Dataset Information

Rivaroxaban with Aspirin Versus Aspirin for Peripheral Arterial Disease and Intermittent Claudication. Rationale and Design of the COMPASS CLAUDICATION Trial.

ABSTRACT:

Background

The COMPASS trial demonstrated that in patients with peripheral arterial disease, the combination of rivaroxaban and aspirin compared with aspirin reduces the risk of major adverse limb events, but it is not known whether this combination can also improve symptoms in patients with intermittent claudication. The primary objective of this study is to evaluate the effect of the combination on claudication distance.

Study design

Eighty-eight patients with intermittent claudication will be randomized to receive rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily or aspirin 100 mg once daily for 24 weeks. The primary outcome is the change in claudication distance from the baseline to 24 weeks, measured by 6 min walking test and treadmill test. The primary safety outcome is the incidence of major bleeding and clinically relevant non-major bleeding according to the International Society on Thrombosis and Hemostasis criteria.

Summary

The COMPASS CLAUDICATION trial will provide high-quality evidence regarding the effect of the combination of rivaroxaban and aspirin on claudication distance in patients with peripheral arterial disease.

SUBMITTER: Ramacciotti E

PROVIDER: S-EPMC8796110 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundLittle is known about the extent to which routine care management of peripheral arterial disease (PAD) and intermittent claudication (IC) align with best practice recommendations on exercise therapy. We conducted a scoping review to examine the published literature on the availability and workings of exercise therapy in the routine management of patients with PAD and IC, and the attitude and practice of health professionals and patients.MethodsA systematic search was conducted in February 2018. The Cumulative Index of Nursing and Allied Health Literature, Ovid MEDLINE, Allied and Complementary Medicine Database, ScienceDirect, Web of Science and the Directory of Open Access Repositories were searched. Hand searching of reference lists of identified studies was also performed. Inclusion criteria were based on study aim, and included studies that reported on the perceptions, practices, and workings of routine exercise programs for patients with IC, their availability, access, and perceived barriers.ResultsEight studies met the eligibility criteria and were included in the review. Studies conducted within Europe were included. Findings indicated that vascular surgeons in parts of Europe generally recognize supervised exercise therapy as a best practice treatment for IC, but do not often refer their patients for supervised exercise therapy due to the unavailability of, or lack of access to supervised exercise therapy programs. Available supervised exercise therapy programs do not implement best practice recommendations, and in the majority, patients only undergo one session per week. Some challenges were cited as the cause of the suboptimal program implementation. These included issues related to patients' engagement and adherence as well as resource constraints.ConclusionThere is a dearth of published research on exercise therapy in the routine management of PAD and IC. Available data from a few countries within Europe indicated that supervised exercise is underutilized despite health professionals recognizing the benefits. Research is needed to understand how to improve the availability, access, uptake, and adherence to the best exercise recommendations in the routine management of people with PAD and IC.

Project description:ImportancePatients 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.ObjectiveTo 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.Design, setting, and participantsThis 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.InterventionsA combination of low-dose rivaroxaban and aspirin compared with aspirin alone.Main outcomes and measuresThirty-month incidence risk of myocardial infarction, stroke and cardiovascular death (MACE), major adverse limb events (MALE) including major vascular amputation, and bleeding.ResultsThe 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%).Conclusions and relevancePatients 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.

Project description:ContextNeither supervised treadmill exercise nor strength training for patients with peripheral arterial disease (PAD) without intermittent claudication have been established as beneficial.ObjectiveTo determine whether supervised treadmill exercise or lower extremity resistance training improve functional performance of patients with PAD with or without claudication.Design, setting, and participantsRandomized controlled clinical trial performed at an urban academic medical center between April 1, 2004, and August 8, 2008, involving 156 patients with PAD who were randomly assigned to supervised treadmill exercise, to lower extremity resistance training, or to a control group.Main outcome measuresSix-minute walk performance and the short physical performance battery. Secondary outcomes were brachial artery flow-mediated dilation, treadmill walking performance, the Walking Impairment Questionnaire, and the 36-Item Short Form Health Survey physical functioning (SF-36 PF) score.ResultsFor the 6-minute walk, those in the supervised treadmill exercise group increased their distance walked by 35.9 m (95% confidence interval [CI], 15.3-56.5 m; P < .001) compared with the control group, whereas those in the resistance training group increased their distance walked by 12.4 m (95% CI, -8.42 to 33.3 m; P = .24) compared with the control group. Neither exercise group improved its short physical performance battery scores. For brachial artery flow-mediated dilation, those in the treadmill group had a mean improvement of 1.53% (95% CI, 0.35%-2.70%; P = .02) compared with the control group. The treadmill group had greater increases in maximal treadmill walking time (3.44 minutes; 95% CI, 2.05-4.84 minutes; P < .001); walking impairment distance score (10.7; 95% CI, 1.56-19.9; P = .02); and SF-36 PF score (7.5; 95% CI, 0.00-15.0; P = .02) than the control group. The resistance training group had greater increases in maximal treadmill walking time (1.90 minutes; 95% CI, 0.49-3.31 minutes; P = .009); walking impairment scores for distance (6.92; 95% CI, 1.07-12.8; P = .02) and stair climbing (10.4; 95% CI, 0.00-20.8; P = .03); and SF-36 PF score (7.5; 95% CI, 0.0-15.0; P = .04) than the control group.ConclusionsSupervised treadmill training improved 6-minute walk performance, treadmill walking performance, brachial artery flow-mediated dilation, and quality of life but did not improve the short physical performance battery scores of PAD participants with and without intermittent claudication. Lower extremity resistance training improved functional performance measured by treadmill walking, quality of life, and stair climbing ability.Trial registrationclinicaltrials.gov Identifier: NCT00106327.

Project description:Patients with peripheral arterial disease (PAD) benefit from combination therapy with acetylsalicylic acid (ASA, 100 mg, one time per day) plus low-dose rivaroxaban (2.5 mg, two times per day) compared to ASA monotherapy. In particular, major adverse cardiac and limb events were significantly reduced after peripheral endovascular revascularization (EVR). In this pilot study, the platelet activation status in vivo and platelet reactivity in vitro were longitudinally analyzed by flow cytometric assays and calibrated automated thrombography in platelet-rich plasma (PRP) from 10 patients with PAD receiving ASA (100 mg, one time per day) before EVR, ASA plus clopidogrel (75 mg, one time per day) after EVR, and ASA plus rivaroxaban (2.5 mg, two times per day) during a long-term follow-up. Platelet responsiveness to clopidogrel was compared to additional 10 patients with stable PAD and clopidogrel (75 mg, one time per day) monotherapy. ASA plus rivaroxaban treatment resulted in a significantly decreased thrombin peak in PRP for two triggers, namely, low concentration of tissue factor (TF) and thrombin, compared to ASA monotherapy. TF-controlled thrombin generation was additionally characterized by a significantly prolonged lag time in PRP and platelet-free plasma during ASA plus rivaroxaban combination therapy. In comparison, ASA plus clopidogrel treatment presented a significant reduction of the thrombin peak in PRP, which was less pronounced than during subsequent ASA plus rivaroxaban therapy. Platelet responsiveness to clopidogrel was observed for 60% of patients receiving ASA plus clopidogrel and clopidogrel monotherapy, respectively. Blocking of CD36 on the platelet surface further reduced the thrombin peak in PRP induced by TF for all three therapy regimes. Platelet activation in vivo and in response to the GPVI-agonist convulxin or thrombin in vitro was similar, whereas integrin αIIbβ3 activation and α-granule release induced by the PAR-1 activating peptide TRAP-6 were significantly diminished during ASA plus rivaroxaban treatment compared to ASA monotherapy. In conclusion, the data of this pilot study indicate an inhibitory effect of rivaroxaban on the thrombin propagation phase of CD36-sensitive platelet thrombin formation in patients with PAD treated with ASA plus rivaroxaban combination therapy, which is associated with decreased PAR-1 but not thrombin-mediated platelet activation.