Ticagrelor Loading Dose Research Articles

TICA-CLOP STUDY: Ticagrelor Versus Clopidogrel in Acute Moderate and Moderate-to-Severe Ischemic Stroke, a Randomized Controlled Multi-Center Trial.

Many studies evaluated the efficacy and safety of ticagrelor versus clopidogrel in patients with ischemic stroke; none of these trials included North African participants, and all of these trials comprised only participants who experienced transient ischemic attack (TIA) or minor stroke. We compared the efficacy and safety of ticagrelor versus clopidogrel in patients with first-ever noncardioembolic moderate or moderate-to-severe ischemic stroke. Our trial involved 900 first-ever noncardioembolic patients with acute ischemic stroke (AIS) who randomly received either loading and maintenance doses of ticagrelor or clopidogrel within the first 24 h of stroke onset. We involved 900 patients in the intention-to-treat analysis. A total of 39 (8.7%) patients in ticagrelor arm and 62 (13.8%) in clopidogrel arm experienced a new stroke [hazard ratio (HR) 0.46; 95% confidence interval (CI) 0.34-0.83; P value = 0.006]. A total of 57 (12.7%) patients in ticagrelor group and 80 (17.8%) patients in clopidogrel group experienced composite of new stroke, myocardial infarction (MI), or death due to vascular insults (HR 0.51; 95% CI 0.43-0.82; P value = 0.004). Participants who received ticagrelor experienced less frequent unfavorable outcomes. We found no significant variation between our study's two arms concerning the hemorrhagic and non-hemorrhagic complications. Patients with noncardioembolic moderate or moderate-to-severe ischemic stroke who received ticagrelor within the first 24 h after ischemic stroke had better clinical outcomes based on recurrent stroke rates and unfavorable modified Rankin Scale (mRS) rates compared with those who received clopidogrel. There were no significant variations between ticagrelor and clopidogrel regarding hemorrhagic and non-hemorrhagic complications. ClinicalTrials.gov identifier number NCT05553613.

Cangrelor use in ticagrelor-loaded ST-elevation myocardial infarction patients with high residual platelet reactivity: a randomized controlled trial

Abstract Background Despite the use of potent P2Y12 inhibitor, many patients still present with high platelet reactivity (HPR) at the time of primary percutaneous coronary intervention (PCI). HPR is associated with impaired myocardial reperfusion and the subsequent poor outcome. Purpose We sought to determine the impact of Cangrelor -a rapid and potent intravenous P2Y12 inhibitor- on myocardial reperfusion in patients with HPR admitted for primary PCI in a randomized trial. Methods Patients pre-treated with ticagrelor and aspirin with residual HPR (baseline platelet reactivity unit (PRU) > 208) were randomly assigned in a 1:1 ratio to receive cangrelor (experimental group) or not (control group) just before PCI. The primary endpoint was optimal myocardial reperfusion defined as a final myocardial blush grade (MBG) 3 assessed by an independent core laboratory. Results After screening of 128 patients, a total of 60 patients were with HPR were enrolled and randomized. The ticagrelor loading dose to PRU measurement times were 83 ± 32 and 90 ± 47 minutes in the experimental and control groups, respectively. Baseline PRU were 245 ± 30 and 252 ± 35 in the experimental and standard group, respectively. A final MBG 3 was observed in 21/30 (55%) and 17/30 (45%) the experimental and standard groups (p=0.29). A final TIMI flow grade 3 was observed in 30/30 (100%) and 27/30 (90%) the experimental and standard groups (p=0.24). Peak troponin levels after PCI were 51381 ± 50047 and 51078 ± 63960 ng/L (p=0.98) in the experimental and standard group, respectively. At the end of the PCI, control PRU were 36 ± 57 and 198 ± 107 (p<0.0001) in the experimental and standard group, respectively. One patient of the experimental group presented an in-hospital major bleeding (BARC 3). Conclusion In ticagrelor-loaded STEMI patients with residual HPR at the time of PCI, cangrelor use was associated with a more effective platelet inhibition but failed to significantly improve the rates of optimal final myocardial blush grades.

Temporal Effect of CYP3A4/5 Induction on Ticagrelor's Pharmacodynamic Effects: A Case Series.

Ticagrelor is contraindicated in combination with cytochrome P450 3A4 and 3A5 enzyme (CYP3A4/5) inducers due to increased clearance, causing diminished antiplatelet effects. The emergent nature of acute coronary syndromes (ACS) may preclude scrutinization of home medications before P2Y12 inhibitor administration. The purpose of this case series is to establish the temporal impact of CYP3A4/5 enzyme induction on ticagrelor's pharmacodynamic effect by utilizing VerifyNow platelet aggregation studies. This was a retrospective case series of three patients who were taking a CYP3A4/5-inducing medication and loaded with ticagrelor for ACS. The duration of ticagrelor's antiplatelet effect was dramatically shortened in the presence of background CYP3A4/5 induction. The offset of antiplatelet effect, defined by platelet reactivity units (PRU), was 10-24hours in the presence of CYP3A4/5 enzyme induction compared to the anticipated 36-48 hours. This was consistent across CYP3A4/5-inducing medications including carbamazepine, phenobarbital, and phenytoin. This study demonstrates rapid return of platelet function after a ticagrelor loading dose in the presence of CYP3A4/5-inducing medications. Monitoring of PRU every 6-12hours with subsequent loading with clopidogrel or prasugrel should be considered. Larger scale studies are warranted to confirm these results.

Ticagrelor versus Clopidogrel in Prevention of No Reflow after 1ry PCI in Diabetic Patients with STEMI

Abstract Background Adequacy of coronary flow can be judged upon using several methods like TIMI Grade and myocardial blush grade. No-reflow phenomenon, defined as incomplete reperfusion at the microvascular level despite adequate patency of the occluded artery, remains an important limitation of primary percutaneous intervention in STEMI patients nowadays. We aim in this study to investigate the relationship between the antiplatelet loading dose whether to be Ticagrelor or Clopidogrel and post intervention coronary flow, bleeding risk in these patients. Aim of the Work To compare between the effects of preoperative loading dose of Ticagrelor and clopidogrel in Diabetic STEMI patients undergoing primary percutaneous coronary intervention regarding prevention of no reflow, Instent thrombosis and short term bleeding risk. Myocardial reperfusion was judged upon using TIMI Grade and myocardial blush grade. Patients and Methods a single center prospective randomized controlled trial based at the coronary care units in Ain shams university hospitals. The study included Three hundred Diabetic patients presenting to Ain shams university hospitals diagnosed with STEMI in the ER fulfilling the inclusion criteria were randomized to receive Ticagrelor (150 patients) or receiving clopidogrel (150 patients) Results As regard TIMI flow there was statistically highly significant highly significant difference between two studied groups with P value 0.000 where in group A 64 % of patients developed TIMI III flow, 22.7 % with TIMI II flow, 12.7% with TIMI I and 0.7% with TIMI 0 While in group B 86% of patients developed TIMI III flow, 9.3% of them developed TIMI II, 3.3 % developed TIMI I flow and 1.3 % developed TIMI 0. As regard MBG there was statistically highly significant difference between two groups with P value 0.00 where in group A where percentage of patients with MBG grades 0,1,2 and 3 were 4%, 16 %,18 % and 62 % respectively while in group B percentage of patients with MBG grades 0,1,2 and 3 were 1.3 %, 3.3 %, 9.3 % and 86 % respectively. As regard echo EF, there was statistically significant difference between two groups with P value 0.036 where mean EF in patients with group A was 40.50 ± 7.93 while the mean EF in patients with group B was 42.55 ± 8.88 . Conclusion Ticagrelor loading before primary PCI resulted in improved post-procedural TIMI flow. It also increased the post-procedural MBG. This resulted in a significant increase in the number of patients having more post-procedural Ejection fraction as measured by modified Simpson’s method. However, it did not decrease incidence of in-hospital MACE. Also there was no significant increase in risk of major nor minor bleeding in both young and elderly patients.

Ticagrelor versus Clopidogrel in Prevention of No Reflow after 1ry PCI in Diabetic Patients with STEMI

Abstract Background Adequacy of coronary flow can be judged upon using several methods like TIMI Grade and myocardial blush grade. No-reflow phenomenon, defined as incomplete reperfusion at the microvascular level despite adequate patency of the occluded artery, remains an important limitation of primary percutaneous intervention in STEMI patients nowadays. We aim in this study to investigate the relationship between the antiplatelet loading dose whether to be Ticagrelor or Clopidogrel and post intervention coronary flow, bleeding risk in these patients. Aim of the Work To compare between the effects of preoperative loading dose of Ticagrelor and clopidogrel in Diabetic STEMI patients undergoing primary percutaneous coronary intervention regarding prevention of no reflow, Instent thrombosis and short term bleeding risk. Myocardial reperfusion was judged upon using TIMI Grade and myocardial blush grade. Patients and Methods a single center prospective randomized controlled trial based at the coronary care units in Ain shams university hospitals. The study included Three hundred Diabetic patients presenting to Ain shams university hospitals diagnosed with STEMI in the ER fulfilling the inclusion criteria were randomized to receive Ticagrelor (150 patients) or receiving clopidogrel (150 patients) Results As regard TIMI flow there was statistically highly significant highly significant difference between two studied groups with P value 0.000 where in group A 64 % of patients developed TIMI III flow, 22.7 % with TIMI II flow, 12.7% with TIMI I and 0.7% with TIMI 0 While in group B 86% of patients developed TIMI III flow, 9.3% of them developed TIMI II, 3.3 % developed TIMI I flow and 1.3 % developed TIMI 0. As regard MBG there was statistically highly significant difference between two groups with P value 0.00 where in group A where percentage of patients with MBG grades 0,1,2 and 3 were 4%, 16 %,18 % and 62 % respectively while in group B percentage of patients with MBG grades 0,1,2 and 3 were 1.3 %, 3.3 %, 9.3 % and 86 % respectively. As regard echo EF, there was statistically significant difference between two groups with P value 0.036 where mean EF in patients with group A was 40.50 ± 7.93 while the mean EF in patients with group B was 42.55 ± 8.88 . Conclusion Ticagrelor loading before primary PCI resulted in improved post-procedural TIMI flow. It also increased the post-procedural MBG. This resulted in a significant increase in the number of patients having more post-procedural Ejection fraction as measured by modified Simpson’s method. However, it did not decrease incidence of in-hospital MACE. Also there was no significant increase in risk of major nor minor bleeding in both young and elderly patients.

Safety of Ticagrelor in Post – PCI (Percutaneous Coronary Intervention) Patients at a Tertiary Care Hospital

Background: Coronary artery disease (CAD) remains a leading cause of mortality and morbidity worldwide, despite advances in diagnosis and management. In acute coronary syndrome (ACS) patients, the combination of aspirin and clopidogrel is the standard therapy against recurrent cardiovascular events. However, clopidogrel has a delayed onset and variability in platelet response. Objective: To examine the safety profile of ticagrelor in post-PCI patients at a tertiary care hospital. Methods: This descriptive study was conducted at the Department of Cardiology, North-West General Hospital, Peshawar, from 1st April 2023 to 31st March 2024. Patients aged 30 to 80 years who underwent PCI and were started on ticagrelor were included. Baseline data such as age, gender, BMI, and cardiovascular risk factors (smoking, hypertension, diabetes mellitus) were collected. Patients received a loading dose of ticagrelor 180 mg orally followed by 90 mg twice daily. Adverse effects, including bleeding, dyspnea, and arrhythmias, were evaluated within 24 hours and at one-month follow-up. Data were analyzed using IBM SPSS version 25, with categorical variables presented as frequencies and percentages, and quantitative variables as means and standard deviations. Results: A total of 137 post-PCI patients participated in the study, with a mean age of 58 ± 10 years. The cohort included 85 men (62%) and 52 women (38%). The average BMI was 27.5 ± 3.5 kg/m². Risk factors included smoking (30%), hypertension (45%), and diabetes mellitus (25%). Within 24 hours, minor bleeding occurred in 10 patients (7.3%), dyspnea in 15 patients (10.9%), and arrhythmias in 4 patients (2.9%). At the one-month follow-up, minor bleeding was observed in 12 patients (8.8%), major bleeding in 2 patients (1.5%), dyspnea in 18 patients (13.1%), and arrhythmias in 5 patients (3.6%). Conclusion: The study supports the safety of ticagrelor as an antiplatelet therapy in post-PCI patients, with manageable adverse effects. However, careful monitoring for complications such as bleeding, dyspnea, and arrhythmias is recommended.

Differential impact of fentanyl and morphine doses on ticagrelor-induced platelet inhibition in ST-segment elevation myocardial infarction: a subgroup analysis from the PERSEUS randomized trial.

Among patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI), intravenous fentanyl does not enhance ticagrelor-induced platelet inhibition within 2 h compared to morphine. The impact of the total dose of fentanyl and morphine received on ticagrelor pharmacodynamic and pharmacokinetic responses in patients with STEMI remains however undetermined. We performed a post-hoc subanalysis of the prospective, open-label, single-center, randomized PERSEUS trial (NCT02531165) that compared treatment with intravenous fentanyl vs. morphine among symptomatic patients with STEMI treated with primary PCI after ticagrelor pretreatment. Patients from the same population as PERSEUS were further stratified according to the total dose of intravenous opioids received. The primary outcome was platelet reactivity using P2Y12 reaction units (PRU) at 2 h following administration of a loading dose (LD) of ticagrelor. Secondary outcomes were platelet reactivity and peak plasma levels of ticagrelor and AR-C124910XX, its active metabolite, at up to 12 h after ticagrelor LD administration. Generalized linear models for repeated measures were built to determine the relationship between raw and weight-weighted doses of fentanyl and morphine. 38 patients with STEMI were included between December 18, 2015, and June 22, 2017. Baseline clinical and procedural characteristics were similar between low- and high-dose opioid subgroups. At 2 h, there was a significant correlation between PRU and both raw [regression coefficient (B), 0.51; 95% confidence interval (CI), 0.02-0.99; p = 0.043] and weight-weighted (B, 0.54; 95% CI, 0.49-0.59; p < 0.001) doses of fentanyl, but not morphine. Median PRU at 2 h was significantly lower in patients receiving low, as compared to high, doses of fentanyl [147; interquartile range (IQR), 63-202; vs. 255; IQR, 183-274; p = 0.028], whereas no significant difference was found in those receiving morphine (217; IQR, 165-266; vs. 237; IQR, 165-269; p = 0.09). At 2 h, weight-weighted doses of fentanyl and morphine were significantly correlated to plasma levels of ticagrelor and AR-C124910XX. In symptomatic patients with STEMI who underwent primary PCI after ticagrelor pretreatment and who received intravenous opioids, we found a dose-dependent relationship between the administration of intravenous fentanyl, but not morphine, and ticagrelor-induced platelet inhibition.

Impact of Preloading Strategy With Ticagrelor on Periprocedural Myocardial Injury in Patients With Non-ST Elevation Myocardial Infarction Undergoing Early Invasive Strategy.

Pretreatment with an oral P2Y12 receptor blocker (before coronary angiography) versus treatment in the catheterization laboratory has been a matter of debate in patients presenting with non-ST segment elevation myocardial infarction (NSTEMI). The primary aim of this study was to assess the impact of an immediate preloading strategy with ticagrelor on periprocedural myocardial injury in patients with NSTEMI treated with an early invasive strategy. NSTEMI patients who underwent coronary angiography and subsequent percutaneous coronary intervention (PCI) within 24 hours after hospital admission were divided into 2 groups: the first group (pretreatment group) included patients who received ticagrelor pretreatment as soon as possible after admission and the second group (no pretreatment group) included patients who received a loading dose of ticagrelor after coronary angiography. The pretreatment group included 232 patients, and the no pretreatment group included 87 patients. Male patients represented the majority of the patients. The 2 groups were similar in baseline characteristics, except for a greater incidence of hypertension ( P = 0.014) and higher hemoglobin levels ( P = 0.01) in the pretreatment group in comparison with the no pretreatment group. Patients in the ticagrelor pretreatment group had less myocardial injury until coronary angiography based on troponin measurements collected at 12 hours after admission ( P = 0.025). Patients in the ticagrelor pretreatment group also had fewer periprocedural myocardial injuries based on troponin measurements taken between 12 and 24 hours after the PCI ( P = 0.026 and P = 0.022, respectively). Our findings suggested that ticagrelor pretreatment reduces periprocedural myocardial injury in NSTEMI patients who underwent PCI within 24 hours after admission.

Interactions between aspirin and ticagrelor during experimental human endotoxaemia

Abstract Introduction Dual antiplatelet therapy (DAPT) with aspirin 75-100mg once daily (OD) and the P2Y12 inhibitor ticagrelor is a standard treatment for acute coronary syndromes. De-escalating DAPT to ticagrelor monotherapy reduces bleeding risk yet appears to have minimal ischaemic penalty in most groups. The reason for this is unclear. P2Y12 inhibition can inhibit inflammatory processes relevant to atherothrombosis but aspirin may hypothetically counter these via platelet PGE2 inhibition. We studied the regimen-dependent effects of aspirin +/- ticagrelor in a human model of endotoxaemia. Endotoxin activates toll-like receptor 4, a key damage receptor in atherogenesis. Methods 72 healthy volunteers were randomised to receive either no aspirin or aspirin 20mg twice daily (BD), 75mg OD or 300mg OD for 10 days +/- a loading dose of ticagrelor on the last day prior to receiving intravenous endotoxin administration (2ng/kg). Blood was collected at 9 timepoints from 1h pre to 6h post endotoxin. Key cytokines and prostanoids in the blood/urine were measured by ELISA, platelet function by light transmittance aggregometry and platelet-leukocyte interaction by flow cytometry. Bleeding time was measured pre and 3h post endotoxin. After &amp;gt;5 weeks, in a 2nd period they received the same dose of aspirin as the 1st but received ticagrelor if they had not already, and vice versa, undergoing a 2nd endotoxin challenge at the end of the period. The primary endpoint was plasma tumour necrosis factor (TNF)-α. Results 72 participants were randomised (median 22.5yrs [range 18-59], 6F:66M). A total of 128 endotoxin challenges were performed. Endotoxaemia was associated with flu-like symptoms, pyrexia, tachycardia and relative hypotension but was safe. In those not receiving aspirin, plasma TNF-α was significantly lower when receiving ticagrelor vs. no ticagrelor, but in those receiving any dose of aspirin the significant effect of ticagrelor was abolished (Fig 1). All doses of aspirin fully suppressed arachidonic acid-induced PA with or without ticagrelor despite the thromboinflammatory stimulus of endotoxaemia (Fig 2A), and significantly augmented the inhibitory effect of ticagrelor on collagen-induced PA (2B). Aspirin 75mg OD and 300mg OD, but not 20mg BD, significantly prolonged bleeding time from baseline (2C). Ticagrelor significantly prolonged bleeding time in combination with any dose of aspirin or no aspirin. Aspirin dose-dependently inhibited PGE2 release. Conclusions All doses of aspirin tested prevented the ability of ticagrelor to significantly inhibit cytokine release during experimental endotoxaemia. Aspirin 20mg BD may offer improved bleeding risk with maintained antiplatelet effect compared to standard regimens. Where ticagrelor monotherapy is an option, dropping aspirin may allow ticagrelor to exert greater beneficial effect on inflammatory pathways relevant to atherothrombosis, potentially reducing ischaemic risk whilst also reducing bleeding risk.Figure 1Figure 2

Ticagrelor or Clopidogrel to reduce ischemic events after Percutaneous Coronary Intervention in chronic coronary syndrome in clopidogrel naive patient: the ALPHEUS Naive sub-study

Abstract Background The ALPHEUS trial showed a similar rate of type 4 myocardial infarction (MI) or major myocardial injury in elective PCI treated by clopidogrel or ticagrelor. Whether clopidogrel therapy at baseline might have affected these results is unknown. Purpose We evaluated the impact of ticagrelor versus clopidogrel loading dose in clopidogrel naïve patients as compared to patients already treated by clopidogrel in this pre-specified analysis. Methods We divided 1882 randomized patients with complete data on baseline clopidogrel into 2 groups according to presence of clopidogrel therapy &amp;gt; 7 days (long term clopidogrel = Clopi+) or its absence (clopidogrel naïve = Clopi-). The primary endpoint was the rate of PCI-related MI and myocardial injury as defined by the 3rd and 4th universal definition of MI evaluated within 48 h of PCI (or hospital discharge if earlier) and major and minor bleeding. Angiographic complications evaluated by the core laboratory (coronary slow flow, no flow, dissection, and thrombus) were also compared. Event rates were compared and the interaction of the allocated treatment in the randomized groups was evaluated. Results 1077 patients (57.2%) were Clopi- and 805 patients were Clopi+. Patients in the Clopi- group were less frequently male (78.0% vs 81.9%, p= 0.04) with less often dyslipidemia (57.8% vs 65.6%, p&amp;lt; 0.001) and peripheral artery disease (11.1% vs 14.4%, p= 0.03) and had less acute coronary syndrome in the last 12 months (3.4% vs 8.7% p= 0.002). The primary endpoint was less frequent in Clopi- as compared to tClopi+ (32.8% vs 40%, OR =0.73, CI [0.60-0.88], p=0.001). This difference was mainly driven by a lower rate of major myocardial injury 24.% vs 31.6% while the rate of type 4a MI and stent thrombosis were similar (8.4% vs 8.2%) and (0.4% vs 0.2%) respectively. Angiographic complication rate was similar in the Clopi- and the Clopi+ groups (14.6% vs 12.9%) OR=1.15 CI [0.88-1.5], p=0.31. Major bleedings were infrequent in the trial. (0.1% vs 0%), and minor bleeding did not differ significantly between Clopi- and Clopi+ patients (7.0% vs 4.8% OR=1.47, CI [0.99-2.19], p=0.06). At 30 days, no difference in any outcomes were reported between the two groups. Alike for the main trial results, in the Clopi- group, ticagrelor was not superior to clopidogrel in reducing periprocedural myocardial necrosis, p for interaction was 0.83. Conclusions Periprocedural MI and procedural angiographic complications were less frequent in clopidogrel naïve patients as compared to patients already on clopidogrel therapy, and not influenced by the potency of the P2Y12 inhibitor’s loading dose prior to PCI. These results globally suggest no benefit of a long term clopidogrel pretreatment in patients receiving a loading dose of P2Y12 in the 24 hours prior to PCI in chronic coronary syndrome undergoing elective PCI and support the use of clopidogrel as the standard of care.

Comparison of ticagrelor and prasugrel just before PCI in NSTE acute coronary syndromes, LIKE-ACCOAST analysis

Abstract Background Recommendations for the preference of prasugrel over ticagrelor just before PCI in NSTE ACS are based on limited and controversial evidence. Furthermore, prasugrel can’t be used in patients after a stroke/TIA, and the risk of bleeding in older and low-weight patients annuls its benefit. Purpose We aimed to add to the current evidence comparing the benefit of prasugrel and ticagrelor just before PCI (without pretreatment) in NSTE ACS patients. Methods The prasugrel population comprised the ACCOAST study non-pretreatment arm undergoing PCI (N 1372) (ref 1). The ticagrelor study population was selected from the long-term all-comers National Registry of Cardiovascular Surgery and Interventions: Module of Cardiovascular interventions of Institute of Health Information and Statistics of the Czech Republic (N 15126)who were 1) undergoing PCI for NSTE ACS, 2) received ticagrelor loading dose 180 mg just before the procedure, 3) fulfilled the inclusion and exclusion criteria of the ACCOAST trial (N 1370). The endpoint (identically to the ACCOAST primary EP) was a composite of cardiovascular death, myocardial infarction, stroke, urgent revascularization, or glycoprotein IIb/IIIa bailout seven days after PCI. The data were matched to the structure of published ACCOAST no pre-treatment group using R with maic package, which provides a generalized workflow for the generation of subject weights to be used in Matching-Adjusted Indirect Comparison (MAIC) (Ref 3,4). In MAIC, unbiased comparison between outcomes of two trials is facilitated by weighting the subject-level outcomes of one trial with weights derived such that the weighted aggregate measures of the prognostic or effect modifying variables are equal to those of the sample in the comparator trial. Results The study population characteristics are presented in Table. We did not find any difference in the efficacy endpoint at seven and 30 days after PCI between the groups treated with prasugrel and ticagrelor (Figure). Conclusion Prasugrel and ticagrelor given just before PCI for NSTE ACS are equally effective in reducing ischemic risk.Table.Efficacy endpoint occurence.

Platelet inhibition with orodispersible ticagrelor in acute coronary syndromes according to morphine use: the TASTER study final results.

To date, it is still unknown whether orodispersible tablet (ODT) ticagrelor might represent a suitable way to reach a proper antiaggregation in acute coronary syndrome (ACS) patients receiving morphine. Aim of the present study was to evaluate platelet inhibition with 180 mg ticagrelor loading dose (LD) administered as ODT compared with standard coated tablet ticagrelor formulation in ACS patients undergoing percutaneous coronary intervention (PCI) according to morphine use. One-hundred and 30 patients presenting with STEMI or very high-risk NSTE-ACS were randomly assigned to receive ODT or standard ticagrelor LD. Potential morphine-ticagrelor interaction was assessed by stratified randomization according to morphine use. Platelet reactivity was evaluated by Platelet Reactivity Units (PRU) VerifyNow™ฏ 1, 2, 4 and 6 hours after ticagrelor LD. The primary endpoint was residual platelet reactivity 1 hour after LD across the two ticagrelor formulation and according to morphine use. Safety endpoints were major bleedings and other in-hospital ticagrelor administration-related adverse events. One hour after LD, PRU median value was higher in morphine-treated patients (N=32) as compared with patients not receiving morphine (N=98; PRU= 187 [70-217]) vs 73 [7-187]; p=0.012). In patients with morphine, 1-hour PRU values were similar between study groups (192 [114-236] vs 173 [16-215] in ODT and standard tablet ticagrelor, respectively). Similarly, in patients without morphine, 1-hour PRU values were not significantly different between study groups (69 [8-152] vs 110 [6 - 193] in ODT and standard tablet ticagrelor, respectively). Platelet reactivity appeared similar in the 2 study arms at 2, 4 and 6 hours after LD. No significant difference was observed among patients with or without morphine regarding in-hospital adverse events or drug side-effects, even if a reinfarction due to acute stent thrombosis was observed in a patient treated with morphine. There was no difference between ODT and standard ticagrelor tablets in terms of post-LD residual platelet reactivity, percentage of platelet inhibition or safety regardless to morphine use.

Effects of ticagrelor and prasugrel on coronary microcirculation in elective percutaneous coronary intervention

ObjectiveTo compare the effects of ticagrelor and prasugrel on absolute coronary blood flow (Q) and microvascular resistance (R) in patients with stable coronary artery disease (CAD) treated with elective percutaneous...

Impact of renal function on Ticagrelor-induced antiplatelet effects in coronary artery disease patients.

Chronic renal failure (CKD) is associated with the presence of increased platelet reactivity and lower clinical benefit of clopidogrel. Ticagrelor has a more favorable pharmacodynamic and pharmacokinetic profile compared to clopidogrel, which has translated into better clinical outcomes in patients with acute coronary syndrome (ACS). We conducted a prospective mechanistic cohort study in order to investigate the impact of renal failure on the pharmacokinetics and pharmacodynamics of ticagrelor in patients with acute ACS. Patients were divided into two groups based on their estimated renal clearances (eGFR≥60mL/min and eGFR<60mL/min). Platelet function was determined using the VerifyNow system at baseline, after the ticagrelor loading dose and at discharge. In addition, levels of ticagrelor and its active metabolite (AR-C124910XX) were determined in the first hour after loading dose. 48 patients were recruited (eGFR≥60mL/min: 35 and eGFR<60mL/min: 13). There were no significant differences between the groups in terms of platelet inhibition after the loading or after 7days of treatment (p=0.219). However, the levels of ticagrelor and its active metabolite were lower in subjects with normal renal function than in CKD, especially at 4 (p=0.02 and 0.04 respectively) and 6h of loading (p=0.042 and 0.08 respectively). No differences in platelet inhibition were observed after treatment with ticagrelor in patients with different renal function, although patients with renal impairment showed higher levels of ticagrelor and AR-C124910XX after 4h of the loading dose.

Single antiplatelet therapy directly after percutaneous coronary intervention in non-ST-segment elevation acute coronary syndrome patients: the OPTICA study.

Early P2Y12 inhibitor monotherapy has emerged as a promising alternative to 12 months of dual antiplatelet therapy following percutaneous coronary intervention (PCI). In this single-arm pilot study, we evaluated the feasibility and safety of ticagrelor or prasugrel monotherapy directly following PCI in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Patients received a loading dose of ticagrelor or prasugrel before undergoing platelet function testing and subsequent PCI using new-generation drug-eluting stents. The stent result was adjudicated with optical coherence tomography in the first 35 patients. Ticagrelor or prasugrel monotherapy was continued for 12 months. The primary ischaemic endpoint was the composite of all-cause mortality, myocardial infarction, definite or probable stent thrombosis or stroke within 6 months. The primary bleeding endpoint was Bleeding Academic Research Consortium type 2, 3 or 5 bleeding within 6 months. From March 2021 to March 2022, 125 patients were enrolled, of whom 75 ultimately met all in- and exclusion criteria (mean age 64.5 years, 29.3% women). Overall, 70 out of 75 (93.3%) patients were treated with ticagrelor or prasugrel monotherapy directly following PCI. The primary ischaemic endpoint occurred in 3 (4.0%) patients within 6 months. No cases of stent thrombosis or spontaneous myocardial infarction occurred. The primary bleeding endpoint occurred in 7 (9.3%) patients within 6 months. This study provides first-in-human evidence that P2Y12 inhibitor monotherapy directly following PCI for NSTE-ACS is feasible, without any overt safety concerns, and highlights the need for randomised controlled trials comparing direct P2Y12 inhibitor monotherapy with the current standard of care.

TIcagrelor in Rotational Atherectomy to Reduce TROPonin Enhancement: The TIRATROP Study, A Randomized Controlled Trial.

Because rotational atherectomy (RA) is associated with arterial trauma and platelet activation, patients treated with RA may benefit from more potent antiplatelet drugs. The aim of this trial was to assess the superiority of ticagrelor over clopidogrel in reducing post procedure troponin release. TIRATROP (TIcagrelor in Rotational Atherectomy to reduce TROPonin enhancement) is a multicenter double-blind randomized controlled trial that included 180 patients with severe calcified lesions requiring RA who received either clopidogrel (300 mg loading dose, then 75 mg/d) or ticagrelor (loading dose 180 mg then 90 mg twice daily). Blood samples were collected at the beginning (T0), and 6, 12, 18, 24 and 36 h after the procedure. Primary end point was troponin release within the first 24 h using area under the curve analysis (troponin level as a function of time). The mean age of patients was 76 ± 10 years, 35% had diabetes. RA was used to treat 1, 2 or 3 calcified lesions in 72%, 23% and 5% of patients, respectively. Troponin release within the first 24 h was similar in both the ticagrelor (adjusted mean ±SD of ln AUC 8.85 ± 0.33) and the clopidogrel (8.77 ± 0.34, p = 0.60) arms. Independent predictors for troponin enhancement were acute coronary syndrome presentation, renal failure, elevated C-Reactive protein and multiple lesions treated with RA. Troponin release did not differ among treatment arms. Our results suggest that greater platelet inhibition does not affect periprocedural myocardial necrosis in the setting of RA.

The use of ticagrelor versus clopidogrel in Malaysian patients with coronary artery disease undergoing percutaneous coronary intervention (PCI): Does the age tertile affect the platelet reactivity?

Abstract Funding Acknowledgements Type of funding sources: None. Background Previous studies have shown that the prevalence of cardiovascular diseases is related to the patient's age and gender differences, but the effect of age on platelet function remains controversial. Platelet function should be tested and its efficacy correlates with the age of patients undergoing percutaneous coronary intervention (PCI) using vasodilator-associated stimulated phosphoprotein (VASP). VASP is a gold standard to assess P2Y12 receptor inhibition among patients using ticagrelor or clopidogrel. Purpose We sought to compare the effect of ticagrelor versus clopidogrel on the platelet function of patients undergoing PCI and the correlation of age in this effect. Method This study was a prospective, randomized, parallel design, an open-label investigation conducted on Malaysian patients undergoing PCI. It included 84 patients (40 patients taking ticagrelor, and 44 patients taking clopidogrel). The induced platelet reactivity was assessed by measuring total whole blood at one standardized time point after 4 hours of loading dose of ticagrelor 180 mg or clopidogrel with 600 mg and by age tertiles. Result The study population consisted of 23 (57.5%) patients in Tertile 1 &amp;lt;60 years of age, 11 (27.5%) patients in Tertile 2 between 60-70 years of age and 6 (15.0%) patients in Tertile 3 &amp;gt;70 years of age. The number of patients who used ticagrelor was 17 (38.64%) in Tertile 1, 21 (47.73%) in Tertile 2, and 6 (13.64%) in Tertile 3 of those who used clopidogrel. The results of platelet reactivity index was high in the patients who used clopidogrel compared to the ticagrelor group, which were 52.3% and 2.5 %, P &amp;lt;0.001. This effect in the clopidogrel group included all age groups without exception and at different rates (52.9%, 52.4%, and 50%, P= 0.992), respectively, but this effect was numerical and not statistically significant. In contrast to the ticagrelor group, no numerical or significant effect was observed in all age groups (4.3%, 0.0%, and 0.0%, P= 0.259), respectively (Figure 1). In addition, the results of the current cross-sectional age classification study showed no statistical differences between the clopidogrel and ticagrelor groups based on non high platelet reactivity (NHPR) (P = 0.284, P = 0.270, P = 0.796 respectively) (Figure2). Conclusion Our study showed that age could not be considered a risk factor in the Malaysian population, as it did not significantly affect platelet aggregation in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI).

673 A CRACK AND A CLOT

Abstract A 74-year-old man with a history of ischaemic heart disease (multiple percutaneous coronary interventions (PCI)), broke his ankle. Therefore, he discontinued dual antiplatelet therapy (DAPT) -acetylsalicylic acid plus clopidogrel- and started enoxaparin sodium 4000 UI/day on medical advice. A few days later, he was admitted to the emergency department for refractory chest pain, vomit and syncope. Twelve-lead electrocardiogram (ECG) showed a sinus rhythm interrupted by frequent premature ventricular contractions in a pattern of trigeminy. The transthoracic echocardiogram revealed a mildly dilated LV with normal wall thickness and marked hypokinesis/ akinesis in apical, infero-lateral and antero-lateral walls, with a 33% ejection fraction. High sensitivity cardiac troponin was increased, and a second ECG showed a diffuse ST segment depression. The patient was loaded with aspirin and emergently taken to the cardiac catheterization lab. Coronary angiography showed a very late stent thrombosis of the left circumflex artery (LCx), with occlusion of the extreme distality of the second obtuse marginal artery and a 50-60% intrastent restenosis of the ostium-proximal tract of the left anterior descending artery (LAD). Given the non-obstructive nature of the thrombus, risk of peripheral embolization, TIMI flow grade 3 and improvement of symptoms, the decision was made to adopt a conservative strategy with loading dose of ticagrelor, heparin and tirofiban infusion. Besides, an optical coherence tomography (OCT) control was scheduled for the next day. OCT of the LCx revealed a well apposed and well expanded stent with a non-obstructive residual thrombus, nevertheless not visible on angiography. Thus, the tirofiban infusion was prolonged up to 48 hours. OCT of the LAD detected a fibro-calcific disease determining a significant restenosis of the distal left main (LM)-LAD ostium. OCT-guided provisional stenting with two drug eluting stents on LM-LAD-LCx was performed successfully. The patient was discharged home on acetylsalicylic acid (lifelong), ticagrelor (for 12 months) and enoxaparin sodium 4000 UI/day (according to specialist indication). DAPT is superior to anticoagulant therapy in preventing stent thrombosis in patients undergoing PCI, and a more informed inter-specialist communication is needed. Intracoronary imaging can help in the management of stent failure and in the guidance of complex PCI, allowing a patient-tailored treatment.

339 INTRAVENOUS CANGRELOR VERSUS ORAL TICAGRELOR IN PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION UNDERGOING PRIMARY PERCUTANEOUS CORONARY INTERVENTION: A PROPENSITY SCORE-MATCHED ANALYSIS

Abstract Background In patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), potent oral inhibitors of the adenosine diphosphate (ADP)–activated platelet P2Y12 receptor (i.e., prasugrel, ticagrelor) are recommended in addition to acetylsalicylic acid, given as a loading dose as soon as possible, and followed by a maintenance dose. However, the onset of action of oral P2Y12 inhibitors is relatively slower in STEMI patients. In comparison with oral P2Y12 inhibitors, cangrelor has several pharmacokinetic advantages due to its intravenous route of administration, including platelet inhibition within minutes. There is no randomized study so far comparing cangrelor with ticagrelor. The aim of this study was to investigate the comparative effectiveness of intravenous cangrelor and ticagrelor pre-treatment in STEMI patients undergoing primary PCI. Methods We looked for patients with STEMI undergoing primary PCI at a single high-volume center who were naïve from oral P2Y12 inhibitors at presentation and who received cangrelor (in-lab) or ticagrelor pretreatment. The primary endpoint of the study was a composite of all-cause death, myocardial infarction (MI), definite or probable stent thrombosis and unplanned repeat revascularization within hospital discharge. Secondary outcomes were represented by individual components of the primary composite endpoint, cardiovascular death, non-cardiovascular death, and major bleeding within 72 hours from PCI. Propensity score matching was used to account for potential confounders. Results A total of 396 patients with STEMI (October 2019-March 2022) met the eligibility criteria and entered the analysis; of them, 186 (47%) received intravenous cangrelor. The ticagrelor loading dose was administered before invasive coronary angiography in 210 patients (53%). In the unadjusted analysis, no statistically significant difference between cangrelor and ticagrelor was observed with respect to the primary composite outcome (odds ratio [OR], 1.49, 95% CI, 0.79 to 2.82; P=0.22) and all the other secondary outcomes. Consistently, after propensity-score matching of 133 matched pairs of patients receiving cangrelor or ticagrelor, no significant differences emerged with respect to the primary outcome (OR, 1.12, 95% CI, 0.44 to 2.85; P=0.81) and all the other secondary outcomes. Conclusion In patients with STEMI undergoing primary who were naïve from oral P2Y12 inhibitors at presentation cangrelor and ticagrelor yielded similar results. Thanks to its pharmacologic characteristics, cangrelor could be especially useful in the acute setting.

1156 CANGRELOR IN PATIENTS WITH CORONARY ARTERY DISEASE PRE-TREATED WITH TICAGRELOR: THE SWITCHING ANTIPLATELET (SWAP)-5 STUDY

Abstract Objectives To rule out a drug-drug interaction (DDI) among cangrelor-treated patients who have been pre-treated with ticagrelor. Background There are no studies specifically designed to rule out a DDI when cangrelor is used among patients who have been pre-treated with ticagrelor. Methods In this prospective, randomized, double-blind, placebo-controlled, cross-over, pharmacokinetic (PK) and pharmacodynamic (PD) study, patients with coronary artery disease (n = 20) were pre-treated with a 180-mg ticagrelor loading dose (LD) and after 1 hour randomized to placebo or cangrelor (bolus and infusion for 2 hours). Patients crossed over after 1-4 weeks of washout. PK analysis included ticagrelor plasma levels and its active metabolite. PD assessments included: VerifyNow P2Y12 reaction units (PRU), light transmittance aggregometry vasodilatorstimulated phosphoprotein, and Total Thrombus-Formation Analysis System. PK/PD assessments were performed at 7-time points. Results Compared to placebo, adding cangrelor to patients pre-treated with ticagrelor resulted in a significant reduction in PRU at 30 min and 1 hour after starting infusion. At 2 hours after stopping cangrelor/placebo infusion, PRU was low and similar in both groups (16.9 vs. 12.6; mean difference: 4.3; 95%CI: -28.6; 37.3), meeting the non-inferiority primary endpoint (predefined non-inferiority margin 45 PRU). Consistent findings were shown with all PD assays. PK tracked PD findings with no differences between groups in plasma levels of ticagrelor and its metabolite. Conclusions Compared with placebo, the use of cangrelor in patients pre-treated with ticagrelor results in enhanced platelet inhibition with no differences in PK/PD profiles after discontinuation of drug infusion indicating the absence of a DDI.