IJCS | Volume 32, Nº5, September/October 2019

458 Esporcatte & Rangel Platelet and elderly Int J Cardiovasc Sci. 2019;32(5):457-459 Editorial was associated as an independent variable for major bleeding. When associated with the CRUSADE score (area under the ROC curve = 0.64), this index modestly improved the predictive capacity (AUC = 0.68). 3 The use of the SHARE-FI (Survey of Health, Ageing and Retirement in Europe Frailty Index) frailty index in patients > 75 years and admitted for SCA (STEMI = 36.5%) showed that frailty was an independent predictor of the composite of death and reinfarction (adjusted HR 2.81; 95%CI = 1.16 – 6.78) and overall mortality (HR: 3.07; 95% CI = 1.35 – 6.98). 4 These patients were also older, with higher comorbidity, GRACE and CRUSADE scores. A recent systematic review comparing the use of more potent P2Y12 inhibitors (ticagrelor and prasugrel) with clopidogrel in elderly and non-elderly patients withACS, demonstrated a significant reduction in efficacy outcomes in non-elderly patients (RR = 0.85; 95% CI = 0.79- 0.93) but only a tendency of reduction in elderly patients (RR = 0.95; 95%CI = 0.86 - 1.05), with similar risks of bleeding among elderly (RR = 1.19; 95%CI = 0.95 - 1.49]) and non- elderly patients (RR = 1.16; 95%CI = 0.95 - 1.41]. 5 In order to minimize this elevated bleeding risk of older patients, the ELDERLYACS-2 study compared conventional doses of clopidogrel (300mg/75mg) with reducedmaintenance doses of prasugrel (60 mg/5 mg) in patients (mean age: 80 years) admitted with ACS and submitted to PCI. 6 Discontinuation of the trial due to futility for efficacy precludes correct interpretation of the non-significant 48% reduction in the rate of relevant bleedings. Regarding the timing of first administration of P2Y12 inhibitors, a recent meta-analysis including 9,649 STEMI patients submitted to PCI, early administration compared to delayed usewas associatedwith a significant reduction in major cardiac adverse events, myocardial infarction, “bail-out” use of glycoprotein inhibitors and better coronary TIMI flow 2/3 prior to PCI, without increasing bleeding rates. 7 Paradoxically, elderly patients present lower response to antiplatelet agents and higher rates of hemorrhagic complications, a fact only partially understood. In the SENIOR-PLATELETS study involving patients with stable coronary artery disease and chronic use (> 14 days) of acetylsalicylic acid and thienopyridine (clopidogrel 75 mg, clopidogrel 150 mg or prasugrel 10 mg), the elderly group had a higher rate of reactivity compared to younger patients (OR: 2.58, 95% CI: 1.76 - 3.79, p < 0.0001). A similar trend, although attenuated and without statistical significance, was observed with clopidogrel 150 mg and prasugrel 10 mg. 8 Elevated platelet reactivity appears to be due to higher baseline level in the elderly, but also to lower response to the drug. With regard to hyperresponding patients, elderly patients were in a smaller number, which should attenuate the higher hemorrhagic risk of this subgroup, a fact not observed in clinical practice, denoting that platelet activity is not the only determinant, and suggesting relevant interferences from comorbidities. Individualization of antiplatelet doses based on functional tests has been evaluated as a strategy to modulate hemorrhagic and ischemic risks, but it has not been routinely recommended, even for the elderly. In the ANTARCTIC (Assessment of a Normal versus Tailored dose of prasugrel after stenting in patients Aged > 75 years to Reduce the Composite of bleeding, stent Thrombosis and Ischemic Complications) trial involving a population of high risk, constituted by elderly patients with ACS and PCI, the evaluation of platelet function by VerifyNow/P2Y12 modified the initial dose of prasugrel in 45% of patients but did not improve clinical outcomes. 9 In the TROPICAL-ACS (Testing Responsiveness To Platelet Inhibition On Chronic Antiplatelet Treatment For Acute Coronary Syndromes) study, a strategy of dose titration of prasugrel guided by platelet functional assessment, compared to standard dose, did not prove to be non-inferior in terms of net clinical benefit. In patients ≤ 70 years, the combined clinical events were more favorable in the guided group, especially for the reduction of hemorrhagic complications, but the same did not occur in the subgroup of older patients. 10 In conclusion, ideal dual antiplatelet therapy in elderly patients remains unclear and clinical trials are especially recommended to define the type of drug, loading andmaintenance dosing and duration of therapy. The development of new tools for better ischemic and hemorrhagic risk stratification in the increasing population of elderly patients admitted for ACS is also urgently needed.