rivaroxaban and Peripheral-Arterial-Disease

Despite availability of effective preventive therapies based on guidelines, patients with vascular diseases continue to be at a high risk for recurrent ischemic events. Therefore, novel therapeutic strategies are required to further reduce the residual risk present in these patients. Platelet aggregation and fibrin organization are involved in arterial thrombosis. Rivaroxaban is capable of targeting both processes and has a synergistic effect when used in combination with acetylsalicylic acid (ASA), providing the so‑called dual pathway inhibition (DPI). The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial showed that the DPI (a combination of rivaroxaban at 2.5 mg twice daily [vascular dose] and ASA at 100 mg once daily) reduced cardiovascular death, stroke, or myocardial infarction by 24% in patients with chronic coronary artery disease (CAD) and peripheral artery disease (PAD). Subsequently, the VOYAGER PAD (Vascular Outcomes Study of ASA Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) trial confirmed the effectiveness of the vascular dose of rivaroxaban in patients with PAD after lower‑extremity revascularization, as compared with ASA alone. Therefore, DPI is recommended in the patients with CAD (+/- PAD) or symptomatic PAD at a high risk of ischemia. The purpose of this review is to examine the clinical benefits and practical implications of DPI in the CAD and PAD patients.

Topics: Aspirin; Cardiovascular Diseases; Drug Therapy, Combination; Factor Xa Inhibitors; Humans; Ischemia; Outpatients; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban

To perform a systematic literature review and indirect treatment comparison (ITC) to identify, summarize and quantify randomized controlled trial (RCT) evidence evaluating combination anticoagulant or P2Y12 inhibitor with low-dose aspirin versus low-dose aspirin alone for the prevention of atherothrombotic events in patients with stable coronary artery disease (CAD) and/or peripheral artery disease (PAD).. We performed an updated search of CENTRAL, MEDLINE and EMBASE through 23 August 2021 to identify RCTs of adult patients with chronic CAD and/or PAD that compared combination anticoagulant or P2Y12 inhibitor with low-dose aspirin to low-dose aspirin alone. Outcomes of interest included major adverse cardiovascular events (MACEs) including cardiovascular death, stroke, or myocardial infarction (MI) and bleeding. When needed, outcomes were pooled using random-effects models to generate hazard or risk ratios (HRs or RRs) and accompanying 95% confidence intervals (CIs). Adjusted ITCs using subsequent pooled HRs/RRs were then performed.. Six publications reporting the results of two unique RCTs (one evaluating clopidogrel + aspirin vs. aspirin alone and the other rivaroxaban 2.5 mg twice daily + aspirin vs. aspirin alone) were analyzed. The ITC suggested that rivaroxaban + aspirin was associated with a lower risk of MACEs compared with clopidogrel + aspirin (HR = 0.82, 95% CI = 0.68-0.98). When looking at the individual components of MACE, rivaroxaban + aspirin was associated with lower risk of cardiovascular death (HR = 0.75, 95% CI = 0.57-0.98) and stroke (RR = 0.67, 95 CI = 0.49-0.93) and similar risk of MI (RR = 0.93, 95% CI = 0.70-1.23) versus clopidogrel + aspirin. No evidence of a difference in moderate-to-severe bleeding, fatal bleeding or intracranial hemorrhage (ICH) was seen between the two treatment strategies.. Compared to clopidogrel + low-dose aspirin, the use of rivaroxaban 2.5 mg twice daily + low-dose aspirin reduced the risk of MACE, CV death and stroke including ischemic stroke in patients with or at high risk for chronic CAD and/or PAD. These benefits of rivaroxaban 2.5 mg twice daily + low-dose aspirin compared to clopidogrel + low-dose aspirin appear to be achieved without significantly increasing patients' risk of moderate-to-severe bleeding, including ICH or fatal bleeding.

Topics: Adult; Anticoagulants; Aspirin; Coronary Artery Disease; Drug Therapy, Combination; Factor Xa Inhibitors; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Rivaroxaban

Patients with peripheral artery disease (PAD) are an underrecognised group with significant thrombotic risk. This risk is modifiable with the use of aggressive secondary preventative efforts, including optimisation of antithrombotic therapy. Appropriate antithrombotic selection for patients with PAD requires appropriate assessment of thrombotic and bleeding risk. Recent Canadian guidelines have recommended dual pathway therapy initiation for stable PAD and post-revascularisation patients. However, there is ongoing discussion about how to identify PAD patients who stand to benefit most from these therapies while trying to minimise harm from bleeding. Clinical equipoise also persists around questions such as the utility of dual antiplatelet therapy in conjunction with rivaroxaban after high-risk endovascular interventions and the optimal therapy for patients experiencing acute limb ischemia. In patients with chronic PAD and high-risk comorbidities or limb features, or in patients after revascularisation, dual pathway therapy with low-dose rivaroxaban and aspirin has emerged as the only regimen to reduce major adverse cardiovascular and limb events while maintaining an acceptable bleeding profile. After endovascular revascularisation, limited-duration (< 30 days) clopidogrel may be added to rivaroxaban and aspirin in selected high-risk patients at the provider's discretion. After acute limb ischemia, the risk of another vascular event is exceptionally high, but there is no high-quality evidence to guide decision making for intensified antithrombotic therapy. Randomised investigations addressing this question are urgently needed to better serve this high-risk and vulnerable population.

Topics: Aspirin; Canada; Clinical Decision-Making; Drug Therapy, Combination; Fibrinolytic Agents; Hemorrhage; Humans; Ischemia; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Risk Assessment; Rivaroxaban

High-quality evidence from trials directly comparing single antiplatelet therapies in symptomatic peripheral arterial disease (PAD) to dual antiplatelet therapies or acetylsalicylic acid (ASA) plus low-dose rivaroxaban is lacking. Therefore, we conducted a network meta-analysis on the effectiveness of all antithrombotic regimens studied in PAD.. A systematic search was conducted to identify randomized controlled trials. The primary endpoints were major adverse cardiovascular events (MACE) and major bleedings. Secondary endpoints were major adverse limb events (MALE) and acute limb ischaemia (ALI). For each outcome, a frequentist network meta-analysis was used to compare relative risks (RRs) between medication and ASA. ASA was the universal comparator since a majority of studies used ASA as in the reference group.. Twenty-four randomized controlled trials were identified including 48,759 patients. With regard to reducing MACE, clopidogrel [RR 0.78, 95% confidence interval (CI) 0.66-0.93], ticagrelor (RR 0.79, 95% CI 0.65-0.97), ASA plus ticagrelor (RR 0.79, 95% CI 0.64-0.97), and ASA plus low-dose rivaroxaban (RR 0.84, 95% CI 0.76-0.93) were more effective than ASA, and equally effective to one another. As compared to ASA, major bleedings occurred more frequently with vitamin K antagonists, rivaroxaban, ASA plus vitamin K antagonists, and ASA plus low-dose rivaroxaban. All regimens were similar to ASA concerning MALE, while ASA plus low-dose rivaroxaban was more effective in preventing ALI (RR 0.67, 95% CI 0.55-0.80). Subgroup analysis in patients undergoing peripheral revascularization revealed that ≥ 3 months after intervention, evidence of benefit regarding clopidogrel, ticagrelor, and ASA plus ticagrelor was lacking, while ASA plus low-dose rivaroxaban was more effective in preventing MACE (RR 0.87, 95% CI 0.78-0.97) and MALE (RR 0.89, 95% CI 0.81-0.97) compared to ASA. ASA plus clopidogrel was not superior to ASA in preventing MACE ≥ 3 months after revascularization. Evidence regarding antithrombotic treatment strategies within 3 months after a peripheral intervention was lacking.. Clopidogrel, ticagrelor, ASA plus ticagrelor, and ASA plus low-dose rivaroxaban are superior to ASA monotherapy and equally effective to one another in preventing MACE in PAD. Of these four therapies, only ASA plus low-dose rivaroxaban provides a higher risk of major bleedings. More than 3 months after peripheral vascular intervention, ASA plus low-dose rivaroxaban is superior in preventing MACE and MALE compared to ASA but again at the cost of a higher risk of bleeding, while other treatment regimens show non-superiority. Based on the current evidence, clopidogrel may be considered the antithrombotic therapy of choice for most PAD patients, while in patients who underwent a peripheral vascular intervention, ASA plus low-dose rivaroxaban could be considered for the long-term (> 3 months) prevention of MACE and MALE.

Topics: Aspirin; Clopidogrel; Fibrinolytic Agents; Hemorrhage; Humans; Network Meta-Analysis; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Ticagrelor; Vitamin K

The guidelines on antithrombotic treatment in patients with symptomatic peripheral artery disease (PAD) undergoing peripheral revascularization of the lower extremities were developed based on heterogeneous trials, assessing various dose regimens and recruiting patients who were subjected to different revascularization procedures.. To compare efficacy and safety of treatments used in patients with PAD undergoing peripheral revascularization accounting for between-trial heterogeneity and large dispersion of the quality of evidence.. A systematic literature review of randomised controlled trials (RCTs) recruiting adult patients with PAD receiving antithrombotics was conducted until January 2020. Hazard ratios (HR) were pooled using Bayesian network meta-analysis. The estimated between-treatment effects were presented as HR together with 95% credible intervals. The base case analysis included studies recruiting patients following recent peripheral revascularization, who received treatment regimens administered within the recommended therapeutic window, while a sensitivity scenario included all identified trials.. Thirteen RCTs were identified (8 RCTs enrolled patients following peripheral revascularization and 5 RCTs regardless of the previous revascularization). Five trials, recruiting an overall of 8349 patients, were considered for the base case analysis. Of those, 6564 patients were recruited in the VOYAGER PAD trial comparing rivaroxaban plus aspirin (RIV plus ASA) versus ASA. RIV plus ASA was associated with a lower risk of repeated peripheral revascularization versus ASA monotherapy (HR = 0.88 [0.79, 0.99]), however having a trend towards an increased rate of major bleeding (HR = 1.43 [0.98, 2.11]). There was no evidence for differences between RIV plus ASA and dual antiplatelet therapy and vitamin K antagonists plus ASA. Similar results were observed in sensitivity analyses.. RIV plus ASA is associated with reduced risk of revascularization compared with ASA monotherapy, but the evidence for other comparators, in particular antiplatelet regimens, was insufficient to guide treatment decisions and highlights the challenge in establishing the magnitude of comparative efficacy using existing RCTs.

Topics: Adult; Aspirin; Humans; Network Meta-Analysis; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban

To provide an overview of new concepts in the pharmacotherapy of patients with peripheral artery disease (PAD).. Modern therapeutic strategies for patients with PAD include specific symptom management and multidisciplinary prevention of cardiovascular events. Low-dose rivaroxaban in combination with aspirin improves outcomes compared with aspirin monotherapy among patients with PAD. Other novel concepts include the use of bosentan, vorapaxar or sildenafil among symptomatic patients with PAD. Likewise, lipid-lowering therapy reduces the risk of major cardiovascular and limb events.. Personalized management, identification of risk factors and shared-decision making are crucial in improving the best medical therapy for patients with PAD. Further studies are needed to assess the long-term safety and efficacy of novel strategies in real-world patients.

Topics: Aspirin; Drug Therapy, Combination; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban

Patients with lower extremity peripheral artery disease (PAD) are at increased risk of major adverse limb events (MALE). The efficacy and safety of direct oral anticoagulants (DOACs) in this context is evolving. To assess the efficacy and safety of DOAC combined with aspirin compared to the use of antiplatelet agents in patients with symptomatic lower extremity (LE) PAD. We systematically searched PubMed, Embase and Cochrane databases, in September 2020, for randomized controlled trials (RCTs) that were designed to investigate the effect of DOACs in the treatment of PAD. A random-effects meta-analysis was performed targeting ischemic and bleeding events. Three randomized clinical trials were included, providing a total of 9533 patients, and 744 pooled MALE events (316 in DOAC plus aspirin and 428 in control). Only data on rivaroxaban and edoxaban were available. The use of DOAC plus aspirin in PAD patients significantly decreased the rate of MALE (pooled OR 0.70 [0.61-0.83], P < 0.001; I

Topics: Anticoagulants; Aspirin; Factor Xa Inhibitors; Hemorrhage; Humans; Ischemia; Lower Extremity; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Rivaroxaban

We performed a systematic review and meta-analysis to evaluate the efficacy and safety of rivaroxaban in patients with PAD for the first time.. We searched MEDLINE, EMBASE and the Cochrane Library database for randomized controlled trials (RCTs) conducted for PAD.. Three trials which contained 14873 patients were included for final meta-analysis. The results showed patients with rivaroxaban was associated with reduction in primary efficacy outcome (RR 0.83; 95% CI 0.76 to 0.90; p < 0.001). The RR was 0.85 (0.71 to 1.01) for patients with rivaroxaban alone and 0.81 (0.74 to 0.89) for those with rivaroxaban plus aspirin (p for heterogeneity between groups = 0.65). Patients with rivaroxaban showed a lower rate of acute limb ischemia (0.56; 0.47 to 0.66; p < 0.001). There was a trend toward a reduction in the rate of major amputation for vascular causes in the rivaroxaban arm (0.81; 0.63 to 1.03; p = 0.08). Compared with control, rivaroxaban therapy did not reduce the risks of myocardial infarction (0.87, 0.73 to 1.04, p = 0.12), ischemic stroke (0.85, CI 0.68 to 1.06, p = 0.15), death from cardiovascular causes (0.99, 0.85 to 1.15, p = 0.91) or death from any cause (1.00, 0.90 to 1.12, p = 0.98). Rivaroxaban therapy was associated with a 1.57-fold higher major bleeding rate as compared with those with aspirin or warfarin alone.. Overall, the risks of the primary efficacy outcomes or adverse limb events were significantly lower with rivaroxaban than with aspirin or warfarin alone in patients with PAD. It also points out the significant major bleeding that occur because of such therapies.

Topics: Aged; Amputation, Surgical; Disease Progression; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Limb Salvage; Male; Peripheral Arterial Disease; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome

To identify randomized controlled trials that compared antiplatelet monotherapy to combination antiplatelet plus anticoagulant therapy and evaluated major adverse cardiovascular events (MACE) or major adverse limb events (MALE), death, or bleeding in patients with lower extremity peripheral artery disease (PAD).. A systematic search of MEDLINE, Embase, and CENTRAL databases revealed 5 trials. Two trials consisted of patients with stable PAD, while 3 trials examined patients with PAD post revascularization. Antiplatelet therapy was mostly aspirin (81-325 mg daily), and anticoagulation included rivaroxaban 2.5 mg twice daily or warfarin. Duration of follow-up ranged from 12 to 38 months. Two trials had low risk of bias, whereas 3 trials had high/unclear risk of bias. For patients with stable PAD, one trial showed that use of warfarin (or acenocoumarol) with antiplatelet therapy did not reduce MACE, MALE, or cardiovascular or all-cause death but increased the risk of life-threatening bleeding. A second trial demonstrated that low-dose rivaroxaban plus antiplatelet therapy lowered the risk of MACE and MALE, with no effect in preventing cardiovascular or all-cause death, but increased the risk of major bleeding. For patients with PAD post revascularization receiving warfarin and antiplatelet therapy, 2 trials showed no benefit in MACE or MALE but increased or similar rates of all-cause death and major bleeding. In a third trial, low-dose rivaroxaban plus aspirin reduced occurrence of the composite of MACE and MALE but increased major bleeding, with no effect on cardiovascular or all-cause death.. Dual-pathway inhibition with low-dose rivaroxaban and aspirin reduced MACE and MALE in patients with stable or revascularized PAD, but net clinical benefit is questionable.

Topics: Anticoagulants; Drug Therapy, Combination; Factor Xa Inhibitors; Humans; Lower Extremity; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban

Peripheral artery disease (PAD) is a major cause of morbidity and mortality but it is usually underdiagnosed and undertreated. Patients with PAD present dysregulated procoagulant, anticoagulant, and fibrinolytic pathways leading to arterial and venous thrombosis. The risk of several ischemic-related complications could be mitigated with appropriate antithrombotic therapy, which plays a central role in all types of PAD. For years, antiplatelets have been indicated in patients with symptomatic PAD or those who have undergone revascularization. Unfortunately, a non-negligible proportion of patients with PAD will suffer from adverse events during the follow-up, even despite proper medical therapies for the prevention of PAD complications. Thus, there is room for improving clinical outcomes in these patients. Given the implication of both, primary and secondary hemostasis in arterial thrombosis and the pathophysiology of PAD, the combination of antiplatelets and anticoagulants has emerged as a potential antithrombotic alternative to antiplatelets alone. In this narrative review article, we have highlighted the most recent evidence about antithrombotic therapy in PAD patients, with a special focus on oral anticoagulation. Certainly, COMPASS and VOYAGER PAD trials have shown promising results. Thus, rivaroxaban in combination with aspirin seem to reduce cardiovascular outcomes with a similar bleeding risk compared to aspirin alone. Nevertheless, results from real-world studies are needed to confirm these observations, and other trials will provide novel evidence about the safety and efficacy of emerging anticoagulant agents.

Topics: Anticoagulants; Aspirin; Blood Coagulation; Drug Therapy, Combination; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Thrombolytic Therapy; Thrombosis

To evaluate the efficacy and safety of Xa inhibitors in patients with heart failure (HF) and coronary artery disease (CAD) or peripheral artery disease (PAD).. A systematic electronic literature search was performed using the PubMed, Web of Science, EMBASE, and Cochrane Library databases from inception to June 26, 2019. A total of four randomized controlled trials involving 14,694 patients were included in this meta-analysis.. The meta-analysis showed that there was no statistical difference between the Xa inhibitor and control group regarding the primary efficacy outcome [rivaroxaban 2.5 mg group: relative risk (RR) 0.82, 95% CI: 0.66-1.01, P=0.06; rivaroxaban 5 mg group: RR 0.86, 95% CI: 0.73-1.02, P=0.08]. The risk of the primary safety outcome was significantly increased among patients who received Xa inhibitors compared with the control group (rivaroxaban 2.5 mg group: RR 1.55, 95% CI: 1.21-1.98, P=0.0006; rivaroxaban 5 mg group: RR 1.66, 95% CI: 1.30-2.12, P<0.0001). There was no significant difference in the risk of cardiovascular death between the Xa inhibitor and control group (rivaroxaban 2.5 mg group: RR 0.79, 95% CI: 0.54-1.14, P=0.21; rivaroxaban 5 mg group: RR 0.89, 95% CI: 0.73-1.08, P=0.24). The risk of myocardial infarction (MI) in the rivaroxaban 5 mg group was significantly lower than that of the control group (RR 0.83, 95% CI: 0.69-0.99, P=0.04). However, the risk of MI in the rivaroxaban 2.5 mg group was similar to that of the control group (RR 0.85, 95% CI: 0.71-1.01, P=0.07).. Xa inhibitors were associated with a higher risk of major adverse cardiovascular events and bleeding among HF and CAD or PAD patients. Therefore, Xa inhibitors should be used cautiously in patients with HF and CAD or PAD.

Topics: Factor Xa Inhibitors; Heart Failure; Humans; Peripheral Arterial Disease; Randomized Controlled Trials as Topic; Rivaroxaban

Topics: Aged; Aspirin; Clopidogrel; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Hemorrhage; Humans; Lower Extremity; Male; Middle Aged; Network Meta-Analysis; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Rivaroxaban; Treatment Outcome

: Despite substantial progress in the treatment of atherosclerotic disease a non-negligible rate of acute atherothrombotic events persists. Evidence suggesting a safer profile of direct oral anticoagulants (DOACs) compared with vitamin K antagonists and the involvement of coagulation in the atherosclerotic process has led to exploration of the role of DOACs in the prevention of atherothrombotic events. In this review, we discuss the findings of recent studies on DOACs, particularly rivaroxaban, in atherothrombotic disease which represents a new clinical setting for oral anticoagulants.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Coronary Artery Disease; Humans; Peripheral Arterial Disease; Risk Factors; Rivaroxaban; Thrombosis; Treatment Outcome

Despite advances in secondary prevention strategies in patients with cardiovascular disease, the residual risk of recurrent atherothrombotic events remains high. Dual-antiplatelet therapy is the standard of care for secondary prevention in patients with acute coronary syndrome (ACS), whereas single antiplatelet therapy, generally with aspirin, is the standard of care for secondary prevention in stable patients with coronary artery disease (CAD), peripheral artery disease (PAD), or cerebrovascular disease. However, atherosclerotic plaque disruption not only triggers platelet activation but also results in thrombin generation because of tissue factor exposure. Therefore, blocking both pathways by combining antiplatelet therapy with an anticoagulant, or dual pathway inhibition (DPI), has the potential to be more effective than inhibiting either pathway alone. The benefit of DPI has been demonstrated in the ATLAS ACS 2-TIMI 51, COMPASS, and VOYAGER PAD trials, where the combination of rivaroxaban vascular dose (2.5 mg twice daily) plus aspirin significantly reduced the risk of atherothrombotic events compared with aspirin across a broad range of patients, including those with recent ACS, those with chronic CAD and/or PAD, and patients with PAD who have undergone peripheral revascularization. This article provides the rationale for this regimen in more detail, including why the DPI regimen with the rivaroxaban vascular dose was developed for vascular protection in a broad spectrum of patients with atherosclerotic disease.

Topics: Acute Coronary Syndrome; Anticoagulants; Aspirin; Atherosclerosis; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Synergism; Drug Therapy, Combination; Forecasting; Hemorrhage; Humans; Peripheral Arterial Disease; Platelet Activation; Platelet Aggregation Inhibitors; Recurrence; Rivaroxaban; Secondary Prevention; Thrombin

Cardiovascular disease is the leading cause of morbidity and mortality in adults in western nations. In the last decades, tremendous research has been conducted in the field of secondary prevention in order to reduce recurrent cardiovascular events. This review summarizes the novel dual pathway concept of aspirin and very low-dose rivaroxaban, from mechanisms to clinical practice.. The COMPASS trial demonstrated that in patients with stable atherosclerotic disease, very low-dose rivaroxaban, a direct factor Xa inhibitor, when combined with aspirin, reduced the rate of recurrent ischemic events, at the cost of increased bleeding. This effect was present in patients with ischemic heart disease, as well as in patients with atherosclerosis in other beds, such as in peripheral arterial disease. Sub-studies from the COMPASS trial examined other high-risk populations who might benefit the most from this regimen.. There are currently multiple antiplatelet and anticoagulation treatment regimens for patients with stable atherosclerotic disease. The dual pathway concept is a novel approach that combines both mechanisms. Identifying patients who might benefit the most in terms of ischemic events at the least bleeding events still remains a challenge, yet prescribing this combination to high-risk patients might be the most effective.

Topics: Aspirin; Atherosclerosis; Drug Therapy, Combination; Factor Xa Inhibitors; Hemorrhage; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Secondary Prevention

Peripheral artery disease (PAD) affects an estimated 200 million people worldwide and is associated with significant cardiovascular morbidity and mortality. Cardiovascular risk is further increased among individuals with polyvascular disease, where either cerebrovascular or coronary artery disease is present in addition to PAD. In this review, we present common clinical scenarios encountered when managing patients with PAD and provide an evidence-based approach to prescribing optimal antithrombotics in this population.. The COMPASS trial recently demonstrated that rivaroxaban 2.5 mg BID + ASA daily significantly reduces major adverse cardiac and limb events in patients with PAD. Despite these advances, morbidity following MALE events remains high. With widespread approval by federal health regulators, the COMPASS regimen should be strongly considered in PAD patients who do not have a high bleeding risk. Implementing the COMPASS regimen in patients with PAD, along with other vascular risk reduction strategies, will have a substantial impact on reducing atherothromboembolic risk in patients with established vascular disease.

Topics: Anticoagulants; Aspirin; Cardiovascular Diseases; Drug Therapy, Combination; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Thrombolytic Therapy

In the review article are provided the approaches to the therapy for improvement of prognosis in patients with peripheral and multifocal atherosclerosis which are available now; some limitations and a real situation are designated for the antithrombotic therapy in this category of patients. According to the clinical trial COMPASS the prospects of wide use of a combination of acetylsalicylic acid and a rivaroxsaban of 2.5 mg 2 times a day in the patients with chronic coronary heart disease and/or symptom peripheral atherosclerosis are designated.. Нуждаются ли пациенты с атеросклерозом периферических артерий в медикаментозной терапии до проведения реваскуляризации? В обзорной статье представлены имеющиеся в настоящее время подходы к назначению терапии, улучшающей прогноз у пациентов с периферическим и мультифокальным атеросклерозом, обозначены ограничения и реальная ситуация с назначением антитромботической терапии у этой категории пациентов. На основании данных исследования COMPASS обозначены перспективы широкого использования комбинации ацетилсалициловой кислоты и ривароксабана 2,5 мг 2 раза в день у пациентов с хронической ишемической болезнью сердца и/или симптомным периферическим атеросклерозом.

Topics: Aspirin; Atherosclerosis; Drug Therapy, Combination; Humans; Peripheral Arterial Disease; Rivaroxaban

To suggest a practical approach for the application of data from the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial in patients with peripheral artery disease (PAD).. The COMPASS trial showed that low-dose rivaroxaban 2.5 mg twice daily plus daily aspirin was superior to aspirin alone in reducing major adverse cardiovascular and cerebrovascular events, and major adverse limb events among patients with stable atherosclerotic vascular disease, including those with PAD. The risk for major bleeding, however, was higher with rivaroxaban plus aspirin. Critical limb ischemia at baseline (rest pain, ulcer, or gangrene), previous limb or foot amputation, or a history of peripheral revascularization surgery or stenting were independently associated with increased major adverse limb events within the trial.. Intensification of antithrombotic therapy with low-dose rivaroxaban plus aspirin should be considered in low bleeding risk PAD patients who are at increased risk for ischemic and/or limb events. A practical approach for clinicians is presented to help incorporate COMPASS data into practice.

Topics: Drug Therapy, Combination; Factor Xa Inhibitors; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Rivaroxaban; Surgeons

Recent advances in our understanding of the contribution of thrombin generation to arterial thrombosis and the role of platelets in venous thrombosis have prompted new treatment paradigms. Nonetheless, bleeding remains the major side effect of such treatments spurring the quest for new antithrombotic regimens with better benefit-risk profiles and for safer anticoagulants for existing and new indications. The aims of this article are to review the results of recent trials aimed at enhancing the benefit-risk profile of antithrombotic therapy and explain how these findings are changing our approach to the management of arterial and venous thrombosis. Focusing on these 2 aspects of thrombosis management, this article discusses 4 advances: (1) the observation that in some indications, lowering the dose of some direct oral anticoagulants reduces the risk of bleeding without compromising efficacy, (2) the recognition that aspirin is not only effective for secondary prevention of atherothrombosis but also for prevention of venous thromboembolism, (3) the finding that dual pathway inhibition with the combination of low-dose rivaroxaban to attenuate thrombin generation plus aspirin to reduce thromboxane A2-mediated platelet activation is superior to aspirin or rivaroxaban alone for prevention of atherothrombosis in patients with coronary or peripheral artery disease, and (4) the development of inhibitors of factor XI or XII as potentially safer anticoagulants.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Aspirin; Atrial Fibrillation; Clinical Trials as Topic; Coronary Disease; Drug Therapy, Combination; Factor Xa Inhibitors; Factor XI; Factor XII; Hemorrhage; Humans; Peripheral Arterial Disease; Plaque, Atherosclerotic; Platelet Aggregation; Platelet Aggregation Inhibitors; Primary Prevention; Risk Assessment; Rivaroxaban; Secondary Prevention; Thrombin; Thrombosis; Venous Thrombosis

Aspirin decreases the risk of recurrent thrombotic events in patients with coronary artery disease or peripheral artery disease but the risk of recurrent events remains high. Long‑term dual antiplatelet therapy or the combination of aspirin and warfarin further reduces the risk of recurrent events, but at the cost of increased bleeding, and neither of these treatments reduce mortality. The COMPASS (Cardiovascular Outcomes in People Using Anticoagulation Strategies) randomized controlled trial involving 27 395 patients from 602 sites in 33 countries (Poland: 9 sites, 518 patients) tested whether low‑dose anticoagulant therapy with the coagulation factor Xa inhibitor rivaroxaban given alone or combined with aspirin reduced thrombotic risk compared with aspirin in patients with apparently stable chronic coronary and/or peripheral artery disease. In patients treated with the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily, compared with aspirin alone, the primary outcome of the composite of cardiovascular death, stroke, or myocardial infarction was decreased by 24% (hazard ratio, 0.76; 95% confidence interval, 0.66 to 0.86; P <0.001), and mortality by 18% at the cost of a 70% increase in major bleeding but no significant increase in fatal or intracranial bleeding. Results were consistent in patients with coronary artery disease or peripheral artery disease, and the greatest absolute benefit was evident in the highest risk patients, including those with polyvascular disease, mild or moderate heart failure, chronic kidney disease, or diabetes. These results establish the combination of low‑dose rivaroxaban and aspirin as a highly effective treatment to decrease morbidity and mortality rates in patients with atherosclerotic vascular disease..

Topics: Aged; Aspirin; Coronary Artery Disease; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Rivaroxaban

Topics: Anticoagulants; Aspirin; Clopidogrel; Coronary Artery Disease; DNA; Drug Therapy, Combination; Factor Xa; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Histones; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Thrombosis; Warfarin

Patients with peripheral artery disease are at high-risk for cardiovascular events. Anti-thrombotic treatment is very important for secondary prevention. In symptomatic patients single antiplatelet therapy with clopidogrel or Aspirin is recommended. After peripheral revascularisation transient dual antiplatelet therapy is widely used although there is only little evidence. Following peripheral bypass surgery most patients are treated with single antiplatelet therapy, in some cases (prostetic bypass grafts) dual antiplated therapy can be useful and selected patients with complex venous grafts might profit from anticoagulation with vitamin K antagonists.The recent publication of the COMPASS (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS) study showed relevant reduction of MACE (Major Adverse Cariac Events) and MALE (Major Adverse Limb Events) for the combined therapy of rivaroxaban 2 × 2,5 mg compared to Aspirin 100 mg with increased risk for gastrointestinal bleeding. In the current VOYAGER PAD (Vascular Outcomes Study of Aspirin along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) study this concept is tested after peripheral revascularisation.. Die aktuellen deutschen und europäischen Leitlinien empfehlen bei Patienten mit einer peripheren arteriellen Verschlusskrankheit (PAVK) die Monotherapie mit einem Thrombozytenaggregationshemmer (ASS 100 mg oder Clopidogrel 75 mg).In der COMPASS (Cardiovascular OutcoMes for People using Anticoagulation StrategieS) -Studie wurde Patienten mit PAVK 2 × 2,5 mg Rivaroxaban zusätzlich zu ASS 100 mg gegeben. Dies führte zur signifikanten Reduktion kardiovaskulärer Ereignisse (MACE = Major Adverse Cardiovascular Events) wie kardiovaskulärer Tod, Myokardinfarkt und Schlaganfall. Ebenfalls signifikant reduziert wurden periphere Ereignisse (MALE = Major Adverse Limb Events) wie ischämiebedingte Major-Amputation und eine akute schwere Ischämie.Liegt bei Patienten mit einer PAVK die Indikation zur oralen Antikoagulation vor (z. B. bei Vorhofflimmern), empfehlen die aktuellen deutschen und europäischen Leitlinien die Monotherapie mit oralen Antikoagulantien ohne zusätzliche Thrombozytenaggregationshemmung.. Nach peripherer Intervention wird in Analogie zur Koronarintervention meist passager eine duale Plättchenhemmung durchgeführt. Nach peripherer Bypass-Anlage wird in der Regel die Monotherapie mit einem Thrombozytenaggregationshemmer empfohlen. In Einzelfällen kann bei komplexem Venenbypass eine orale Antikoagulation und bei Kunststoffbypass eine duale Plättchenhemmung eingesetzt werden.

Topics: Administration, Oral; Anticoagulants; Aspirin; Blood Vessel Prosthesis Implantation; Clopidogrel; Drug Therapy, Combination; Fibrinolytic Agents; Germany; Guideline Adherence; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Postoperative Care; Rivaroxaban; Secondary Prevention; Ticlopidine; Veins

The prevention of atherothrombotic events is an essential therapeutic goal in the treatment of patients with arteriosclerotic diseases. After plaque rupture, a rapidly growing thrombus can lead to acute vascular occlusion and thus heart attack, stroke or limb ischaemia. The acute therapy combines anticoagulation and platelet inhibition. However, the only available therapy so far in the primary and secondary prevention of stable patients is the platelet inhibitors aspirin and clopidogrel. Despite the use of antiplatelet therapies, including aspirin and P2Y. Die Verhinderung atherothrombotischer Ereignisse ist ein wesentliches therapeutisches Ziel bei der Behandlung von Patienten mit arteriosklerotischen Erkrankungen. Ein schnell wachsender Thrombus kann nach Plaqueruptur zu akutem Gefäßverschluss und damit zu Herzinfarkt, Schlaganfall oder Ischämie der Extremitäten führen. Die Akuttherapie kombiniert Antikoagulation und Thrombozytenhemmung. Die bislang einzige verfügbare Therapie in der Primär- und Sekundärprävention stabiler Patienten sind jedoch die Thrombozytenaggregationshemmer Aspirin und Clopidogrel. Trotz der Verwendung von Thrombozytenaggregationshemmern, einschließlich Aspirin und P2Y12-Rezeptorantagonisten, leiden einige Patienten mit Arterienerkrankungen weiterhin unter kardiovaskulären ischämischen Ereignissen, die auf eine übermäßige Thrombinbildung nach der akuten Phase zurückzuführen sind. Als ein Ergebnis haben Studien Nicht-Vitamin-K-Antagonist-orale Antikoagulantien (NOAKs) getestet, insbesondere die Faktor-Xa-Inhibitoren, entweder allein oder in Kombination mit einer Antiplättchen-Therapie bei der Behandlung von arteriellen Erkrankungen. Die COMPASS-Studie untersuchte erstmals die niedrig dosierte Antikoagulation bei stabiler koronarer Herzkrankheit oder peripherer arterieller Verschlusskrankheit. Die Zugabe von 2 × 2,5 mg Rivaroxaban zur Langzeit-Aspirintherapie verhinderte nicht nur kardiovaskulären Tod, Myokardinfarkt und Schlaganfall, sondern reduzierte sogar die Gesamtmortalität um 18% nach einer mittleren Nachbeobachtungszeit von 23 Monaten. Dieser Vorteil ging auf Kosten von mehr gastrointestinalen Blutungen, die durch die Zugabe eines Protonenpumpenhemmers reduziert werden könnten (Untersuchungen laufen noch). Interessanterweise gab es jedoch keine Zunahme von tödlichen oder intrakraniellen Blutungen. Daher könnte in naher Zukunft eine neue Standardtherapie für Hochrisikopatienten mit atherosklerotischer Erkrankung verfügbar werden.

Topics: Animals; Anticoagulants; Atherosclerosis; Coronary Disease; Heart Failure; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Thrombosis

Peripheral artery disease (PAD) is the third most common manifestation of atherosclerosis after coronary artery (CAD) and cerebrovascular disease (CVD). People with PAD have plaque findings in other vascular territories as well and, thus, are at increased risk of major adverse cardiovascular or cerebrovascular events (MACCE), including myocardial infarction, and stroke. In that context, the COMPASS multicenter, randomized controlled trial showed that the risk of MACCE was significantly reduced by 24% in the rivaroxaban plus aspirin arm compared with aspirin alone (4.1% vs 5.4% respectively; HR: 0.76, 95% CI: 0.66 to 0.86). Interestingly, the rivaroxaban/aspirin arm also showed a reduction in cardiovascular death (HR: 0.78; 95% CI: 0.64-0.96]) and allcause mortality (HR: 0.82; 95% CI: 0.71-0.96) by 22% and 18%, respectively. Recently, the FDA approved the use of the dual pathway approach, rivaroxaban 2.5 mg twice daily plus aspirin 75-100mg once daily, to reduce the risk of major cardiovascular (CV) events, such as CV death, myocardial infarction and stroke, in people with CAD as well as PAD. In comparing rivaroxaban plus aspirin versus aspirin alone, a preliminary economic analysis showed that saving per patient was USD 462 for events and USD 220 for procedures with a total reduction of USD 682 per participant in the US with the combination group (rivaroxaban plus aspirin). The data from COMPASS trial suggest that low dose rivaroxaban plus aspirin may be a preferred treatment strategy in PAD patients in whom the bleeding risk is deemed to be favourable.

Topics: Anticoagulants; Aspirin; Cardiovascular Diseases; Clopidogrel; Cost-Benefit Analysis; Drug Therapy, Combination; Humans; Peripheral Arterial Disease; Randomized Controlled Trials as Topic; Rivaroxaban; Treatment Outcome

The Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial demonstrated that rivaroxaban 2.5 mg BID with aspirin 100 mg was more effective than aspirin 100 mg daily alone for the prevention of cardiovascular (CV) death, stroke, or myocardial infarction in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD). We aimed to examine the cost-effectiveness of rivaroxaban using patient-level data from the COMPASS trial.. We performed an in-trial analysis and extrapolated our results for 33 years using a two-state Markov model with a 1-year cycle length. Hospitalization events, procedures, and study drugs were documented for patients. We applied country-specific (Canada, France, and Germany) direct healthcare system costs (in USD) to healthcare resources consumed by patients. Average cost per patient during the trial (mean follow-up of 23 months), quality-adjusted life years (QALYs), and lifetime cost-effectiveness were calculated. Costs of events and procedures were reduced with rivaroxaban 2.5 mg BID with aspirin. The addition of rivaroxaban 2.5 mg BID increased total costs for the combination group. Over a lifetime horizon (in trial +33 years), rivaroxaban plus aspirin was associated with 1.17 QALYs gained, yielding an incremental cost-effectiveness ratio (ICER) of $3946/QALY, $9962/QALY, and $10 264/QALY in Canada, France, and Germany, respectively. PAD and polyvascular disease subgroups had lower ICERs.. Rivaroxaban 2.5 mg twice daily plus aspirin compared with aspirin alone reduces direct healthcare costs. After acquisition costs of rivaroxaban, the lifetime cost-effectiveness of 2.5 mg twice daily plus aspirin is highly cost-effective in Canada, France, and Germany.(COMPASS ClinicalTrials.gov identifier: NCT01776424).

Topics: Aspirin; Cost-Benefit Analysis; Drug Therapy, Combination; Factor Xa Inhibitors; Humans; Peripheral Arterial Disease; Rivaroxaban

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

Low dose rivaroxaban with aspirin reduced major cardiovascular events (MACE) compared to aspirin alone in patients with cardiovascular disease although effects on total events are unknown.. The COMPASS clinical trial randomized 27,395 participants with chronic coronary and/or peripheral artery disease to rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily, rivaroxaban 5 mg twice daily alone, or aspirin 100 mg daily. We analyzed total (first and recurrent) MACE outcomes of cardiovascular death, stroke, or myocardial infarction, and the primary safety outcome of major bleeding. Exploratory analyses included on-treatment and net clinical benefit. Total MACE and safety events were modeled for each treatment.. MACE events were lowest in rivaroxaban with aspirin (379 first MACE, 432 total MACE) compared with rivaroxaban (448 first, 508 total) or aspirin alone (496 first, 574 total). Rivaroxaban and aspirin reduced total MACE events compared with aspirin alone [HR 0.75, 95% CI 0.66-0.85, P < .0001, number needed to treat for 2 years (NNT. Low dose rivaroxaban with aspirin significantly reduces first and total cardiovascular events compared with aspirin alone with a NNT. NCT01776424. https://clinicaltrials.gov/ct2/show/NCT01776424.

Topics: Aspirin; Coronary Artery Disease; Drug Therapy, Combination; Factor Xa Inhibitors; Hemorrhage; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban

Systolic blood pressure interarm difference (IAD) predicts cardiovascular morbidity and mortality in primary prevention populations. We examined the predictive value of IAD and the effects of treatment with the combination of rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily versus aspirin 100 mg once daily according to IAD in patients with chronic coronary artery disease or peripheral artery disease.. COMPASS trial patients with IAD <15 mmHg and IAD >15 mmHg were compared with respect to thirty-month incidence risk of: 1) composite of stroke, myocardial infarction, or cardiovascular death (MACE), 2) composite of acute limb-ischemia or vascular amputation (MALE), 3) composite of MACE or MALE, and 4) effects of treatment with the combination versus aspirin alone on these outcomes.. 24,539 patients had IAD<15 mmHg and 2,776 had IAD ≥15 mmHg. Relative to patients with IAD ≥15 mm Hg, those with IAD<15 mmHg had similar incidence rates for all measured outcomes including the composite of MACE or MALE (HR 1.12 [95% CI: 0.95 to 1.31], p = 0.19), with the exception of stroke (HR 1.38 [95% CI: 1.02 to 1.88], p = 0.04). Compared to aspirin alone, the combination consistently reduced the composite of MACE or MALE in both IAD <15 mmHg (HR 0.74 [95% CI: 0.65-0.85], p < 0.0001, ARR = -23.1) and IAD>15 mmHg (HR 0.65 [95% CI: 0.44-0.96], p = 0.03; ARR = -32.6, p interaction = 0.53) groups.. Unlike primary prevention populations, measuring IAD for risk stratification purposes does not appear to be useful in patients with established vascular disease.

Topics: Aspirin; Blood Pressure; Drug Therapy, Combination; Factor Xa Inhibitors; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Stroke

Vascular disease burden after lower extremity revascularization (LER) comprises more than the first event, more vascular beds than the local arteries, and more than one clinical event type.. Assess total arterial and venous thrombotic burden after LER for symptomatic peripheral artery disease (PAD) and effect of low-dose anticoagulation added to low-dose antiplatelet therapy.. VOYAGER PAD randomized 6564 symptomatic PAD patients undergoing LER to rivaroxaban 2.5 mg twice-daily or placebo on aspirin background. Marginal proportional-hazards models used to generate treatment hazard ratios and associated 95% CIs for first and total events; non-thrombotic deaths treated as competing terminal events. Incidence rates calculated as number of events per 100 patient-years follow-up.. Over 2.5 years (median), first and total thrombotic event rates: 7.1 and 10.3 events/100 patient-years, respectively, in placebo group. Two-thirds (925/1372) of total thrombotic events (arterial 95%, venous 5%) were nonfatal first events. Nearly one-third of patients with first event had a second arterial or venous thrombotic event. Rivaroxaban plus aspirin reduced first and total arterial and venous thrombotic events to 5.4 and 7.9 events/100 patient-years, respectively, a reduction in total thrombotic events over aspirin of 23% (HR: 0.77, 95%CI: 0.67-0.89, p = .0005), preventing 6.1 total arterial and venous thrombotic events at 3 years.. Assessing total arterial and venous thrombotic events, not just first events, provides more complete information about disease burden and absolute on-treatment impact. Following LER, judicious modulation of more than one coagulation pathway can provide broader benefit than intensifying inhibition of one hemostatic system component.

Topics: Anticoagulants; Arteries; Aspirin; Endovascular Procedures; Humans; Lower Extremity; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Thrombosis

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

To determine the characteristics of patients with coronary artery disease (CAD), peripheral artery disease (PAD), or both, initiating dual pathway inhibition (DPI) using rivaroxaban 2.5 mg twice daily plus aspirin, and to report their clinical outcomes and bleeding rates in clinical practice compared to the COMPASS randomized trial, which provided the basis for using DPI in this patient population.. XATOA is a prospective registry of 5532 patients: of which, 72.7% had CAD, 58.9% had PAD, and 31.6% had both. The mean age of patients was 68 years and 25.5% were women. The mean follow-up period was 15 months. The most frequently reported reason for initiating DPI was the presence of existing, worsening or newly diagnosed risk characteristics (n = 4753, 85.9%). Before initiating DPI, 75.3% received a single antiplatelet and 18.3% received various antiplatelet combinations. The incidence of major adverse cardiovascular events (MACE), major adverse limb events (MALE) and acute or severe limb ischaemia was 2.26, 3.57, and 1.54 per 100 patient-years, respectively, among the 5532 patients in XATOA. Corresponding rates in COMPASS were 2.18, 0.19, and 0.12 per 100 patient-years, respectively. Major bleeding rates were 0.95 and 1.67 per 100 patient-years in XATOA and COMPASS, respectively.. High-risk vascular patients are prioritized for DPI in clinical practice, and rates of MACE are similar to COMPASS, but MALE rates are higher in XATOA, consistent with the greater proportion of PAD patients. Major bleeding rates were lower in XATOA. The findings provide support for favourable net clinical benefit of DPI in high-risk vascular patients.. The characteristics of patients initiated on dual pathway inhibition (DPI: rivaroxaban 2.5  mg twice daily plus aspirin) have not previously been defined in clinical practice and the XATOA registry findings demonstrate patient outcomes are consistent with those of the COMPASS trial, despite geographic differences in recruitment and the higher proportion of PAD patients.

Topics: Aged; Aspirin; Coronary Artery Disease; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Peripheral Arterial Disease; Registries; Rivaroxaban

Topics: Arteries; Aspirin; Endovascular Procedures; Female; Hemorrhage; Humans; Lower Extremity; Male; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Risk Factors; Rivaroxaban; Treatment Outcome

Prior studies have observed an association between the burden of atherosclerotic vascular disease and the risk of venous thromboembolism (VTE). The association is not well described in peripheral artery disease (PAD) after lower extremity revascularization (LER).. To describe the risk of, factors associated with, and outcomes after VTE, as well as the association of low-dose rivaroxaban plus antiplatelet therapy with VTE after LER.. This global, multicenter cohort study used data from the Vascular Outcomes Study of ASA (acetylsalicylic acid) Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD (VOYAGER PAD) randomized clinical trial, which enrolled patients from 2015 to 2018 with median follow-up of 28 months. Participants included patients with PAD undergoing LER. Patients with an indication for therapeutic anticoagulation were excluded. Data were analyzed from September 2020 to September 2021.. Randomization to rivaroxaban 2.5 mg twice daily or placebo on a background of aspirin 100 mg daily; short-term clopidogrel was used at the discretion of the treating physician.. Symptomatic VTE was a prespecified secondary outcome and prospectively collected.. Among 6564 patients (median [IQR] age, 67 [61-73] years; 4860 [74.0%] men), 66 patients had at least 1 VTE. The 3-year rate of VTE in patients receiving placebo was 1.7%, and the pattern of risk was linear (year 1: 0.5%; year 2: 1.1%). After multivariable modeling, weight (hazard ratio [HR], 3.04; 95% CI, 1.09-8.43), hypertension (HR, 2.11; 95% CI, 0.91-4.89), prior amputation (HR, 2.07; 95% CI, 0.95-4.53), and older age (HR, 1.81; 95% CI, 1.06-3.11) were associated with increased risk of VTE. VTE was associated with risk of subsequent mortality (HR, 7.22; 95% CI, 4.66-11.19). Compared with aspirin alone, rivaroxaban plus aspirin was associated with lower VTE risk (HR, 0.61; 95% CI, 0.37-0.998; P = .047), with benefit apparent early and sustained over time. This association was not modified by use of clopidogrel at randomization (without clopidogrel: HR, 0.55; 95% CI, 0.29-1.07; with clopidogrel: HR, 0.69; 95% CI, 0.32-1.48; P for interaction = .67).. In this cohort study, there was continuous risk for VTE after LER in patients with PAD, with greater risk in patients who were older and had obesity and those with more severe PAD, as reflected by prior amputation. Low-dose rivaroxaban plus aspirin was associated with lower VTE risk compared with aspirin alone, with benefits apparent early and continued over time. The spectrum of venous and arterial thrombotic events and overall benefits of more potent antithrombotic strategies for prevention should be considered after LER for PAD.

Topics: Aged; Aspirin; Clopidogrel; Cohort Studies; Female; Humans; Lower Extremity; Male; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Venous Thromboembolism

It is unknown whether Asian and non-Asian patients with atherosclerotic vascular disease derive similar benefits from long-term antithrombotic therapy.. In patients with chronic coronary artery disease (CAD) and/or peripheral artery disease (PAD) enrolled in The Cardiovascular Outcomes for People Using Anticoagulation Strategies trial, the effects of rivaroxaban 2.5 mg b.i.d. plus aspirin 100 mg o.d. were compared with those of aspirin 100 mg o.d. in Asian vs. non-Asian patients (race was self-identified). Asians (n = 4269) vs. non-Asians (n = 23 126) had similar rates of major adverse cardiovascular events (MACEs) (4.85% vs. 4.83%, P = 0.30) and modified International Society on Thrombosis and Haemostasis (ISTH) major bleeding (2.72% vs. 2.58%, P = 0.22), but higher rates of intracranial haemorrhage (ICH) (0.63% vs. 0.29%, P = 0.01) and minor bleeding (13.61% vs. 6.49%, P < 0.001). In Asians vs. non-Asians, the combination of rivaroxaban and aspirin compared with aspirin alone produced consistent reductions in MACE [Asians: hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.45-0.90; non-Asians: HR: 0.78, 95% CI: 0.67-0.90; P(heterogeneity) = 0.29], increases in modified ISTH major bleeding (Asians: HR 2.24, 95% CI: 1.40-3.58; non-Asians: HR: 1.60, 95% CI: 1.30-1.97; P = 0.20), and net clinical outcome (Asians: HR: 0.77, 95% CI: 0.56-1.05; non-Asians: HR: 0.81, 95% CI: 0.70-0.93, P = 0.78), but borderline higher rates of ICH (Asians: HR: 3.50, 95% CI: 0.98-12.56; non-Asians: HR: 0.81, 95% CI: 0.43, 1.53; P = 0.04).. Asian compared with non-Asian patients with chronic CAD and/or PAD have higher rates of ICH and minor bleeding. The combination of rivaroxaban and aspirin vs. aspirin alone produces similar effects for MACE, modified ISTH major bleeding, and net clinical outcome but may be associated with higher rates of ICH in Asian patients.

Topics: Asian People; Aspirin; Coronary Artery Disease; Drug Therapy, Combination; Hemorrhage; Humans; Peripheral Arterial Disease; Rivaroxaban

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

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

Low-dose rivaroxaban reduced major adverse cardiac and limb events among patients with stable atherosclerotic vascular disease (ASCVD) in the COMPASS trial. The objective of our study was to evaluate the eligibility and budgetary impact of the COMPASS trial in a real-world population.. The VA administrative and clinical databases were utilized to conduct a cross-sectional study to identify patients eligible for low-dose rivaroxaban receiving care at all 141 facilities between October 1, 2014 and September 30, 2015. Proportion of patients with stable ASCVD eligible for low-dose rivaroxaban and prevalence of multiple risk enrichment criteria among eligible patients. Pharmaceutical budgetary impact using VA pharmacy pricing. Chi-squared and Student's t tests were used to compare patients eligible versus ineligible patients.. From an initial cohort of 1,248,214 patients with ASCVD, 488,495 patients (39.1%) met trial eligibility criteria. Eligible patients were older (74.2 vs 64.5 years) with higher proportion of hypertension (84.1% vs 82.1%) and diabetes (46.2% vs 32.9) compared with ineligible patients (p < 0.001 for all comparisons). A median of 38.7% (IQR 4.6%) of total ASCVD patients per facility were rivaroxaban eligible. Estimated annual VA pharmacy budgetary impact would range from $0.47 billion to $1.88 billion for 25% to 100% treatment penetration. Annual facility level pharmaceutical budgetary impact would be a median of $12.3 million (IQR $8.0-$16.3 million) for treatment of all eligible patients. Among eligible patients, age greater than 65 years was the most common risk enrichment factor (86.9%). Prevalence of eligible patients with multiple enrichment factors varied from 34.2% (one factor) to 6.2% (four or more).. Over one third of patients with stable ASCVD may qualify for low-dose rivaroxaban within the VA. Additional studies are needed to understand eligibility in other populations and a formal cost-effectiveness analysis is warranted.

Topics: Age Factors; Aged; Aged, 80 and over; Aspirin; Atherosclerosis; Budgets; Cardiovascular Diseases; Cigarette Smoking; Cross-Sectional Studies; Diabetes Mellitus; Dose-Response Relationship, Drug; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Health Expenditures; Hemorrhage; Humans; Male; Middle Aged; Peripheral Arterial Disease; Renal Insufficiency, Chronic; Rivaroxaban; United States; United States Department of Veterans Affairs

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

Patients with peripheral artery disease (PAD) undergoing lower extremity revascularization (LER) are at high risk of major adverse limb and cardiovascular events. 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 demonstrated that rivaroxaban 2.5 mg twice daily reduced first events by 15%. The benefit of rivaroxaban on total (first and subsequent) events in this population is unknown.. This study sought to evaluate the total burden of vascular events in patients with PAD after LER and the efficacy of low-dose rivaroxaban on total events.. VOYAGER PAD randomized patients with PAD undergoing LER to rivaroxaban 2.5 mg twice daily plus aspirin or aspirin alone. The primary endpoint was time to first event of acute limb ischemia, major amputation of a vascular cause, myocardial infarction, ischemic stroke, or cardiovascular death. The current analysis considered all events (first and subsequent) for components of the primary endpoint as well as additional vascular events including peripheral revascularizations and venous thromboembolism. HRs were estimated by marginal proportional hazards models.. Among 6,564 randomized events, there were 4,714 total first and subsequent vascular events including 1,614 primary endpoint events and 3,100 other vascular events. Rivaroxaban reduced total primary endpoint events (HR: 0.86; 95% CI: 0.75-0.98; P = 0.02) and total vascular events (HR: 0.86; 95% CI: 0.79-0.95; P = 0.003). An estimated 4.4 primary and 12.5 vascular events per 100 participants were avoided with rivaroxaban over 3 years.. Patients with symptomatic PAD who are undergoing LER have a high total event burden that is significantly reduced with rivaroxaban. Total event reduction may be a useful metric to quantify the efficacy of rivaroxaban in this setting. (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 [VOYAGER PAD]; NCT02504216).

Topics: Aged; Dose-Response Relationship, Drug; Drug Therapy, Combination; Factor Xa Inhibitors; Global Health; Humans; Incidence; Ischemia; Lower Extremity; Male; Middle Aged; Peripheral Arterial Disease; Rivaroxaban; Treatment Outcome; Vascular Surgical Procedures

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

The combination of 2.5 mg rivaroxaban twice daily and 100 mg aspirin once daily compared with 100 mg aspirin once daily reduces major adverse cardiovascular (CV) events in patients with chronic coronary artery disease (CAD) or peripheral artery disease (PAD).. The aim of this work was to report the effects of the combination on overall and cause-specific mortality.. The COMPASS trial enrolled 27,395 patients of whom 18,278 were randomized to the combination (n = 9,152) or aspirin alone (n = 9,126). Deaths were adjudicated by a committee blinded to treatment allocation. Previously identified high-risk baseline features were polyvascular disease, chronic kidney disease, mild or moderate heart failure, and diabetes.. During a median of 23 months of follow-up (maximum 47 months), 313 patients (3.4%) allocated to the combination and 378 patients (4.1%) allocated to aspirin alone died (hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.71-0.96; P = 0.01). Compared with aspirin, the combination reduced CV death (160 [1.7%] vs 203 [2.2%]; HR: 0.78; 95% CI: 0.64-0.96; P = 0.02) but not non-CV death. There were fewer deaths following MI, stroke, and CV procedures, as well as fewer sudden cardiac, other, and unknown causes of CV deaths and coronary heart disease deaths. Patients with 0, 1, 2, and 3 or 4 high-risk features at baseline had 4.2, 4.8, 25.0, and 53.9 fewer deaths, respectively, per 1000 patients treated for 30 months.. The combination of rivaroxaban and aspirin compared with aspirin reduced overall and CV mortality with consistent reductions in cause specific CV mortality in patients with chronic CAD or PAD. The absolute mortality benefits are greater with increasing baseline risk. (Cardiovascular Outcomes for People Using Anticoagulant Strategies [COMPASS]; NCT01776424).

Topics: Aged; Aspirin; Coronary Artery Disease; Diabetes Mellitus; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Heart Failure; Humans; Male; Outcome Assessment, Health Care; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Risk Assessment; Risk Factors; Rivaroxaban; Severity of Illness Index

Patients with peripheral artery disease requiring lower extremity revascularization (LER) are at high risk of adverse limb and cardiovascular events. The VOYAGER PAD trial (Vascular Outcomes Study of ASA [Acetylsalicylic Acid] Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) demonstrated that rivaroxaban significantly reduced this risk. The efficacy and safety of rivaroxaban has not been described in patients who underwent surgical LER.. The VOYAGER PAD trial randomized patients with peripheral artery disease after surgical and endovascular LER to rivaroxaban 2.5 mg twice daily plus aspirin or matching placebo plus aspirin and followed for a median of 28 months. The primary end point was a composite of acute limb ischemia, major vascular amputation, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety outcome was Thrombolysis in Myocardial Infarction major bleeding. International Society on Thrombosis and Haemostasis bleeding was a secondary safety outcome. All efficacy and safety outcomes were adjudicated by a blinded independent committee.. Of the 6564 randomized, 2185 (33%) underwent surgical LER and 4379 (67%) endovascular. Compared with placebo, rivaroxaban reduced the primary end point consistently regardless of LER method (. The efficacy of rivaroxaban is associated with a benefit in patients who underwent surgical LER. Although bleeding was increased with rivaroxaban plus aspirin, the incidence was low, with no significant increase in fatal bleeding, intracranial hemorrhage, or postprocedural bleeds requiring intervention. Registration: URL: http://www.clinicaltrials.gov; Unique Identifier: NCT02504216.

Topics: Aged; Aspirin; Female; Humans; Male; Middle Aged; Peripheral Arterial Disease; Rivaroxaban

Topics: Aged; Factor Xa Inhibitors; Female; Humans; Male; Peripheral Arterial Disease; Renal Insufficiency; Rivaroxaban; Vascular Surgical Procedures

In this secondary analysis of the VOYAGER trial, rivaroxaban 2.5 mg twice/day plus aspirin 100 mg/day was assessed in older adults. Advanced age is associated with elevated bleeding risk and unfavourable net benefit for dual antiplatelet therapy in chronic coronary artery disease. The risk-benefit of low-dose rivaroxaban in patients ≥75 years with peripheral artery disease (PAD) after lower extremity revascularization (LER) has not been described.. The primary endpoint was a composite of acute limb ischaemia, major amputation, myocardial infarction, ischaemic stroke, or cardiovascular death. The principal safety outcome was thrombolysis in myocardial infarction (TIMI) major bleeding analysed by the pre-specified age cut-off of 75 years. Of 6564 patients randomized, 1330 (20%) were >75 years. Absolute 3-year Kaplan-Meier cumulative incidence rates for primary efficacy (23.4% vs. 19.0%) and safety (3.5% vs. 1.5%) endpoints were higher in elderly vs. non-elderly patients. Efficacy of rivaroxaban (P-interaction 0.83) and safety (P-interaction 0.38) was consistent irrespective of age. The combination of intracranial and fatal bleeding was not increased in patients >75 years (2 rivaroxaban vs. 8 placebo). Overall, benefits (absolute risk reduction 3.8%, number needed to treat 26 for the primary endpoint) exceeded risks (absolute risk increase 0.81%, number needed to harm 123 for TIMI major bleeding).. Patients ≥75 years with PAD are at both heightened ischaemic and bleeding risk after LER. No excess harm with respect to major, intracranial or fatal bleeding was seen in older patients yet numerically greater absolute benefits were observed. This suggests that low-dose rivaroxaban combined with aspirin should be considered in PAD after LER regardless of age.

Topics: Aged; Aspirin; Brain Ischemia; Drug Therapy, Combination; Factor Xa Inhibitors; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Stroke

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 (. More favorable risk factor status and low-dose rivaroxaban were independently associated with lower risk of cardiovascular events.

Topics: Aged; Anticoagulants; Aspirin; Chronic Disease; Coronary Artery Disease; Double-Blind Method; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Heart Disease Risk Factors; Humans; Male; Middle Aged; Peripheral Arterial Disease; Prospective Studies; Recurrence; Risk Assessment; Rivaroxaban; Secondary Prevention; Time Factors; Treatment Outcome

Patients with coronary artery disease (CAD), peripheral artery disease (PAD), or both remain at risk of cardiovascular events (including peripheral ischemic events), even when they receive the current guideline-recommended treatment. The phase III COMPASS trial demonstrated that treatment with rivaroxaban vascular dose 2.5 mg twice daily plus aspirin (dual pathway inhibition [DPI] regimen) significantly reduced the risk of major adverse cardiovascular events (including peripheral ischemic events) and increased the risk of major bleeding, but not fatal bleeding or intracranial hemorrhage, versus aspirin alone in patients with CAD, PAD, or both. The results of the COMPASS trial supported the regulatory approval of the DPI regimen in several geographic regions. However, it is unclear whether the patients selected for treatment with the DPI regimen in clinical practice will have a similar risk profile and event rates compared with the COMPASS trial population. The prospective post-approval XATOA registry study aims to assess treatment patterns, as well as ischemic and bleeding outcomes in patients with CAD, PAD, or both, who receive DPI therapy in routine clinical practice. Up to 10,000 patients from at least 400 centers in 22 countries will be enrolled and followed up for a minimum of 12 months, and all treatment will be at the discretion of the prescribing physician. The primary objective of the XATOA study will be to describe early treatment patterns, while ischemic and bleeding outcomes will be described as a secondary objective. TRIAL REGISTRATION NUMBER: NCT03746275.

Topics: Aspirin; Atherosclerosis; Coronary Thrombosis; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Male; Middle Aged; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Prospective Studies; Registries; Rivaroxaban; Treatment Outcome

COMPASS study demonstrated efficacy of dual pathway inhibition with 2.5 mg twice daily rivaroxaban and aspirin in patients with polyvascular disease (coronary artery disease, peripheral arterial disease or both), the underlying mechanism of which is not clearly understood. In this Phase IV, prospective, open-label and randomized study, we hypothesize that treatment with rivaroxaban is associated with a reduction in platelet activation and aggregation, inflammation and coagulation markers. 30 patients will be randomly treated with aspirin (81 mg q.d.) or aspirin plus rivaroxaban (2.5 mg b.i.d.) for 12 weeks. Platelet aggregation, platelet activation and inflammation markers, thrombin generation kinetics and tissue factor-induced platelet-fibrin clot strength will be measured at baseline, and 4 and 12 weeks after randomization.

Topics: Aged; Aspirin; Biomarkers; Blood Coagulation; Coronary Artery Disease; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Humans; Inflammation; Male; Peripheral Arterial Disease; Platelet Activation; Platelet Aggregation Inhibitors; Prospective Studies; Rivaroxaban

Patients with peripheral artery disease who have undergone lower-extremity revascularization are at high risk for major adverse limb and cardiovascular events. The efficacy and safety of rivaroxaban in this context are uncertain.. In a double-blind trial, patients with peripheral artery disease who had undergone revascularization were randomly assigned to receive rivaroxaban (2.5 mg twice daily) plus aspirin or placebo plus aspirin. The primary efficacy outcome was a composite of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes. The principal safety outcome was major bleeding, defined according to the Thrombolysis in Myocardial Infarction (TIMI) classification; major bleeding as defined by the International Society on Thrombosis and Haemostasis (ISTH) was a secondary safety outcome.. A total of 6564 patients underwent randomization; 3286 were assigned to the rivaroxaban group, and 3278 were assigned to the placebo group. The primary efficacy outcome occurred in 508 patients in the rivaroxaban group and in 584 in the placebo group; the Kaplan-Meier estimates of the incidence at 3 years were 17.3% and 19.9%, respectively (hazard ratio, 0.85, 95% confidence interval [CI], 0.76 to 0.96; P = 0.009). TIMI major bleeding occurred in 62 patients in the rivaroxaban group and in 44 patients in the placebo group (2.65% and 1.87%; hazard ratio, 1.43; 95% CI, 0.97 to 2.10; P = 0.07). ISTH major bleeding occurred in 140 patients in the rivaroxaban group, as compared with 100 patients in the placebo group (5.94% and 4.06%; hazard ratio, 1.42; 95% CI, 1.10 to 1.84; P = 0.007).. In patients with peripheral artery disease who had undergone lower-extremity revascularization, rivaroxaban at a dose of 2.5 mg twice daily plus aspirin was associated with a significantly lower incidence of the composite outcome of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes than aspirin alone. The incidence of TIMI major bleeding did not differ significantly between the groups. The incidence of ISTH major bleeding was significantly higher with rivaroxaban and aspirin than with aspirin alone. (Funded by Bayer and Janssen Pharmaceuticals; VOYAGER PAD ClinicalTrials.gov number, NCT02504216.).

Topics: Aged; Aspirin; Cardiovascular Diseases; Combined Modality Therapy; Double-Blind Method; Drug Therapy, Combination; Endovascular Procedures; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Incidence; Ischemia; Kaplan-Meier Estimate; Lower Extremity; Male; Middle Aged; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban

Non-stenotic intracranial and systemic atherosclerosis are associated with ischemic stroke. We report frequency and response to anticoagulant vs. antiplatelet prophylaxis of patients with embolic stroke of undetermined source (ESUS) who have non-stenotic intracranial atherosclerosis and/or systemic atherosclerosis.. Exploratory analysis of the international NAVIGATE ESUS randomized trial comparing rivaroxaban 15mg daily with aspirin 100mg daily in 7213 patients with recent ESUS. Among participants with results of intracranial arterial imaging with either computed tomographic angiography (CTA) or magnetic resonance angiography (MRA), the frequency and predictors of non-stenotic intracranial and systemic atherosclerosis and responses to antithrombotic therapy were assessed.. East Asia region was the strongest factor associated with intracranial atherosclerosis. There were no statistically significant differences between rivaroxaban and aspirin prophylaxis for recurrent ischemic stroke in patients with non-stenotic intracranial atherosclerosis and/or systemic atherosclerosis.

Topics: Aged; Aspirin; Double-Blind Method; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Humans; Intracranial Arteriosclerosis; Intracranial Embolism; Male; Middle Aged; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Prevalence; Recurrence; Risk Assessment; Risk Factors; Rivaroxaban; Stroke; Time Factors; Treatment Outcome

The VOYAGER PAD trial (Vascular Outcomes Study of ASA Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease) demonstrated superiority of rivaroxaban plus aspirin versus aspirin to reduce major cardiac and ischemic limb events after lower extremity revascularization. Clopidogrel is commonly used as a short-term adjunct to aspirin after endovascular revascularization. Whether clopidogrel modifies the efficacy and safety of rivaroxaban has not been described.. VOYAGER PAD was a phase 3, international, double-blind, placebo-controlled trial in patients with symptomatic PAD undergoing lower extremity revascularization randomized to rivaroxaban 2.5 mg twice daily plus 100 mg aspirin daily or rivaroxaban placebo plus aspirin. The primary efficacy outcome was a composite of acute limb ischemia, major amputation of a vascular cause, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety end point was TIMI (Thrombolysis in Myocardial Infarction) major bleeding, with International Society on Thrombosis and Haemostasis major bleeding a secondary safety outcome. Clopidogrel use was allowed at the discretion of the investigator for up to 6 months after the qualifying revascularization.. In the VOYAGER PAD trial, rivaroxaban plus aspirin reduced the risk of adverse cardiovascular and limb events with an early benefit for acute limb ischemia regardless of clopidogrel use. The safety of rivaroxaban was consistent regardless of clopidogrel use but with a trend for more International Society on Thrombosis and Haemostasis major bleeding with clopidogrel use >30 days than with a shorter duration. These data support the addition of rivaroxaban to aspirin after lower extremity revascularization regardless of concomitant clopidogrel, with a short course (≤30 days) associated with less bleeding. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02504216.

Topics: Aged; Aspirin; Clopidogrel; Double-Blind Method; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Humans; Internationality; Lower Extremity; Male; Middle Aged; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Treatment Outcome

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

In patients with coronary or peripheral artery disease, 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 and mortality and increased bleeding.. This study sought to explore the effects of the combination of rivaroxaban and aspirin compared with aspirin on sites, timing, severity, and management of bleeding in the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) study.. This study reports, by treatment group, the number and proportion of patients; hazard rate ratios for bleeding according to site and severity; the timing of bleeding using landmark analyses; and the number and proportion of patients who received blood products and other hemostatic treatments.. Of 27,395 patients enrolled (mean age 68 years, 22% women), 18,278 were randomized to the combination of rivaroxaban and aspirin or to aspirin alone and followed for a mean of 23 months. Compared with aspirin alone, the combination increased modified International Society on Thrombosis and Hemostasis major bleeding (288 of 9,152 [3.1%] vs. 170 of 9,126 [1.9%]), (HR: 1.70; 95% CI: 1.40 to 2.05; p < 0.001), International Society on Thrombosis and Hemostasis major bleeding (206 of 9,152 [2.3%] vs. 116 of 9,126 [1.3%]), (HR: 1.78; 95% CI: 1.41 to 2.23; p < 0.0001), and minor bleeding (838 of 9,152 [9.2%] vs. 503 of 9,126 [5.5%]), (HR: 1.70; 95% CI 1.52 to 1.90; p < 0.0001); the combination also increased the need for any red cell transfusion (87 of 9,152 [1.0%] vs. 44 of 9,126 [0.5%]), (HR: 1.97; 95% CI 1.37 to 2.83, p = 0.0002). The gastrointestinal (GI) tract was the most common site of increased major bleeding (140 of 9,152 [1.5%] vs. 65 of 9,126 [0.7%]), (HR: 2.15; 95% CI: 1.60 to 2.89; p < 0.001), and the increase in bleeding was predominantly in the first year after randomization. Approximately one-third of major GI bleeding was gastric or duodenal, one-third was colonic or rectal, and one-third was from an unknown GI site. The study investigators reported that approximately three-quarters of major bleeding episodes were of mild or moderate intensity. A similar proportion of patients in each treatment group who experienced major bleeding received platelets, clotting factors, or other hemostatic agents.. The combination of rivaroxaban and aspirin compared with aspirin alone increased major bleeding, mainly from the GI tract. Most excess bleeding occurred during the first year after randomization, was of mild or moderate intensity, and was managed with conventional supportive therapy. (Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease [COMPASS]; NCT01776424).

Topics: Aged; Aspirin; Coronary Artery Disease; Drug Combinations; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Severity of Illness Index

Strokes were significantly reduced by the combination of rivaroxaban plus aspirin in comparison with aspirin in the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies). We present detailed analyses of stroke by type, predictors, and antithrombotic effects in key subgroups.. Participants had stable coronary artery or peripheral artery disease and were randomly assigned to receive aspirin 100 mg once daily (n=9126), rivaroxaban 5 mg twice daily (n=9117), or rivaroxaban 2.5 mg twice daily plus aspirin (n=9152). Patients who required anticoagulation or had a stroke within 1 month, previous lacunar stroke, or intracerebral hemorrhage were excluded.. During a mean follow-up of 23 months, fewer patients had strokes in the rivaroxaban plus aspirin group than in the aspirin group (83 [0.9% per year] versus 142 [1.6% per year]; hazard ratio [HR], 0.58; 95% CI, 0.44-0.76; P<0.0001). Ischemic/uncertain strokes were reduced by nearly half (68 [0.7% per year] versus 132 [1.4% per year]; HR, 0.51; 95% CI, 0.38-0.68; P<0.0001) by the combination in comparison with aspirin. No significant difference was noted in the occurrence of stroke in the rivaroxaban alone group in comparison with aspirin: annualized rate of 0.7% (HR, 0.82; 95% CI, 0.65-1.05). The occurrence of fatal and disabling stroke (modified Rankin Scale, 3-6) was decreased by the combination (32 [0.3% per year] versus 55 [0.6% per year]; HR, 0.58; 95% CI, 0.37-0.89; P=0.01). Independent predictors of stroke were prior stroke, hypertension, systolic blood pressure at baseline, age, diabetes mellitus, and Asian ethnicity. Prior stroke was the strongest predictor of incident stroke (HR, 3.63; 95% CI, 2.65-4.97; P<0.0001) and was associated with a 3.4% per year rate of stroke recurrence on aspirin. The effect of the combination in comparison with aspirin was consistent across subgroups with high stroke risk, including those with prior stroke.. Low-dose rivaroxaban plus aspirin is an important new antithrombotic option for primary and secondary stroke prevention in patients with clinical atherosclerosis.. URL: https://www.clinicaltrials.gov . Unique identifier: NCT01776424.

Topics: Aged; Aged, 80 and over; Aspirin; Coronary Artery Disease; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Peripheral Arterial Disease; Risk Factors; Rivaroxaban; Stroke

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

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

Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial.. We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n = 8791) or placebo (n = 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow-up.. There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant.. In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. ClinicalTrials.gov Number: NCT01776424.

Topics: Aged; Aspirin; Cardiovascular Diseases; Double-Blind Method; Drug Administration Schedule; Enterocolitis, Pseudomembranous; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Pantoprazole; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Prospective Studies; Proton Pump Inhibitors; Risk Assessment; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome

Patients with chronic coronary artery disease or peripheral artery disease and history of heart failure (HF) are at high risk for major adverse cardiovascular events. We explored the effects of rivaroxaban with or without aspirin in these patients.. The COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies) randomized 27 395 participants with chronic coronary artery disease or peripheral artery disease to rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily, rivaroxaban 5 mg twice daily alone, or aspirin 100 mg alone. Patients with New York Heart Association functional class III or IV HF or left ventricular ejection fraction (EF) <30% were excluded. The primary major adverse cardiovascular events outcome comprised cardiovascular death, stroke, or myocardial infarction, and the primary safety outcome was major bleeding using modified International Society of Thrombosis and Haemostasis criteria. Investigators recorded a history of HF and EF at baseline, if available. We examined the effects of rivaroxaban on major adverse cardiovascular events and major bleeding in patients with or without a history of HF and an EF <40% or ≥40% at baseline.. Of the 5902 participants (22%) with a history of HF, 4971 (84%) had EF recorded at baseline, and 12% had EF <40%. Rivaroxaban and aspirin had similar relative reduction in major adverse cardiovascular events compared with aspirin in participants with HF (5.5% versus 7.9%; hazard ratio [HR], 0.68; 95% CI, 0.53-0.86) and those without HF (3.8% versus 4.7%; HR, 0.79; 95% CI, 0.68-0.93; P for interaction 0.28) but larger absolute risk reduction in those with HF (HF absolute risk reduction 2.4%, number needed to treat=42; no HF absolute risk reduction 1.0%, number needed to treat=103). The primary major adverse cardiovascular events outcome was not statistically different between those with EF <40% (HR, 0.88; 95% CI, 0.55-1.42) and ≥40% (HR, 0.81; 95% CI, 0.67-0.98; P for interaction 0.36). The excess hazard for major bleeding was not different in participants with HF (2.5% versus 1.8%; HR, 1.36; 95% CI, 0.88-2.09) than in those without HF (3.3% versus 1.9%; HR, 1.79; 95% CI, 1.45-2.21; P for interaction 0.26). There were no significant differences in the primary outcomes with rivaroxaban alone.. In patients with chronic coronary artery disease or peripheral artery disease and a history of mild or moderate HF, combination rivaroxaban and aspirin compared with aspirin alone produces similar relative but larger absolute benefits than in those without HF.. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01776424.

Topics: Aged; Aspirin; Chronic Disease; Coronary Artery Disease; Double-Blind Method; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Heart Failure; Humans; Male; Middle Aged; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban

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

Patients with lower extremity peripheral artery disease (PAD) are at increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). There is limited information on the prognosis of patients who experience MALE.. Among participants with lower extremity PAD, this study investigated: 1) if hospitalizations, MACE, amputations, and deaths are higher after the first episode of MALE compared with patients with PAD who do not experience MALE; and 2) the impact of treatment with low-dose rivaroxaban and aspirin compared with aspirin alone on the incidence of MALE, peripheral vascular interventions, and all peripheral vascular outcomes over a median follow-up of 21 months.. We analyzed outcomes in 6,391 patients with lower extremity PAD who were enrolled in the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial. COMPASS was a randomized, double-blind placebo-controlled study of low-dose rivaroxaban and aspirin combination or rivaroxaban alone compared with aspirin alone. MALE was defined as severe limb ischemia leading to an intervention or major vascular amputation.. A total of 128 patients experienced an incident of MALE. After MALE, the 1-year cumulative risk of a subsequent hospitalization was 61.5%; for vascular amputations, it was 20.5%; for death, it was 8.3%; and for MACE, it was 3.7%. The MALE index event significantly increased the risk of experiencing subsequent hospitalizations (hazard ratio [HR]: 7.21; p < 0.0001), subsequent amputations (HR: 197.5; p < 0.0001), and death (HR: 3.23; p < 0.001). Compared with aspirin alone, the combination of rivaroxaban 2.5 mg twice daily and aspirin lowered the incidence of MALE by 43% (p = 0.01), total vascular amputations by 58% (p = 0.01), peripheral vascular interventions by 24% (p = 0.03), and all peripheral vascular outcomes by 24% (p = 0.02).. Among individuals with lower extremity PAD, the development of MALE is associated with a poor prognosis, making prevention of this condition of utmost importance. The combination of rivaroxaban 2.5 mg twice daily and aspirin significantly lowered the incidence of MALE and the related complications, and this combination should be considered as an important therapy for patients with PAD. (Cardiovascular Outcomes for People Using Anticoagulation Strategies [COMPASS]; NCT01776424).

Topics: Aged; Aspirin; Double-Blind Method; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Lower Extremity; Male; Middle Aged; Mortality; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban

Patients with peripheral artery disease (PAD) undergoing a lower-extremity revascularization are at heightened risk for ischemic cardiac and limb events. Although intensification of antithrombotic therapy after revascularization has demonstrated benefit in coronary disease populations, this approach has not been well studied or shown consistent benefit in PAD. Recent trial evidence demonstrated that a treatment strategy of rivaroxaban added to background antiplatelet therapy reduced ischemic risk in patients following recent acute coronary syndromes, as well as in patients with stable atherosclerotic vascular disease. Whether these benefits extend to the population of patients with symptomatic lower-extremity PAD undergoing revascularization is the objective of the VOYAGER PAD trial.. VOYAGER PAD is an international randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of rivaroxaban in symptomatic PAD patients undergoing a peripheral surgical and/or endovascular revascularization. Patients are randomized in a 1:1 ratio to either rivaroxaban 2.5 mg twice daily or placebo, on a background of low-dose aspirin (100 mg daily). In addition, the use of a limited course of P2Y. VOYAGER PAD is evaluating the efficacy of rivaroxaban added to background antiplatelet therapy to reduce major cardiovascular and limb ischemic vascular outcomes in the high-risk population of PAD patients undergoing peripheral revascularization.

Topics: Aspirin; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Endovascular Procedures; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Lower Extremity; Male; Middle Aged; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Rivaroxaban; Treatment Outcome

Vascular disease is included in a risk scoring system to predict stroke in patients with non-valvular atrial fibrillation (AF). This post hoc analysis of ROCKET AF aimed to determine the absolute rates of stroke and bleeding, and the relative effectiveness and safety of rivaroxaban vs. warfarin in patients with and without peripheral artery disease (PAD). Peripheral artery disease was defined on the case-report form as the presences of intermittent claudication, amputation for arterial insufficiency, vascular reconstruction, bypass surgery, or percutaneous intervention to the extremities, or previously documented abdominal aortic aneurysm.. ROCKET AF was a double-blind, double-dummy, randomized-controlled trial comparing rivaroxaban and warfarin for the prevention of stroke or systemic embolism. A total of 839 (5.9%) patients in ROCKET AF had PAD. Patients with and without PAD had similar rates of stroke or systemic embolism [HR: 1.04, 95% CI (0.72, 1.50), P = 0.84] and major or non-major clinically relevant (NMCR) bleeding [HR: 1.11, 95% CI (0.96, 1.28), P = 0.17], respectively. The efficacy of rivaroxaban when compared with warfarin for the prevention of stroke or systemic embolism was similar in patients with PAD (HR: 1.19, 95% CI: 0.63-2.22) and without PAD (HR: 0.86, 95% CI: 0.73-1.02; interaction P = 0.34). There was a significant interaction for major or NMCR bleeding in patients with PAD treated with rivaroxaban compared with warfarin (HR: 1.40, 95% CI: 1.06-1.86) compared with those without PAD (HR: 1.03, 95% CI: 0.95-1.11; interaction P = 0.037).. Patients with PAD in ROCKET AF did not have a statistically significant higher risk of stroke or systemic embolism than patients without PAD, and there were similar efficacy outcomes in patients treated with rivaroxaban and warfarin. In PAD patients, there was a higher risk of major bleeding or NMCR bleeding with rivaroxaban when compared with warfarin (interaction P = 0.037). Further investigation is warranted to validate this subgroup analysis and determine the optimal treatment in this high-risk cohort of AF patients with PAD.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Embolism; Female; Humans; Male; Morpholines; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Risk Factors; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Warfarin

The innovative pharmacological combination of low-dose rivaroxaban plus aspirin provides clinicians with an ideal opportunity to intensify the medical treatment of patients with coronary artery disease (CAD) and comorbid peripheral artery disease (PAD). We aimed to determine the cost-effectiveness of PAD screening using the ankle-brachial index (ABI) test in patients with CAD (with rivaroxaban administered if the PAD screening was positive) compared with no-screening strategy in China.. A Markov decision model using a 1-month cycle was developed to simulate the 25-year effectiveness and cost of PAD screening on 75-year-old patients with CAD in China, evaluating the quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER). One-way, two-way, and probabilistic sensitivity analyses were conducted to assess the impact of variations in the key parameters for ICERs.. Our model found an incremental cost of RMB4,959 (US$740) and an incremental QALY of 0.054 after one-time ABI screening, leading to an ICER of RMB91,936 (US$13,717) per QALY gained over a 25-year period. The reduction in all-cause mortality related to rivaroxaban and its cost were the factors most affecting the ICER. The screening would become cost-effective by decreasing the monthly cost of rivaroxaban to RMB184.5 (US$27.5) or by using domestic-brand rivaroxaban according to the threshold of a willingness to pay RMB72,447 (US$10,809) per QALY gained.. Our study demonstrated that ABI screening for PAD to decide on low-dose rivaroxaban administration was not cost-effective for patients with CAD in China. Nevertheless, policy-guided cost changes for domestic-brand rivaroxaban could easily resolve this issue.

Topics: Aged; Aspirin; China; Coronary Artery Disease; Cost-Benefit Analysis; Cost-Effectiveness Analysis; Humans; Markov Chains; Peripheral Arterial Disease; Quality-Adjusted Life Years; Rivaroxaban

Dual pathway inhibition (DPI) with low-dose rivaroxaban and aspirin in patients with coronary artery disease (CAD) and/or peripheral artery disease (PAD) reduces the occurrence of cardiovascular (CV) events; however, the underlying mechanisms explaining these latter CV benefits are not clearly understood. Our explorative observational study aimed to evaluate the effect of dual pathway inhibition on plasma inflammation and coagulation markers among real-world patients with CAD and/or PAD. We prospectively included all consecutive patients with an established diagnosis of CAD and/or PAD treated with aspirin 100 mg once daily (OD) and rivaroxaban 2.5 mg twice daily (TD). Clinical evaluation and laboratory analyses, including hemoglobin, renal function (creatinine, urea, and cystatin-C), coagulation markers (INR and aPTT), inflammation markers (IL-6, CRP, lipoprotein-associated phospholipase A2, and copeptin), and growth differentiation factor-15 (GDF-15), were conducted at baseline, before starting treatment, and at 4 and 24 weeks after study drug administration. Fifty-four consecutive patients (mean age 66 ± 7 years; male 83%) who completed the 6-month follow-up were included. At 24-week follow-up, a statistically significant reduction in IL-6 serum levels [4.6 (3.5-6.5) vs. 3.4 (2.4-4.3) pg/mL ; P = 0.0001] and fibrinogen [336 (290-390) vs. 310 (275-364) mg/dL; P = 0.04] was shown; moreover, a significant increase in GDF-15 serum level [1309 (974-1961) vs. 1538 (1286-2913) pg/mL; P = 0.002] was observed. Hemoglobin, renal function, and cardiovascular homeostasis biomarkers remain stable over the time. The anti-Xa activity at both [0.005 (0-0.02) vs. 0.2 (0.1-0.34); P < 0.0001) significantly increased. The dual pathway inhibitions with low-dose rivaroxaban and aspirin in patients with CAD and/or PAD were associated with the reduction of inflammation biomarkers.

Topics: Aged; Aspirin; Atherosclerosis; Biomarkers; Coronary Artery Disease; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Growth Differentiation Factor 15; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban

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Topics: Factor Xa Inhibitors; Humans; Peripheral Arterial Disease; Rivaroxaban

Peripheral artery disease (PAD) patients suffer a high risk of major cardiovascular (CV) events, with athero-thrombo-embolism as the underlying pathophysiologic mechanism. Recently, two large randomized clinical trials evaluated the efficacy and safety of low-dose rivaroxaban twice daily plus aspirin in stable PAD outpatients and those immediately after peripheral revascularization. We sought to determine if the effects of low-dose rivaroxaban and aspirin compared to aspirin alone are consistent across this broad spectrum of PAD patients.. We conducted a random-effects meta-analysis of the COMPASS and VOYAGER randomized trials among 11 560 PAD patients (4996 from COMPASS and 6564 from VOYAGER) in the primary analysis and 9332 (2768 from COMPASS and 6564 from VOYAGER) with lower extremity (LE)-PAD in the secondary analysis. The hazard ratio (HR) for the composite of CV death, myocardial infarction, ischaemic stroke, acute limb ischaemia, or major vascular amputation was 0.79 (95% confidence interval, CI: 0.65-0.95) comparing low-dose rivaroxaban plus aspirin to aspirin alone. While the risk of major bleeding was increased with low-dose rivaroxaban plus aspirin compared to aspirin alone [HR: 1.51 (95% CI: 1.22-1.87)], there was no significant increase in severe bleeding [HR: 1.18 (95% CI: 0.79-1.76)]. Similar effects were observed in the subset with symptomatic LE-PAD.. Among PAD patients, low-dose rivaroxaban plus aspirin is superior to aspirin alone in reducing CV and limb outcomes including acute limb ischaemia and major vascular amputation. This reduction is offset by a relative increase in major bleeding, but not by an excess of fatal or critical organ bleeding. The consistency of findings of these trials supports the use of combination low-dose rivaroxaban plus aspirin in PAD patients across a broad spectrum of disease.

Topics: Aspirin; Brain Ischemia; Drug Therapy, Combination; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Ischemia; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Stroke

Topics: Aspirin; Fibrinolytic Agents; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban

The VOYAGER PAD trial investigated data on dual pathway inhibition after lower limb revascularization for peripheral arterial disease (PAD). Multiple exclusion criteria were applied. However, neither data on the prevalence of exclusion criteria nor on the total number of patients screened for inclusion was discussed.. We performed a single-center prospective observational study in unselected PAD patients undergoing lower limb revascularization. Demographic and disease-specific data was collected.. One hundred fifty patients were included with only 29 patients (19.3%) as potential candidates for the VOYAGER PAD study medication. Poorly controlled diabetes or severe uncontrolled hypertension (33.3%), major tissue loss (18.7%), acute limb ischaemia within prior 2 weeks (17.3%) and a history of intracranial hemorrhage, stroke or TIA (16%) were amongst the exclusion criteria most frequently met. Compared to VOYAGER PAD study patients, significant differences regarding sex (36.7% female vs. 25.8%), renal insufficiency (29.0% vs. 20.1%), previous myocardial infarction (16.7% vs. 11.1%) and known carotid artery disease (18.7% vs. 8.6%) revealed. Patients presented significantly more frequently with critical limb ischemia (56.7% vs. 30.4%) and a history of previous peripheral revascularization (72.0% vs. 35.9%). Fewer endovascular interventions (52% vs. 65.5%) and more surgeries (58% vs. 34.5%) were performed.. In unselected patients undergoing revascularization for peripheral arterial disease, the majority presents with characteristics that, at present, preclude prescription of rivaroxaban in addition to aspirin. This patient cohort represents a population with higher rates of comorbidities and more complex vascular interventions, but might also benefit from dual pathway inhibition strategy.

Topics: Aspirin; Female; Humans; Lower Extremity; Male; Peripheral Arterial Disease; Prevalence; Risk Factors; Rivaroxaban; Treatment Outcome

In the VOYAGER PAD trial, rivaroxaban 2.5 mg plus aspirin significantly reduced the primary composite efficacy outcome of acute limb ischaemia, major amputation, myocardial infarction, ischaemic stroke, or cardiovascular death compared with aspirin alone. However, patients enrolled in the trial may not reflect patients encountered in daily clinical practice. This study described the proportion of patients eligible for VOYAGER PAD within the nationwide Danish Vascular Registry (DVR), reasons for ineligibility, and outcomes according to eligibility.. In total, 32 911 patients who underwent lower extremity revascularisation for symptomatic peripheral arterial disease (PAD) in the DVR (2000-2016) were identified. Trial inclusion and exclusion criteria were applied, and the three year cumulative incidence of primary and secondary trial outcomes was estimated.. Altogether, 27.1% of patients with PAD in the DVR were "VOYAGER eligible". Of those not included, 30.7% had at least one exclusion criterion ("VOYAGER excluded"), and an additional 42.3% did not fulfil the inclusion criteria ("VOYAGER not included"). The main reasons for exclusion were atrial fibrillation (32.3%), poorly regulated hypertension (20.6%), requirement for long term dual antiplatelet therapy (10.9%), cytochrome P450 inhibitors or inducers (9.7%), and renal failure (9.3%). The three year rate of the primary efficacy outcome was 10.08 per 100 person years among the "VOYAGER eligible", 16.32 among "VOYAGER excluded", and 6.98 among the "VOYAGER not included". For the primary safety outcome of thrombolysis in myocardial infarction (TIMI) major bleeding, rates were 2.24, 3.76, and 1.17, respectively. Rates of secondary endpoints were also consistently lower for patients who did not meet the inclusion criteria (predominantly due to central aorto-iliac procedures) and highest for "VOYAGER excluded" patients. "VOYAGER eligible" patients experienced a higher cumulative incidence of most endpoints than patients enrolled in the control arm of the VOYAGER PAD trial.. Among patients in routine clinical practice, 27.1% were eligible for the VOYAGER PAD trial. These patients were older, had more severe vascular symptoms, higher bleeding risk, and worse prognosis than trial participants.

Topics: Aged; Aspirin; Clinical Trials, Phase III as Topic; Denmark; Dose-Response Relationship, Drug; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Multicenter Studies as Topic; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Postoperative Complications; Randomized Controlled Trials as Topic; Rivaroxaban; Treatment Outcome; Vascular Surgical Procedures

Topics: COVID-19; Humans; Mesenteric Artery, Superior; Mesenteric Vascular Occlusion; Mesenteric Veins; Peripheral Arterial Disease; Rivaroxaban; Thrombosis

Topics: Aspirin; Atherosclerosis; Drug Therapy, Combination; Factor Xa Inhibitors; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Venous Thromboembolism

Topics: Aspirin; Coronary Artery Disease; Fibrinolytic Agents; Humans; Peripheral Arterial Disease; Rivaroxaban

Globally, the prevalence of chronic coronary syndrome (CCS) increases with age. In India, there is a rapidly growing burden of coronary artery disease (CAD), which has become the leading cause of morbidity and mortality. Despite recommended medical therapy, patients with CCS are still at risk of ischemic events. Currently, dual antiplatelet therapy (DAPT) is recommended in the form of aspirin and a P2Y12 inhibitor or low dose rivaroxaban in patients with stable CAD and/or peripheral artery disease (PAD). A low dose of rivaroxaban in combination with aspirin is a promising approach; however, for patients who might benefit the most, it still remains a challenge. Clinical trial data on this new drug was certainly very encouraging, with evidence from the COMPASS trial and prespecified subgroups of COMPASS trials suggesting that the addition of rivaroxaban to aspirin was associated with a significantly lower risk of ischemic events, mortality, and tolerable bleeding profile in patients with CCS and high-risk factors. This combination is cost-effective and generally well tolerated in patients with CAD and/or PAD, as well as patients with CCS and multimorbidity or high-risk populations.

Topics: Aspirin; Coronary Artery Disease; Drug Therapy, Combination; Factor Xa Inhibitors; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban

In patients with atherosclerotic disease, the occurrence of atherothrombotic events is the main determinant of morbidity and mortality. Growing evidence suggests the involvement of the coagulation pathway in the atherosclerotic process and the benefit of antithrombotic agents, such as direct oral anticoagulants, which interfere with both platelet aggregation and the coagulation cascade. The COMPASS trial has shown that in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD), low-dose rivaroxaban (2.5 mg twice daily) added to acetylsalicylic acid (ASA) 100 mg reduces major vascular events and mortality, with an increase in major bleeding but not in fatal bleeding or involving a critical organ. The reduction in major cardiovascular events has been confirmed in the overall population with CAD and in both patients with and without a previous percutaneous coronary revascularization, and also in patients with previous coronary bypass surgery. In patients with PAD, the combination of rivaroxaban 2.5 mg twice daily and ASA was found to reduce both major adverse cardiovascular events and major adverse limb events, including major limb amputations. In clinical practice, the use of rivaroxaban 2.5 mg co-administered with ASA has been approved in both patients with CAD and symptomatic PAD at high risk of ischemic events. However, in Italy, the national health system reimbursement is provided only for patients with PAD. In patients treated with rivaroxaban 2.5 mg, assessment and monitoring of bleeding risk is crucial to achieve the maximum clinical benefit.

Topics: Aspirin; Coronary Artery Disease; Humans; Percutaneous Coronary Intervention; Peripheral Arterial Disease; Rivaroxaban

Background The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial decreased major adverse cardiovascular events with very low-dose rivaroxaban and aspirin in patients with coronary artery disease and peripheral artery disease. We examined the eligibility and potential real-world impact of this strategy on the COMPASS-eligible population. Methods and Results COMPASS eligibility criteria were applied to the CANHEART (Cardiovascular Health in Ambulatory Care Research Team) registry, a population-based cohort of Ontario adults. We compared 5-year major adverse cardiovascular events and major bleeding rates stratified by COMPASS eligibility and by clinical risk factors. We applied COMPASS trial rivaroxaban/aspirin arm hazard ratios to estimate the potential impact on the COMPASS-eligible cohort. Among 362 797 patients with coronary artery disease or peripheral artery disease, 38% were deemed eligible, 47% ineligible, and 15% indeterminate. Among eligible patients, a greater number of risk factors was associated with higher rates of cardiovascular outcomes, whereas bleeding rates increased minimally. Over 5 years, applying COMPASS treatment effects to eligible patients resulted in a 2.4% absolute risk reduction of major adverse cardiovascular events and a number needed to treat of 42, and a 1.3% absolute risk increase of major bleeding and number needed to harm (NNH) of 77. Those with at least 2 risk factors had a 3.0% absolute risk reduction of major adverse cardiovascular events (number needed to treat =34) and a 1.6% absolute risk increase of major bleeding (number needed to harm =61). Conclusions Implementation of very-low-dose rivaroxaban therapy would potentially impact

Topics: Aspirin; Coronary Artery Disease; Drug Therapy, Combination; Factor Xa Inhibitors; Hemorrhage; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Secondary Prevention

Atherosclerotic cardiovascular disease (ASCVD), which includes coronary artery disease (CAD), cerebrovascular disease, and peripheral arterial disease (PAD) is associated with significant morbidity, mortality, and healthcare costs. Antiplatelet therapy has long been the mainstay of antithrombotic therapy for the prevention of first-ever and recurrent ASCVD events. More recently, however, randomized trials have demonstrated the benefits and cost-effectiveness of a dual pathway inhibition (DPI) strategy in acute and chronic ASCVD. When used in combination, aspirin and low-dose rivaroxaban work synergistically to inhibit platelet activation and thrombin generation, thereby preventing thrombus formation. Among patients with recent acute coronary syndrome (ACS), those with positive cardiac biomarkers or ST-segment elevation myocardial infarction, or a history of heart failure derive the greatest absolute benefits. Among patients with chronic ASCVD, those with involvement of two or more vascular beds, heart failure, chronic kidney disease, or diabetes derive the greatest absolute benefits. Additional trials are underway to assess the impact of DPI therapy in other populations of interest, including patients with ACS at high risk of left ventricular thrombus formation, intracranial atherosclerotic disease with recent transient ischemic attack or stroke, peripheral arterial disease with limiting claudication or post lower extremity revascularization, and advanced chronic kidney disease with ASCVD or risk factors for ASCVD. Further work is required to assess the possible added benefit of combining rivaroxaban with clopidogrel or ticagrelor instead of aspirin.

Topics: Acute Coronary Syndrome; Aspirin; Atherosclerosis; Cardiovascular Diseases; Drug Therapy, Combination; Heart Failure; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Renal Insufficiency, Chronic; Rivaroxaban; Thrombosis

Topics: Aged; Aspirin; Factor Xa Inhibitors; Humans; Peripheral Arterial Disease; Rivaroxaban

Topics: Factor Xa Inhibitors; Humans; Peripheral Arterial Disease; Rivaroxaban; Secondary Prevention

Topics: Administration, Oral; Drug Interactions; Factor Xa Inhibitors; Humans; Peripheral Arterial Disease; Rivaroxaban; Treatment Outcome

This study aimed to investigate the cost-effectiveness of low-dose rivaroxaban plus aspirin versus aspirin alone for patients with stable cardiovascular diseases in the Taiwan setting.. We constructed a Markov model to project the lifetime direct medical costs and quality-adjusted life-years of both therapies. Transitional probabilities were derived from the COMPASS trial, and the costs and utilities were obtained from the Taiwan National Health Insurance Database and published studies. One-way, scenario, subgroup, and probabilistic sensitivity analyses were performed to assess the uncertainty. Incremental cost-effectiveness ratio was presented as the outcome. The threshold of willingness-to-pay was set at US$76,368 (3 times the gross domestic product per capita of Taiwan). All analyses were operated by TreeAge 2019 and Microsoft Excel.. The incremental cost-effectiveness ratios of rivaroxaban plus aspirin versus aspirin alone in the patients with stable cardiovascular diseases, coronary artery diseases, and peripheral artery diseases were US$83,459, US$69,852 and -US$13,823 per quality-adjusted life-year gained, respectively. The probabilistic sensitivity analyses showed that the probabilities of cost-effectiveness for the regimen with rivaroxaban among those with cardiovascular diseases and coronary artery diseases were 44.1% and 65.3% at US$76,368.. Low-dose rivaroxaban plus aspirin is less likely to be a cost-effective alternative to aspirin in secondary prevention for the patients with stable cardiovascular diseases; however, among these patients, the regimen may have pharmacoeconomic incentives for the group merely having chronic coronary artery diseases from the Taiwan national payer's perspective. The pharmacoeconomic incentives are influenced by the drug price, event treatment fees, and willingness-to-pay threshold.

Topics: Anticoagulants; Aspirin; Cardiovascular Diseases; Coronary Artery Disease; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Drug Therapy, Combination; Factor Xa Inhibitors; Health Expenditures; Humans; Markov Chains; Peripheral Arterial Disease; Quality-Adjusted Life Years; Rivaroxaban; Secondary Prevention; Taiwan

Patients with lower extremity arterial disease are at increased risk for cardiovascular events. Antithrombotic therapy improves prognosis in these patients especially after peripheral revascularization. After endovascular revascularization duale anti-platelet therapy with Aspirin and Clopidogrel is used for up to 3 months in most cases, although there is only little evidence for this practice. Following peripheral bypass grafting most guidelines recommend single anti-platelet therapy. In some patients, anticoagulation with Vitamin K antagonists or dual anti-platelet therapy is indicated. But this practice is also based on small studies. The Vascular Outcomes Study of ASA Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease (VOYAGER PAD) study is the largest randomized trial concerning antithrombotic therapy after peripheral revascularization. In total 6564 patients were included after successful surgical or endovascular lower-extremity revascularization. Rivaroxaban 2.5 mg twice daily plus Aspirin 100 mg reduced cardiac and peripheral events compared with Aspirin 100 mg alone with increased risk for relevant but not for critical bleeding complications. In addition to antithrombotic medication risk factor management and regular follow-up examinations are important improve long-term prognosis after peripheral revascularization.. In Analogie zur Koronarintervention wird nach Katheterinterventionen peripherer Gefäße meist passager eine duale Thrombozytenaggregationshemmung (TZAH) mit ASS 100 mg und Clopidogrel 75 mg durchgeführt. Größere Studien zu diesem Vorgehen fehlten bisher und die Empfehlungen der aktuellen Leitlinien haben den Charakter eines Expertenkonsens.. Nach peripherer Bypassanlage empfehlen die aktuellen Leitlinien in der Regel die Monotherapie mit einem TZAH (ASS 100 mg oder Clopidogrel 75 mg). In Einzelfällen wird bei venösen Bypässen eine orale Antikoagulation oder bei Kunststoffbypässen eine duale TZAH eingesetzt. Diese Empfehlungen beruhen jedoch auf wenigen, teils kleinen Studien. DUALE GERINNUNGSHEMMENDE THERAPIE MIT NIEDRIGDOSIERTEM RIVAROXABAN UND ASS:  Die VOYAGER-PAD-Studie ist mit 6564 Patienten die größte randomisierte Studie zur gerinnungshemmenden Therapie nach Revaskularisation. Es wurde das Konzept einer niedrigdosierten Rivaroxaban-Gabe (2-mal 2,5 mg) plus ASS 100 mg nach erfolgreicher peripherer Revaskularisation untersucht. Die Studie zeigte unter der Kombinationstherapie im Vergleich zur Therapie mit ASS 100 mg allein eine signifikant niedrigere Inzidenz des kombinierten Endpunkts aus akuter Extremitätenischämie, Amputation, Myokardinfarkt, ischämischem Schlaganfall oder Tod aus kardiovaskulärer Ursache. Getriggert wurde dieses Ergebnis primär durch die Reduktion von akuten Gefäßverschlüssen. Es kam zwar insgesamt zu mehr klinisch relevanten Blutungen unter der Kombinationstherapie, eine Erhöhung von intrazerebralen oder vital bedrohlichen Blutungen zeigte sich jedoch nicht. Wenn man Risiko und Nutzen in Bezug setzt, dann verhindert in einer Population von 10 000 Patienten die zusätzliche Gabe von Rivaroxaban 2-mal 2,5 mg pro Jahr 181 primäre Endpunkte auf Kosten von 29 relevante Blutungen.

Topics: Aspirin; Endovascular Procedures; Fibrinolytic Agents; Humans; Lower Extremity; Peripheral Arterial Disease; Randomized Controlled Trials as Topic; 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

Rivaroxaban is a selective inhibitor of coagulation factor Xa and its combination with aspirin showed better outcomes in the prevention of recurrent cardiovascular disease than aspirin alone.. This analysis aimed to economically compare the cost effectiveness of rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily) with aspirin alone in patients with coronary artery disease (CAD) or peripheral artery disease (PAD) and related subgroups.. The analysis simulates the perspective of the Italian National Healthcare Service and used a state-transition decision Markov model. Clinical efficacy data and health events risks were gathered from the COMPASS trial. Health outcomes and costs (in Euros) were evaluated over a lifetime horizon and were discounted at 3.5% per annum. Direct healthcare costs entered the analysis. Results were expressed in terms of incremental cost-effectiveness ratio (ICER), defined as cost per quality-adjusted life-year (QALY) gained. One-way deterministic and probabilistic sensitivity analyses were performed.. For the CAD or PAD population, rivaroxaban plus aspirin was more effective and costly compared with aspirin alone. Incremental costs and efficacy produced an ICER of €16,522 per QALY gained. Analyses found similar trends for the PAD and CAD groups, with respective ICERs of €8003 and €18,599, while ICERs for the other groups were lower than €13,000 per QALY. Sensitivity analyses confirmed these findings.. Compared with aspirin alone, rivaroxaban plus aspirin is cost effective in preventing recurrent cardiovascular events in all patients with CAD or PAD, from the Italian perspective. These results could help clinicians and decision makers to develop improved strategies for cardiovascular disease prevention.

Topics: Aged; Aspirin; Coronary Artery Disease; Cost-Benefit Analysis; Drug Therapy, Combination; Female; Humans; Italy; Male; Middle Aged; Peripheral Arterial Disease; Quality-Adjusted Life Years; Rivaroxaban; Treatment Outcome

Multifocal arterial injury is common in patients with atherosclerotic cardiovascular diseases and is associated with increased risk of cardiovascular complications and death. Administration of more intensive antithrombotic therapy, particularly combinations of acetylsalicylic acid and a "vascular" dose of rivaroxaban, in patients with multifocal arterial injury is characterized by a beneficial ratio of efficiency and safety due to a pronounced decrease in the risk of cardiovascular complications. Detection of peripheral artery diseases in patients with ischemic heart disease and atherosclerotic cerebrovascular pathology makes it possible to improve the risk stratification, optimize the diagnostic tactics and clarify indications for more intensive antithrombotic therapy.

Topics: Aspirin; Drug Therapy, Combination; Fibrinolytic Agents; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban

Topics: Aspirin; Continuity of Patient Care; Coronary Disease; Early Termination of Clinical Trials; Fibrinolytic Agents; Humans; Peripheral Arterial Disease; Randomized Controlled Trials as Topic; Rivaroxaban; Treatment Outcome

Discussed in the article are the main problems related to surgical treatment of patients with peripheral artery disease, particularly taking into consideration that in the world there are from 160 to 202 million people suffering from this disease, with two thirds of such patients having signs of lesions of coronary or cerebral arteries. Vascular reconstructive interventions cannot completely eliminate the problem, since in the postoperative period there may develop cardiovascular complications related to both the limb involved as either acute or progressing chronic ischaemia and arteries of other localization (coronary, cerebral). The risk of serious cardiovascular complications in patients with a history of endured adverse ischaemic events on the part of limbs is severalfold higher. To solve these problems and decrease complications, salicylic acid is used as basic therapy. Attempts at replacing it by another drug or combined therapy with an alternative antiaggregant showed no advantages in increased risk of massive haemorrhage. On the other hand, a combination of salicylic acid with an anticoagulant at a low dose, i. e., rivaroxaban 2.5 mg twice daily as compared with acetylsalicylic acid monotherapy made it possible to significantly decrease the incidence of various cardiovascular complications in the form of myocardial infarction, stroke, adverse ischaemic events on the part of the extremity, limb amputation.. В статье обсуждаются основные проблемы, связанные с хирургическим лечением пациентов с заболеванием периферических артерий. В частности, речь идет о том, что в мире насчитывается от 160 до 202 млн человек с данным заболеванием, при этом у 2/3 таких пациентов имеются признаки поражения коронарных или церебральных артерий. Сосудистые реконструктивные вмешательства не способны полностью устранить проблему, поскольку в послеоперационном периоде могут развиться сердечно-сосудистые осложнения, связанные как с самой конечностью в виде острой или прогрессирующей хронической ишемии, так и артериями другой локализации (коронарные, церебральные). Риск серьезных сердечно-сосудистых осложнений у пациентов, перенесших в анамнезе нежелательные ишемические события со стороны конечностей в несколько раз выше. Для решения этих проблем и снижения осложнений в качестве базовой терапии применяют ацетилсалициловую кислоту. Попытки заменить ее на другой препарат или комбинированную терапию с альтернативным антиагрегантом не показали преимуществ при увеличении риска больших кровотечений. С другой стороны, комбинация ацетилсалициловой кислоты с антикоагулянтом в низкой дозе – ривароксабаном 2,5 мг 2 р/сут по сравнению с монотерапией ацетилсалициловой кислотой позволила значительно снизить частоту различных сердечно-сосудистых осложнений в виде инфаркта миокарда, инсульта, нежелательных ишемических событий со стороны конечности, ампутации конечности.

Topics: Arteries; Drug Therapy, Combination; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Treatment Outcome

Screening for peripheral artery disease (PAD) with the ankle-brachial index (ABI) test is currently not recommended in the general population; however, previous studies advocate screening in high-risk populations. Although providers may be hesitant to prescribe low-dose rivaroxaban to patients with coronary artery disease (CAD) alone, given the reduction in cardiovascular events and death associated with rivaroxaban, screening for PAD with the ABI test and accordingly prescribing rivaroxaban may provide additional benefits. We sought to describe the cost-effectiveness of screening for PAD in patients with CAD to optimize this high-risk populations' medical management.. We used a Markov model to evaluate the ABI test in patients with CAD. We assumed that all patients screened would be candidates for low-dose rivaroxaban. We assessed the cost of ABI screening at $100 per patient and added additional charges for physician visits ($100) and rivaroxaban cost ($470 per month). We used a 30-day cycle and performed analysis over 35 years. We evaluated quality-adjusted life years (QALYs) from previous studies and determined the incremental cost-effectiveness ratio (ICER) according to our model. We performed a deterministic and probabilistic sensitivity analyses of variables with uncertainty and reported them in a Tornado diagram showing the variables with the greatest effect on the ICER.. Our model estimates decision costs to screen or not screen at $94,953 and $82,553, respectively. The QALYs gained from screening was 0.060, generating an ICER of $207,491 per QALY. Factors most influential on the ICER were the reduction in all-cause mortality associated with rivaroxaban and the prohibitively high cost of rivaroxaban. If rivaroxaban cost less than $95 per month, this would make screening cost-effective based on a willingness to pay threshold of $50,000 per QALY.. According to our model, screening patients with CAD for PAD to start low-dose rivaroxaban is not currently cost-effective due to insufficient reduction in all-cause mortality and high medication costs. Nevertheless, vascular surgeons have a unique opportunity to prescribe or advocate for low-dose rivaroxaban in patients with PAD to improve cardiovascular outcomes.

Topics: Aged; Aged, 80 and over; Ankle Brachial Index; Comorbidity; Coronary Artery Disease; Cost-Benefit Analysis; Decision Trees; Diagnostic Screening Programs; Factor Xa Inhibitors; Female; Health Care Costs; Humans; Male; Markov Chains; Middle Aged; Models, Economic; Peripheral Arterial Disease; Predictive Value of Tests; Prevalence; Prognosis; Quality-Adjusted Life Years; Risk Assessment; Risk Factors; Rivaroxaban

Peripheral artery disease (PAD), also abbreviated as LEAD or lower extremity artery disease, is an important predictor of cardiovascular morbidity and mortality. Rivaroxaban, a selective direct factor Xa inhibitor, is proposed as an additional pharmacologic option for managing this disease. Two patients presented with PAD and high-risk comorbidities. The first case showed how the evaluation of the cardiovascular risk guided the therapeutic management of the patient. The second case was about a patient diagnosed with LEAD who experienced worsening from exertional ischemia toward critical ischemia requiring amputation despite distal revascularization, and parenteral vasodilator therapy to relieve pain. This case suggested a comprehensive care management approach, adapted to PAD progression stages. The PAD management consists nowadays of optimizing the management of cardiovascular risk factors and disease progression. Diagnosis, treatment, monitoring, and patient education should be handled by a vascular specialist in a specialized care unit.

Topics: Factor Xa Inhibitors; Female; Humans; Lower Extremity; Male; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Vasodilator Agents

Topics: Humans; Peripheral Arterial Disease; Rivaroxaban

The aim of this study was to examine the external applicability of the COMPASS and the VOYAGER-PAD trials in patients with lower extremity artery disease (LEAD) in the real world.. This was a multicentre retrospective analysis of prospectively collected COPART data, a French multicentre registry of patients hospitalised for symptomatic LEAD. The proportion of patients eligible for the combination of rivaroxaban 2.5 mg twice daily plus aspirin based on either COMPASS or VOYAGER-PAD criteria is reported. The one year cumulative incidence of outcomes between eligible and non-eligible patients, as well as eligible patients vs. control arms of the COMPASS (LEAD patient subgroup) and the VOYAGER-PAD trials were compared. Analyses were performed using Cox models.. Of 2 259 evaluable patients, only 679 (30.1%) were eligible for a low dose rivaroxaban plus aspirin regimen. Others were not eligible because of the need for anticoagulant (48.5% and 38.9% of patients meeting COMPASS and VOYAGER-PAD exclusion criteria, respectively) or dual antiplatelet therapy use (15.7% and 16.5%, respectively), high bleeding risk (14.4% and 11.6%, respectively), malignancy (26.1% and 21.0%, respectively), history of ischaemic/haemorrhagic stroke (21.1% and 19.8%, respectively), and severe renal failure (13.2% and 10.5%, respectively). COMPASS and VOYAGER-PAD eligible and ineligible patients were at higher risk of ischaemic events than participants in these trials. The one year cumulative incidences were 6.0% (95% CI 4.3 - 8.1) in the COMPASS eligible subset vs. 3.5% (95% CI 2.9 - 4.3) in the COMPASS control arm for major adverse cardiovascular events, and 27.9% (95% CI 19.9 - 38.3) in the VOYAGER-PAD eligible subset vs. 6.0% (95% CI 5.3 - 6.9) in the VOYAGER-PAD control arm for major adverse limb events.. Many patients hospitalised for symptomatic LEAD in France are not eligible for the low dose rivaroxaban plus aspirin combination. In turn, those eligible may potentially have greater absolute benefit because of higher risk than those enrolled in the trials.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aspirin; Drug Administration Schedule; Drug Therapy, Combination; Factor Xa Inhibitors; Female; France; Hospitalization; Humans; Incidence; Ischemia; Lower Extremity; Male; Middle Aged; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Registries; Retrospective Studies; Rivaroxaban; Treatment Outcome; Young Adult

There are scarce data evaluating the effectiveness and safety of rivaroxaban vs. warfarin in non-valvular atrial fibrillation (NVAF) patients with concomitant coronary artery disease (CAD) and/or peripheral artery disease (PAD) treated in routine practice.. Using MarketScan data from January 2012 to December 2017, we identified oral anticoagulant (OAC)-naïve NVAF patients receiving rivaroxaban (15-20 mg once daily) or warfarin, with comorbid CAD and/or PAD and ≥12 months of insurance coverage before OAC initiation. Differences in baseline covariates between cohorts were adjusted using inverse probability-of-treatment weights based on propensity scores (standardized differences <0.1 achieved for all covariates after adjustment). Endpoints included a composite of major thrombotic vascular events (MTVEs) (including ischaemic stroke, myocardial infarction, or need for lower limb revascularization/major amputation) and major bleeding. Patients were followed until an event-of-interest, discontinuation/switch of index OAC, insurance disenrolment, or end-of-data availability. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression. We identified 3257 rivaroxaban (30.4% received a 15 mg dose) and 5046 warfarin users with NVAF and comorbid CAD and/or PAD. Rivaroxaban was associated with a 32% (95% CI = 8-50%) reduction in the composite of MTVE. No significant difference in major bleeding was observed (HR = 1.13, 95% CI = 0.84-1.52). No statistical interactions were noted in subgroup analyses performed on the MTVE (P-interaction ≥ 0.35 for all) or major bleeding endpoints (P-interaction ≥ 0.09 for all).. Among patients with NVAF and comorbid CAD and/or PAD, rivaroxaban use was associated with a reduced risk of MTVEs vs. warfarin, without significantly increasing major bleeding risk.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Comorbidity; Coronary Artery Disease; Databases, Factual; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Peripheral Arterial Disease; Retrospective Studies; Risk Assessment; Risk Factors; Rivaroxaban; Thrombosis; Time Factors; Treatment Outcome; United States; Warfarin

In the COMPASS trial, rivaroxaban 2.5 mg twice daily (bid) plus acetylsalicylic acid (ASA) 100 mg once daily (od) performed better than ASA 100 mg od alone in reducing the rate of cardiovascular disease, stroke, or myocardial infarction (MI) in patients with coronary artery disease (CAD) and peripheral artery disease (PAD). A Markov model was developed to assess the cost-effectiveness of rivaroxaban plus ASA vs. ASA alone over a lifetime horizon, from the UK National Health System perspective.. The base case analysis assumed that patients entered the model in the event-free health state, with the possibility to experience ≤2 events, transitioning every three-month cycle, through acute and post-acute health states of MI, ischaemic stroke (IS), or intracranial haemorrhage (ICH), and death. Costs, quality-adjusted life-years (QALYs), life years-all discounted at 3.5%-and incremental cost-effectiveness ratios (ICERs) were calculated. Deterministic and probabilistic sensitivity analyses were conducted, as well as scenario analyses. In the model, patients on rivaroxaban plus ASA lived for an average of 14.0 years with no IS/MI/ICH, and gained 9.7 QALYs at a cost of £13 947, while those receiving ASA alone lived for an average of 12.7 years and gained 9.3 QALYs at a cost of £8126. The ICER was £16 360 per QALY. This treatment was cost-effective in 98% of 5000 iterations at a willingness-to-pay threshold of £30 000 per QALY.. This Markov model suggests that rivaroxaban 2.5 mg bid plus ASA is a cost-effective alternative to ASA alone in patients with chronic CAD or PAD.

Topics: Aspirin; Coronary Artery Disease; Cost-Benefit Analysis; Drug Costs; Drug Therapy, Combination; Factor Xa Inhibitors; Humans; Markov Chains; Models, Economic; Peripheral Arterial Disease; Progression-Free Survival; Quality of Life; Quality-Adjusted Life Years; Rivaroxaban; State Medicine; Time Factors; United Kingdom

Dual pathway inhibition with 2.5 mg rivaroxaban twice daily plus 100 mg aspirin once daily may be a promising alternative to 100 mg aspirin antiplatelet therapy for the prevention of cardiovascular events in patients with coronary artery disease and/or peripheral arterial disease. However, treatment costs and bleeding risks are higher, and there is another treatment option for peripheral arterial disease, 75 mg clopidogrel. A comprehensive assessment of benefits, risks and costs of dual pathway inhibition versus standard of care is needed.. We used a state transition model including cardiovascular, ischaemic limb and bleeding events to compare dual pathway inhibition to aspirin antiplatelet therapy in coronary artery disease, and additionally to clopidogrel antiplatelet therapy in peripheral arterial disease patients. We calculated the incremental cost-effectiveness ratio from costs and quality-adjusted life-years of lifelong treatment, and the cost-effectiveness probability at a €50,000/quality-adjusted life-year threshold.. Quality-adjusted life-years and costs of dual pathway inhibition were highest, the incremental cost-effectiveness ratios versus aspirin were €32,109 in coronary artery disease and €26,381 in peripheral arterial disease patients, with 92% and 56% cost-effectiveness probability, respectively (clopidogrel was extendedly dominated). Incremental cost-effectiveness ratios were below €20,000 in comorbid peripheral arterial disease patients and coronary artery disease patients younger than 65 years, incremental cost-effectiveness ratios were above €50,000 in carotid artery disease patients and coronary artery disease patients older than 75 years.. Lifelong preventive treatment of coronary artery disease and peripheral arterial disease patients at risk of cardiovascular events with dual pathway inhibition improves health outcomes and seems overall cost-effective relative to aspirin antiplatelet therapy and also to clopidogrel antiplatelet therapy for peripheral arterial disease, particularly in comorbid patients, but not in older patients and in carotid artery disease patients. These findings may warrant a targeted approach.

Topics: Aspirin; Cardiovascular Diseases; Cost-Benefit Analysis; Drug Therapy, Combination; Factor Xa Inhibitors; Humans; Models, Economic; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Quality-Adjusted Life Years; Rivaroxaban

Topics: Factor Xa Inhibitors; Humans; Peripheral Arterial Disease; Randomized Controlled Trials as Topic; Rivaroxaban; Vascular Surgical Procedures

The stenosis or occlusion of extremities defining peripheral artery disease (PAD) is a risk factor for adverse cardiovascular events and adverse limb events including amputation. PAD is common, can occur without symptoms or with claudication, and is easily diagnosed. Proper diagnosis and adherence to guideline-directed therapy can reduce the morbidity and potential mortality associated with PAD.

Topics: Ankle Brachial Index; Anticholesteremic Agents; Cilostazol; Diet, Healthy; Dual Anti-Platelet Therapy; Endovascular Procedures; Exercise Therapy; Factor Xa Inhibitors; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Intermittent Claudication; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Smoking Cessation; Thrombosis; Vascular Surgical Procedures; Vasodilator Agents

Topics: Cardiovascular Abnormalities; Humans; Peripheral Arterial Disease; Rivaroxaban; Vascular Surgical Procedures

Topics: Humans; Peripheral Arterial Disease; Rivaroxaban; Vascular Surgical Procedures

Currently, 15-20% of individuals with coronary artery disease (chronic coronary syndrome [CCS]) or peripheral artery disease (PAD) receiving routine treatment experience cardiovascular events (CVEs) within 3-4 years. Using PICOSTEPS (Patients-Intervention-Comparators-Outcomes-Setting-Time-Effects-Perspective-Sensitivity analysis) reporting, we evaluated the cost-effectiveness of recently approved rivaroxaban 2.5 mg twice daily in combination with acetylsalicylic acid 100 mg daily (RIV + ASA) for the prevention of CVEs among Finns with CCS or symptomatic PAD.. Myocardial infarction, ischemic stroke, intracranial hemorrhage, acute limb ischemia, amputations, major extracranial bleeding, venous thromboembolism, and cardiovascular deaths were modeled in a Markov model examining a cohort of patients with CCS or symptomatic PAD. Relative effects of the intervention (RIV + ASA) and comparator (ASA) were based on the COMPASS trial. The primary outcome was 3%/year discounted incremental cost-effectiveness ratio (ICER), defined as cost (2019 euros) per quality-adjusted life year (QALY) gained in the Finnish setting over a lifetime horizon. In addition to nonfatal and fatal CVEs, the effects factored Finnish non-CVE mortality, quality of life, and direct costs from a public payer perspective. Disaggregated costs and QALYs, costs per life year gained (LYG), and ischemic strokes avoided, net monetary benefit (NMB), expected value of perfect information (EVPI), economic value-added (EVA), cost-effectiveness table, and acceptability frontier were examined. Probabilistic and deterministic sensitivity analyses were conducted.. In the deterministic comparison with ASA over a lifetime horizon, RIV + ASA resulted in a benefit of 0.404 QALYs and 0.474 LYGs for an additional cost of €3241, resulting in an ICER of €8031/QALY. The probabilistic ICER was €4313/QALY (EVPI €1829/patient). RIV + ASA had positive NMB (€8791/patient), low EVPI (€88/patient), high EVA (€8703/patient), and 91% probability of cost-effectiveness using the willingness-to-pay of €25,254/QALY. The primary result was conservative and robust for RIV + ASA.. RIV + ASA was a cost-effective treatment alternative compared with ASA in patients with CCS or symptomatic PAD in Finland.. Finland lacks published evidence on the cost-effectiveness of approved interventions for the prevention of cardiovascular events among individuals with chronic coronary syndrome (stable coronary artery disease) or symptomatic peripheral artery disease at risk of cardiovascular complications. Rivaroxaban 2.5 mg twice daily plus acetylsalicylic acid 100 mg once daily is indicated and reimbursed in Finland for the prevention of cardiovascular events for patients with stable coronary artery disease or symptomatic peripheral artery disease. We assessed the effectiveness and costs of treatment with rivaroxaban plus acetylsalicylic acid in comparison with treatment with acetylsalicylic acid. That is, we examined whether rivaroxaban is cost-effective when prescribed in combination with acetylsalicylic acid.Cardiovascular events with their associated costs and impact on quality of life were modeled over the lifetime of patients. The main effectiveness outcome was quality-adjusted life years (modeled survival multiplied by the expected quality of life), and costs included those relevant to the Finnish public payer in 2019. Extensive sensitivity analyses were carried out to evaluate the impacts of different model inputs and rationale.Rivaroxaban plus acetylsalicylic acid had high probability of being cost-effective, compared with acetylsalicylic acid. By valuing quality-of-life benefit with a plausible willingness-to-pay, net cost savings of €8791 per patient could be gained or economic value added by €8703 per patient if rivaroxaban was used.

Topics: Adult; Aged; Aged, 80 and over; Coronary Artery Disease; Cost-Benefit Analysis; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Finland; Humans; Male; Middle Aged; Peripheral Arterial Disease; Rivaroxaban

In the COMPASS trial, the combination of rivaroxaban 2.5 mg twice daily and low-dose aspirin 75-100 mg daily produced a net clinical benefit of 20% in patients with chronic atherosclerotic vascular disease because it reduced major adverse events by 24% and overall mortality by 18% despite an initial increase in major bleeding. In this paper, we examine the rationale for targeting coagulation factor Xa in patients with atherosclerosis, summarize the pharmacology of the 2.5-mg dose, review the trials that led to the approval of the combination of rivaroxaban and aspirin for the long-term management of patients with chronic coronary artery disease or peripheral artery disease and discuss who would benefit the most. We also address the unresolved issues and challenges in the implementation of this therapy.

Topics: Coronary Artery Disease; Drug Therapy, Combination; Factor Xa Inhibitors; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban

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

Bonaca MP, Bauersachs RM, Anand SS, et al.

Topics: Drug Therapy, Combination; Factor Xa Inhibitors; Hemorrhage; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban

Topics: Factor Xa Inhibitors; Humans; Peripheral Arterial Disease; Rivaroxaban

Topics: Blood Coagulation; Clinical Trials as Topic; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Peripheral Arterial Disease; Risk Assessment; Risk Factors; Rivaroxaban; Treatment Outcome

Topics: Aspirin; Factor Xa Inhibitors; Humans; Peripheral Arterial Disease; Rivaroxaban

Topics: Aspirin; Factor Xa Inhibitors; Humans; Peripheral Arterial Disease; Rivaroxaban

Topics: Aspirin; Factor Xa Inhibitors; Humans; Peripheral Arterial Disease; Rivaroxaban

Topics: Aspirin; Drug Therapy, Combination; Endovascular Procedures; Factor Xa Inhibitors; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Rivaroxaban; Treatment Outcome; Vascular Surgical Procedures

Treatment of patients presenting with peripheral artery disease requires a comprehensive approach: correction of risk factors, drug therapy and, if necessary, an endovascular/hybrid/open intervention. Reconstructive operation may effectively improve a patient's quality of life in intermittent claudication, save the limb and life in case of severe ischaemia. Discussed in the article are advantages and disadvantages of various types of surgical interventions for peripheral artery disease, the concept PLAN (Patient risk, Limb severity, and ANatomic complexity) and the new Global Anatomic Staging System (GLASS). Good remote results may be ensured by adequate medicamentous therapy. Variations of antithrombotic therapy are versatile and debatable. Long-term dual antithrombotic or systemic anticoagulant therapy with administration of vitamin K antagonists are not indicated for peripheral artery disease. In this connection, the findings of the COMPASS and VOYAGER PAD studies are analysed. The VOYAGER PAD trial showed that in patients with peripheral artery disease who underwent revascularization of lower limbs, the addition of rivaroxaban at a dose of 2.5 mg twice daily to aspirin decreased the risk of lower-extremity unfavourable ischaemic events and major adverse cardiovascular events by 15%. The obtained findings open new possibilities of conservative therapy having a significant role in decreasing the risk for development of limb-threatening conditions.. Лечение пациентов с заболеваниями периферических артерий требует комплексного подхода: коррекции факторов риска, лекарственной терапии и при необходимости эндоваскулярного/гибридного/открытого хирургического вмешательства. Реконструктивная операция может эффективно улучшить качество жизни пациента при перемежающейся хромоте, спасти конечность и жизнь в случае возникновения тяжелой ишемии. В статье обсуждаются преимущества, недостатки разных видов хирургических вмешательств при заболеваниях периферических артерий, концепция PLAN (Patient risk, Limb severity, and Anatomic complexity; ОКА – оценка риска для пациента, классификация состояния конечности, анатомическая модель заболевания) и новая система оценки характера поражения артерий конечности GLASS. Обеспечению хороших отдаленных результатов операций может помочь адекватная медикаментозная терапия. Вариации антитромботической терапии многогранны и дискутабельны. Длительная двойная антитромбоцитарная или системная антикоагулянтная терапия с приемом антагонистов витамина К не показана при заболеваниях периферических артерий. В связи с этим проводится анализ результатов исследований COMPASS и VOYAGER PAD. В исследовании VOYAGER PAD было продемонстрировано, что у пациентов с заболеваниями периферических артерий, перенесших реваскуляризацию нижних конечностей, добавление ривароксабана 2,5 мг 2 раза в день к аспирину уменьшает риск неблагоприятных ишемических событий со стороны конечности и значимых нежелательных сердечно-сосудистых событий на 15%. Полученные данные открывают новые возможности консервативной терапии, имеющей существенную роль в снижении рисков развития состояний, угрожающих потерей конечности.

Topics: Drug Therapy, Combination; Humans; Lower Extremity; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Quality of Life; Risk Factors; Rivaroxaban; Treatment Outcome

Topics: Aspirin; Coronary Artery Disease; Heart Failure; Humans; Peripheral Arterial Disease; Rivaroxaban

Topics: Aspirin; Factor Xa Inhibitors; Hemorrhage; Humans; Male; Peripheral Arterial Disease; Rivaroxaban

Dual antithrombotic therapy (DAT) with low-dose rivaroxaban in combination with acetylsalicylic acid (ASA) is available to patients with stable atherosclerotic disease as a new therapeutic option.The results of the COMPASS trial demonstrate a significant relative risk reduction of cardiovascular outcomes by 24 % with low-dose DAT in patients with stable peripheral arterial disease or coronary heart disease.Despite a guideline adherent secondary prevention therapy, the cardiovascular event rate with ASA alone during the mean study period of almost two years was 5.4 %. The absolute reduction of the event rate by the low-dose DAT is low at 1.3 %. Consequently, it is important to identify groups of patients at high risk for cardiovascular events. These patients are particularly qualified to receive a DAT regimen and can be characterized using high-risk features.The individual ischemic risk profile may be further defined by the presence of polyvascular atherosclerosis, concomitant diseases, and ischemic events in the past. The quo ad vitam reduced prognosis of patients with polyvascular atherosclerosis advocates a polyvascular screening, even in supposedly stable patients with coronary heart disease and peripheral arterial disease.An intensification of antithrombotic therapy is naturally associated with an increased risk of bleeding. Therefore, the risk-reduction of ischemic events should be weighed individually against the risk of bleeding.A low-dose DAT is particularly suitable for patients with a high ischemic risk and a low risk of bleeding.. Die duale antithrombotische Therapie (DAT) mit Rivaroxaban in niedriger Dosis in Kombination mit Acetylsalicylsäure (ASS) steht für Patienten mit STABILER: Atherosklerose als neue therapeutische Option zur Verfügung 1.Die Ergebnisse der COMPASS-Studie zeigen unter der niedrig dosierten DAT eine deutliche relative Risikoreduktion der kardiovaskulären Endpunkte um 24 % bei Patienten mit stabiler peripherer arterieller Verschlusskrankheit (PAVK) oder koronarer Herzerkrankung (KHK) 2.Trotz einer leitliniengerechten medikamentösen Sekundärprophylaxe liegt die kardiovaskuläre Ereignisrate unter ASS während der mittleren Studiendauer von fast 2 Jahren bei 5,4 %. Die absolute Reduktion der Ereignisrate durch die niedrig dosierte DAT ist mit 1,3 % gering. Umso wichtiger ist es, anhand von HOCHRISIKOMERKMALEN: Patientengruppen mit einer schlechteren kardiovaskulären Prognose und höherer Ereignisrate zu identifizieren, die sich für diesen Therapieansatz besonders qualifizieren 3. POLYVASKULäRE ATHEROSKLEROSE:  Die quo ad vitam reduzierte Prognose der Patienten mit einer polyvaskulären Atherosklerose spricht für ein polyvaskuläres Screening, auch bei vermeintlich stabilen KHK- und PAVK-Patienten. Das individuelle ischämische Risikoprofil kann durch das Vorhandensein einer polyvaskulären Atherosklerose, von Begleiterkrankungen und bereits stattgehabten ischämischen Ereignissen näher bestimmt werden. EINSCHRäNKUNGEN DER ANWENDUNG:  Die niedrig dosierte Gabe von Rivaroxaban zusätzlich zur ASS-Therapie ersetzt keine therapeutische Antikoagulation. Ebenfalls liegen für die stabile Atherosklerose bisher keine Daten zu einer niedrig dosierten Rivaroxaban-Therapie und einer begleitenden dualen Thrombozytenaggregationshemmung (DAPT) vor. Aus diesem Grund kann eine Therapie nach dem „COMPASS-Schema“ nach einer endovaskulären Therapie in der klinischen Praxis frühestens nach dem Ende der DAPT begonnen werden.. Eine Intensivierung der antithrombotischen Therapie ist naturgemäß mit einer Erhöhung des Blutungsrisikos verknüpft. Daher ist die Reduktion des ischämischen Risikos individuell gegenüber dem Risiko einer Blutung abzuwägen. Eine niedrig dosierte DAT kommt besonders für Patienten mit hohem Ischämie-Risiko und niedrigem Blutungsrisiko infrage.

Topics: Aspirin; Atherosclerosis; Factor Xa Inhibitors; Heart Diseases; Hemorrhage; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban

The article discusses the features of the development and course of the atherosclerotic process in various vascular basins. Variability of factors such as local hemodynamics, differences in the structure of the arteries can influence the formation of atherosclerotic plaque and the progression of the atherosclerotic process. A better understanding of the nature and causes of these differences can help improve the tactics of treatment and prevention of vascular complications. Analysis of the results of the COMPASS study (cardiovascular outomes for people using anticoagulation stategies - evaluation of cardiovascular outcomes in patients receiving anticoagulant therapy) showed for the first time the effectiveness of combination therapy using rivaroxaban direct anticoagulant at a dose of 2.5 mg 2 times a day in combination with acetylsalicylic acid at a dose of 100 mg per day. It was shown that, against the background of combination therapy, patients with coronary heart disease or atherosclerotic peripheral artery disease showed a significant decrease in the incidence of events of the primary end point of efficacy: a reduced risk of stroke, cardiovascular mortality and myocardial infarction, and also a reduction in the risk of major lower amputations extremities and total mortality in patients with stable forms of atherosclerosis. The emergence of combination therapy can help to achieve both an improvement in the overall prognosis and the prognosis of limb preservation in patients with multifocal arterial lesion.. В статье рассматриваются особенности развития и течения атеросклеротического процесса в различных сосудистых бассейнах. Вариабельность таких факторов, как локальная гемодинамика, различия в структуре артерий могут влиять на формирование атеросклеротической бляшки и прогрессирование атеросклеротического процесса. Лучшее понимание природы и причины этих различий может способствовать совершенствованию тактики лечения и профилактики сосудистых осложнений. Анализ результатов исследования COMPASS (cardiovascular outomes for people using anticoagulation stategies - оценка сердечно - сосудистых исходов у пациентов, получающих антикоагулянтную терапию) впервые показал эффективность комбинированной терапии с использованием прямого антикоагулянта ривароксабана в дозе 2,5 мг 2 раза в день в сочетании с ацетилсалициловой кислотой в дозе 100 мг в сутки. Показано, что на фоне комбинированной терапии у пациентов с ишемической болезнью сердца или атеросклеротическим заболеванием периферических артерий отмечено достоверное уменьшение частоты развития событий первичной конечной точки эффективности: снижение риска развития инсульта, сердечно - сосудистой смертности и инфаркта миокарда, а также достигнуто снижение риска больших ампутаций нижних конечностей и общей смертности пациентов со стабильными формами атеросклероза. Появление комбинированной терапии может помочь добиться как улучшения общего прогноза, так и прогноза сохранения конечности у пациентов с мультифокальным поражением артериального русла.

Topics: Arteries; Drug Therapy, Combination; Fibrinolytic Agents; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban

Optimal antithrombotic therapy after lower limb infrainguinal revascularization remains a controversial topic. The use of anticoagulants, alone or in combination with antiplatelet drugs, can potentially improve patency rate and limb salvage, particularly in patients with risk factors for early thrombosis. Bleeding is the main complication of long-term anticoagulant use. New oral anticoagulants can represent an attractive alternative to the standard vitamin K antagonists. The objective of the study is to evaluate the effectiveness (bypass occlusion and major amputation) and safety (major bleeding and all-cause mortality) of rivaroxaban compared to acenocumarol after infrainguinal lower limb surgical revascularization.. Retrospective cohort study of patients with peripheral arterial disease submitted to lower limb infrainguinal bypass revascularization with vein or expanded polytetrafluoroethylene conduit, who were anticoagulated with acenocumarol or rivaroxaban after hospital discharge. Patients with proximal revascularization, revascularization due to any pathology other than peripheral arterial disease, coagulation disorder, stroke or acute myocardial infarction in less than 30 days, glomerular filtration rate <15 mL/min, or on hemodialysis were excluded.. One hundred nine patients were included (78.9% male), with a mean age of 64.8 years. After hospital discharge, 40 patients (36.7%) were medicated with rivaroxaban and 69 patients (63.3%) with acenocumarol. At 1 year of follow-up, patients under rivaroxaban and acenocumarol presented comparable major amputation rates (12.5 % vs. 10.1%, P = 0.756), bypass occlusion (22.5% vs. 24.6 %, P = 0.769), and mortality rate (10% vs. 8.7%, P = 0.756). Major bleeding occurred in 13.8% of patients. Patients with renal dysfunction had significantly higher bleeding risk with acenocumarol (45.5% vs. 0%, P = 0.028) compared to rivaroxaban, while patients with normal renal function presented similar bleeding rates with both anticoagulants (6.1% vs. 6.4%, P = 0.953).. Rivaroxaban has equivalent effectiveness to acenocumarol after infrainguinal bypass revascularization, with similar occlusion, major amputation, and mortality rates. Rivaroxaban has an improved safety profile in patients with moderate renal dysfunction due to a significantly lower incidence of major bleeding. In patients with normal renal function, rivaroxaban and acenocumarol present equivalent major bleeding rates.

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Amputation, Surgical; Anticoagulants; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Comorbidity; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Limb Salvage; Lower Extremity; Male; Middle Aged; Peripheral Arterial Disease; Polytetrafluoroethylene; Prosthesis Design; Retrospective Studies; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; Veins

Peripheral artery disease affects 1.2% of the population globally and is associated with an increased risk of atherothrombotic cardiovascular events, major adverse limb events and mortality. The Cardiovascular Outcomes for People Using Anti-coagulation Strategies (COMPASS) trial demonstrated positive results of rivaroxaban plus aspirin therapy compared to aspirin therapy alone in those with peripheral artery disease or carotid artery disease. We sought to estimate the cost-effectiveness from the Australian healthcare system perspective.. A Markov model was developed to simulate the experiences of a hypothetical population of 1000 individuals with peripheral artery disease or carotid artery disease, profiled on the COMPASS trial, treated with rivaroxaban plus aspirin therapy versus aspirin therapy alone. With each annual cycle, individuals were at risk of having non-fatal cardiovascular disease events, major adverse limb events, or dying. Individuals were also at risk of non-fatal major bleeding. The model had a lifetime time horizon. Costs and utilities were sourced from the literature and discounted at 5.0% annually. Rivaroxaban plus aspirin therapy prevented 143 non-fatal cardiovascular disease events, 118 major adverse limb events and 10 deaths compared to aspirin therapy alone. Conversely, 156 additional major non-fatal bleeds were accrued. With an additional 256 quality-adjusted life years gained, at an additional cost of AUD$6,858,103, the incremental cost-effectiveness ratio was AUD$26,769 (discounted) per quality-adjusted life year gained, which is below Australia's arbitrary willingness to pay threshold of AUD$50,000.. In those with peripheral artery disease or carotid artery disease, rivaroxaban plus aspirin therapy is effective and cost-effective in the prevention of recurrent cardiovascular disease compared to aspirin therapy alone.

Topics: Aged; Aspirin; Australia; Carotid Artery Diseases; Cost-Benefit Analysis; Decision Support Techniques; Drug Costs; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Markov Chains; Middle Aged; Models, Economic; Peripheral Arterial Disease; Quality of Life; Quality-Adjusted Life Years; Recurrence; Rivaroxaban; Time Factors; Treatment Outcome

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

To assess the effectiveness and safety of rivaroxaban versus warfarin for the prevention of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with type 2 diabetes (T2D) and non-valvular atrial fibrillation (NVAF).. Using MarketScan data from January 2012 to December 2017, we identified oral anticoagulant-naïve patients with NVAF and comorbid T2D and ≥12 months of insurance coverage prior to rivaroxaban or warfarin initiation. Differences in baseline covariates between cohorts were adjusted for using inverse probability of treatment weights based on propensity scores (absolute standardized differences <0.1 achieved for all covariates after adjustment). Patients were followed until a MACE, MALE or major bleeding event, oral anticoagulant discontinuation/switch, insurance disenrolment or end of data availability. Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing the cohorts were calculated using Cox regression.. We identified 10 700 rivaroxaban users (24.1% received a reduced dose) and 13 946 warfarin users. The median (25%, 75% range) age was 70 (62, 79) years, CHA2DS2-VASc score was 4 (3, 5) and duration of available follow-up was 1.4 (0.6, 2.7) years. Eleven percent of patients had peripheral artery disease, 5.1% had coronary artery disease, and 5.1% had a prior MALE, at baseline. Rivaroxaban was associated with a 25% (95% CI 4-41) reduced risk of MACE and a 63% (95% CI 35-79) reduced risk of MALE compared to warfarin. Major bleeding risk did not significantly differ between cohorts (HR 0.95).. Among patients with NVAF and T2D treated in routine practice, rivaroxaban was associated with lower risks of both MACE and MALE versus warfarin, with no significant difference in major bleeding.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Peripheral Arterial Disease; Propensity Score; Retrospective Studies; Rivaroxaban; Treatment Outcome; Warfarin; Young Adult

Peripheral arterial disease can cause devastating health outcomes, and few therapies are available to treat this condition. Results of a secondary analysis of the COMPASS trial suggest benefit with the use of rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily. This treatment regimen could change the standard pharmacotherapeutic management practice for many patients with peripheral arterial disease.

Topics: Aspirin; Humans; Peripheral Arterial Disease; Rivaroxaban

The aims of the present study were to describe the proportion of patients eligible for the COMPASS trial within the Reduction of Atherothrombosis for Continued Health (REACH) registry, the reasons for ineligibility, and to put in perspective the characteristics and outcomes of trial-eligible patients from the REACH registry compared with those of patients enrolled in the reference aspirin arm of the COMPASS trial.. The COMPASS selection and exclusion criteria were applied to REACH patients with either coronary artery disease (CAD) or peripheral artery disease (PAD). We used the COMPASS primary composite outcome of cardiovascular (CV) death, myocardial infarction (MI), or stroke. In REACH, 31 873 patients had CAD or PAD and detailed information allowing evaluation of eligibility. Among these, 9518 (29.9%) patients had exclusion criteria and an additional 5480 patients (17.2%) did not fulfil the inclusion criteria and thus were not eligible. The 'COMPASS-Eligible' population therefore comprised 52.9% of the evaluable REACH patients (n = 16 875). The main reasons for exclusion were high-bleeding risk (51.8%), anticoagulant use (44.8%), requirement for dual antiplatelet therapy within 1 year of an ACS or PCI with stent, (25.9%), history of ischaemic stroke <1 year (12.4%), and severe renal failure (2.2%). Eligibility was highest among patients with PAD alone (68.4%). COMPASS-Eligible patients from REACH experienced higher annualized primary outcome event rates than patients actually enrolled in the reference aspirin arm of COMPASS (4.2% vs. 2.9% per year, P < 0.001).. COMPASS-Eligible patients represent a substantial fraction of stable CAD/PAD patients encountered in routine clinical practice in the large international REACH registry suggesting good external applicability. COMPASS-Eligible patients experienced a higher rate of the primary outcome compared with COMPASS participants in the aspirin alone treatment arm.

Topics: Aged; Aspirin; Clinical Trials, Phase III as Topic; Coronary Artery Disease; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Humans; Male; Patient Selection; Peripheral Arterial Disease; Randomized Controlled Trials as Topic; Registries; Rivaroxaban; Thrombosis

Topics: Blood Coagulation; Clinical Trials as Topic; Drug Therapy, Combination; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Risk Factors; Rivaroxaban; Treatment Outcome

Topics: Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban

Topics: Extremities; Fibrinolytic Agents; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban

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

Topics: Aspirin; Cardiovascular Diseases; Drug Therapy, Combination; Hemorrhage; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk Adjustment; Rivaroxaban; Secondary Prevention

Topics: Acute Coronary Syndrome; Aspirin; Drug Therapy, Combination; Factor Xa Inhibitors; Hemorrhage; Humans; Percutaneous Coronary Intervention; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Risk Assessment; Risk Factors; Rivaroxaban; Thrombosis; Treatment Outcome

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

Rivaroxaban is a United States Food and Drug Administration-approved oral anticoagulant for venous thromboembolic disease; however, there is no information regarding the safety and its efficacy to support its use in patients after open or endovascular arterial interventions. We report the safety and efficacy of rivaroxaban vs warfarin in patients undergoing peripheral arterial interventions.. This single-institution retrospective study analyzed all sequential patients from December 2012 to August 2014 (21 months) who were prescribed rivaroxaban or warfarin after a peripheral arterial procedure. Our study population was then compared using American College of Chest Physicians guidelines with patients then stratified as low, medium, or high risk for bleeding complications. Statistical analyses were performed using the Student t-test and χ. There were 44 patients in the rivaroxaban group and 50 patients in the warfarin group. Differences between demographics and risk factors for bleeding between groups or reintervention rate were not statistically significant (P = .297). However, subgroup evaluation of the safety profile suggests that patients who were aged ≤65 years and on warfarin had an overall higher incidence of major bleeding (P = .020). Patients who were aged >65 years, undergoing open operation, had a significant risk for reintervention (P = .047) when they received rivaroxaban.. Real-world experience using rivaroxaban and warfarin in patients after peripheral arterial procedures suggests a comparable safety and efficacy profile. Subgroup analysis of those requiring an open operation demonstrated a decreased bleeding risk when rivaroxaban was used (in those aged <65 years) but an increased risk for secondary interventions. Further studies with a larger cohort are required to validate our results.

Topics: Aged; Anticoagulants; Chi-Square Distribution; Endovascular Procedures; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Indiana; Logistic Models; Male; Middle Aged; Peripheral Arterial Disease; Retrospective Studies; Risk Factors; Rivaroxaban; Treatment Outcome; Vascular Surgical Procedures; Warfarin

Topics: Acenocoumarol; Administration, Oral; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Drug Monitoring; Drug Substitution; Epistaxis; Factor Xa Inhibitors; Female; Frail Elderly; Humans; Medication Therapy Management; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Renal Insufficiency; Rivaroxaban; Stroke