Comparison of rivaroxaban-based dual antithrombotic and antiplatelet therapies for symptomatic patients with lower-extremity peripheral artery disease post-revascularization: a retrospective cohort study
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PROVIDER: S-EPMC10699158 | biostudies-literature | 2023 Jan
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Project description:ImportancePrior 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).ObjectiveTo 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.Design, setting, and participantsThis 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.ExposureRandomization 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.Main outcomes and measuresSymptomatic VTE was a prespecified secondary outcome and prospectively collected.ResultsAmong 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).Conclusions and relevanceIn 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.
| S-EPMC9218845 | biostudies-literature
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.
| S-EPMC7527938 | biostudies-literature
Project description:AimsThe impact of diabetes mellitus (DM) on outcomes of lower extremity revascularization (LER) for peripheral artery disease (PAD) is uncertain. We characterized associations between DM and post-procedural outcomes in PAD patients undergoing LER.Methods and resultsAdults undergoing surgical or endovascular LER were identified from the 2014 Nationwide Readmissions Database. DM was defined by ICD-9 diagnosis codes and sub-classified based on the presence or absence of complications (poor glycaemic control or end-organ damage). Major adverse cardiovascular and limb events (MACLEs) were defined as the composite of death, myocardial infarction, ischaemic stroke, or major limb amputation during the index hospitalization for LER. For survivors, all-cause 6-month hospital readmission was determined. Among 39 441 patients with PAD hospitalized for LER, 50.8% had DM. The composite of MACLE after LER was not different in patients with and without DM after covariate adjustment, but patients with DM were more likely to require major limb amputation [5.5% vs. 3.2%, P < 0.001; adjusted odds ratio (aOR) 1.22, 95% confidence interval (CI) 1.03-1.44] and hospital readmission (59.2% vs. 41.3%, P < 0.001; aOR 1.44, 95% CI 1.34-1.55). Of 20 039 patients with DM hospitalized for LER, 55.7% had DM with complications. These patients were more likely to have MACLE after LER (11.1% vs. 5.2%, P < 0.001; aOR 1.56 95% CI 1.28-1.89) and require hospital readmission (61.1% vs. 47.2%, P < 0.001; aOR 1.41 95% CI 1.27-1.57) than patients with uncomplicated DM.ConclusionsDM is present in ≈50% of patients undergoing LER for PAD and is an independent risk factor for major limb amputation and 6-month hospital readmission.
| S-EPMC9630873 | biostudies-literature
Project description:Background & aimsRenal disease is a risk factor for peripheral artery disease (PAD), yet its impact on outcomes after lower extremity (LE) revascularization is not well established. We aimed to characterize the association between chronic kidney disease (CKD) and/or end stage renal disease (ESRD) and post-procedural outcomes in PAD patients undergoing LE revascularization in the United States.MethodsAdults age ≥18 years undergoing surgical or endovascular LE revascularization for PAD with and without CKD or ESRD were identified from the 2014 Nationwide Readmissions Database. Major adverse cardiovascular events (MACE), defined as a composite of death, myocardial infarction or ischemic stroke, were identified for patients with and without renal disease. All-cause hospital readmissions within 6 months of discharge were determined for all survivors.ResultsAmong 39,441 patients with PAD hospitalized for LE revascularization, 10,530 had renal disease (26.7%), of whom 69% had CKD without ESRD and 31% had ESRD. Patients with renal disease were more likely to have MACE after LE revascularization (5.2% vs. 2.5%; adjusted OR [aOR] 1.74, 95% CI 1.40-2.16), require LE amputation (26.1% vs. 12.2%; aOR 1.33, 95% CI 1.19-1.50), and require hospital readmission within 6 months (61.0% vs. 43.6%; adjusted HR [aHR] 1.38, 95% CI 1.28-1.48) compared to those without renal disease.ConclusionsRenal disease is common among patients undergoing LE revascularization for PAD and was independently associated with in-hospital MACE, LE amputation, and hospital readmission within 6 months. Additional efforts to improve outcomes of patients with renal disease and PAD requiring LE revascularization are necessary.
| S-EPMC7141968 | biostudies-literature
Project description:The efficacy of dual antiplatelet therapy (DAPT) for patients with peripheral artery disease (PAD) after lower-limb intervention remains controversial. Currently, the prescription of DAPT after an intervention is not fully recommended in guidelines due to limited evidence. This study compares and analyzes the prognosis for symptomatic PAD patients receiving DAPT versus monotherapy after lower-limb revascularization. Up to November 2021, PubMed/MEDLINE, Embase, and Cochrane databases were searched to identify studies reporting the efficacy, duration, and bleeding complications when either DAPT or monotherapy were used to treat PAD patients after revascularization. Three randomized controlled trials and seven nonrandomized controlled trials were included in our study. In total, 74,651 patients made up these ten studies. DAPT in PAD patients after intervention was associated with lower rates of all-cause mortality (HR = 0.86; 95% CI, 0.79−0.94; p < 0.01), major adverse limb events (HR = 0.60; 95% CI, 0.47−0.78; p < 0.01), and major amputation (HR = 0.78; 95% CI, 0.64−0.96) when follow-up was for more than 1-year. DAPT was not associated with major bleeding events when compared with monotherapy (OR = 1.22; 95% CI, 0.69−2.18; p = 0.50) but was associated with a higher rate of minor bleeding as a complication (OR = 2.54; 95% CI, 1.59−4.08; p < 0.01). More prospective randomized studies are needed to provide further solid evidence regarding the important issue of prescribing DAPT.
| S-EPMC9144146 | biostudies-literature
Project description:PurposeOnly a few Asian studies have discussed the impact of statin intensity on clinical outcomes in patients with peripheral artery disease (PAD). We aimed to investigate the clinical impact of statin intensity in patients with PAD after endovascular revascularization.Materials and methodsFrom April 2009 to June 2019, 376 patients with lower extremity PAD treated with endovascular revascularization were enrolled. They were classified into three groups according to statin intensity: no-statin, low-to-moderate intensity (LMI), and high-intensity (HI). The primary outcomes were major adverse cardiovascular events (MACE) and major adverse limb events (MALE).ResultsDuring the 40-month follow-up, MACE occurred less frequently in the HI and LMI groups than the no-statin group (11.4% vs. 16.0% vs. 39%, p<0.001). In adjusted Cox models, the HI group had the fewest MACE [hazard ratio (HR): 0.447; 95% confidence interval (CI): 0.244-0.834; p=0.018] and MALE (HR: 0.360; 95% CI: 0.129-1.006; p=0.051) events, while the LMI group had fewer MACE (HR: 0.571; 95% CI: 0.326-1.0; p=0.050) events than the no-statin group. HI statin therapy was associated with better outcomes in terms of MALE (HR: 0.432; 95% CI: 0.223-0.837; p=0.003) than LMI statin therapy after inverse probability treatment weighting analysis.ConclusionHI and LMI statin use is associated with a significant reduction in MACE events than no-statin use. HI statin use was associated with better MALE outcomes than no-statin or LMI statin use.
| S-EPMC8965427 | biostudies-literature
Project description:BackgroundVascular 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.ObjectivesAssess 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.Patients/methodsVOYAGER 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.ResultsOver 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.ConclusionsAssessing 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.
| S-EPMC9314576 | biostudies-literature
Project description:BackgroundDual antiplatelet therapy (DAPT) after coronary stenting prolongs survival by preventing both in-stent thrombosis and other cardiovascular atherothrombotic events. Patients with peripheral artery disease (PAD) typically have a heavy burden of unrevascularized coronary artery disease and also stand to benefit from increased atherothrombotic protection with DAPT. The potential benefit of DAPT compared with aspirin alone in patients with PAD is not well described.MethodsWe identified all patients undergoing an initial elective lower extremity revascularization (bypass or endovascular) from 2003 to 2016 in the Vascular Quality Initiative registry discharged on aspirin or aspirin plus a thienopyridine antiplatelet agent (DAPT). We first estimated models predicting the likelihood of receiving DAPT and then used inverse probability weighting to account for baseline differences in the likelihood of receiving DAPT and compared late survival. For sensitivity analysis, we also performed Cox proportion hazard modeling on the unweighted cohorts and generated adjusted survival curves.ResultsWe identified 57,041 patients undergoing lower extremity revascularization (28% bypass). Of 15,985 bypasses (69% for critical limb ischemia [CLI]), 38% were discharged on DAPT. Of 41,056 endovascular interventions (39% for CLI), 69% were discharged on DAPT. Analyses using inverse probability weighting demonstrated a small survival benefit to DAPT at 1 year for bypass (93% vs 92% [P = .001]) and endovascular interventions (93% vs 92% [P = .005]) that was sustained through 5 years of follow-up (bypass, 80% vs 78% [P = .004]; endovascular, 76% vs 73% [P = .002]). When stratified by severity of PAD, DAPT had a survival benefit for patients with CLI undergoing bypass (5 years, 70% vs 66% [P = .04]) and endovascular intervention (5 years, 71% vs 67% [P = .01]) but not for patients with claudication (bypass, 89% vs 88% [P = .36]; endovascular, 87% vs 85% [P = .46]). The protective effect of DAPT was similar when using Cox proportional hazard models after bypass (hazard ratio, 0.81 [95% confidence interval, 0.72-0.90]) and endovascular intervention (hazard ratio, 0.89 [95% confidence interval, 0.83-0.95]).ConclusionsDAPT at time of discharge was associated with prolonged survival for patients with CLI undergoing lower extremity revascularization but not for those with claudication. Further research is needed to quantify the risks associated with DAPT and to identify subgroups at increased risk of thrombotic and bleeding complications to guide medical management of patients with PAD.
| S-EPMC5121016 | biostudies-literature
Project description:BackgroundTo evaluate the efficacy and safety of clopidogrel-rivaroxaban combination compared to aspirin-rivaroxaban combination in patients with symptomatic peripheral artery disease (PAD).MethodsConsecutive patients with symptomatic PAD patients were analyzed from January, 2018 to June, 2022 at Nanjing Drum Tower Hospital. Patients were divided into two groups based on the antithrombotic therapy. The primary efficacy outcome was a composite of major adverse cardiovascular events (MACE) and major adverse limb events (MALE), and the primary safety outcome was major bleeding. Patients were followed until the first occurrence of any outcomes or the study end date (30 June 2024).ResultsA total of 695 patients were enrolled into this study. The clopidogrel-rivaroxaban combination significantly reduced the risk of composite outcome (HR: 0.59, 95%CI: 0.41-0.83) without increasing the risk of major bleeding (HR: 0.68, 95%CI: 0.27-1.69). When analyzed separately, clopidogrel-rivaroxaban combination was associated with a reduced risk of MALE (HR: 0.61, 95%CI: 0.41-0.91), although no significant differences were observed in terms of MACE (HR: 0.64, 95%CI: 0.34-1.20) or all bleeding events (HR: 1.00, 95%CI: 0.52-1.93). In the subgroup analysis, there were no significant interactions between the treatment groups and the subgroups of age, diabetes, lesion sites, Rutherford classifications and renal function for composite outcome, MACE and MALE.ConclusionThe clopidogrel-rivaroxaban combination in PAD patients may offer enhanced cardiovascular protection without increasing the risk of bleeding complications. These findings suggested that clopidogrel could be a superior alternative to aspirin in dual antithrombotic therapy for PAD management.
| S-EPMC11770050 | biostudies-literature
Project description: Not available
| S-EPMC8996288 | biostudies-literature