Ticagrelor Group Research Articles

Efficacy and safety with ticagrelor in patients with prior myocardial infarction in the approved European label: insights from PEGASUS-TIMI 54.

AimsIn PEGASUS-TIMI 54, ticagrelor significantly reduced the risk of the composite of major adverse cardiovascular (CV) events by 15–16% in stable patients with a prior myocardial infarction (MI) 1–3 years earlier. We report the efficacy and safety in the subpopulation recommended for treatment in the European (EU) label, i.e. treatment with 60 mg b.i.d. initiated up to 2 years from the MI, or within 1 year after stopping previous adenosine diphosphate receptor inhibitor treatment.Methods and resultsOf the 21 162 patients enrolled in PEGASUS-TIMI 54, 10 779 patients were included in the primary analysis for this study, randomized to ticagrelor 60 mg (n = 5388) or matching placebo (n = 5391). The cumulative proportions of patients with events at 36 months were calculated by the Kaplan–Meier (KM) method. The composite of CV death, MI, or stroke occurred less frequently in the ticagrelor group (7.9% KM rate vs. 9.6%), hazard ratio (HR) 0.80 [95% confidence interval (CI) 0.70–0.91; P = 0.001]. Ticagrelor also reduced the risk of all-cause mortality, HR 0.80 (0.67–0.96; P = 0.018). Thrombolysis in myocardial infarction major bleeding was more frequent in the ticagrelor group 2.5% vs. 1.1%; HR 2.36 (1.65–3.39; P < 0.001). The corresponding HR for fatal or intracranial bleeding was 1.17 (0.68–2.01; P = 0.58).ConclusionIn PEGASUS-TIMI 54, treatment with ticagrelor 60 mg as recommended in the EU label, was associated with a relative risk reduction of 20% in CV death, MI, or stroke. Thrombolysis in myocardial infarction major bleeding was increased, but fatal or intracranial bleeding was similar to placebo. There appears to be a favourable benefit-risk ratio for long-term ticagrelor 60 mg in this population.Clinical trial registration http://www.clinicaltrials.gov NCT01225562

Double antiplatelet therapy in patients with acute coronary syndrome after percutaneous coronary intervention: individual efficacy and hemorrhagic safety of P2Y12 blockers of ticagrelor and clopidogrel in actual clinical practice

To study the comparative efficacy and safety of clopidogrel and ticagrelor in the "double" antiplatelet therapy (DATT) in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI) in the early and late periods in real clinical practice, and to assess adherence to treatment. The study included 109 patients with ACS, whounderwent PCI. Patients were divided into two groups: the 1st group (n=57) - received ticagrelor and the 2nd group (n = 52) - received clopidogrel in the DATT for 12 months. The frequency of ischemic events (death from cardiovascular causes, repeated myocardial infarction (MI) and stent thrombosis (ST)) and hemorrhagic events was analyzed during hospitalization, in 3 months, 6 months and in 12 months. Also, the reasons of repeated hospitalizations during the year were analyzed. The adherence of patients was assessed using the Moriski-Green scale. There were no significant differences in the ticagrelor and clopidogrel groups (8.8% vs. 11.5%, p=0.87) for the incidence of stent thrombosis (ST). In the correlation analysis, in half of all cases of subacute ST in the total sample (n=109) (in 4 (3.65%) cases from 8 (7.3%)), the main reason for its development was the lack of adherence of patients to DATT (τ=0,6; p&lt;0,001). The frequency of minor bleeding significantly prevailed in the ticagrelor group versus the clopidogrel group (38.6% vs. 21.2%, p=0.047). No significant difference in the rates of major bleeding was found between the ticagrelor and clopidogrel groups (1.8% and 1.9%, p=0.52). However, the difference in the rates of fatal bleeding, including more instances of fatal intracranial bleeding (1.8% vs. 0%; p=0,34), allows us to talk about the best hemorrhagic safety of clopidogrel. In this study, ticagrelor and clopidogrel were comparable in their effectiveness. Ischemic events and repeated hospitalizations in both groups are associated with the progression of atherosclerosis, confirmed by angiography; the development of stent restenosis, as well as low adherence, which is the main predictor of subacute TS. In addition, clopidogrel versus ticagrelor showed better hemorrhagic safety in the frequency of development of minor bleeding.

The effect of ticagrelor on growth of small abdominal aortic aneurysms-a randomized controlled trial.

To evaluate if ticagrelor, an effective platelet inhibitor without known non-responders, could inhibit growth of small abdominal aortic aneurysms (AAAs). In this multi-centre randomized controlled trial, double-blinded for ticagrelor and placebo, acetylic salicylic acid naïve patients with AAA and with a maximum aortic diameter 35-49 mm were included. The primary outcome was mean reduction in log-transformed AAA volume growth rate (%) measured with magnetic resonance imaging (MRI) at 12 months compared with baseline. Secondary outcomes include AAA-diameter growth rate and intraluminal thrombus (ILT) volume enlargement rate. A total of 144 patients from eight Swedish centres were randomized (72 in each group). MRI AAA volume increase was 9.1% for the ticagrelor group and 7.5% for the placebo group (P = 0.205) based on intention-to-treat analysis, and 8.5% vs. 7.4% in a per-protocol analysis (P = 0.372). MRI diameter change was 2.5 mm vs. 1.8 mm (P = 0.113), US diameter change 2.3 mm vs. 2.2 mm (P = 0.778), and ILT volume change 12.9% vs. 10.4% (P = 0.590). In this RCT, platelet inhibition with ticagrelor did not reduce growth of small AAAs. Whether the ILT has an important pathophysiological role for AAA growth cannot be determined based on this study due to the observed lack of thrombus modulating effect of ticagrelor. The TicAAA trial is registered at the US National Institutes of Health (ClinicalTrials.gov) #NCT02070653.

COMPARATIVE EVALUATION OF EFFICACY AND SAFETY OF ASPIRIN + CLOPIDOGREL WITH ASPIRIN+TICAGRELOR IN PATIENTS WITH CARDIOVASCULAR DISEASES. AN OBSERVATIONAL STUDY.

Background: Coronary artery disease (CAD) is one of the most common causes of mortality and morbidity in both developed and developing countries. It is a leading cause of death in India, and its contribution to mortality is rising. Platelets play an essential role in the pathogenesis of acute coronary syndromes (ACS). Therefore an important part of the treatment of ACS, and of primary and secondary preventive measures in coronary heart disease, consists of antiplatelet treatment. Dual antiplatelet therapy (DAPT) provides more intense platelet inhibition than single antiplatelet therapy resulting in incremental reductions in the risk of thrombotic events after percutaneous coronary intervention (PCI) or ACS, but it has been associated with an increased risk of major bleeding. It is interesting to consider that there is no Indian data on the efficacy of recently developed antiplatelet drugs other than in combination with aspirin, and that we remain unaware of the extent to which combinations with aspirin improve efficacy but increase risk.&#x0D; Methodology: Study was prospective, observational clinical study carried out in the Department of Medicine, of Index Medical College Hospital &amp; Research Centre. A total of 80 patients with CAD were enrolled for the study and were equally divided in two groups each of 40 for evaluating efficacy and safety of dual antiplatelet therapy. Follow-up was done at 8 weeks, 16 weeks, and 24 weeks, patients were asked to provide information regarding their current medications, any morbidity and their complications [if any]. Demographic parameters were analyzed by descriptive statistics. Comparison between groups was done by Chi–square Test. Survival analysis was done by suitable statistical method.&#x0D; Result: The median age was 55 years in group 1 and 57 years in group 2. Hypertension was most common associated disorders in group 1 [25 (62.55%)] and group 2 [27 (67.5%)], which was followed by diabetes and dyslipidemia. index events for present study enrolment was unstable angina, non–ST-segment elevation MI, ST-segment elevation MI and others amongs the study groups. With 6 months of follow-up, the rate of the primary event like death from any cause was 7.5 percent in the clopidogrel plus aspirin group and 2.5 percent in the ticagrelor plus aspirin group. The primary safety end point (severe bleeding) was 2.5 % in the clopidogrel plus group 1 and none in group 2.&#x0D; Conclusion: the combination of clopidogrel plus aspirin was found to be non inferior to aspirin plus ticagrelor dual therapy in reducing the rate of myocardial infarction, stroke, or death from cardiovascular causes among patients with stable cardiovascular disease or multiple cardiovascular risk factors. The risk of moderate to severe bleeding was increased slightly in both the groups. Our findings do support the use of dual antiplatelet therapy across the broad population tested where single antiplatelet therapy are not giving maximum benefits&#x0D; Keywords: Acute coronary syndrome (ACS), percutaneous coronary intervention (PCI), Coronary artery disease (CAD), Dual antiplatelet therapy (DAPT)

Evaluation of anti-atherogenic effects of P2Y12 receptor antagonists in Apolipoprotein E-deficient mice

Prasugrel and Ticagrelor, two P2Y12 receptors antagonists commonly used for the treatment of acute coronary syndrome, are suspected to exert anti-inflammatory effects, which may decrease atherosclerotic lesions. Moreover, Ticagrelor, through its interaction with adenosine metabolism, may have supplemental positive effect on inflammation and atherosclerosis. We evaluated in this study the effects of these two molecules on atherosclerotic lesions and inflammation on a murine model of atherosclerosis. Firstly, twelve C57BL/6 mice treated by vehicule ( N = 4), Prasugrel ( N = 4) or Ticagrelor ( N = 4) were used to evaluate the comparability of the anti-platelet effects by aggregometry. Then, twenty-one Apolipoprotein E deficient mice (ApoE -/-) fed a paigen diet (1.25% cholesterol, 0.5% cholic acid, 15% fat) were treated with vehicule ( N = 7), Prasugrel 5 mg/kg/day ( N = 7), or Ticagrelor 180 mg/kg/day ( N = 7) during 6 weeks. Anti-atherosclerotic effects of these molecules were evaluated in vivo using 99mTc-cAbVCAM1-5, an imaging agent evaluating the expression of the inflammatory marker Vascular Cell Adhesion Molecule-1 (VCAM-1). Maximum platelet aggregation was lower in C57BL/6 mice treated by Prasugrel and Ticagrelor (8%), than in mice treated by vehicule (70%). 99mTc-cAbVCAM1-5 uptake in the aortic root evaluated by in vivo Single Photon Emission Computed Tomography (SPECT) imaging (2.1 ± 0.6%ID/mm 3 vs 2.2 ± 0.7ID/mm 3 vs 1.9 ± 0.7ID/mm 3 ), ex-vivo biodistribution (2.9 ± 0.8%ID/g vs 2.5 ± 0.4%ID/g vs 2.6 ± 0.5%ID/g), and autoradiography (3.9 ± 1.0%ID/g vs 4.2 ± 1.0%ID/g vs 4.0 ± 0.6%ID/g) were not different between the control group, Prasugrel group and Ticagrelor group respectively. Ex vivo analysis confirmed that plaque surface and lipid content were identical between the three groups. Neither Prasugrel nor Ticagrelor has anti-atherosclerotic effects in this specific model of ApoE -/- mice fed a Paigen diet.

Ticagrelor Versus Clopidogrel in Patients With STEMI Treated With Fibrinolysis: TREAT Trial

BackgroundThe efficacy of ticagrelor in the long-term post–ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain. ObjectivesThe purpose of this study was to evaluate the efficacy of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy. MethodsThis international, multicenter, randomized, open-label with blinded endpoint adjudication trial enrolled 3,799 patients (age <75 years) with STEMI receiving fibrinolytic therapy. Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose, 75 mg daily thereafter). The key outcomes were cardiovascular mortality, myocardial infarction, or stroke, and the same composite outcome with the addition of severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events at 12 months. ResultsThe combined outcome of cardiovascular mortality, myocardial infarction, or stroke occurred in 129 of 1,913 patients (6.7%) receiving ticagrelor and in 137 of 1,886 patients (7.3%) receiving clopidogrel (hazard ratio: 0.93; 95% confidence interval: 0.73 to 1.18; p = 0.53). The composite of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) treated with ticagrelor and in 171 of 1,886 patients (9.1%) receiving clopidogrel (hazard ratio: 0.88; 95% confidence interval: 0.71 to 1.09; p = 0.25). The rates of major, fatal, and intracranial bleeding were similar between the ticagrelor and clopidogrel groups. ConclusionAmong patients age <75 years with STEMI, administration of ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular events when compared with clopidogrel. (Ticagrelor in Patients With ST Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis [TREAT]; NCT02298088)

Comparison of two preventive dual antiplatelet regimens for unruptured intracranial aneurysm embolization with flow diverter/disrupter: A matched-cohort study comparing clopidogrel with ticagrelor

PurposeStandard dual antiplatelet therapy (DAPT) for complex aneurysms treated with flow diversion and flow disruption is acetylsalicylic acid (ASA) plus clopidogrel. However, clopidogrel resistance frequently occurs and can lead to thromboembolic events. Ticagrelor is an alternative not requiring platelet inhibition testing. We compared two DAPT regimens (ASA with clopidogrel or ticagrelor) on morbi-mortality, safety and efficacy of unruptured aneurysm embolization with flow diverter/disrupter. Materials and methodsThis retrospective analysis of a 1:1 matched cohort compares patients treated with ASA + clopidogrel (March 2013–December 2015) vs. ASA + ticagrelor (January 2016–March 2017). No platelet inhibition testing was conducted. Patients matched for age (±10 years), type of treatment and aneurysm sac size ( ± 2 mm). Primary outcome measures were morbidity and mortality at 1-month; secondary outcomes were thromboembolic and hemorrhagic complications [on angiography and magnetic resonance imaging (MRI)] and groin complications. Outcomes were compared using bivariate analyses. ResultsNinety patients fulfilled inclusion criteria, of which 80 remained after matching (40 per group). There was no statistical difference in 1-month morbidity between the ticagrelor and clopidogrel groups (2.5% vs. 10%, P = 0.36) and no deaths reported. We observed no significant differences between ticagrelor and clopidogrel groups in terms of angiographic thromboembolic complications (5% vs. 12.5%, P = 0.43), territorial infarction on DWI (2.5% vs. 7.5%, P = 0.61), angiographic (0% vs. 0%, P = 1) and MRI (5% vs 5%, P = 1) hemorrhagic complications, new microbleeds (57.5% vs. 40%, P = 0.12) and groin puncture complications (2.5% vs. 0%, P = 1). At three months, there was no delayed territorial infarction or hemorrhage in either group. ConclusionsTicagrelor is safe and effective in replacing clopidogrel as DAPT for unruptured aneurysms.

Temporal Variability of Platelet Reactivity in Patients Treated with Clopidogrel or Ticagrelor.

Background and ObjectivesThe degree of antiplatelet response to P2Y12 inhibitors has been associated with clinical outcomes. The aim of this study was to test the variability of platelet reactivity over time among patients treated with clopidogrel or ticagrelor.MethodsA single-center cohort of acute coronary syndrome patients that underwent percutaneous coronary intervention (PCI) was analyzed. Platelet reactivity was measured at baseline, 48 hours after PCI, 1 month, and 6 months after clopidogrel (n=79) or ticagrelor (n=93) treatment. High on-treatment platelet reactivity (HPR) was defined as ≥47 U, assessed by multiple electrode platelet aggregometry.ResultsPlatelet reactivity in the clopidogrel group increased over time, 38.2±21.7 U at 48 hours, 41.4±22.3 U at 1 month, and 44.7±25.5 U at 6 months (p=0.018, 48 hours to 6 months). However, platelet reactivity in the ticagrelor group was not significantly changed, 21.4±12.6 U at 48 hours, 20.0±12.2 U at 1 month, and 22.8±13.8 U at 6 months (p=0.392). A platelet reactivity change over time of more than 20U was found in 67.1% of the patients with clopidogrel group and 34.4% of ticagrelor group (p<0.001). Between 48 hours and 6 months, 43% of patients changed their responder status in the clopidogrel group, and 13% in the ticagrelor group (p<0.001).ConclusionsAlthough ticagrelor treatment resulted in less temporal variability of platelet reactivity than clopidogrel treatment in terms of HPR, platelet reactivity varied over time in a significant proportion of patients.

Effects of Clopidogrel Versus Ticagrelor on Peripheral Endothelial Function After Non-ST Elevation Acute Coronary Syndrome (NSTE-ACS): a Randomised Trial

Background: Ticagrelor has been shown to improve peripheral endothelial function compared to clopidogrel in stable patients. We sought to investigate the effects of clopidogrel versus ticagrelor on peripheral endothelial function in NSTE-ACS patients. Methods: From Mar 2018-Jan 2019, patients hospitalised for NSTE-ACS were prospectively randomised 1:1 to clopidogrel (300mg loading then 75mg daily) or ticagrelor (180mg loading then 90mg twice-daily). Peripheral endothelial function was assessed in a subset of these patients with flow-mediated vasodilation (FMD) of the brachial artery, performed on admission prior to antiplatelet loading and again before discharge, using a pneumatic cuff and 10MHz linear ultrasound transducer. Results: 23 patients were included for analysis (9 clopidogrel, 14 ticagrelor). Median age 51(IQR 47–60.5) years, 21(91.3%) were male, 8(34.8%) had diabetes, 9(39.1%) were smokers. Median peak troponin T was 564 (245.5–876)ng/L and median GRACE score 94 (76.5–104.5). Admission median %FMD (change in post-stimulus diameter as a percentage of the baseline diameter) was similar between the 2 groups (clopidogrel 13.2% [10.1–17.6] vs ticagrelor 12.2% [10.2–15.8], p = 0.41). There was a trend towards higher median pre-discharge %FMD in the ticagrelor group (12.8% [12.2–18.0]) compared to the clopidogrel group (10.4% [9.5–11.2], p = 0.09). There was a trend towards lower pre-discharge %FMD compared to admission in the clopidogrel group (10.4% vs 13.2%, p = 0.05) but not the ticagrelor group (12.8% vs 12.2%, p = 0.43). Conclusions: Ticagrelor did not significantly improve peripheral endothelial function compared to clopidogrel in our NSTE-ACS cohort. However, there was a trend towards beneficial effects with ticagrelor. Further data including longer-term follow-up are awaited.

Platelet Blockage: Prasugrel versus Ticagrelor: Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5

The Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5 trial randomized patients with acute coronary syndrome for whom invasive treatment was planned to ticagrelor versus prasugrel. At 1-year, prasugrel was associated with a 2.4% absolute reduction in the primary outcome. The trial suggests that prasugrel may be superior to ticagrelor in reducing the thrombotic outcomes. It could be that once daily dosing with prasugrel and higher rate of drug discontinuation in the ticagrelor group may be the mechanism.

Compared efficacy of clopidogrel and ticagrelor in treating acute coronary syndrome: a meta-analysis

Background & AimsTicagrelor has been acknowledged as a new oral antagonist of P2Y12-adenosine diphosphate receptor, as a strategy with more rapid onset as well as more significant platelet inhibition function in acute coronary syndrome (ACS) patients. The clinical benefit of ticagrelor compared with clopidogrel remains controversial. The current meta-analysis was conducted to better evaluate the role of ticagrelor in comparison of clopidogrel in treating ACS patients.MethodsThe publications involving the safety as well as the efficacy of clopidogrel versus ticagrelor were screened and identified updated to June 2018. After rigorous review, eligible randomized controlled trials (RCTs) were extracted and propensity score matching (PSM) analysis was conducted. To analyze the summary odds ratios (ORs) of the endpoints of interest, we applied Meta-analysis Revman 5.3 software.ResultsThere were a total of 10 studies that met our inclusion criteria, of which the risk of bleeding rate (P = 0.43), MI (P = 0.14), and stroke (P = 0.70) had no association with significant differences between patients receiving ticagrelor or clopidogrel. Nonetheless, higher rate of dyspnea was observed in ticagrelor group (OR = 1.87, 95% CI: 1.70–2.05, P<0.00001 = .ConclusionsOur present findings suggest similar efficacy and safety profiles for clopidogrel and ticagrelor Ticagrelor should be considered as a valuable option to reduce the risk of bleeding, MI and stroke, whereas potentially increases the incidence of dyspnea. Given the metabolic process, ticagrelor may be a valid and even more potent antiplatelet drug than clopidogrel, as an alternative strategy in treating patients with clopidogrel intolerance or resistance.

Switching from ticagrelor to clopidogrel in patients with ST-segment elevation myocardial infarction undergoing successful percutaneous coronary intervention in real-world China: Occurrences, reasons, and long-term clinical outcomes.

Although switching between ticagrelor and clopidogrel is common in clinical practice, the efficacy and safety of this de-escalation remain controversial. We assessed the occurrences, reasons, and outcomes of switching from ticagrelor to clopidogrel in patients with ST-segment elevation myocardial infarction (STEMI) undergoing successful primary percutaneous coronary intervention (PCI). A total of 653 patients with STEMI were randomly assigned to receive loading dose of ticagrelor or clopidogrel before PCI and then received maintenance dose, respectively, for 12 months follow-up. The primary outcome was major adverse cardiac events (MACE), including cardiovascular death, nonfatal myocardial infarction, and stroke. The secondary outcome included unexpected rehospitalization for angina, coronary revascularization, and stent thrombosis. The safety outcome was bleeding described by the Bleeding Academic Research Consortium (BARC) criteria. A total of 602 participants completed the study. The rate of switching from ticagrelor to clopidogrel was 48.6% and the main reason was financial burden. The rate of secondary ischemic events in the de-escalation group was higher than that in the ticagrelor group (15.1% vs 5.6%, P = 0.008), but lower than that in the clopidogrel group (15.1% vs 24.6%, P = 0.03), while there were no significant differences in MACE among the three groups (P = 0.16). De-escalation, ticagrelor, and clopidogrel did not cause significant differences in the rates of major bleeding among the three groups (BARC ≥ 2, P = 0.34). Switching from ticagrelor to clopidogrel is very common in patients with STEMI in China. De-escalation might be safe but associated with high risk of ischemic events as compared to ticagrelor.

Effects of switching ticagrelor to clopidogrel on cardiovascular outcomes in patients with acute coronary syndrome

Present study was to evaluate whether switching ticagrelor to clopidogrel would impact platelet reactivity and cardiovascular outcomes in acute coronary syndrome (ACS) patients after percutaneous coronary intervention (PCI).A total of 202 ACS patients after PCI were enrolled and prescribed ticagrelor. Before discharge, 138 (68%) patients were switched to clopidogrel. Peripheral blood was obtained before switching and at 48 hours after switching to measure platelet reactivity. Patients were followed for 30 days to evaluate cardiovascular events.Compared to ticagrelor group, patients in clopidogrel group were more likely to be male (69.6% vs 65.6%), smokers (34.1% vs 31.3%) and had higher prevalence of hypertension (75.4% vs 71.9%). The frequency of right coronary artery lesion was significantly higher in ticagrelor group (34.4% vs 30.4%). There were no significant differences in baseline platelet reactivity (37.6 ± 5.2% vs 38.4 ± 4.9%). Forty-eight hours after switching to clopidogrel, platelet reactivity in clopidogrel group was significantly higher (46.3 ± 5.6% vs 38.1 ± 5.0%, P <.05). Patients in clopidogrel group had significantly higher incidence of cardiovascular events (3.6% vs 1.6%, P <.05). However, after further adjusted for platelet reactivity at 48 hours of switching, clopidogrel switching was not significantly associated with composite outcomes, with hazard ratio 1.08 (95% confidence interval 0.98–1.21, P = .063), indicating that platelet reactivity was a critical mediator between antiplatelet drug switching and cardiovascular outcomes.ACS patients after PCI treatment, early switching ticagrelor to clopidogrel results in increased platelet reactivity and higher incidence of short-term cardiovascular events.

Antiplatelet effects of ticagrelor versus clopidogrel after coronary artery bypass graft surgery: A single-center randomized controlled trial

ObjectiveThe study objective was to compare the onset of platelet inhibition (inhibition of platelet aggregation) between ticagrelor 90 mg twice per day and clopidogrel 75 mg once per day in patients receiving coronary artery bypass grafting. MethodsIn a single-center, randomized, open-label study, 140 patients receiving coronary artery bypass grafting were randomly assigned to the aspirin + ticagrelor group or the aspirin + clopidogrel group in a 1:1 ratio. Participants in the aspirin + ticagrelor group took aspirin 100 mg once per day and ticagrelor 90 mg twice per day. Participants in the aspirin + clopidogrel group took aspirin 100 mg once per day and clopidogrel 75 mg once per day. Platelet function was determined before study treatment (0 hours); at 2 hours, 8 hours, 24 hours, and 72 hours after medication; and during follow-up at 30 days after surgery. ResultsInhibition of platelet aggregation at 2 hours after the first drug administration was greater for the aspirin + ticagrelor group than for the aspirin + clopidogrel group (34.2% [interquartile range, 9.1-66.0] vs 5.3% [interquartile range, −14.3-22.0], P < .001) and at all times in the study period (P < .001). More patients reached inhibition of platelet aggregation maximum within 24 hours in the aspirin + ticagrelor group than in the aspirin + clopidogrel group (52.9% vs 27.5%, P = .006). The average inhibition of platelet aggregation maximum from 2 to 24 hours was still greater in the aspirin + ticagrelor group than in the aspirin + clopidogrel group (72.3% ± 15.4% vs 49.2% ± 46.8%, P < .001). There were no differences in terms of bleeding or major adverse cardiac events between the 2 groups. ConclusionsIn patients receiving coronary artery bypass grafting, the onset of action was faster and the peak inhibition of platelet aggregation was higher with ticagrelor than with clopidogrel.

Choosing between ticagrelor and clopidogrel following percutaneous coronary intervention: A systematic review and Meta-Analysis (2007-2017).

Background:Limitations have been observed with the use of clopidogrel following percutaneous coronary intervention (PCI) indicating the urgent need of a more potent anti-platelet agent. We aimed to compare the efficacy and safety of ticagrelor versus clopidogrel following PCI.Methods:Online databases were searched for relevant studies (published between the years 2007 and 2017) comparing ticagrelor versus clopidogrel following coronary stenting. Primary outcomes assessed efficacy whereas secondary outcomes assessed safety. Odds ratios (OR) with 95% confidence intervals (CIs) based on a random effect model were calculated and the analysis was carried out by the RevMan 5.3 software.Results:A total number of 25,632 patients with acute coronary syndrome (ACS) [12,992 patients with ST segment elevation myocardial infarction (STEMI) and 14,215 patients with non-ST segment elevation myocardial infarction (NSTEMI)] were included in this analysis, of whom 23,714 patients were revascularized by PCI. Results of this analysis did not show any significant difference in all-cause mortality, major adverse cardiac events (MACEs), myocardial infarction, stroke and stent thrombosis observed between ticagrelor and clopidogrel with (OR: 0.83, 95% CI: 0.67–1.03; P = .09), (OR: 0.64, 95% CI: 0.41–1.01; P = .06), (OR: 0.77, 95% CI: 0.57–1.03; P = .08), (OR: 0.85, 95% CI: 0.57–1.26; P = .42) and (OR: 0.70, 95% CI: 0.47–1.05; P =.09).However, ticagrelor was associated with a significantly higher minor and major bleeding with (OR: 1.57, 95% CI: 1.30–1.89; P = .00001) and (OR: 1.52, 95% CI: 1.01–2.29; P = 0.04) respectively. Dyspnea was also significantly higher in the ticagrelor group (OR: 2.64, 95% CI: 1.87–3.72; P = .00001).Conclusion:Ticagrelor and clopidogrel were comparable in terms of efficacy in these patients with ACS. However, the safety outcomes of ticagrelor should further be investigated.

Prasugrel or ticagrelor in patients with acute coronary syndrome and diabetes: a propensity matched substudy of RENAMI.

The safety and efficacy of prasugrel and ticagrelor in patients with diabetes mellitus presenting with acute coronary syndrome and treated with percutaneous coronary intervention remain to be assessed. All diabetes patients admitted for acute coronary syndrome and enrolled in the REgistry of New Antiplatelets in patients with Myocardial Infarction (RENAMI) were compared before and after propensity score matching. Net adverse cardiovascular events (composite of death, stroke, myocardial infarction and BARC 3-5 bleedings) and major adverse cardiovascular events (composite of death, stroke and myocardial infarction) were the co-primary endpoints. Single components of primary endpoints were secondary endpoints. Among 4424 patients enrolled in RENAMI, 462 and 862 diabetes patients treated with prasugrel and ticagrelor, respectively, were considered. After propensity score matching, 386 patients from each group were selected. At 19±5 months, major adverse cardiovascular events and net adverse cardiovascular events were similar in the prasugrel and ticagrelor groups (5.4% vs. 3.4%, P=0.16 and 6.7% vs. 4.1%, P=0.11, respectively). Ticagrelor was associated with a lower risk of death and BARC 2-5 bleeding when compared to prasugrel (2.8% vs. 0.8%, P=0.031 and 6.0% vs. 2.6%, P=0.02, respectively) and a clear but not significant trend for a reduction of BARC 3-5 bleeding (2.3% vs. 0.8%, P=0.08). There were no significant differences in myocardial infarction recurrence and stent thrombosis. Diabetes patients admitted for acute coronary syndrome seem to benefit equally in terms of major adverse cardiovascular events from ticagrelor or prasugrel use. Ticagrelor was associated with a significant reduction in all-cause death and bleedings, without differences in recurrent ischaemic events, which should be confirmed in dedicated randomised controlled trials.

Effects of different doses of ticagrelor on platelet aggregation and endothelial function in diabetic patients with stable coronary artery disease

We performed this study to observe the effects of different doses of ticagrelor and standard-dose clopidogrel on platelet reactivity and endothelial function in diabetic patients with stable coronary artery disease (CAD). Sixty type 2 diabetic patients were assigned to one-quarter standard-dose ticagrelor, half standard-dose ticagrelor, standard-dose ticagrelor and standard-dose clopidogrel groups. Light transmission aggregometry (LTA) and VerifyNow assay were used to measure platelet function. Endothelial function was assessed by measurement of flow-mediated vasodilation (FMD) and plasma von Willebrand factor (VWF) levels were detected. Enzyme-linked immunosorbent assay (ELISA) examined the Interleukin-8(IL-8) and IL-10. The results suggested that the one-quarter dose (34.0%± 14.7%), half-dose (26.9%± 11.6%) and standard-dose (17.3%± 10.3%) ticagrelor showed lower platelet aggregation rate than clopidogrel (52.8%± 18.3%; P ＜0.0001). PRU values in three ticagrelor groups were lower than that in clopidogrel group (102 (76–184)；75 (33–88)；38 (11–52) versus 194 (138–271) and；P ＜0.0001). FMD levels were higher in ticagrelor groups compared with baseline levels while lower in clopidogrel group after treatment. However, no significant differences were found in the percentage increase in the FMD between ticagrelor groups and clopidogrel group. The levels of VWF after treatment were lower than the baseline levels, but there was no statistically significant difference between ticagrelor group and clopidogrel group after treatment. The concentration of IL-8 and IL-10 were decreased in patients with half and standard-dose ticagrelor group. In conclusion, one-quarter standard-dose ticagrelor produced similar inhibitory effects on platelet aggregation as standard-dose clopidogrel in diabetic patients with stable CAD. The half standard-dose ticagrelor had a similar inhibitory effect on platelet inhibition as standard-dose ticagrelor, which was stronger than that of clopidogrel. Moreover, the half-dose ticagrelor had equal protection of endothelial function and inhibition of inflammatory factor as standard-dose ticagrelor.

Ticagrelor and thrombolysis in myocardial infarction: what does the TREAT study change?

Primary percutaneous intervention (PCI) is a preferable reperfusion method in patients with STEMI. If on-time PCI is not possible, pharmacoinvasive approach is recommended that includes urgent systemic thrombolysis. Regardless the broad usage of ticagrelor in MI patients, its safety in combination with thrombolysis (first 24 hours from STEMI onset) before the year 2018 was unknown. In the TREAT study the patients 18-75 year old with STEMI (symptom onset within 24 hours), received thrombolytic drug, were randomized to ticagrelor or clopidogrel group. In 30 days from randomization it was shown that hemorrhagic safety of ticagrelor, at the level of major bleedings, was non-inferior than of clopidogrel. Therefore the TREAT study results, together with PLATO, make it to widen the indications for ticagrelor (and shift from clopidogrel) within first 24 hours of MI onset in patients received thrombolysis as a method of primary reperfusion.

Utility of GRACE and ACUITY-HORIZONS risk scores to guide dual antiplatelet therapy in Korean patients with acute myocardial infarction undergoing drug-eluting stenting

BackgroundDual antiplatelet therapy (DAPT) is recommended in patients receiving drug-eluting stents (DES). However, bleeding risk should be weighed against ischemic risk. Utility of GRACE risk score and ACUITY-HORIZONS bleeding risk score was assessed in patients with acute myocardial infarction (MI) according to use of P2Y12 blocker. MethodsFrom the Korea Acute Myocardial Infarction Registry-National Institute of Health database, 7791 patients with acute MI receiving DES were divided into ticagrelor (n=1554) and clopidogrel (n=6237) groups. Propensity-matched 12-month mortality and bleeding event rates were compared according to GRACE and ACUITY-HORIZONS scores. Patients who received thrombolysis, prasugrel or anticoagulants, or who discontinued or switched DAPT were excluded. ResultsIn all patients, high-risk patients more often received clopidogrel. After propensity score matching (n=1553 in each group), 12-month mortality was not different, but TIMI major bleeding rate was higher with ticagrelor (2.8% vs. 1.4%, p=0.007). On subgroup analysis, 12-month mortality was lower with ticagrelor in patients with high (>140) compared to low-to-moderate risk GRACE score (5.1% vs. 7.9%, p=0.04). When combined with ACUITY-HORIZONS bleeding score, 12-month mortality was lower with ticagrelor in patients with high GRACE score but without very high (≥20) ACUITY-HORIZONS score (2.4% vs. 5.3%, p=0.03). ConclusionsIn patients with acute MI receiving DES, GRACE and ACUITY-HORIZONS scores may help guide DAPT. In patients with high GRACE score, a more potent P2Y12 blocker may be considered, particularly in the subset not at very high risk of bleeding.

Impact of Baseline Bleeding Risk on Efficacy and Safety of Ticagrelor versus Clopidogrel in Chinese Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

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.