Cardiology and Cardiovascular Medicine Department, Fondazione Toscana G. Monasterio, via Giuseppe Moruzzi 1, 56124 Pisa, Italy.
Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.
Eur Heart J Cardiovasc Pharmacother. 2021 May 23;7(3):180-188. doi: 10.1093/ehjcvp/pvaa089.
Dyspnoea often occurs in patients with acute coronary syndrome (ACS) treated with ticagrelor compared with other anti-platelet agents and is a cause of drug discontinuation. We aimed to explore the contribution of central apnoeas (CA) and chemoreflex sensitization to ticagrelor-related dyspnoea in patients with ACS.
Sixty consecutive patients with ACS, preserved left ventricular ejection fraction, and no history of obstructive sleep apnoea, treated either with ticagrelor 90 mg b.i.d. (n = 30) or prasugrel 10 mg o.d. (n = 30) were consecutively enrolled. One week after ACS, all patients underwent two-dimensional Doppler echocardiography, pulmonary static/dynamic testing, carbon monoxide diffusion capacity assessment, 24-h cardiorespiratory monitoring for hypopnoea-apnoea detection, and evaluation of the chemosensitivity to hypercapnia by rebreathing technique. No differences were found in baseline demographic and clinical characteristics, echocardiographic, and pulmonary data between the two groups. Patients on ticagrelor, when compared with those on prasugrel, reported more frequently dyspnoea (43.3% vs. 6.7%, P = 0.001; severe dyspnoea 23.3% vs. 0%, P = 0.005), and showed higher apnoea-hypopnoea index (AHI) and central apnoea index (CAI) during the day, the night and the entire 24-h period (all P < 0.001). Similarly, they showed a higher chemosensitivity to hypercapnia (P = 0.001). Among patients treated with ticagrelor, those referring dyspnoea had the highest AHI, CAI, and chemosensitivity to hypercapnia (all P < 0.05).
Central apnoeas are a likely mechanism of dyspnoea and should be screened for in patients treated with ticagrelor. A drug-related sensitization of the chemoreflex may be the cause of ventilatory instability and breathlessness in this setting.
与其他抗血小板药物相比，接受替格瑞洛治疗的急性冠脉综合征（ACS）患者常出现呼吸困难，这也是导致药物停药的一个原因。本研究旨在探讨中枢性呼吸暂停（CA）和化学感受器敏感性对 ACS 患者替格瑞洛相关呼吸困难的影响。
连续纳入 60 例 ACS 患者，左心室射血分数正常，无阻塞性睡眠呼吸暂停史，分别接受替格瑞洛 90mg，每日 2 次（n=30）或普拉格雷 10mg，每日 1 次（n=30）治疗。ACS 后 1 周，所有患者均接受二维多普勒超声心动图、肺静态/动态检测、一氧化碳弥散能力评估、24 小时心肺监测以检测低通气/呼吸暂停、重复呼吸技术评估对高碳酸血症的化学敏感性。两组患者在基线人口统计学和临床特征、超声心动图和肺功能数据方面无差异。与普拉格雷组相比，替格瑞洛组患者报告呼吸困难的频率更高（43.3%比 6.7%，P=0.001；严重呼吸困难 23.3%比 0%，P=0.005），且日间、夜间和 24 小时的呼吸暂停-低通气指数（AHI）和中枢性呼吸暂停指数（CAI）更高（均 P<0.001）。同样，他们对高碳酸血症的化学敏感性更高（P=0.001）。在接受替格瑞洛治疗的患者中，出现呼吸困难的患者 AHI、CAI 和对高碳酸血症的化学敏感性最高（均 P<0.05）。
中枢性呼吸暂停可能是呼吸困难的机制之一，应在接受替格瑞洛治疗的患者中进行筛查。在这种情况下，化学感受器的药物相关敏感性可能是导致通气不稳定和呼吸困难的原因。
