Verdoia Monica, Pergolini Patrizia, Rolla Roberta, Nardin Matteo, Barbieri Lucia, Schaffer Alon, Bellomo Giorgio, Marino Paolo, Suryapranata Harry, De Luca Giuseppe
Department of Cardiology, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
Clinical Chemistry, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
Cardiovasc Ther. 2016 Aug;34(4):209-15. doi: 10.1111/1755-5922.12188.
High-residual-on-treatment platelet reactivity still represents a challenging issue, potentially vanishing the benefits of dual antiplatelet treatment in patients with coronary artery disease. However, very few is known on the determinants of suboptimal response to antiplatelet agents. Recent interests have emerged on the potential prothrombotic effect of parathyroid hormone (PTH). Therefore, the aim of the present study was to assess the impact of parathyroid hormone (PTH) on platelet reactivity in patients receiving DAPT after an acute coronary syndrome or PCI.
Patients treated with DAPT (ASA and clopidogrel or ticagrelor) were scheduled for platelet function assessment at 30- to 90-days postdischarge. By whole blood impedance aggregometry, HRPR was considered for ASPI test >862 AUmin (for ASA) and ADP test values ≥417 AUmin (for ADP antagonists).
We included 362 patients on DAPT, 125 (34.5%) receiving clopidogrel, and 237 (65.5%) on ticagrelor. Patients were divided according to PTH quartiles values (<45.8; 45.8-60.3; 60.4-88; ≥88.1 pg/mL). Higher PTH was associated with older age (P = 0.001); renal failure (P < 0.001), higher HDL cholesterol (P = 0.006) and creatinine (P < 0.001) and lower 25-OH cholecalciferol (P < 0.001). Suboptimal response to ASA was infrequent (2.8%), and not influenced by the levels of PTH (P = 0.57). ADP-mediated platelet aggregation was significantly increased in patients with higher PTH (P = 0.03), with an absolute increase in the prevalence of HRPR to ADP antagonists for higher PTH (24.7% vs. 40%, P = 0.007 for 4th vs. 1-3rd quartiles, adjusted OR[95%CI] = 2.04[1.14-3.64], P = 0.02). By the use of the ROC curve, we identified PTH levels above 96.7 pg/mL as the best predictor of HRPR with ADP antagonists (adjusted OR[95%CI] = 2.52[1.31-4.87], P = 0.006). Higher rate of HRPR was confirmed for PTH >96.7 pg/mL among the subgroup of patients on clopidogrel (51.5 vs. 85.7%, P = 0.001; adjusted OR[95%CI] = 12.5[2.6-60.9], P = 0.002), but not among ticagrelor-treated patients (11.3 vs. 16.7%, P = 0.31; adjusted OR[95%CI] = 1.55[0.56-4.6], P = 0.42).
In patients receiving dual antiplatelet therapy for coronary artery disease, higher PTH levels are associated with an increased ADP-mediated platelet reactivity and suboptimal response to clopidogrel, especially for values above 96.7 pg/mL, while not influencing the effectiveness of ASA and ticagrelor.
治疗中高残余血小板反应性仍是一个具有挑战性的问题，可能会抵消冠心病患者双重抗血小板治疗的益处。然而，关于抗血小板药物反应欠佳的决定因素，人们了解得非常少。近期，甲状旁腺激素（PTH）的潜在促血栓形成作用引起了关注。因此，本研究旨在评估甲状旁腺激素（PTH）对急性冠脉综合征或经皮冠状动脉介入治疗（PCI）后接受双重抗血小板治疗（DAPT）患者血小板反应性的影响。
接受DAPT（阿司匹林和氯吡格雷或替格瑞洛）治疗的患者计划在出院后30至90天进行血小板功能评估。通过全血阻抗聚集法，对于阿司匹林试验，阿司匹林诱导的血小板聚集（ASPI）试验>862 AUmin被视为高残余血小板反应性（HRPR）；对于ADP拮抗剂，ADP试验值≥417 AUmin被视为HRPR。
我们纳入了362例接受DAPT的患者，其中125例（34.5%）接受氯吡格雷治疗，237例（65.5%）接受替格瑞洛治疗。患者根据PTH四分位数（<45.8；45.8 - 60.3；60.4 - 88；≥88.1 pg/mL）进行分组。较高的PTH与年龄较大（P = 0.001）、肾衰竭（P < 0.001）、较高的高密度脂蛋白胆固醇（P = 0.006）和肌酐（P < 0.001）以及较低的25 - 羟基胆钙化醇（P < 0.001）相关。对阿司匹林反应欠佳的情况不常见（2.8%），且不受PTH水平影响（P = 0.57）。PTH较高的患者中，ADP介导的血小板聚集显著增加（P = 0.03），较高PTH患者中对ADP拮抗剂的HRPR患病率绝对增加（第四四分位数与第一至第三四分位数相比，24.7%对40%，P = 0.007，调整后的比值比[95%置信区间]=2.04[1.14 - 3.64]，P = 0.02）。通过使用ROC曲线，我们确定PTH水平高于96.7 pg/mL是对ADP拮抗剂HRPR的最佳预测指标（调整后的比值比[95%置信区间]=2.52[1.31 - 4.87]，P = 0.006）。在氯吡格雷治疗的患者亚组中，PTH>96.7 pg/mL的患者HRPR发生率更高（51.5%对85.7%，P = 0.001；调整后的比值比[95%置信区间]=12.5[2.6 - 60.9]，P = 0.002），但在替格瑞洛治疗的患者中并非如此（11.3%对16.7%，P = 0.31；调整后的比值比[95%置信区间]=1.55[0.56 - 4.6]，P = 0.42）。
在接受冠心病双重抗血小板治疗的患者中，较高的PTH水平与ADP介导的血小板反应性增加以及对氯吡格雷反应欠佳相关，尤其是PTH水平高于96.7 pg/mL时，而对阿司匹林和替格瑞洛的有效性无影响。
