Elisa Grifoni1, Anna Maria Gori2, Betti Giusti3, Renato Valenti4, Angela Migliorini4, Stefania Basili5, Rita Paniccia1, Mahmoud Farouk Elmahdy6, Raffaele Pulli7, Carlo Pratesi3, David Antoniucci4, Francesco Violi5, Rossella Marcucci3. 1. Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy. 2. Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Azienda Ospedaliero-Universitaria Careggi, Florence, Italy. Electronic address: annamaria.gori@unifi.it. 3. Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Azienda Ospedaliero-Universitaria Careggi, Florence, Italy. 4. Azienda Ospedaliero-Universitaria Careggi, Florence, Italy. 5. Clinica Medica I, La Sapienza University, Rome, Italy. 6. Division of Cardiology, Kasr Alaini Hospital, Cairo University, Egypt; Division of Cardiology, Aswan Heart Centre, Aswan, Egypt. 7. University of Bari, Bari, Italy.
Abstract
OBJECTIVES: Few data are available on the association between a different entity of platelet inhibition on antiplatelet treatment and clinical outcomes in patients with peripheral artery disease (PAD). The aim of this study was to evaluate the degree of on-treatment platelet reactivity, and its association with ischaemic and haemorrhagic adverse events at follow up in PAD patients undergoing percutaneous transluminal angioplasty (PTA). METHODS: In this observational, prospective, single centre study, 177 consecutive patients with PAD undergoing PTA were enrolled, and treated with dual antiplatelet therapy with aspirin and a P2Y12 inhibitor. Platelet function was assessed on blood samples obtained within 24 h from PTA by light transmission aggregometry (LTA) using arachidonic acid (AA) and adenosine diphosphate (ADP) as agonists of platelet aggregation. High on-treatment platelet reactivity (HPR) was defined by LTA ≥ 20% if induced by AA, and LTA ≥ 70% if induced by ADP. Follow up was performed to record outcomes (death, major amputation, target vessel re-intervention, acute myocardial infarction and/or myocardial revascularisation, stroke/TIA, and bleeding). RESULTS: HPR by AA and HPR by ADP were found in 45% and 32% of patients, respectively. During follow up (median duration 23 months) 23 deaths (13%) were recorded; 27 patients (17.5%) underwent target limb revascularisation (TLR), two (1.3%) amputation, and six (3.9%) myocardial revascularisation. Twenty-four patients (15.6%) experienced minor bleeding. On multivariable analysis, HPR by AA and HPR by ADP were independent predictors of death [HR 3.8 (1.2-11.7), p = .023 and HR 4.8 (1.6-14.5), p = .006, respectively]. 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 < .001). LTA by ADP ≤ 41% was independently associated with bleeding HR 14.6 (2.6-24.0), p = .001] on multivariable analysis. CONCLUSIONS: In this study a high prevalence of on-clopidogrel and aspirin high platelet reactivity was found, which was significantly associated with the risk of death. Conversely, a low on-clopidogrel platelet reactivity was associated with a higher risk of bleeding. These results document that the entity of platelet inhibition is associated with both thrombotic and bleeding complications in PAD patients.
OBJECTIVES: Few data are available on the association between a different entity of platelet inhibition on antiplatelet treatment and clinical outcomes in patients with peripheral artery disease (PAD). The aim of this study was to evaluate the degree of on-treatment platelet reactivity, and its association with ischaemic and haemorrhagic adverse events at follow up in PAD patients undergoing percutaneous transluminal angioplasty (PTA). METHODS: In this observational, prospective, single centre study, 177 consecutive patients with PAD undergoing PTA were enrolled, and treated with dual antiplatelet therapy with aspirin and a P2Y12 inhibitor. Platelet function was assessed on blood samples obtained within 24 h from PTA by light transmission aggregometry (LTA) using arachidonic acid (AA) and adenosine diphosphate (ADP) as agonists of platelet aggregation. High on-treatment platelet reactivity (HPR) was defined by LTA ≥ 20% if induced by AA, and LTA ≥ 70% if induced by ADP. Follow up was performed to record outcomes (death, major amputation, target vessel re-intervention, acute myocardial infarction and/or myocardial revascularisation, stroke/TIA, and bleeding). RESULTS: HPR by AA and HPR by ADP were found in 45% and 32% of patients, respectively. During follow up (median duration 23 months) 23 deaths (13%) were recorded; 27 patients (17.5%) underwent target limb revascularisation (TLR), two (1.3%) amputation, and six (3.9%) myocardial revascularisation. Twenty-four patients (15.6%) experienced minor bleeding. On multivariable analysis, HPR by AA and HPR by ADP were independent predictors of death [HR 3.8 (1.2-11.7), p = .023 and HR 4.8 (1.6-14.5), p = .006, respectively]. 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 < .001). LTA by ADP ≤ 41% was independently associated with bleeding HR 14.6 (2.6-24.0), p = .001] on multivariable analysis. CONCLUSIONS: In this study a high prevalence of on-clopidogrel and aspirin high platelet reactivity was found, which was significantly associated with the risk of death. Conversely, a low on-clopidogrel platelet reactivity was associated with a higher risk of bleeding. These results document that the entity of platelet inhibition is associated with both thrombotic and bleeding complications in PAD patients.