Department of Cardiology, St. Antonius Hospital, Nieuwegein, the Netherlands; Department of Cardiology, Isala Hospital, Zwolle, the Netherlands.
Department of Cardiology, St. Antonius Hospital, Nieuwegein, the Netherlands.
Int J Cardiol. 2021 Jul 1;334:10-17. doi: 10.1016/j.ijcard.2021.04.029. Epub 2021 Apr 20.
Patients with acute coronary syndrome (ACS) who are carrying CYP2C19 loss-of-function alleles derive less benefit from clopidogrel treatment. Despite this, in elderly patients, clopidogrel might be preferred over more potent P2Y inhibitors due to a lower bleeding risk. Whether CYP2C19 genotype-guided antiplatelet treatment in the elderly could be of benefit has not been studied specifically.
Patients aged 70 years and older with known CYP2C19*2 and *3 genotype were identified from the POPular Genetics and POPular Age trials. Noncarriers of loss-of-function alleles treated with clopidogrel were compared to patients, irrespective of CYP2C19 genotype, treated with ticagrelor and to clopidogrel treated carriers of loss-of-function alleles. We assessed net clinical benefit (all-cause death, myocardial infarction, stroke and Platelet Inhibition and Patient Outcomes (PLATO) major bleeding), atherothrombotic outcomes (cardiovascular death, myocardial infarction, stroke) and bleeding outcomes (PLATO major and minor bleeding).
A total of 991 patients were assessed. There was no significant difference in net clinical benefit (17.2% vs. 15.1%, adjusted hazard ratio (adjHR) 1.05, 95% confidence interval (CI) 0.77-1.44), atherothrombotic outcomes (9.7% vs. 9.2%, adjHR 1.00, 95%CI 0.66-1.50), and bleeding outcomes (17.7% vs. 19.8%, adjHR 0.80, 95%CI 0.62-1.12) between clopidogrel in noncarriers of loss-of-function alleles and ticagrelor respectively.
In ACS patients aged 70 years and older, there was no significant difference in net clinical benefit and atherothrombotic outcomes between noncarriers of a loss-of-function allele treated with clopidogrel and patients treated with ticagrelor. The bleeding rate was numerically; though not statistically significant, lower in patients using clopidogrel.
携带 CYP2C19 失活等位基因的急性冠脉综合征（ACS）患者从氯吡格雷治疗中获益较少。尽管如此，由于出血风险较低，氯吡格雷在老年患者中可能优于更有效的 P2Y 抑制剂。CYP2C19 基因型指导的抗血小板治疗在老年人中是否有益尚未专门研究。
从 POPular Genetics 和 POPular Age 试验中确定了年龄在 70 岁及以上且已知 CYP2C192 和3 基因型的患者。未携带失活等位基因的氯吡格雷治疗患者与无论 CYP2C19 基因型如何均接受替格瑞洛治疗的患者以及携带失活等位基因的氯吡格雷治疗患者进行比较。我们评估了净临床获益（全因死亡、心肌梗死、卒中和血小板抑制和患者结局（PLATO）大出血）、动脉粥样硬化血栓形成结局（心血管死亡、心肌梗死、卒中和 PLATO 大出血和次要出血）。
共评估了 991 例患者。净临床获益（17.2% vs. 15.1%，调整后的危险比（adjHR）1.05，95%置信区间（CI）0.77-1.44）、动脉粥样硬化血栓形成结局（9.7% vs. 9.2%，adjHR 1.00，95%CI 0.66-1.50）和出血结局（17.7% vs. 19.8%，adjHR 0.80，95%CI 0.62-1.12）在无失活等位基因的氯吡格雷治疗患者与替格瑞洛治疗患者之间无显著差异。
在年龄在 70 岁及以上的 ACS 患者中，无失活等位基因的氯吡格雷治疗患者与替格瑞洛治疗患者在净临床获益和动脉粥样硬化血栓形成结局方面无显著差异。使用氯吡格雷的患者出血率虽无统计学意义，但数值上较低。
