New “biopsychosocial” roadmap set out to address PAD treatment and mental health impacts

A RECENT PROPOSAL HAS CALLED FOR “whole-person, multidisciplinary interventions” after an interrogation of the interplay between lower extremity peripheral arterial disease (PAD) and mental health impacts. Published in the Journal of the American College of Cardiology, Kim G Smolderen, clinical psychologist, and Carlos Mena-Hurtado, interventional cardiologist (Yale University, New Haven, USA) et al have put forward a “biopsychosocial” PAD management roadmap, offering solutions to current care “obstacles” to better attend to both behavioural and social health needs throughout vascular treatment.

The “PAD experience,” including the clinical and financial burden of the comorbid conditions linked with PAD, have received “little consideration,” Smolderen and Mena, who are founders of the Vascular medicine outcomes (VAMOS) lab at Yale, et al opine. This lack is driving the need to “expand the PAD care paradigm” to a biopsychosocial one which acknowledges the contribution of both behaviour and psychosocial factors on disease management and outcomes. Their roadmap identifies four domains that, once addressed, can redesign vascular specialty care services to attend to the behavioural and social health needs of all patients.

Identifying first a “fundamental problem” in the way physical and mental health are divided when providing care, the authors pinpoint the “major advocacy efforts” that are needed across professional organisations

“We seek to evaluate the safety and efficacy of PMEG using a US Food and Drug Administration [FDA]-approved, off-the-shelf device in order to increase the applicability of these technologies to more patients and thus save more lives,” the description reads.

In the study reported in JVS, reinterventions after PMEG were categorised as open or percutaneous and major or minor by Society for Vascular Surgery reporting standards according to high or low magnitude based on physiological impact. The investigators also categorised reinterventions by timing, as well as those interventions which occurred within one week of PMEG. They compared survival between patients who did and did not undergo reintervention and between reintervention subcategories.

Communicating their findings, Tachida and colleagues relay that a total of 170 patients underwent PMEG in the 11-year study time period, 50 (29%) of whom underwent a total of 91 reinterventions (mean reinterventions/ patient, 1.8). They report that freedom from reintervention was 84% at one year and 60% at five years. The authors specify that reinterventions were most often percutaneous (80%), minor (55%) and low magnitude (77%), with the most common reintervention being renal stenting (26%). They also note that there were 10 early reinterventions within one week of PMEG and that two aortic-related mortalities occurred after reintervention.

There were no differences in survival between patients who underwent reintervention and those who did not, Tachida et al also communicate in the results section of the paper. However, they continue, survival differed based on the timing of reintervention.

Tachida and colleagues further share that, after adjusted analysis, reintervention within one week of PMEG was associated with an increased risk of mortality both compared with late reintervention (hazard ratio [HR], 11.1; 95% confidence interval [CI], 2.7–46.5) and no reintervention (HR, 5.2; 95% CI, 1.6–16.8).

In their conclusion, Tachida et al summarise: “Reinterventions after PMEG were most commonly associated with percutaneous, minor and low magnitude procedures, and [were] non-detrimental to long-term survival.” However, they note that early reinterventions were associated with increased mortality risk.

“These data suggest that a modest frequency of reinterventions should be expected after PMEG, emphasising the critical importance of lifelong surveillance,” the authors state in their closing remarks.

A total of 170 patients underwent PMEG in the 11-year study time period serving populations of PAD patients. Their recommendations begin at trainee level, defining “core competencies” which reduce stigma and “unawareness” around mental illness and its effects on PAD.

Second, they outline the evolution of highly technological and procedural care which has been “valued disproportionately” over preventative and psychosocial care in the context of reimbursement and code availability—which the authors note are both presently absent from cardiovascular speciality care. To rectify this, they believe payment reform is needed, allowing for “codes and compensation for integrated care models” which should be piloted to integrate quality metrics of care delivery, including mental health screening and treatment tracking in such a manner to affect payment of services.

Thirdly, Smolderen, Mena and colleagues emphasise that despite several evidence-based interventions stemming from high-level randomised controlled trial evidence across cardiovascular populations, there is a prevalent “lack of awareness” among health administrators regarding the “scope of practice” of allied mental and behavioural health physicians in the context of chronic disease. They believe adopting a formal approach to assessing behavioural health could be a solution for this, assigning “routine components of care” and “expanding system capacity to address health disparities and behavioural health conditions”.

As an extension of their solution, they assert that “interprofessional team-based training” that promotes “a climate of mutual respect and shared values, moving away from a hierarchical system of care delivery and delineating roles” be established. Furthermore, Smolderen, Mena et al state that investments in programme building and co-ordination for vascular patients must be made, as well as the promotion of integrated care for diverse and uninsured populations, to “broaden access” and remove barriers to PAD care. Their fourth and final area of proposed reform concerns integrated behavioural care practice guidelines for PAD management, and the formation of better evidence-based workflows derived from comparative effectiveness and implementation research— which they currently believe to be “lacking”.

“Funding budgets for research,” the authors state, “is needed to generate evidence for implementation models of integrated care delivery, tailored to the PAD context”. Smolderen, Mena et al conclude that research is needed to address “clinical, operational and financial” outcomes— which includes decreased cost of care for comorbid patients—relevant to multiple stakeholders. To this end, they believe quality efforts at a national level will help to “benchmark data” for PAD care, “integrating social determinants of health, and tracking the use of integrated care services for vascular populations”.

Chris Twine Stavros Kakkos

Point of View

Chris Twine and Stavros Kakkos, respectively chair and cochair of new guidelines on antithrombotic therapy for vascular diseases, outline key points and unanswered questions from the document which they say represents an “important milestone” in the field.

The European Society for Vascular Surgery (ESVS) is publishing its first guideline on antithrombotic therapy for people with vascular diseases in the May issue of the European Journal of Vascular and Endovascular Surgery (EJVES).1 The guideline covers many topics and conditions including antithrombotics for patients with acute and chronic arterial and venous diseases and interventions.

Three new studies were performed for the guideline; a risk score for predicting bleeding risk in patients with peripheral arterial disease (PAD; the OAC3-PAD score which needs validating)2 and two systematic reviews; one on platelet function testing (high on treatment platelet reactivity) for patients undergoing endovascular arterial intervention3 and one on antithrombotics for patients with abdominal aortic aneurysm (AAA).4 A Cochrane review was updated to aid recommendations on antithrombotics for patients with dialysis access.5

Some of the key points of the guideline are updated recommendations based on the publication of new trials. Both COMPASS6 and VOYAGER7 feature heavily in the PAD recommendations. Some of these recommendations were difficult to formulate, for example how do you give clinical recommendations as to when to use clopidogrel or aspirin plus rivaroxaban for patients with chronic symptomatic lower extremity arterial disease (LEAD) when there are no comparative data? A network metaanalysis found no clear difference between the two combinations, but these have to compare very different trial populations so have questionable validity.8 Clopidogrel alone, or aspirin plus rivaroxaban for chronic symptomatic LEAD now have IIa recommendations for use.1

Another difficult question is around the antithrombic choices after endovascular intervention for LEAD. We know aspirin plus clopidogrel are used commonly despite a lack of evidence,9 and now we also have aspirin plus rivaroxaban as a choice. The endovascular subgroup in VOYAGER did not reach significance, but is it fair to consider this unpowered subgroup separate to the whole trial? In the end the whole trial results were considered, so aspirin plus rivaroxaban has a IIa recommendation. Dual antiplatelet therapy with aspirin plus clopidogrel had to be IIb because of the lack of evidence supporting its use, even if this is clinically widespread.9 We had to update older ESVS guideline recommendations, sometimes with minimal new data so that older recommendations do not clash with the new.

Contemporary treatment of deep vein thrombosis (DVT) with a direct oral anticoagulant (DOAC) agent, as opposed to a vitamin K antagonist, was recommended. However, for patients with unprovoked DVT requiring extended anticoagulation, a reduced dose of apixaban or rivaroxaban was suggested. Both recommendations were based on reduced bleeding rates with DOACs. Patients with cancerassociated venous thromboembolism are recommended to receive low molecular weight heparin (LMWH), but those with a low risk of gastrointestinal or genitourinary bleeding are now recommended to be considered for anticoagulation with a DOAC, preferably apixaban, alternatively rivaroxaban or edoxaban.

Superficial vein thrombosis is mostly treated with prophylactic doses of fondaparinux for 45 days based on the large CALISTO trial, with a LMWH or oral rivaroxaban being an alternative. Anticoagulation following intervention for DVT is given at least as long as standard treatment to prevent recurrent thromboembolic events, while for chronic obstructive lesions, an individualised approach is suggested.

The risk of the patient bleeding must always be considered when making decisions on antithrombotic therapy. The challenge for recommendations was that there is no validated way of doing this for populations with arterial disease. Members of the guideline writing committee have started the process of trying to measure this risk for patients with PAD with a new scoring system, but it will be some time before it can be validated.2 Until then we have formulated recommendations to try and help clinicians think about and potentially reduce individual bleeding risk (for example use of proton pump inhibitors for patients at higher risk of bleeding), especially when using anticoagulants or dual antiplatelet therapy.

There are still many unanswered questions including the role of platelet function testing, antithrombotics following endovascular intervention and for patients with AAA, and antithrombotics for patients with certain presentations of superficial venous thrombosis or undergoing deep venous intervention. We hope the guideline will provide useful day-to-day guidance for clinicians and will be an important milestone in reinforcing the significance of medcial therapy alongside interventions for our patients.

References:

1. Twine CP, Kakkos S, Aboyans V, Baumgartner I, Behrendt CA, Bellmunt-Montoya S, et al. European Society for Vascular Surgery (ESVS) 2023 Clinical Practice Guidelines on Antithrombotic Therapy for Vascular Diseases. Eur J Vasc Endovasc Surg 2023.

2. Behrendt CA, Kreutzburg T, Nordanstig J, Twine CP, Marschall U, Kakkos S, et al. The OAC3-PAD risk score predicts major bleeding events at one year after hospitalisation for peripheral artery disease. Eur J Vasc Endovasc Surg. 2022;63:50310.

3. Zlatanovic P, Wong KHF, Kakkos SK and Twine CP. A Systematic Review and Meta-Analysis on the Impact of High On-Treatment Platelet Reactivity on Clinical Outcomes for Patients Taking ADP Receptor Inhibitors Following Lower Limb Arterial Endovascular Intervention. Eur J Vasc Endovasc Surg. 2022;63:91-101.

4. Wong KHF, Zlatanovic P, Bosanquet DC, Saratzis A, Kakkos S, Aboyans V, et al. Antithrombotic therapy for aortic and peripheral artery aneurysms: a systematic review and meta-analysis. Eur J Vasc Endovasc Surg. 2022;64:544-556.

5. Mohamed I, Kamarizan MFA and Da Silva A. Medical adjuvant treatment to increase patency of arteriovenous fistulae and grafts. Cochrane Database Syst Rev. 2021;7:Cd002786.

6. Anand SS, Bosch J, Eikelboom JW, Connolly SJ, Diaz R, Widimsky P, et al. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet. 2018;391:219-229.

7. Bonaca MP, Bauersachs RM, Anand SS, Debus ES, Nehler MR, Patel MR, et al. Rivaroxaban in Peripheral Artery Disease after Revascularization. N Engl J Med. 2020;382:1994-2004.

8. Ambler GK, Nordanstig J, Behrendt CA and Twine CP. Network Meta-analysis of the Benefit of Aspirin with Rivaroxaban vs. Clopidogrel for Patients with Stable Symptomatic Lower Extremity Arterial Disease. Eur J Vasc Endovasc Surg. 2021;62:654655.

9. Wong KHF, Bosanquet DC, Ambler GK, Qureshi MI, Hinchliffe RJ and Twine CP. The CLEAR (Considering Leading Experts’ Antithrombotic Regimes around peripheral angioplasty) survey: an international perspective on antiplatelet and anticoagulant practice for peripheral arterial endovascular intervention. CVIR Endovasc 2019;2:37.

Chris Twine is a vascular surgeon at North Bristol NHS Trust in Bristol, UK. Stavros Kakkos is a professor of vascular surgery at the University of Patras in Patras, Greece.