Society for Vascular Surgery appropriate use criteria for management of intermittent claudication.

The Society for Vascular Surgery appropriate use criteria (AUC) for the management of intermittent claudication were created using the RAND appropriateness method, a validated and standardized method that combines the best available evidence from medical literature with expert opinion, using a modified Delphi process. These criteria serve as a framework on which individualized patient and clinician shared decision-making can grow. These criteria are not absolute. AUC should not be interpreted as a requirement to administer treatments rated as appropriate (benefit outweighs risk). Nor should AUC be interpreted as a prohibition of treatments rated as inappropriate (risk outweighs benefit). Clinical situations will occur in which moderating factors, not included in these AUC, will shift the appropriateness level of a treatment for an individual patient. Proper implementation of AUC requires a description of those moderating patient factors. For scenarios with an indeterminate rating, clinician judgement combined with the best available evidence should determine the treatment strategy. These scenarios require mechanisms to track the treatment decisions and outcomes. AUC should be revisited periodically to ensure that they remain relevant. The panelists rated 2280 unique scenarios for the treatment of intermittent claudication (IC) in the aortoiliac, common femoral, and femoropopliteal segments in the round 2 rating. Of these, only nine (0.4%) showed a disagreement using the interpercentile range adjusted for symmetry formula, indicating an exceptionally high degree of consensus among the panelists. Post hoc, the term "inappropriate" was replaced with the phrase "risk outweighs benefit." The term "appropriate" was also replaced with "benefit outweighs risk." The key principles for the management of IC reflected within these AUC are as follows. First, exercise therapy is the preferred initial management strategy for all patients with IC. Second, for patients who have not completed exercise therapy, invasive therapy might provide net a benefit for selected patients with IC who are nonsmokers, are taking optimal medical therapy, are considered to have a low physiologic and technical risk, and who are experiencing severe lifestyle limitations and/or a short walking distance. Third, considering the long-term durability of the currently available technology, invasive interventions for femoropopliteal disease should be reserved for patients with severe lifestyle limitations and a short walking distance. Fourth, in the common femoral segment, open common femoral endarterectomy will provide greater net benefit than endovascular intervention for the treatment of IC. Finally, in the infrapopliteal segment, invasive intervention for the treatment of IC is of unclear benefit and could be harmful.

An update of safety and efficacy results from phase 1 dose-escalation and expansion study of vodobatinib, a novel oral BCR-ABL1 tyrosine kinase inhibitor (TKI), in patients with chronic myeloid leukemia (CML) and philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ All) failing prior tki therapies

Introduction: Vodobatinib is a novel third generation TKI effective against wild-type and mutated BCR-ABL1 (except T315I) with limited off-target activity. We present updated results from the Phase 1 dose-escalation (DEs) and expansion (DEx) study in CML and Ph+ALL patients (pts) failing ≥ 3 prior TKIs (< 3 prior TKIs if approved TKI is not clinically advised or available);patients with T315I are not eligible (NCT02629692). Methods: This is an open-label, phase 1, multicentre, 3+3 study evaluating maximum tolerated dose (MTD), safety and efficacy of vodobatinib administered once daily in 28 day cycles (dose range: 12 to 240 mg). MTD was established at 204 mg. DEx study enrolled chronic phase CML (CP-CML) patients at 174 mg dose of vodobatinib. Treatment continued until unacceptable toxicity, disease progression, consent withdrawal or death. Adverse events were assessed using NCI-CTCAE v4.03. Results: As of 15 Jul 2021, 52 pts are enrolled in DEs and DEx cohorts. Forty one of these pts received doses from 12 to 240 mg in the DEs cohort;32 chronic phase (CP-CML), 3 accelerated phase CML (AP-CML), 4 blast phase CML (BP-CML), 2 Ph+ ALL. Eleven CPCML pts were enrolled in DEx cohort at 174 mg dose. The baseline demographics and disease history are represented in Table 1. Efficacy: Of the 32 CP-CML pts enrolled in DEs: At baseline, 21 (65%) pts had no cytogenetic response, 4 (12.5%) were in PCyR, 7 (22%) were in CCyR. On vodobatinib therapy, 11(34%) pts achieved CCyR, 3 (9%) achieved PCyR and 7 (22%) maintained baseline CCyR. Baseline major molecular response (MMR) was present in 1 (3%) pt;and 14 pts (44%) achieved MMR on study. Of the remaining 11 pts, 5 (16%) had haematologically stable disease (no CyR and molecular response) and 6 (19%) had disease progression (cytogenetic or hematological) as their best response (Table 2 and 3). Seventeen CP-CML pts had prior ponatinib treatment, of which 11 (65%) had MCyR (4 achieved CCyR, 4 maintained CCyR, 3 achieved PCyR);while 8 (47%) achieved MMR. In the remaining 15 pts ponatinib naïve CP-CML: 10 (66%) had CCyR (7 achieved CCyR, 3 maintained CCyR);with 7 (47%) with MMR (6 achieved, 1 maintained). Two of the 3, AP-CML pts had baseline hematological response (CHR) with absence of cytogenetic and molecular response. The 3 pts further deepened their responses with 1 pt achieving CCyR with MMR and 2 pts in PCyR. Of the 4 BP-CML pts, 2 achieved CHR and 2 patients had disease progression as their best response;Of the 2 Ph+ ALL pts, 1 pt maintained CCyR and MMR while the other reported disease progression as the best response. Median duration of treatment overall was 23 (0.5-51) months [CP-CML 23 (0.5-51);AP-CML 36 (9-40);BP-CML 3 (0.5-18) and Ph+ ALL 4 (0.7-7.3) months]. Twenty one pts continue in study. In the DEx cohort, 1 of the 11 CP-CML pts was in PCyR at baseline. No pts had molecular response. Of the 11 patients, 6 (54 %) pts achieved CCyR, 1(10%) pt achieved PCyR. MMR was achieved by 1 pt (10%). Data is maturing for 1 pt. Median duration of treatment is 16 (0.3-19) months and 10 pts continue in study. Safety: Forty nine of 52 pts reported at least 1 TEAE. Most common any grade TEAEs included thrombocytopenia (33%), cough (19%), anaemia & diarrhoea (17% each). Thirty one pts (60%) reported Grade 3 and 4 treatment emergent AEs: most common were thrombocytopenia (15%), neutropenia and anaemia (12%), increased amylase and lipase (8% each). Ten (19%) pts reported cardiovascular TEAEs (Grade 1: angina pectoris, palpitations, ventricular extra-systoles, arteriosclerosis, hot flush, hypotension, intermittent claudication;Grade 2: hypertension, hypotension;Grade 3: cardiac failure congestive, hypertension);with a Grade 2 hypertension being vodobatinib related. Nineteen pts (37%) reported SAEs;vodobatinib related SAEs were reported in 3 pts (fatal intracranial haemorrhage (ICH), Grade 2 back pain and Grade 3 amnesia reported in 1 pt each). There were 5 deaths on study: 1 was related to use of vodobatinib (1 ICH, confounded by disease progression to blast phase that include extra-medullary sites) and the remaining unrelated (1 sudden death, 1 disease progression, 1 pneumonia fungal, 1 suspected COVID-19). Conclusion: Vodobatinib continues to be associated with favourable long term safety and efficacy in heavily pre-treated CML failing ≥ 3 prior TKIs, including ponatinib. Phase 2 study evaluating vodobatinib in pts failing at least 3 prior lines of therapy, including ponatinib, is ongoing.

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

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.

Feasibility of a remotely supervised exercise programme

Aim: To assess feasibility of a novel remotely-supervised exercise programme at a vascular hub during the COVID-19 lockdown. Methods: Participants with arterial claudication (ABPI <0.90) who were able to walk 50m were enrolled into a 3-month programme by a vascular specialist nurse. The initial appointment addressed smoking cessation and best medical therapy. Baseline walking distance, ABPI and quality of life (QoL) were measured using the Intermittent Claudication Questionnaire. Following this, up to 8 WhatsApp video calls with a vascular specialist physiotherapist were undertaken to provide a tailored exercise programme. The MapmywalkVC App, or a pedometer, were used to monitor walking distances. Participants were instructed to record their daily longest walk and email results to their physiotherapist before each consultation. Results: 12 participants were enrolled, of these 2 participants were unsuitable. Median age was 63 years and 2 (20%) were female. Baseline median ABPI was 0.7 (IQR 0.5-0.8), median baseline absolute walking distance was 75m (IQR 50-140) and median baseline QoL was 51/80 (IQR 15-79). 7 participants (70%) successfully completed the programme and were discharged. Their median daily longest walk was 2000m (IQR 200- 4000) and QoL scores improved to 6/80 (IQR 2-20) (p=0.02). Remaining 3 participants required revascularisation for disease progression. Reimbursement tariffs for the supervised exercise programme were £700 per patient, whereas for revascularisation were £2000 - £5000. Conclusion: Remotely supervised exercise was feasible and improved walking distance and quality of life in 70% of participants. Approximately £3000 per patient was saved from a reduction in revascularisation procedures in our unit.

Few UK vascular centres offer a fully NICE-compliant supervised exercise programme: a national audit.

INTRODUCTION: To determine the current (pre-COVID-19) provision of supervised exercise training (SET) for patients with peripheral arterial disease (PAD) in UK Vascular Centres. METHODS: Hospital Trusts delivering vascular care to patients with PAD were identified from the National Vascular Registry and asked to complete an online questionnaire on their provisions for SET. If a centre offered SET, they were asked questions to determine whether the programme was compliant with NICE guidelines and the difficulties they faced delivering the service. If centres did not offer SET, they were asked what obstacles prevented them implement SET. RESULTS: Of the 78 UK vascular centres, 59 (76%) responded and were included in the audit. Of these, 27 (46%) were able to offer SET but only 21 (36%) could offer it to all their patients with PAD. Only four (6.8%) offered SET that was fully compliant with current NICE guidelines. Reasons identified included insufficient funding, lack of resource and poor patient compliance. CONCLUSIONS: The benefits of SET are well established yet the availability of the service in the UK is poor. The reasons for this are readily identified but have not yet been overcome. Research on novel methods of delivering supervised exercise that mitigates existing barriers, such as home exercise with remote monitoring, should be prioritised to facilitate optimal management for our patients with PAD.

Impact of the COVID-19 pandemic on drug treatment of patients with peripheral arterial disease: an observational cross-sectional study.

BACKGROUND: The Coronavirus 2019 (COVID-19) pandemic has had a negative impact on the population's behavior. In this context, the effect of the COVID-19 pandemic on drug treatment of patients with peripheral arterial disease (PAD) and intermittent claudication (IC) remains unclear. OBJECTIVES: To analyze the impact of the COVID-19 pandemic on drug treatment of patients with PAD and IC. METHODS: In this cross-sectional, observational study, 136 patients with PAD and IC were recruited from our database and answered a questionnaire by telephone involving the following questions: a) precautions related to COVID-19; b) general health status; and c) treatment of diseases. Subsequently, patients were divided into two groups according to difficulty in obtaining their drugs (DOD: difficulty obtaining drugs, or NDOD: no difficulty obtaining drugs) and overall health was compared between groups. RESULTS: Seventeen percent of patients reported difficulties with obtaining drugs during the pandemic. A higher proportion of these patients reported being sadder (56.5% vs. 24.8%, P < 0.01) and having more difficulty sleeping (56.5% vs. 24.8%, P < 0.01) than of the patients in the NDOD group (P <0.01). The groups did not differ in terms of impairment of walking capability, anxiety, stress, or depression (P> 0.05). CONCLUSIONS: A higher proportion of patients in the DOD group reported being sadder and having greater difficulty sleeping compared to the NDOD group during the COVID-19 pandemic.

Considerations for Patients With Peripheral Artery Disease During the COVID-19 Pandemic.

New York City was one of the epicenters of the COVID-19 pandemic. The management of peripheral artery disease (PAD) during this time has been a major challenge for health care systems and medical personnel. This document is based on the experiences of experts from various medical fields involved in the treatment of patients with PAD practicing in hospitals across New York City during the outbreak. The recommendations are based on certain aspects including the COVID-19 infection status as well as the clinical PAD presentation of the patient. Our case-based algorithm aims at guiding the treatment of patients with PAD during the pandemic in a safe and efficient way.