BACKGROUND

Dual-antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is the standard for the prevention of thrombotic events in patients undergoing percutaneous coronary intervention (PCI). Type 2 diabetes mellitus (DM) patients are a subgroup with a higher risk of bleeding and thrombotic events after PCI.

This meta-analysis aimed to determine whether ticagrelor monotherapy after an initial short-course DAPT is an effective and safe option in preventing thrombotic events among DM patients undergoing PC.

A systematic review and meta-analysis was done on randomized controlled trials (RCT) comparing ticagrelor monotherapy following short-course DAPT versus conventional DAPT in T2DM patients who underwent PCI. Outcome measures for major bleeding, myocardial infarction, and all-cause mortality were extracted and analyzed using a random-effects model via RevMan version 5.3.

A total of three RCTs, with 7482 patients, were analyzed. There were no significant differences in major bleeding (P = 0.26) and myocardial infarction (P = 0.66) events between the ticagrelor and DAPT groups. However, there was a higher rate of all-cause mortality in the DAPT group, which was statistically significant (risk ratio, 0.76; 95% confidence interval, 0.59–0.98; P = 0.03).

Ticagrelor monotherapy following short course DAPT and conventional DAPT have similar rates of major bleeding and myocardial infarction among DM patients undergoing PCI with DES. However, conventional DAPT has a higher incidence of all-cause mortality, which suggests that ticagrelor monotherapy after short-course DAPT may be a preferable antiplatelet strategy in DM patients undergoing PCI.

Objective To examine the antiplatelet effect of ticagrelor by microfluidic chip and flow cytometry under shear stress in vitro. Methods Microfluidic chip was used to examine the effect of ticagrelor on platelet aggregation at the shear rates of 300/s and 1500/s.We adopted the surface coverage of platelet aggregation to calculate the half inhibition rate of ticagrelor.The inhibitory effect of ticagrelor on ADP-induced platelet aggregation was verified by optical turbidimetry.Microfluidic chip was used to construct an in vitro vascular stenosis model,with which the platelet reactivity under high shear rate was determined.Furthermore,the effect of ticagrelor on the expression of fibrinogen receptor (PAC-1) and P-selectin (CD62P) on platelet membrane activated by high shear rate was analyzed by flow cytometry. Results At the shear rates of 300/s and 1500/s,ticagrelor inhibited platelet aggregation in a concentration-dependent manner,and the inhibition at 300/s was stronger than that at 1500/s (both P<0.001).Ticagrelor at a concentration ≥4 μmol/L almost completely inhibited platelet aggregation.The inhibition of ADP-induced platelet aggregation by ticagrelor was similar to the results under flow conditions and also in a concentration-dependent manner.Ticagrelor inhibited the expression of PAC-1 and CD62P. Conclusion We employed microfluidic chip to analyze platelet aggregation and flow cytometry to detect platelet activation,which can reveal the responses of different patients to ticagrelor.
Humans ; Ticagrelor/pharmacology* ; Platelet Aggregation Inhibitors/pharmacology* ; Flow Cytometry/methods* ; Microfluidics ; Platelet Aggregation

Objective: To investigate the effects of ticagrelor on cardiorespiratory fitness in patients with coronary heart disease after percutaneous coronary intervention (PCI). Methods: A total of 1 073 patients, who were diagnosed as coronary heart disease and underwent cardiopulmonary exercise testing (CPET) within 1 year after PCI, were enrolled from September 2017 to September 2019 in Peking University Third Hospital, including 309 patients in ticagrelor group and 764 patients in clopidogrel group. Clinical information, blood test results, echocardiographic parameters, cardiorespiratory fitness related parameters (including peak oxygen uptake (VO(2)), anaerobic threshold VO(2), peak oxygen pulse (VO(2)/HR) and carbon dioxide ventilation equivalent (VE/VCO(2)) slope), coronary lesions and intervention information were obtained. Cardiopulmonary fitness related indexes were compared between the two groups, and the correlation between ticagrelor use and cardiopulmonary fitness related indexes was analyzed by multivariate logistic regression. Patients who underwent CPET within 1 month after PCI were included in the subgroup analysis. Results: In ticagrelor group, the age was (60.3±10.3) years, and 253(81.9%) cases were male. The age of clopidogrel group was (60.6±10.0) years, and there were 608(79.6%) males. No significant differences were observed in peak VO(2), anaerobic threshold VO(2), and peak VO(2)/HR between the two groups (all P>0.05), but the VE/VCO(2) slope was significantly higher in the ticagrelor group than in the clopidogrel group (30.075 (27.207, 33.603) vs. 28.853 (25.970, 32.336), P<0.001). Logistic regression analysis suggested that the peak VO(2), anaerobic threshold VO(2) and peak VO(2)/HR were not significantly correlated with the ticagrelor use (all P>0.05), while the VE/VCO(2) slope was independently correlated with ticagrelor use (OR=1.098, 95%CI 1.032-1.168, P=0.003). Subgroup analysis of patients who underwent CPET within 1 month after PCI also indicated that no significant difference were observed in peak VO(2), anaerobic threshold VO(2), peak VO(2)/HR and VE/VCO(2) slope between the two groups (all P>0.05). Logistic regression analysis suggested that the peak VO(2), anaerobic threshold VO(2) and peak VO(2)/HR were not significantly correlated with ticagrelor use (all P>0.05), while the VE/VCO(2) slope was significantly correlated with ticagrelor use (OR=1.132, 95%CI 1.030-1.244, P=0.010). Conclusion: Among coronary heart disease patients after PCI, treatment with clopidogrel does not result in significant decrease in exercise endurance as compared with patients treated with ticagrelor.
Aged ; Cardiorespiratory Fitness ; Exercise Test ; Female ; Heart Failure ; Humans ; Male ; Middle Aged ; Oxygen Consumption ; Percutaneous Coronary Intervention ; Ticagrelor

Objective: To compare the efficacy and safety of ticagrelor and clopidogrel in elderly Chinese patients with acute coronary syndrome (ACS) underwent percutaneous coronary intervention (PCI) in the real world. Methods: This study is a post-hoc analysis of a single center, retrospective cohort study. Between March 2016 and March 2018, elderly (age≥65) ACS patients who underwent PCI in the General Hospital of Northern Theater Command were included in the study. The patients were grouped according to P2Y₁₂ receptor inhibitor. The primary endpoints of this study were ischemic events during the 2-year follow-up, which were defined as the composite of cardiac death, myocardial or stroke. The secondary efficiency endpoints included all-cause death and BARC 2, 3, 5 bleeding events. Results: A total of 4 022 elderly (mean age: (71.5±5.3) years) ACS patients were included in this study. Based on the choice of P2Y₁₂ receptor inhibitor, patients were divided into clopidogrel (n=3 201) and ticagrelor (n=821) groups. Incidences of ischemic events (3.2% (26/821) vs. 5.6% (179/3 201), P=0.005) at 2 years were significantly lower in ticagrelor group compared to clopidogrel group. BARC 2, 3, 5 bleeding events (1.7% (14/821) vs. 1.6% (52/3 201), P=0.818) were comparable between the two groups. The incidence of all-cause death (1.5% (12/821) vs. 4.1% (132/3 201), P=0.005) were also lower in the ticagrelor group compared to the clopidogrel group. Clinical outcomes were consistent after adjusting for confounding factors, the incidence of ischemic events (HR= 0.637, 95%CI 0.409-0.991, P=0.046) and all-cause mortality (HR=0.402, 95%CI 0.213-0.758, P=0.005) was significantly lower in the ticagrelor group compared with the clopidogrel group. Risk of BARC 2, 3, 5 bleeding events were similar between the two groups (HR=0.957, 95%CI 0.496-1.848, P=0.897). Conclusion: In real-world clinical practice, for elderly patients with ACS undergoing PCI, ticagrelor use might reduce the incidence of long-term ischemic events and all-cause death without increasing the risk of bleeding.
Acute Coronary Syndrome/surgery* ; Aged ; Clopidogrel/therapeutic use* ; Humans ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors/therapeutic use* ; Retrospective Studies ; Ticagrelor/therapeutic use* ; Treatment Outcome

Angioplasty, Balloon, Coronary ; Aspirin ; therapeutic use ; Coronary Angiography ; Coronary Restenosis ; drug therapy ; therapy ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; therapeutic use ; Male ; Middle Aged ; Stents ; Ticagrelor ; therapeutic use

Objectives: To compare the impact of ticagrelor or clopidogrel on serum uric acid levels among patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI) and further evaluate the effects of variation of serum uric acid levels on platelet reactivity. Methods: STEMI patients who admitted to Fuwai Hospital from April 2017 to January 2020, and underwent primary PCI and discharged alive with aspirin and ticagrelor or clopidogrel were included in this study. Patients were divided into ticagrelor group and clopidogrel group. The baseline clinical data were collected. Serum uric acid and creatinine levels at baseline and 30 days post-PCI were measured. Light transmittance aggregometry was used to assess maximum aggregation rate induced by adenosine diphosphate and arachidonic acid. The changes of serum uric acid and creatinine were compared between the two groups. Multivariate logistic regression was performed to evaluate independent related factors for rise in the uric acid levels, and the effect of variation of serum uric acid level on platelet reactivity was analyzed. Results: A total of 967 patients were included, the age was (59.4±12.1) years, and 163 case were female. There were 550 cases in ticagrelor group (56.9%) and 417 cases in clopidogrel group (43.1%). Baseline serum uric acid and creatinine levels were similar between the 2 groups. At 30 days, the serum uric acid level [(347.2±96.5) mmol/L vs. (341.2±105.3) mmol/L, P=0.009] and absolute [46.4 (-2.4, 88.1) mmol/L vs. 25.0 (-21.9, 73.0) mmol/L, P=0.001] and percentage [13.2 (-0.01, 29.0) % vs. 7.9 (-5.7, 25.0) %, P=0.007] increase in the serum uric acid levels were significantly higher in ticagrelor group than in clopidogrel group. The level of serum creatinine at 30 days was significantly lower in ticagrelor group than in clopidogrel group [(89.7±21.3) μmol/L vs. (94.4±43.9) μmol/L, P<0.05], whereas there were no differences in absolute [8.0 (-1.4, 16.6) μmol/L vs. 7.8 (-2.0, 16.6) μmol/L] and percentage [10.5 (-1.7%, 22.6%) vs. 9.8 (-2.4%, 22.1%)] change in the serum creatinine between the 2 groups (all P>0.05). Logistic regression analysis showed that, after adjusting for confounding factors, ticagrelor therapy was an independent related factor of serum uric acid elevation (OR=1.582, 95% CI:1.023-2.447, P=0.039). The variation of the serum uric acid levels did not affect platelet aggregation and the percentage of high platelet reactivity in both groups. Conclusions: Ticagrelor use is related to a significant increase in the serum uric acid levels at 30 days post-PCI in this patient cohort. The variations in the uric acid levels do not increase the percentage of high platelet reactivity in STEMI patients treated with ticagrelor or clopidogrel.
Adenosine/therapeutic use* ; Aged ; Female ; Humans ; Middle Aged ; Myocardial Infarction/drug therapy* ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors/therapeutic use* ; ST Elevation Myocardial Infarction ; Ticagrelor/therapeutic use* ; Ticlopidine ; Time Factors ; Treatment Outcome ; Uric Acid

Acute Coronary Syndrome/drug therapy* ; Aged ; Clopidogrel/therapeutic use* ; Humans ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors/therapeutic use* ; Purinergic P2Y Receptor Antagonists/therapeutic use* ; Ticagrelor/therapeutic use* ; Treatment Outcome

Background: There was still conflict on the antithrombotic advantage of ticagrelor versus clopidogrel among East Asian population with acute coronary syndrome (ACS). We considered that the baseline bleeding risk might be an undetected key factor that significantly affected the efficacy of ticagrelor. Methods: A total of 20,816 serial patients who underwent percutaneous coronary intervention (PCI) from October 2011 to August 2014 in the General Hospital of Shenyang Military Region were enrolled in the present study. Patients receiving ticagrelor or clopidogrel were further subdivided according to basic bleeding risk. The primary outcome was net adverse clinical events (NACEs) defined as major adverse cardiac or cerebral events (MACCE, including all-cause death, myocardial infarction, ischemia-driven target vessel revascularization, or stroke) and any bleeding during 1-year follow-up. Comparison between ticagrelor and clopidogrel was adjusted by propensity score matching (PSM). Results: Among the 20,816 eligible PCI patients who were included in this study, there were 1578 and 779 patients in the clopidogrel and ticagrelor groups, respectively, after PSM, their clinical parameters were well matched. Patients receiving ticagrelor showed comparable NACE risk compared with those treated by clopidogrel (5.3% vs. 5.1%, P = 0.842). Furthermore, ticagrelor might reduce the MACCE risk in patients with low bleeding risk but increase MACCE in patients with moderate-to-high bleeding potential (ticagrelor vs. clopidogrel, low bleeding risk: 2.5% vs. 4.9%, P = 0.022; moderate-to-high bleeding risk: 4.8% vs. 3.0%, P = 0.225; interaction P = 0.021), with vast differences in all bleeding (low bleeding risk: 1.5% vs. 0.8%, P = 0.210; moderate-to-high bleeding risk: 4.8% vs. 3.0%, P = 0.002; interaction P = 0.296). Conclusion Among real-world Chinese patients with ACS treated by PCI, ticagrelor only showed superior efficacy in patients with low bleeding risk but lost its advantage in patients with moderate-to-high bleeding potential.
Acute Coronary Syndrome ; therapy ; Adenosine ; Clopidogrel ; adverse effects ; therapeutic use ; Female ; Hemorrhage ; chemically induced ; Humans ; Male ; Middle Aged ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors ; adverse effects ; therapeutic use ; Ticagrelor ; adverse effects ; therapeutic use ; Ticlopidine ; Treatment Outcome