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Objective: Dual pathway inhibition (DPI) by combining acetylsalicylic acid (ASA) with low-dose rivaroxaban has been shown to reduce cardiovascular events in patients with peripheral arterial disease (PAD) when compared to ASA monotherapy. A potential explanation is that inhibition of factor Xa improves endothelial function through crosstalk between coagulation and inflammatory pathways, subsequently attenuating the occurrence of cardiovascular events. We hypothesize that the addition of rivaroxaban to ASA in PAD patients leads to improved endothelial function., Design: An investigator-initiated, multicentre trial investigating the effect of DPI on endothelial function., Methods: Patients, diagnosed with PAD, were enrolled in two cohorts: cohort A (Rutherford I-III) and cohort B (Rutherford IV-VI). Participants received ASA monotherapy for a 4-weeks run-in period, followed by 12 weeks of DPI. Macro- and microvascular endothelial dysfunction were studied by measuring carotid artery reactivity upon sympathetic stimulus and by measuring plasma endothelin-1 concentrations, respectively. All measurements were performed during the use of ASA (baseline) and after 12 weeks of DPI., Results: 159 PAD patients (111 cohort A, 48 cohort B) were enrolled. Twenty patients discontinued study drugs early. Carotid artery constriction upon sympathetic stimulation at baseline (ASA) and after 12 weeks of DPI was similar in the total group, 22.0 vs. 22.7% ( p = 1.000), and in the subgroups (Cohort A 22.6 vs. 23.7%, p = 1.000; cohort B 20.5 vs. 20.5%, p = 1.000), respectively. The mean concentration of plasma endothelin-1 at baseline and after 12 weeks of DPI did not differ, 1.70 ± 0.5 vs. 1.66 ± 0.64 pmol/L ( p = 0.4 40) in the total group, 1.69 ± 0.59 vs. 1.62 ± 0.55 pmol/L in cohort A ( p = 0.202), and 1.73 ± 0.53 vs. 1.77 ± 0.82 pmol/L in cohort B ( p = 0.6 82), respectively., Conclusion: Macro- and microvascular endothelial dysfunction, as reflected by carotid artery reactivity and plasma endothelin-1 concentrations, are not influenced in PAD patients by addition of low-dose rivaroxaban to ASA monotherapy for 12 weeks., Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04218656., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Willems, Thijssen, Groh, Kooijman, Ten Cate, Spronk, Donders, van der Vijver-Coppen, van Hoek, Nagy, Reijnen and Warlé.)

Background: 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., Methods: 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., Results: 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., Conclusion: 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., (© 2022. The Author(s).)

Peripheral artery disease affects 202 million patients worldwide and may cause disabling intermittent claudication and critical limb ischemia. Next to life style changes, best medical treatment and supervised exercise therapy, it can be necessary to re-vascularize the limb. Treatment of femoropopliteal lesions poses a challenge and a surgical bypass remains recommended in the guidelines for longer and more complex lesions. Bypass surgery is associated with substantial morbidity and even mortality. Endovascular alternatives are quickly evolving from plain balloon angioplasty to drug-eluting stents, drug-coated balloons, polytetrafluoroethylene-covered stents and atherectomy. These developments might challenge the gold standard in the near future. This article focuses on which technique can be used for which femoropopliteal lesion, particularly complex lesions, and summarizes the most recent and important literature on this topic.

Purpose: To describe 2 patients with a distally migrated endograft causing a type Ia endoleak and treatment with a proximal cuff and chimney grafts that required EndoAnchors to finally seal the leak., Case Report: Two men, ages 86 and 72 years, presented with stent-graft migration and type Ia endoleak at 5 and 15 years after endovascular repair, respectively. Both were treated with a proximal cuff in combination with a chimney graft to the left renal artery. In both cases, the type Ia endoleak persisted, likely due to gutter formation. Both patients were treated in the same setting with EndoAnchors that instantly resolved the endoleak. At 1-year follow-up, there was no recurrent endoleak or migration, with patent chimney grafts and renal arteries and stable renal function., Conclusion: EndoAnchors may effectively resolve a persistent type Ia endoleak arising from gutter formation after placement of a proximal cuff and chimney grafts., (© The Author(s) 2015.)