Lipid-lowering and anti-thrombotic therapy in patients with peripheral arterial disease

Abstract

Summary: Patients with peripheral arterial disease (PAD) are at very high risk of cardiovascular events, but risk factor management is usually suboptimal. This Joint Task Force from the European Atherosclerosis Society and the European Society of Vascular Medicine has updated evidence on the management on dyslipidaemia and thrombotic factors in patients with PAD. Guidelines recommend a low-density lipoprotein cholesterol (LDLC) goal of more than 50% reduction from baseline and <1.4 mmol/L (<55 mg/dL) in PAD patients. As demonstrated by randomized controlled trials, lowering LDL-C not only reduces cardiovascular events but also major adverse limb events (MALE), including amputations, of the order of 25%. Addition of ezetimibe or a PCSK9 inhibitor further decreases the risk of cardiovascular events, and PCSK9 inhibition has also been associated with reduction in the risk of MALE by up to 40%. Furthermore, statin- based treatment improved walking performance, including maximum walking distance, and pain-free walking distance and duration. This Task Force recommends strategies for managing statin-associated muscle symptoms to ensure that PAD patients benefit from lipid-lowering therapy. Antiplatelet therapy, either daily clopidogrel 75 mg or the combination of aspirin 100 mg and rivaroxaban (2×2.5 mg) is also indicated to prevent cardiovascular events. Dual pathway inhibition (aspirin and rivaroxaban) may be considered following revascularization, taking into account bleeding risk. This Joint Task Force believes that adherence with these recommendations for lipid-lowering and antithrombotic therapy will improve the morbidity and mortality in patients with PAD.

Role of Lipid-Lowering Therapy in Peripheral Artery Disease

“…Mondillo et al, reported a 90-m increase in pain-free walking distance in PAD patients after 6 months of simvastatin therapy ( p < 0.005) [ 38 ]. In addition to increasing pain-free walking distance [ 39 ], statins have been shown to increase total walking distance [ 40 , 41 , 42 , 43 , 44 ], reduce severity of IC [ 45 ] and improve overall quality of life [ 43 , 46 , 47 ], especially when combined with an exercise regimen [ 48 ].…”

The cholesterol-lowering effect of statins is modified by LILRB5 intolerance genotype: Results from a recruit-by-genotype clinical trial

“…While this might limit the generalizability of our findings, the age of the study subjects represents the typical age of patients prescribed statins ( Melhem et al, 2021 ). Statin ADRs, and statin-induced myopathy among them, are more common in aged individuals and senescent animal models ( Camerino et al, 2016 ; Arrigoni et al, 2017 ; Ward et al, 2019 ; Belch et al, 2021 ). The potential mechanism for the effect of LILRB5 on statin tolerance is based on the reduced expression of Foxp3+ T regulatory cells in Asp247Asp carriers, resulting in poorer muscle repair.…”

Vascular risk assessment and management

“…Therefore, we have selected the guideline "2021 ESC Guidelines on cardiovascular disease prevention in clinical practice", developed by the Task Force for cardiovascular disease prevention in clinical practice with representatives of the European Society of Cardiology and 12 medical societies, With the special contribution of the European Association of Preventive Cardiology (EAPC)" (10), which was considered more applicable to the European Health System. However, for some specific aspects of the care pathway, we have decided to take into consideration also the recommendations in the guidelines "2019 ACC/AHA Guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines" (11), "2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS)" (2), "2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: The Task Force for diabetes, prediabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD)" (12), " The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH)" (13), "Guidelines on peripheral artery disease of The European Society of Vascular Medicine (ESVM)" ( 6), "Lipid-lowering and anti-thrombotic therapy in patients with peripheral arterial disease a Joint Statement of the European Atherosclerosis Society (EAS) and the European Society of Vascular Medicine(ESVM)" (7).…”

“…Managed care and clinical governance are among the most adopted strategies in complex health systems to control or influence health care quality, accessibility, costs and prices, use and outcomes. The European Society of Vascular Medicine (ESVM) is in the process of producing Guidelines as "Guidelines on peripheral artery disease of The European Society of Vascular Medicine (ESVM) and "Lipid-lowering and anti-thrombotic therapy in patients with peripheral arterial disease a Joint Statement of the European Atherosclerosis Society (EAS) and the European Society of Vascular Medicine (ESVM)" (6,7) and is spreading ICPs to facilitate guideline implementation into clinical practice. Proper ICPs development must be tailored to the needs of a single reality or operating territory.…”