Optimal strategy of switching from clopidogrel to ticagrelor in Chinese acute coronary syndrome patients with complicated coronary artery disease: the switching from clopidogrel to ticagrelor (SHIFT-CACS) study

Abstract

Background: The dose and time point for switching from clopidogrel to ticagrelor remain controversial, especially for Chinese acute coronary syndrome (ACS) patients with complicated coronary artery disease (CAD). Hence, the purpose of this study was to further explore the optimal dose and time point for the switching strategy to balance the increase in platelet inhibition and the decrease in adverse events in Chinese ACS patients with complicated CAD managed by percutaneous coronary intervention (PCI).

Methods: From July 2017 to December 2017, the prospective, randomized, open-label study (the SwitcHIng from clopidogrel to ticagrelor study) assigned the eligible Chinese ACS patients with complicated CAD managed by PCI (n = 102) for 90 mg of ticagrelor at 12 h (T-90 mg-12 h), 90 mg of ticagrelor at 24 h (T-90 mg-24h) or 180 mg ticagrelor at 24 h (T-180 mg-24 h) after the last dose of clopidogrel. The primary endpoint was the comparison of maximal platelet aggregation (MPA) values at 2 h after switching strategies among the three groups. In addition, the MPA values at baseline, 8 h and before discharge and the rates of high on-treatment platelet reactivity were evaluated, the incidences of bleeding episodes and dyspnea during hospitalization and at 30-day follow-up in our study were also recorded. The MPA was measured by light transmittance aggregometry in our study. A repeated-measures analysis of variance (ANOVA) model and one-way ANOVA were used to compare data for the primary endpoint.

Results: The MPA values were significantly decreased in the T-180 mg-24 h group compared with the T-90 mg-12 h group (P = 0.017) and decreased numerically compared with the T-90 mg-24 h group (P = 0.072) at 2 h. In particular, the MPA values were markedly reduced in the T-90 mg-24 h group compared with the T-90 mg-12 h group at 8 h after switching treatment (P = 0.002). There was no significant difference among the three groups in all bleedings and dyspnea events.

Conclusions: The optimal treatment strategy recommended in this study for Chinese ACS patients with complicated CAD managed by PCI is 180 or 90 mg of ticagrelor at 24 h after the last dose of clopidogrel. In addition, a negative interaction was detected in this study between the overlap for clopidogrel and ticagrelor at 12 h after the last dose of clopidogrel.

Trial registration: ClinicalTrials.gov, NCT03577652; https://ichgcp.net/clinical-trials-registry/NCT03577652.

Figures

Figure 1

Study design and patient disposition. (A) Adverse events include bleeding episodes and dyspnea. The MPA was measured by light transmittance aggregometry. Baseline values were measured while on clopidogrel maintenance therapy. Before discharge values were measured at 2 h after the last dose of ticagrelor during hospital. (B) Patient disposition. In total, 102 patients of the intention-to-treat analysis population formed the efficacy and safety endpoint cohorts. T-90 mg-12 h: Maintenance dose of 90 mg of ticagrelor at 12 h after the last clopidogrel treatment; T-90 mg-24 h: Maintenance dose of 90 mg of ticagrelor at 24 h after the last clopidogrel treatment; T-180 mg-24 h: Loading dose of 180 mg of ticagrelor at 24 h after the last clopidogrel treatment. ACS: Acute coronary syndrome; MPA: Maximal platelet aggregation; PCI: Percutaneous coronary intervention; R∗: Randomization.

Figure 2

Pharmacodynamic comparisons among groups. Comparisons of mean maximal platelet aggregation measured by light transmittance aggregometry among groups after switching from clopidogrel to ticagrelor therapy. Data were shown as the mean ± SE. Baseline values were measured while on clopidogrel maintenance therapy. Before discharge values were measured at 2 h after the last dose of ticagrelor during hospital. The P∗ value denoted the T-90 mg-12 h group comparing with the T-180 mg-24 h group at 2 h after switching strategies; the P† value denoted the T-90 mg-12 h group comparing with the T-90 mg-24 h group at 8 h after switching strategies; The P‡ value denoted the T-90 mg-12 h group comparing with the T-180 mg-24 h group at 8 h after switching strategies. MPA: Maximal platelet aggregation; SE: Standard error; T-90 mg-12 h: Maintenance dose of 90 mg of ticagrelor at 12 h after the last clopidogrel treatment; T-90 mg-24 h: Maintenance dose of 90 mg of ticagrelor at 24 h after the last clopidogrel treatment; T-180 mg-24 h: Loading dose of 180 mg of ticagrelor at 24 h after the last clopidogrel treatment.