Funzione piastrinica e rischio di eventi avversi in pazienti con arteriopatia periferica sottoposti a rivascolarizzazione percutanea (Platelet function and risk of adverse events in peripheral artery disease patients undergoing percutaneous revascularization).

Background and Aim: Lots of studies demonstrated that a different entity of on-treatment platelet function inhibition is associated with different clinical outcomes in patients with acute coronary syndromes. In particular, high on-treatment platelet reactivity (HPR) has been associated with an increased risk of ischemic complications (especially stent thrombosis), and there is a growing body of evidence that, on the contrary, low on-treatment platelet reactivity (LPR) could be associated with bleeding risk. Few data are available in the literature on the association between a different entity of platelet inhibition on-antiplatelet treatment and clinical outcomes in patients with peripheral artery disease (PAD). Aim of this study was to evaluate, in patients with PAD undergoing percutaneous revascularization, the degree of on-treatment platelet reactivity, and its association with ischemic and hemorrhagic adverse events at follow-up. Methods: In this observational, prospective, single center study, consecutive patients with PAD undergoing percutaneous transluminal angioplasty (PTA) with or without stenting, were enrolled. All patients were treated with dual antiplatelet therapy with aspirin and a P2Y12 inhibitor. Platelet function was assessed by Light Transmission Aggregometry (LTA) using arachidonic acid (AA) and adenosine diphosphate (ADP) as agonists of platelet aggregation, on blood samples obtained within 24 hours from PTA. HPR was defined by LTA ≥20% if induced by AA, and LTA ≥70% if induced by ADP. Follow-up was performed in order to record the occurrence of ischemic and bleeding events. Results: The study enrolled 177 patients [118 males, median age 75 (IQR 68-81) years]. HPR by AA was found in 52% of patients, and showed a non significant association with older age and a higher prevalence of renal failure, whereas HPR by ADP was found in 32% of patients, and was significantly associated with older age. During follow-up [median duration 23 (IQR 13-27) months] 23 deaths (13%) were recorded; 27 patients (17.5%) underwent target limb revascularization, 2 (1.3%) amputation, and 6 (3.9%) myocardial revascularization. Twenty-four patients (15.6%) experienced a minor bleeding complication. At multivariate analysis HPR by AA and HPR by ADP were independent predictors of death [HR 3.75 (1.20-11.66), P=0.023 and HR 4.78 (1.57-14.52), P=0.006, respectively]. Moreover, patients with dual HPR both by AA and by ADP showed a significantly higher risk of death than those without (P<0.001). The median value of LTA by ADP was significantly lower in patients with bleeding complications than in those without [26.5 (22-39.2)% vs 62 (44.5-74)%, P<0.001). At ROC curve analysis the cut-off of platelet aggregation induced by ADP with the best sensitivity and specificity for increased risk of bleeding was 41%. LTA by ADP lower than 41% was independently associated with bleeding [HR 14.59 (2.55-24.01), P=0.001] at multivariate analysis. Conclusions: In PAD patients undergoing PTA, HPR by ADP and AA were predictors of death, whereas LPR by ADP was predictor of bleeding complications. These results suggest the potential utility of assessing platelet function, even in the setting of PAD, in order to ensure the patient the best tailored antiplatelet therapy.