Antiplatelet Therapy in Peripheral Arterial Disease: An Umbrella Review and Meta-analysis of Preventative and Treatment Outcomes

Abstract

Independent protective factors included trans-tibial operation (OR 0.61, 95% C.I. 0.52-0.72), increased serum albumin (OR per g/L increase 0.97, 95% C.I. 0.95-0.98), previous procedures to the amputated limb (OR 0.79, 95% C.I. 0.68-0.92), and increased patient weight (OR per 10kg increase 0.95, 95% C.I. 0.91-0.99). A multivariate model for risk incorporating these factors had good discrimination (area under ROC curve 0.79, 95% C.I. 0.77-0.80). There was also a high rate of morbidity in the cohort, with 6.6%, 9.7% and 4.3% of patients suffering cardiac, respiratory and renal complications respectively. The model for mortality was also predictive of morbidity outcomes (area under ROC curve 0.74, 0.69 and 0.74 respectively). Conclusion-Morbidity and mortality after major lower limb amputation remain high, but modelling has revealed potentially modifiable factors. We have also developed accurate predictive models to aid patient counselling prior to surgery. Prior procedures to the amputated limb and below knee operations appear to have a protective role, implying that proximal revascularisation to facilitate healing at the below knee level may be a worthwhile strategy. Increased patient weight and serum albumin have similar, though smaller, protective effects, reinforcing the importance of nutrition in this patient population.

The CLEAR (Considering Leading Experts’ Antithrombotic Regimes around peripheral angioplasty) survey: an international perspective on antiplatelet and anticoagulant practice for peripheral arterial endovascular intervention

“…As a result, responders tend to think in terms of patency (84% of responders) post intervention and not in terms of patient-centred outcomes. The widespread use of dual antiplatelet therapy is a concern because of the lack of evidence of benefit but clear evidence of harm (Ambler et al 2019). For example, in all randomised trials comparing dual with mono antiplatelet therapy for peripheral arterial disease, dual antiplatelet therapy caused 37 more major bleeds per 1000 patients than monotherapy (P < 0.001) but did not clearly improve any post endovascular clinical outcome (Ambler et al 2019).…”

“…The widespread use of dual antiplatelet therapy is a concern because of the lack of evidence of benefit but clear evidence of harm (Ambler et al 2019). For example, in all randomised trials comparing dual with mono antiplatelet therapy for peripheral arterial disease, dual antiplatelet therapy caused 37 more major bleeds per 1000 patients than monotherapy (P < 0.001) but did not clearly improve any post endovascular clinical outcome (Ambler et al 2019). The Vascular community is behind cardiology in this respect, as there are a number of trials examining antiplatelet therapy after peripheral coronary intervention.…”

“…It is reccomended in guidelines; predominantly due to a reduction in cardiovascular events (Conte et al 2019;National Institute for Health and Care Excellence 2015). However the clinical benefit to support the use of specific antiplatelet regimens, even for 'established' indications such as a reduction in cardiovascular events, is actually marginal (Ambler et al 2019). As a result, guidelines are conflicted as they interpret the evidence differently (Conte et al 2019; National Institute for Health and Care Excellence 2015).…”

“…As a result, guidelines are conflicted as they interpret the evidence differently (Conte et al 2019; National Institute for Health and Care Excellence 2015). The evidence for maintenance of lower limb bypass patency (Ambler et al 2019) and when used following coronary intervention (Levine et al 2016) is more established. This is probably why randomised trials examining new technologies for use in the peripheral arteries have mandated the use of dual antiplatelet therapy in the intervention arms, but not always the comparator arm (Krankenberg et al 2007).…”

“…Add in the constantly emerging evidence in cardiology (Levine et al 2016), and well publicised trials of direct oral anticoagulants for non-intervened peripheral arterial disease (Anand et al 2018), and it has become even more confusing for peripheral endovascular practitioners. The benefits of any change in drug regimen or new drug have to be balanced against the risks they pose and the cost (Ambler et al 2019). When compared to cardiology there is a huge gap in our knowledge for antiplatelet therapy choice around peripheral arterial endovascular intervention; a high-volume procedure which is becoming more common (Cull et al 2010).…”