Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy; Department of Medicine, ASST "Spedali Civili", University of Brescia, Brescia, Italy.
Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy; Division of Cardiology, "Ospedale degli Infermi", Biella, Italy.
Nutr Metab Cardiovasc Dis. 2021 Apr 9;31(4):1276-1285. doi: 10.1016/j.numecd.2020.12.004. Epub 2020 Dec 10.
Dual antiplatelet therapy (DAPT) and Renin-angiotensin system inhibitors (RASi) represent the cornerstone in the treatment of patients undergoing percutaneous coronary interventions (PCI), mainly after an acute ischemic event. However, high-on treatment residual platelet reactivity (HRPR), is not infrequent despite optimal medical treatment. Homocysteine (Hcy) is a metabolite of methionine catabolism linked to atherothrombosis. Recently, a potential crosstalk between RAS and Hcy has been suggested, potentially favouring platelet aggregation and cardiovascular disease.Therefore, we aimed to investigate the impact of RASi on Hcy levels and platelet aggregation in patients on DAPT after PCI.
Patients undergoing PCI on DAPT with ASA plus an ADP-antagonist (clopidogrel, ticagrelor or prasugrel), were included. RASi comprised angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB). Aggregation tests were performed by Multiple Electrode Aggregometry. We included 1210 patients, of whom 862 (71.2%) were on treatment with RASi. Overall, DAPT composition was ASA+clopidogrel in 566 (46.8%) patients, ASA+ticagrelor in 428 (35.4%) and ASA+prasugrel in 216 (17.9%). Median values of Hcy were higher in RASi patients (p = 0.006), who displayed a higher percentage of Hcy above the median value (52.4% vs. 44.8%, p = 0.019, adjustedOR [95%CI] = 1.40 [1.04-1.88], p = 0.027). No differences in HRPR rate were found according to RASi use for ASPI test (3.6% vs. 3.3%, p = 0.88) and ADP test (25.6% vs. 24.3%,p = 0.62; adjustedOR [95%CI] = 1.23 [0.89-1.70], p = 0.220) and according to ADP-antagonist type. A direct linear relationship was observed between platelet reactivity and Hcy in both patients receiving RASi and untreated ones, with higher values of platelet aggregation being observed in patients with Hcy above the median, independently from RASi administration and DAPT strategy.
In patients on DAPT after PCI, RASi treatment did not emerge as an independent predictor of HRPR. However, the levels of Hcy were significantly elevated in patients on RASi and related to higher values of platelet reactivity, independently from the DAPT strategy.
双联抗血小板治疗（DAPT）和肾素-血管紧张素系统抑制剂（RASi）是经皮冠状动脉介入治疗（PCI）患者治疗的基石，主要用于急性缺血事件后。然而，尽管进行了最佳的药物治疗，仍有相当一部分患者存在高反应性血小板（HRPR）。同型半胱氨酸（Hcy）是蛋氨酸代谢物，与动脉粥样血栓形成有关。最近，有人提出 RAS 和 Hcy 之间可能存在潜在的相互作用，从而可能促进血小板聚集和心血管疾病的发生。因此，我们旨在研究 RASi 对接受 PCI 后接受 DAPT 的患者的 Hcy 水平和血小板聚集的影响。
纳入了接受 DAPT 治疗（ASA 加 ADP 拮抗剂[氯吡格雷、替格瑞洛或普拉格雷]）的 PCI 患者。RASi 包括血管紧张素转换酶抑制剂（ACEi）和血管紧张素受体阻滞剂（ARB）。通过多电极聚集仪进行聚集试验。我们纳入了 1210 名患者，其中 862 名（71.2%）正在接受 RASi 治疗。总体而言，DAPT 组分为 ASA+氯吡格雷（566 名患者，46.8%）、ASA+替格瑞洛（428 名患者，35.4%）和 ASA+普拉格雷（216 名患者，17.9%）。接受 RASi 治疗的患者 Hcy 中位数较高（p=0.006），且 Hcy 中位数以上的患者比例更高（52.4%比 44.8%，p=0.019，调整后的 OR [95%CI]为 1.40 [1.04-1.88]，p=0.027）。根据 RASi 使用情况，在 ASPI 测试（3.6%比 3.3%，p=0.88）和 ADP 测试（25.6%比 24.3%，p=0.62；调整后的 OR [95%CI]为 1.23 [0.89-1.70]，p=0.220）和根据 ADP 拮抗剂类型，HRPR 率无差异。在接受 RASi 和未接受 RASi 治疗的患者中，均观察到血小板反应性与 Hcy 之间存在直接线性关系，且 Hcy 中位数以上的患者血小板聚集值较高，这与 RASi 给药和 DAPT 策略无关。
在接受 PCI 后接受 DAPT 的患者中，RASi 治疗并未成为 HRPR 的独立预测因子。然而，接受 RASi 治疗的患者 Hcy 水平显著升高，且与血小板反应性升高有关，与 DAPT 策略无关。
