD: an analysis of the randomized, double-blind COMPASS trial

Abstract Background Patients with coronary artery disease (CAD) and peripheral artery disease (PAD) are at high risk for cardiovascular death and ischemic events. Secondary prevention requires both optimal control of modifiable cardiovascular risk factors and antithrombotic therapy. The COMPASS study showed a reduction in ischemic events in patients treated with the combination of low-dose rivaroxaban and aspirin, compared with aspirin alone. However, the impact of intensifying antithrombotic therapy by baseline risk factor control is not well studied. Objective To study the association between baseline risk factor status and outcomes, and the effects of treatment with low-dose rivaroxaban and aspirin compared with aspirin alone according to baseline risk factors, in a large contemporary population of patients with CAD or PAD. Methods We studied ischemic events (cardiovascular death, stroke, or MI) in participants from the randomised, double blind COMPASS trial in relation to baseline blood pressure, smoking status, cholesterol level, presence of diabetes, body mass index, and level of physical activity, as well as by the number of cardiovascular risk factors (0–1, 2, 3, 4, or 5–6). Within each risk factor category, we compared rates and hazard ratios of patients treated with rivaroxaban plus aspirin vs aspirin alone and tested for interaction between the treatment effect of rivaroxaban and risk factor status. Results Baseline information on all six risk factors was available in 27,117 (99%) patients. Each risk factor was associated with increased risk of ischemic events (Figure 1, panel A). Patients with 5 or 6 risk factors had more than 2-fold higher rates of ischemic events (HR 2.36; 95% CI: 1.80–3.10) and of cardiovascular death (HR 2.22; 1.48–3.33) compared with patients with 0 or 1 risk factor. The addition of low-dose rivaroxaban on top of aspirin reduced event rates independently of number of risk factors (p for interaction 0.93) (Figure 1, panel B). The largest absolute benefit of low-dose rivaroxaban was seen in patients with the greatest number of risk factors. Figure 1 Conclusion More favourable baseline risk factor status and the use of low-dose rivaroxaban were both independently associated with lower risk of ischemic events. Patients at highest risk, based on number of baseline risk factors, derive the largest absolute benefit of the combination of rivaroxaban and aspirin. Acknowledgement/Funding The COMPASS trial was sponsored by Bayer AG. The sponsor did not influence the analysis plan, drafting of abstract, or the decision to submit

Effect of Procedure and Coronary Lesion Characteristics on Clinical Outcomes Among Atrial Fibrillation Patients Undergoing Percutaneous Coronary Intervention: Insights From the PIONEER AF-PCI Trial

ObjectivesThis 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. BackgroundAmong stented AF patients, the impact of procedural access strategies or lesion characteristics on antithrombotic safety and efficacy outcomes is unclear. MethodsIn 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 P2Y12 inhibitor (n = 709); 2) rivaroxaban 2.5 mg twice a day plus dual antiplatelet therapy (DAPT) (n = 709); and 3) dose-adjusted warfarin plus DAPT (n = 706). Kaplan-Meier rates of clinically significant bleeding and major adverse cardiovascular events were compared between treatments stratified by subgroups of procedure type and lesion characteristics. ResultsCompared 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). ConclusionsAmong 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)

Efficacy and safety of rivaroxaban compared with warfarin in patients with carotid artery disease and nonvalvular atrial fibrillation: Insights from the ROCKET AF trial.

Atrial fibrillation (AF) increases risk of stroke 5-fold. Carotid artery disease (CD) also augments the risk of stroke, yet there are limited data about the interplay of these 2 diseases and clinical outcomes in patients with comorbid AF and CD. Among patients with both AF and CD, use of rivaroxaban when compared with warfarin is associated with a lower risk of stroke. This post hoc analysis from ROCKET AF aimed to determine absolute rates of stroke/systemic embolism (SE) and bleeding, and the efficacy and safety of rivaroxaban compared with warfarin in patients with AF and CD (defined as history of carotid occlusive disease or carotid revascularization [endarterectomy and/or stenting]). A total of 593 (4.2%) patients had CD at enrollment. Patients with and without CD had similar rates of stroke or SE (adjusted hazard ratio [HR]: 0.99, 95% confidence interval [CI]: 0.66-1.48, P = 0.96), and there was no difference in major or nonmajor clinically relevant bleeding (adjusted HR: 1.04, 95% CI: 0.88-1.24, P = 0.62). The efficacy of rivaroxaban compared with warfarin for the prevention of stroke/SE was not statistically significant in patients with vs those without CD (interaction P = 0.25). The safety of rivaroxaban vs warfarin for major or nonmajor clinically relevant bleeding was similar in patients with and without CD (interaction P = 0.64). Patients with CD in ROCKET AF had similar risk of stroke/SE compared with patients without CD. Additionally, there was no interaction between CD and the treatment effect of rivaroxaban or warfarin for stroke prevention or safety endpoints.

Rivaroxaban in the Prevention of Stroke and Systemic Embolism in Patients with Non-Valvular Atrial Fibrillation: Clinical Implications of the ROCKET AF Trial and Its Subanalyses.

Atrial fibrillation (AF) is an increasingly common cause of stroke and systemic embolism. While warfarin has been the mainstay of stroke prevention in patients with AF, newer novel oral anticoagulant medications are now available. Rivaroxaban, a direct factor Xa inhibitor with a rapid onset and offset after oral administration, offers potential advantages over warfarin, predominantly due to its predictable pharmacokinetics across wide patient populations. It requires no coagulation monitoring, and only two different doses are needed (20mg daily for patients with normal renal function and 15mg daily in those with reduced renal function). A large randomized trial (ROCKET AF) has shown non-inferiority to warfarin for preventing stroke or systemic embolism in the per-protocol population and superiority to warfarin in the on-treatment safety population. Several subanalyses confirm that the treatment effect of rivaroxaban is consistent across different patient subgroups, including those with reduced renal function. The tolerability of rivaroxaban appears similar to that of warfarin, with comparable overall bleeding rates in clinical trials. In ROCKET AF, significantly lower rates of fatal and intracranial bleeding were seen with rivaroxaban, while lower rates of gastrointestinal bleeding were seen with warfarin. Important contraindications to rivaroxaban include valvular AF, the presence of a prosthetic valve (mechanical or bioprosthetic) or valve repair, the need for concurrent dual antiplatelet therapy, and creatinine clearance <30ml/min. Once-daily dosing and the lack of coagulation monitoring may increase utilization and adherence compared with warfarin, potentially decreasing the large burden of care associated with stroke secondary to AF. Overall, rivaroxaban offers a useful alternative to warfarin for stroke prevention in patients with AF.

Use and outcomes of antiarrhythmic therapy in patients with atrial fibrillation receiving oral anticoagulation: results from the ROCKET AF trial.

Antiarrhythmic drugs (AADs) and anticoagulation are mainstays of atrial fibrillation (AF) treatment. To study the use and outcomes of AAD therapy in anticoagulated patients with AF. Patients in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation trial (N = 14,264) were stratified by AAD use at baseline: amiodarone, other AAD, or no AAD. Multivariable adjustment was performed to compare stroke, bleeding, and death across AAD groups as well as across treatment assignment (rivaroxaban or warfarin). Of 14,264 patients randomized, 1681 (11.8%) were treated with an AAD (1144 [8%] with amiodarone and 537 [3.8%] with other AADs). Amiodarone-treated patients were less often female (38% vs 48%), had more persistent AF (64% vs 40%), and more concomitant heart failure (71% vs 41%) than were patients receiving other AADs. Patients receiving no AAD more closely resembled amiodarone-treated patients. Time in therapeutic range was significantly lower in warfarin-treated patients receiving amiodarone than in those receiving no AAD (50% vs 58%; P < .0001). Compared with no AAD, neither amiodarone (adjusted hazard ratio [HR] 0.98; 95% confidence interval [CI] 0.74-1.31; P = .9) nor other AADs (adjusted HR 0.66; 95% CI 0.37-1.17; P = .15) were associated with increased mortality. Similar results were observed for embolic and bleeding outcomes. Treatment effects of rivaroxaban vs warfarin in patients receiving no AAD were consistent with results from the overall trial (primary end point: adjusted HR 0.82; 95% CI 0.68-0.98; Pinteraction = .06; safety end point: adjusted HR 1.12; 95% CI 0.90-1.24; Pinteraction = .33). Treatment with AADs was not associated with increased morbidity or mortality in anticoagulated patients with AF. The effect of amiodarone on outcomes in patients receiving rivaroxaban requires further investigation.

Atrial fibrillation and prior MI: searching for balance in ischaemic and bleeding events in patients treated with factor-specific anticoagulants

This editorial refers to ‘Ischaemic cardiac outcomes in patients with atrial fibrillation treated with vitamin K antagonism or factor Xa inhibition: results from the ROCKET AF trial’, by K.W. Mahaffey et al. doi:10.1093/eurheartj/eht428 Patients with both atrial fibrillation (AF) and prior myocardial infarction (MI) represent a unique and potentially high risk population. Strategies for managing these patients using the newer factor-specific oral anticoagulants are somewhat limited, as these patients represent a small fraction of the overall cohorts studied and only limited results have been published previously.1,2 Mahaffey et al. , investigators from 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) trial,3 now report on the prevalence of prior MI in that study; the incidence of new cardiovascular (CV) events; and the treatment effect of rivaroxaban, a direct factor Xa inhibitor, compared with warfarin on the risk of new CV events in those with and without a history of MI. In the ROCKET AF trial, 17% of patients had prior MI at enrolment ( n = 2468/14 264).3 These subjects were significantly more likely to have other co-morbidities and risk factors, notably more heart failure, diabetes, and peripheral arterial disease. Additionally, concomitant aspirin (47% vs. 34%) and thienopyridine (3.4% and 2.1%) were more common in this subgroup. Patients with and without prior MI had similar rates of stroke and systemic embolism during a median 2 years of follow-up, but recurrent CV events and mortality were more frequent …

Rivaroxaban: A Review of its Use in the Prevention of Stroke and Systemic Embolism in Patients with Atrial Fibrillation

Rivaroxaban (Xarelto(®)), a direct factor Xa inhibitor, is approved for the prevention of stroke and systemic embolism in patients with atrial fibrillation (AF) in Canada or those with nonvalvular AF (NVAF) in the EU, US and Japan. It is administered at a fixed oral dose and generally does not require routine monitoring of coagulation parameters. In the ROCKET AF trial in patients with NVAF and a moderate to high risk of stroke, oral rivaroxaban 20mg once daily (15mg once daily in patients with moderate renal impairment) was noninferior to oral dose-adjusted warfarin once daily in preventing primary endpoint events (i.e. stroke and systemic embolism) in the per-protocol population (primary noninferiority analysis) and superior in the on-treatment safety population (primary superiority analysis). Several ROCKET AF subgroup analyses indicated that the treatment effect of rivaroxaban was consistent across patient subgroups stratified according to baseline factors, including the presence or absence of previous stroke or transient ischaemic attack. Patients with moderate renal impairment receiving the reduced rivaroxaban dosage (15 mg once daily) showed a treatment effect consistent with that seen with rivaroxaban 20mg once daily in patients with normal renal function. The tolerability profile of rivaroxaban was generally acceptable in ROCKET AF, with no significant difference between rivaroxaban and warfarin in the incidence of major or nonmajor clinically-relevant bleeding events (primary safety endpoint). In the Japanese ROCKET AF trial, rivaroxaban 15mg once daily (10mg once daily in patients with moderate renal impairment) was noninferior to oral dose-adjusted warfarin once daily in the incidence of major or nonmajor clinically-relevant bleeding (primary study outcome). Thus, rivaroxaban is a reasonable alternative to warfarin for the prevention of stroke and systemic embolism in patients with NVAF.