Antiplatelet therapy has become the cornerstone of the current standardized treatment of acute coronary syndromes . Clopidogrel is widely used as one of the DAPT therapy. It has certain limitations, mainly including the following aspects: 1. As a prodrug, clopidogrel needs to be metabolized by liver enzymes after oral administration, which leads to its slow onset of action. It cannot achieve rapid inhibition of platelets in patients with acute myocardial infarction that require emergency surgery. 2. Clopidogrel metabolism is inconsistent in different patients. Due to individual genetic differences and other reasons, some patients have clopidogrel metabolic resistance, resulting in the drug's anti-platelet effect cannot be effectively exerted, and ischemic events increase in these patients; 3. Clopidogrel caused irreversible platelet aggregation, which leads to a longer recovery time of platelet function after clopidogrel stopped, and it cannot be used in patients who need to quickly reverse the antiplatelet effect. Ticagrelor is a reversible P2Y12 receptor antagonist. Its effect does not need to be metabolized by the liver, and acts very rapidly. Differences in individual genes do not affect the efficacy of the ticagrelor. Ticagrelor can quickly inhibit platelet aggregation [8–11].
The PLATO trial compared ticagrelor with clopidogrel in high-risk ACS patients, and the results showed that the use of ticagrelor decreased the incidence of primary composite endpoint of CV death/myocardial infarction/stroke. There was no significant difference in overall severe bleeding. Based on PLTAO trial, the current world guidelines recommend the use of ticagrelor prior to clopidogrel in ACS patients [12–14]. In recent years, the use of ticagrelor increased fast in Asian country in ACS patients, including unstable angina pectoris and myocardial infarction, however, the clinical outcomes and bleeding risk of ticagrelor in this population is unknown. There are few studies about the platelet aggregation function and PCI-related myocardial injury in patients with unstable angina. Our study aims to investigate this.
The results of our study showed that compared with clopidogrel group, platelet aggregation rate induced by ADP and AA decreased significantly in ticagrelor group after medication treatment, with prolonged R value and K value, decreased α angle and MA value. This suggested that ticagrelor is more effective in inhibiting platelet aggregation and activation. ONSET/OFFSET studies have shown  that platelet aggregation rate is 60% half an hour after a loading dose of 180 mg ticagrelor, and platelet aggregation rate is only 10% after 2–4 hours of administration, and the corresponding platelet inhibition rate is 90%. In this study, two time points, 3 day and 30 day after medication, were selected to determine platelet aggregation rate, which represented steady-state concentration of the drug. Results showed that platelet aggregation rate induced by ADP were 18.23 ± 9.86% (3d) and 17.38 ± 8.71% (30d) after medication in ticagrelor group assessed by TEG. Platelet aggregation rates induced by AA were 21.30 ± 11.17% (3d) and 20.73 ± 22.24% (30d). LTA assay showed the same trend of result. Platelet aggregation rate induced by ADP in ticagrelor group were 20.28 ± 9.93% (3d) and 19.18 ± 9.01% (30d) after medication. Platelet aggregation rates induced by AA were 19.92 ± 10.49% (3d) and 20.25 ± 9.94% (30d) after medication. Compared with clopidogrel group, platelet aggregation rate in ticagrelor group induced by ADP and AA decreased, and the difference between the two groups was statistically significant. This result reflects that ticagrelor can continuously and steadily inhibit platelet activation more effectively than clopidogrel, which is in consistent with the platelet aggregation rate of the drugs in the ONSET/OFFSET study . Platelet aggregation induced by AA depends on the activity of the cyclooxygenase-1 (COX1) enzyme. Both ticagrelor and clopidogrel inhibit the P2Y12 receptor, which is downstream of the COX-1 pathway. Our results indicate that ticagrelor may be superior to clopidogrel not only in inhibiting ADP-induced platelet aggregation, but also in inhibiting AA-induced platelet aggregation.
PCI-related myocardial injury is very common, because the operation itself may cause further damage to the plaque or thrombus on the inner wall of the coronary artery, increasing the risk of recurrent myocardial ischemia and myocardial injury after PCI. Recent study showed that compared with clopidogrel, loading dose pretreatment of ticagrelor can significantly reduce the incidence of PCI-related periprocedural myocardial infarction (PMI) in Asian ACS patients undergoing elective PCI. Multivariate analysis found that the use of ticagrelor was negatively correlated with PCI-related PMI, indicating that ticagrelor treatment is an independent protective predictor of PMI. PCI-related PMI which was defined by an elevation of cardiac high-sensitivity troponin T values more than five times the 99th percentile upper reference limit . High-sensitivity troponin T is recognized as a specific indicator that reflects myocardial injury. H-FABP leaks from the cell when myocardial cells are damaged. Both are sensitive indicators of myocardial injury. Previous studies have reported that peripheral blood H-FABP level of patients with myocardial infarction is related to the severity of coronary artery disease, and can be used to assess the area of myocardial infarction and cardiovascular prognosis in patients with acute ST-segment elevation myocardial infarction . The results of our study suggest that the increase in hs-TnT and H-FABP after PCI in the ticagrelor group was significantly lower than that in the clopidogrel group. It reflects the corresponding protection of myocardial damage, which has positive significance for the maintenance and protection of cardiac function.
Cardiovascular prognosis following up showed that patients in ticagrelor group had a trend of less cardiovascular event but both MACE in hospital and MACE at 12-months showed no significant difference between the two groups. Bleeding events were more common in hospital and at 12-month follow up in ticagrelor group. This correlated with several recent studies, which also conducted the same conclusions. Clopidogrel is proved noninferior to ticagrelor in cardiovascular outcomes with less bleeding in several population, including older patients > 70 years with ACS, STEMI patients, intensive care unit patients with ACS, NSTE-ACS patients, ACS patients underwent PCI, NSTE-ACS old patients in combination use of NOAC and so on [18–23]. More and more real-world evidence showed that ticagrelor has the same clinical cardiovascular benefit with clopidogrel but a higher bleeding risk. Clopidogrel may find its role in more high-bleeding risk situation.
In conclusion, our study proved that ticagrelor was effective in platelet suppression than clopidogrel and may reduce peri-PCI myocardial injury in patients with unstable angina. However, ticagrelor showed no advantages in reducing in hospital and 12-months MACE and increased in hospital and 12-months bleeding events.