From the *New Mexico VA Health Care System and †University of New Mexico College of Pharmacy, Albuquerque, NM.
Cardiol Rev. 2013 Nov-Dec;21(6):309-17. doi: 10.1097/CRD.0b013e3182a72fab.
A significant percentage of patients demonstrate a poor antiplatelet response to clopidogrel. With the emergence of testing for genetic variations in drug-metabolizing enzyme function and testing for platelet function, it is becoming more common to identify patients as poor responders to clopidogrel. This leaves the clinician in a difficult situation when confronted with a patient deemed to be a poor clopidogrel responder as there is no clear therapeutic strategy for treating these patients. In this situation, a number of alternatives to conventional dosing of clopidogrel have been investigated, including increasing the dosage of clopidogrel, switching from clopidogrel to either prasugrel or ticagrelor, or adding cilostazol to clopidogrel therapy. All of these options have demonstrated pharmacologic benefit in terms of greater antiplatelet effects compared with standard clopidogrel dosing in patients with high on-treatment platelet reactivity or a genetic loss-of-function variant of CYP2C19, the main enzyme responsible for clopidogrel activation. However, the impact of each of these alternative therapies on clinical outcomes is poorly understood. Early studies have not shown a clinical benefit by increasing the clopidogrel dosage or switching to prasugrel although there is still much to be discovered in this area. Of the alternatives to standard dosing of clopidogrel, switching to either prasugrel or ticagrelor has the most potential benefit, but again, there is limited evidence to support this practice in patients who demonstrate high on-treatment platelet reactivity while on clopidogrel although the evidence is somewhat more supportive in patients who have a CYP2C19 loss-of-function variant allele. The evidence for increasing the dosage of clopidogrel or adding cilostazol is the least supportive, making these alternatives difficult to justify. Given the limited evidence to support switching treatments, some providers may simply opt to continue standard dosing of clopidogrel pending the results of ongoing trials. Much research is needed and is currently underway in this area, which will be helpful in establishing future treatment protocols for patients with poor clopidogrel response.
相当大比例的患者对氯吡格雷表现出较差的抗血小板反应。随着药物代谢酶功能的遗传变异检测和血小板功能检测的出现，越来越常见的是识别出对氯吡格雷反应不良的患者。这使得临床医生在面对被认为是氯吡格雷反应不良的患者时处于困境，因为目前尚无明确的治疗策略来治疗这些患者。在这种情况下，已经研究了许多替代传统氯吡格雷剂量的方法，包括增加氯吡格雷的剂量、从氯吡格雷转换为普拉格雷或替格瑞洛，或在氯吡格雷治疗中添加西洛他唑。所有这些选择在抗血小板作用方面都优于标准氯吡格雷剂量，与高治疗血小板反应或负责氯吡格雷激活的主要酶 CYP2C19 功能丧失性变异的患者相比。然而，每种替代疗法对临床结果的影响知之甚少。早期研究表明，增加氯吡格雷剂量或转换为普拉格雷并不能带来临床益处，尽管在这一领域仍有许多需要探索。在替代标准氯吡格雷剂量的方法中，转换为普拉格雷或替格瑞洛具有最大的潜在益处，但在接受氯吡格雷治疗时表现出高治疗血小板反应的患者中，支持这种做法的证据仍然有限，尽管在 CYP2C19 功能丧失性变异等位基因的患者中，证据更有支持性。增加氯吡格雷剂量或添加西洛他唑的证据支持最少，使得这些替代方法难以证明其合理性。鉴于支持转换治疗的证据有限，一些提供者可能会简单地选择继续标准剂量的氯吡格雷，等待正在进行的试验结果。在这一领域需要进行大量的研究，这将有助于为氯吡格雷反应不良的患者建立未来的治疗方案。
