Ticagrelor Loading Dose Research Articles

Administration of a soluble ADPase, AZD3366, on top of ticagrelor confers additional cardioprotective benefits to that of ticagrelor alone

Abstract Background Preclinical and pilot human studies suggest platelet-independent cardioprotective effects of ticagrelor most likely due to its ability to block cellular uptake of adenosine. Adenosine is a potent endogenous protective molecule, concentrations of which locally rise as a response to ischemia because of the breakdown of extracellular ATP by an endothelial ADPase (apyrase, CD39) to AMP that is subsequently converted to adenosine by CD73. Purpose In the present study we used cardiac magnetic resonance (CMR) imaging in a pig model of myocardial infarction (MI) to examine whether administration of a recombinant soluble form of ADPase, AZD3366 (APT102), confers additional benefits to that of ticagrelor alone in terms of reduced infarct size and improved heart function. Methods Pigs (n=20) were administered an oral loading dose of ticagrelor (180mg) and 2h later subjected to MI induction (1.5h closed-chest LAD coronary balloon occlusion). Prior to reperfusion, pigs were randomized to intravenously receive 1) vehicle (n=5); 2) 1mg/kg AZD3366 (n=5); or 3) 3mg/kg AZD3366 (n=5). After reperfusion all pigs were administered ticagrelor (90mg/bid) for 42 days. A non-treated control-MI group (n=5) was run for comparative purposes. Serial-CMR imaging was performed at baseline and 3 and 42 days post-MI for global and regional structural and functional assessments. Light transmittance aggregometry (LTA; challenged by 5, 10 and 20μM ADP) and ear bleeding time were monitored throughout the study. Results Ticagrelor significantly reduced edema formation (29.8±1.9 vs. 13.1±0.9%LV) and limited infarct size (17.7±1.5 vs. 8.2±1.2%LV) at 3 days post-MI as compared to control-MI pigs (p<0.05), an effect that persisted up to 42 days. Infusion of 1mg/kg AZD3366 showed a clear signal towards further prevention of myocardial damage that reached significance at doses of 3mg/kg (additional reduction of 35% and 52% in edema and infarct size, respectively, as compared to pigs treated with ticagrelor alone; p<0.05). Left ventricular ejection fraction was higher in all ticagrelor-treated pigs at 3 and 42 days post-MI vs. control (p<0.05). Yet, regional analysis of the jeopardized myocardium revealed that pigs administered 3mg/kg AZD3366 on top of ticagrelor presented minimal dysfunctional segmental contraction as compared to the mild hypokinetic and akinetic disturbances observed in ticagrelor-alone and control-MI pigs (χ2 p<0.05 vs. all). Ticagrelor inhibited ADP-induced platelet aggregation by 30% and addition of AZD3366 acutely abolished (90% inhibition) LTA at all tested ADP doses, an effect remaining significant up to 3 days post-infusion. Ear bleeding time was not affected by AZD3366. Conclusion Infusion of a soluble recombinant ADPase (AZD3366) on top of ticagrelor leads to a greater cardioprotection as compared to ticagrelor alone. Co-administration of both drugs in AMI patients undergoing revascularization deserves to be investigated. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Ministerio de Ciencia, Innovaciόn y Universidades / Instituto de Salud Carlos III

Ticagrelor Pharmacokinetics and Pharmacodynamics in Chinese Patients with STEMI and NSTEMI Without Opioid Administration.

The pharmacodynamics (PD) and pharmacokinetics (PK) study of ticagrelor loading dose (LD) in Chinese patients with acute coronary syndrome (ACS) without opioid administration has never been investigated. Therefore, the aim of this study was to evaluate the antiplatelet effects and the PK parameters of ticagrelor in Chinese patients with ACS without opioid administration. A sample size of 30 eligible patients with ACS were enrolled in this study. Blood samples were obtained predose and 1, 2, 4, 8, and 12h after 180mg LD of ticagrelor. P2Y12 reactivity units (PRU) and plasma concentrations of ticagrelor and its two metabolites were measured. In total, 15 patients were admitted to ST segment elevation myocardial infarction (STEMI) and non-ST segment elevation myocardial infarction (NSTEMI) groups, respectively. For patients with NSTEMI, PRU declined significantly during the first 4h and maintained a relatively stable antiplatelet effect from 4 to 12h after LD. A similar trend was found in the STEMI group without significant differences of PRU in each designed time compared with patients with NSTEMI (P > 0.05). Tmax of metabolite AR-C124910XX was 4h after LD for both groups. There were no significant differences for drug concentration, Cmax, or AUC of ticagrelor and AR-C124910XX between patients with STEMI and NSTEMI (P > 0.05). For Chinese patients with ACS, at least 4h was needed to achieve an adequate antiplatelet effect for ticagrelor LD. There were no differences in PK or PD between Chinese patients with STEMI and NSTEMI. ChiCTR1800014764.

Loading doses of ticagrelor versus clopidogrel in preventing periprocedural myocardial infarction in Asian patients with acute coronary syndrome.

Periprocedural myocardial infarction is a common complication following percutaneous coronary intervention. The present study was conducted with an aim to compare the safety and efficacy of loading doses of ticagrelor versus clopidogrel in preventing periprocedural myocardial infarction in Asian patients with acute coronary syndrome undergoing elective percutaneous coronary intervention. A total of 114 patients with acute coronary syndrome undergoing elective percutaneous coronary intervention were assigned to clopidogrel group (n = 57, the loading and maintenance doses were 300 and 75 mg qd for clopidogrel, and 300 and 100 mg qd for aspirin), or ticagrelor group (n = 57, the loading and maintenance doses were 180 and 90 mg bid for ticagrelor, and 300 and 100 mg qd for aspirin). Cardiac biomarkers were measured before, 8 hours, and 24 hours after percutaneous coronary intervention. The percutaneous coronary intervention-related periprocedural myocardial infarction was defined according to the fourth universal definition of myocardial infarction (2018). The overall incidence of percutaneous coronary intervention-related periprocedural myocardial infarction was 21.1%. The ticagrelor group showed a significantly lower incidence of periprocedural myocardial infarction (12.3% vs 29.8%, p = 0.022) and numerically lower bleeding events (3.5% vs 8.8%, p = 0.242) as compared with clopidogrel group. No patient had major adverse cardiovascular events during the 1-month follow-up. The levels of high-sensitivity C-reactive protein did not differ significantly between the two groups (p > 0.05), indicating that the benefits of ticagrelor were not from its anti-inflammatory effects. Multivariable analysis showed that the use of ticagrelor (odds ratio: 0.50; 95% confidence interval: 0.29-0.87; p = 0.014) and number of stents (odds ratio: 2.75; 95% confidence interval: 1.25-6.06; p = 0.012) were independent predictors of periprocedural myocardial infarction. Pretreatment with a loading dose of ticagrelor seems to be superior in reducing the incidence of percutaneous coronary intervention-related periprocedural myocardial infarction in Asian patients with acute coronary syndrome as compared with clopidogrel.

TicagRelor Or Clopidogrel in severe or terminal chronic kidney patients Undergoing PERcutaneous coronary intervention for acute coronary syndrome: The TROUPER trial

Chronic kidney disease (CKD) is associated with an increased risk of acute coronary syndrome (ACS) and cardiovascular death. CKD patients suffering from ACS are exposed to an increased risk of thrombotic recurrences and a higher bleeding rate than patients with normal renal function. However, CKD patients are excluded or underrepresented in clinical trials. Therefore, determining the optimal antiplatelet strategy in this population is of utmost importance. We designed the TicagRelor Or Clopidogrel in severe or terminal chronic kidney patients Undergoing PERcutaneous coronary intervention for acute coronary syndrome (TROUPER) trial: a prospective, controlled, multicenter, randomized trial to investigate the optimal P2Y12 antagonist in CKD patients with ACS. Patients with stage ≥3b CKD are eligible if the diagnosis of ACS is made and invasive strategy scheduled. Patients are randomized 1:1 between a control group with a 600-mg loading dose of clopidogrel followed by a 75-mg/d maintenance dose for 1 year and an experimental group with a 180-mg loading dose of ticagrelor followed by a 90-mg twice daily maintenance dose for the same duration. The primary end point is defined by the rate of major adverse cardiovascular events, including death, myocardial infarction, urgent revascularization, and stroke at 1 year. Safety will be evaluated by the bleeding rate (Bleeding Academic Research Consortium). To demonstrate the superiority of ticagrelor on major adverse cardiovascular events, we calculated that 508 patients are required. The aim of the TROUPER trial is to compare the efficacy of ticagrelor and clopidogrel in stage >3b CKD patients presenting with ACS and scheduled for an invasive strategy. RCT# NCT03357874.

Blunting periprocedural myocardial necrosis: Rationale and design of the randomized ALPHEUS study

Clopidogrel associated with aspirin is the recommended treatment for patients undergoing elective percutaneous coronary intervention (PCI). Although severe PCI-related events are rare, evidence suggests that PCI-related myocardial infarction and myocardial injury are frequent complications that can impact the clinical prognosis of the patients. Antiplatelet therapy with a potent P2Y12 receptor inhibitor such as ticagrelor may reduce periprocedural ischemic complications while maintaining a similar safety profile as compared with conventional dual antiplatelet therapy by aspirin and clopidogrel in this setting. Assessment of Loading with the P2Y12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting (ALPHEUS) (NCT02617290) is an international, multicenter, randomized, parallel-group, open-label study in patients with stable coronary artery disease who are planned for an elective PCI. In total, 1,900 patients will be randomized before a planned PCI to a loading dose of ticagrelor 180 mg or a loading dose of clopidogrel (300 or 600 mg) in addition to aspirin. Patients will then receive a dual antiplatelet therapy with aspirin and ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily for 30 days. The primary ischemic end point is PCI-related myocardial infarction (myocardial infarction type 4a or 4b) or major myocardial injury within 48 hours (or at hospital discharge if earlier) after elective PCI/stent. Safety will be evaluated by major bleeding events (Bleeding Academic Research Consortium type 3 or 5) at 48 hours (or discharge if it occurs earlier). ALPHEUS is the first properly sized trial comparing ticagrelor to clopidogrel in the setting of elective PCI and is especially designed to show a reduction in periprocedural events, a surrogate end point for mortality.

Ticagrelor hemorrhagic safety in patients with acute coronary syndrome with ST-segment elevation received thrombolytic therapy in daily clinical practice: 30-day observation results.

Objective: to compare the safety of ticagrelor use in patients with STEMI after ineffective thrombolytic treatment (TLT) and successfully performed recanalization of infarct-dependent artery (IDA) by PCI, as ticagrelor loading dose was administered in the time window from TLT to PCI, compared with the TREAT studyresultson the risk of bleeding in real clinical practice.
 Materials and methods: a comparative analysis of the results of a 30-day follow-up of 52 patients with acute coronary syndrome with ST-segment elevation who received thrombolytic therapy with alteplasa and early ticagrelor administration with the ticagrelor group in the TREAT study on the parameters of hemorrhagic safety.
 Results: arterial hypertension, dyslipidemia, generalized atherosclerosis, chronic obstructive pulmonary disease and a history of myocardial infarction were significantly more common in the study group. Analysis of the results revealed no significant differences between the groups in the frequency and risk of hemorrhagic complications.
 Conclusion: there are no significant differences in the frequency of major bleeding according to the TIMI and BARC criteria between the groups, which indicates the safety of early (within 24 hours after thrombolysis) ticagrelor use in the pharmacoinvasive approach in real clinical practice.

Facilitation Through Aggrastat or Cangrelor Bolus and Infusion Over PrasugreL: a MUlticenter Randomized Open-label Trial in PatientS with ST-elevation Myocardial InFarction Referred for PrimAry PercutaneouS InTERvention (FABOLUS FASTER) Trial: Design and Rationale : The FABOLUS FASTER Trial.

Antithrombotic therapy is a critical component of the management of ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). Rapid and profound inhibition of platelet reactivity has been shown to mitigate the ischemic risks and improve myocardial salvage. High residual platelet reactivity (HRPR) has been reported up to 4 or 6h after loading dose of prasugrel or ticagrelor; therefore, multiple alternative strategies, including crushed or chewed oral tables or intravenous agents, have been investigated to provide a more rapid and sustained inhibition of platelet function and bridge the initial treatment gap. The FABOLUS FASTER is the first investigator-initiated, multicentre, open-label, prospective, randomized study to directly compare the pharmacodynamics effects of cangrelor, tirofiban, chewed or integer prasugrel. This study will add new insights in the management of antiplatelet therapy in patients with STEMI undergoing primary PCI and might be hypothesis-generating for future clinical trials in this field. The trial is registered on clinicaltrials.gov NCT02978040, and EudraCT 2017-001065-24.

CRT-100.28 The Impact of Ticagrelor Loading Dose Timing in Patients With STEMI

Patients with STEMI undergoing primary percutaneous coronary intervention (PPCI) frequently have suboptimal platelet inhibition in the early hours after the ticagrelor loading dose. It has been hypothesized that early loading dose administration optimizes platelet inhibition in PPCI and, therefore,

Platelet reactivity inhibition following ticagrelor-loading dose in patients undergoing percutaneous coronary intervention for acute coronary syndrome

Ticagrelor induces more potent platelet reactivity (PR) inhibition with reduced interindividual variability compared to clopidogrel. Although on-clopidogrel PR was shown to correlate with ischemia and bleeding events, data regarding PR from ticagrelor and the outcomes are lacking. We aimed to determine the association between PR after a ticagrelor loading dose (LD), assessed by the vasodilator-stimulated phosphoprotein index (VASP), and thrombotic and bleeding events in patients with acute coronary syndrome (ACS) treated by percutaneous coronary intervention (PCI). We performed a prospective, multicenter observational study on patients treated with PCI for ACS. The VASP index was used to assess PR after ticagrelor LD. The primary endpoint was the link between major adverse cardiovascular events (MACE) and PR. Among the included 530 patients with ACS, 185 (34.5%) were admitted for ST elevation myocardial infarction. We observed high potency and limited interindividual variability after the ticagrelor LD (VASP 19.1 ± 16.6%). At 1 month, 21 (3.8%) MACE and 29 (5.5%) bleedings Academic Research Consortium ≥ 2 events were recorded. Neither MACE nor bleeding were associated with PR ( P = 0.34and p = 0.78 respectively). However, there was a strong association between PR and the occurrence of definite acute stent thrombosis ( P = 0.03). PR was the only factor associated with acute definite stent thrombosis. In patients receiving a ticagrelor LD while undergoing PCI for ACS, PR using the VASP does not predict MACE or bleeding, but it is significantly associated with the occurrence of definite acute ST.

Response to antiplatelet therapy in patients undergoing invasive treatment due to acute coronary syndrome complicated by cardiogenic shock.

IntroductionThere are limited data on platelet reactivity and response to antiplatelet drugs in patients with cardiogenic shock.AimTo assess platelet reactivity on dual antiplatelet therapy with acetylsalicylic acid (ASA) and ticagrelor, a novel potent P2Y12 receptor inhibitor, in patients with cardiogenic shock in the course of acute coronary syndrome (ACS) who received invasive treatment.Material and methodsWe enrolled 12 consecutive patients with ACS complicated by cardiogenic shock. To assess response to antiplatelet therapy during cardiogenic shock, only patients with symptoms persisting for at least 3 days and who completed a 5-day follow-up were included in the study. Patients received a loading dose of ASA (300 mg) and ticagrelor (180 mg), followed by a maintenance dose (ASA, 1 × 75 mg; ticagrelor, 2 × 90 mg). Blood samples for platelet function tests were collected. Platelet aggregation was assessed with a Multiplate whole-blood impedance aggregometer. Arachidonic acid (AA), adenosine diphosphate (ADP), and thrombin receptor-activating peptide (TRAP) were used as aggregation agonists.ResultsResponse to antiplatelet therapy assessed by aggregometry showed numerically higher on-ASA platelet reactivity on day one and statistically significant higher on-ticagrelor platelet reactivity on day one in comparison with following days. There were 2 patients with high on ASA platelet reactivity and 3 with high on ticagrelor platelet reactivity, but only on the day one.ConclusionsSome patients with cardiogenic shock in the course of ACS treated invasively show a lower response to ASA and ticagrelor only on the first day after invasive treatment, with a good response on subsequent days.

Platelet reactivity inhibition following ticagrelor loading dose in patients undergoing percutaneous coronary intervention for acute coronary syndrome

BackgroundTicagrelor induces more potent platelet reactivity (PR) inhibition with reduced interindividual variability compared to clopidogrel. Although on‐clopidogrel PR was shown to correlate with ischemia and bleeding events, no study has investigated the relationship between on‐ticagrelor PR and outcome. ObjectivesWe aimed to evaluate the relationship between on‐ticagrelor PR, assessed by the vasodilator‐stimulated phosphoprotein index (VASP), and thrombotic and bleeding events in patients with acute coronary syndrome (ACS) treated by percutaneous coronary intervention (PCI). MethodsWe performed a prospective, multicenter observational study on patients treated with PCI for ACS. The VASP index was used to assess PR after ticagrelor loading dose (LD). The primary endpoint was the link between major adverse cardiovascular events (MACE) and PR. ResultsAmong the 530 patients with ACS included, 183 (34.5%) were admitted for ST elevation myocardial infarction. We observed high potency and limited interindividual variability after the ticagrelor LD (VASP 19.1% ± 16.6%). At 1 month, 21 (3.8%) MACE and 29 (5.5%) bleedings ≥ 2 according to the Bleedings Academic Research Consortium (BARC) scale were recorded. Neither MACE nor bleeding was associated with PR (P = .34 and P = .78, respectively). However, there was a strong association between PR and the occurrence of definite acute stent thrombosis (P = .03). Platelet reactivity was the only factor associated with acute definite stent thrombosis. ConclusionIn patients receiving a ticagrelor LD while undergoing PCI for ACS, PR using the VASP did not predict MACE or bleeding, but it was significantly associated with the occurrence of definite acute stent thrombosis.

TCT-415 Platelet Reactivity Inhibition Following Ticagrelor Loading Dose in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndrome

TCT-415 Platelet Reactivity Inhibition Following Ticagrelor Loading Dose in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndrome

Ticagrelor Use in Indian Patients Undergoing Neuroendovascular Procedures: A Single Center Experience.

PurposeA safe and efficacious antiplatelet drug is needed for patients with clopidogrel resistance who undergo neuroendovascular procedures. Ticagrelor is a new reversibly binding, oral, direct-acting P2Y receptor antagonist with no known resistance. We describe our clinical experience using ticagrelor for neuroendovascular procedures in Indian patients with clopidogrel resistance at the NH Institute of Neurosciences, Narayana Health City, Bangalore.Materials and MethodsWe retrospectively reviewed our endovascular procedure database for all patients with predefined clopidogrel resistance. Clopidogrel resistance was defined as P2Y12 inhibition <40%. Patients were administered ticagrelor along with aspirin prior to the procedure.ResultsOf 127 patients, 32 (25%) were non-responders to clopidogrel (22 [69%] males, 10 [31%] females; median age, 54 years [range, 20–75]). All patients were treated with a 180-mg loading dose of ticagrelor, followed by 90 mg twice daily. Twenty patients (63%) underwent endovascular intervention for intracranial aneurysm, two (6%) for dissecting aneurysms, nine (28%) for stenotic lesions, and one (3%) for carotico-cavernous fistula. No patient experienced any adverse effects related to the use of Ticagrelor in the postoperative period.ConclusionTicagrelor is an effective alternative to clopidogrel for use in conjunction with aspirin in patients with clopidogrel resistance. None of our patients had adverse effects from ticagrelor. Drug cost, twice-daily dosing, and risk of faster platelet aggregation activation after discontinuation should be taken into consideration prior to its use in such patients.

Effects of Methylnaltrexone on Ticagrelor-Induced Antiplatelet Effects in Coronary Artery Disease Patients Treated With Morphine

ObjectivesThe aim of this study was to assess if intravenous methylnaltrexone can counteract the effects of morphine on the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of ticagrelor. BackgroundMorphine delays the onset of action of oral P2Y12 receptor inhibitors, including ticagrelor, by inhibiting gastric emptying and leading to delayed drug absorption. Methylnaltrexone is a peripheral opioid receptor antagonist that has the potential to prevent opioid-induced peripherally mediated side effects (e.g., gastric emptying inhibition) without affecting analgesia. MethodsIn this prospective, randomized, double-blind, placebo-controlled, crossover study, aspirin-treated patients with stable coronary artery disease (n = 30) were randomized to receive methylnaltrexone (0.3 mg/kg intravenous) or matching placebo. After methylnaltrexone or placebo administration, all patients received morphine (5 mg intravenous). This was followed 15 min later by a 180-mg loading dose of ticagrelor. Patients crossed over to the alternative study treatment after 7 ± 2 days of washout. PK and PD assessments were performed at 12 time points (6 pre- and 6 post-crossover). PK analysis included measurement of plasma levels of ticagrelor and its major active metabolite (AR-C124910XX). PD assessments included VerifyNow P2Y12, light transmittance aggregometry, and vasodilator-stimulated phosphoprotein. ResultsOnly marginal changes in plasma levels of ticagrelor (and its major active metabolite) were observed with ticagrelor: maximum plasma concentration and area under the plasma concentration versus time curve from time 0 to the last measurable concentration were 38% and 30% higher, respectively, in patients receiving methylnaltrexone compared with those receiving placebo, but no differences in time to maximum plasma concentration were observed. There were no differences in P2Y12 reaction units by VerifyNow P2Y12 between groups at each time point, including 2 h (the primary endpoint; p = 0.261). Similarly, there were no differences in PD markers assessed by light transmittance aggregometry and vasodilator-stimulated phosphoprotein. ConclusionsIn patients with coronary artery disease receiving morphine, intravenous administration of the peripheral opioid receptor antagonist methylnaltrexone leads to only marginal changes in plasma levels of ticagrelor and its major metabolite, without affecting levels of platelet reactivity. (Effect of Methylnaltrexone on the PK/PD Profiles of Ticagrelor in Patients Treated With Morphine; NCT02403830)

Hemostasis Management of Patients Undergoing Emergency Cardiac Surgery After Ticagrelor Loading

Summary Ticagrelor, a direct and reversible inhibitor of P2Y12 adenosine diphosphate (ADP) receptor, has become one of the most commonly used oral antiplatelet agents in the treatment of acute coronary syndrome (ACS). Consequently, an increasing number of patients are presenting for emergent cardiac surgery with extensive platelet inhibition, and a potential risk for major perioperative bleeding. Herein, we describe the management of 3 patients, each of whom required an emergent cardiac surgical procedure following a loading or maintenance dose of ticagrelor for presumed ACS. Preoperative platelet function assessment was performed using a whole blood platelet aggregation test to confirm the extent of platelet P2Y12 inhibition. Platelet transfusion in the presence of therapeutic drug levels of ticagrelor have minimal impact on cessation of bleeding. Appropriate timing of surgery, and use of adjunctive hemostatic therapies is therefore imperative to achieve intraoperative hemostasis, and to minimize the need for allogeneic blood transfusion.

Ticagrelor induced neutrophilic eccrine hidradenitis: a unique adverse effect of a new antiplatelet drug

Dear Editor, Ticagrelor is a recently introduced antiplatelet drug that has shown superiority over clopidogrel in reducing overall mortality in acute coronary syndrome (ACS). The drug is an ADP P2Y12...

Determinants of high platelet reactivity in patients with acute coronary syndromes treated with ticagrelor

High platelet reactivity (HPR) is a risk factor for stent thrombosis, a potentially lethal complication of percutaneous coronary intervention. HPR is also associated with increased risk of myocardial infarction and death in invasively-treated patients with acute coronary syndrome (ACS). HPR occurs even in ACS patients treated with ticagrelor, a state-of-the-art antiplatelet agent, especially during the first hours of treatment. Patient-level pharmacodynamic data obtained from 102 ACS subjects enrolled in two prospective, pharmacodynamic trials were analysed in order to identify clinical features related with increased odds of on-ticagrelor HPR during the first two hours after ticagrelor loading dose in ACS patients. Presence of ST-segment elevation myocardial infarction (versus non-ST-segment elevation ACS) and morphine co-administration were the strongest predictors of HPR at 1 and 2 hours after ticagrelor loading dose according to linear regression analyses, multiple backward stepwise logistic regression analyses and generalized estimating equation model. By pinpointing simple to recognize clinical features, the results of this study facilitate identification of ACS patients who have the highest odds of HPR during the initial phase of treatment with ticagrelor, and who could potentially benefit from alternative treatment strategies.

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.

Rationale and design of PREvalence of DyspneA in patients treated with TicagrelOR (PREDATOR) program

Background: Ticagrelor, a reversible P2Y12 inhibitor, is a mainstay of antiplatelet strategy in patients with acute coronary syndrome (ACS). However, a large number of ticagrelor-induced dyspnea decrease patients’ adherence and reduce an overall efficacy of the therapy. Design: The PREDATOR program consists of phase III and IV, multicenter, randomized, double-blind, placebo-controlled clinical trials and preceding pilot studies that assesses the prevalence and treatment of ticagrelor-induced dyspnea in coronary artery disease (CAD) and ACS patients. The PREDATOR LD is designed to evaluate the occurrence of dyspnea after 180 mg ticagrelor loading dose, and relief of dyspnea by theophylline administration in low-to-high risk acute coronary syndromes without ST-segment elevation (NSTE-ACS) and stable CAD designated to undergo invasive treatment. The PREDATOR MD is a cross-over trial in stable CAD patients 1 year after percutaneous coronary intervention for ACS. Enrolled patients will be randomized to one of four antiplatelet treatment regimens (ticagrelor 2x90 mg, ticagrelor 2x60 mg, ticagrelor 2x45 mg or clopidogrel 75 mg [morning]+placebo [evening]) or placebo and will be assessed for dyspnea at the day 7, then undergo a switch of treatment and reassessment at day 14. The sample size will be estimated based on preceding pilot studies. Discussion: The PREDATOR LD is expected to prospectively assess dyspnea rate with a loading dose of ticagrelor, and analyze a potential of theophylline to elevate symptoms of ticagrelor-induced dyspnea, while the PREDATOR MD will prospectively assess dyspnea and adverse events rate with a maintenance dose of P2Y12 inhibitors prospectively assess. All evaluations will be conducted using standardized metrics for dyspnea quantification.

Safety of Ticagrelor Compared to Clopidogrel after Prehospital Initiation of Treatment.

Objectives The objective of this registry was to study the safety of prehospital initiation of ticagrelor compared with clopidogrel. Background Ticagrelor has replaced clopidogrel in many hospitals as the routinely used antiplatelet drug in patients with ST-segment elevation myocardial infarction (STEMI). Nevertheless, in the PLATelet inhibition and patient Outcomes (PLATO) trial, ticagrelor was associated with an increase in non-CABG (non–coronary artery bypass grafting)-related major bleeding. Data comparing the safety of ticagrelor and clopidogrel after prehospital initiation of treatment are not available. Methods A retrospective, multicenter registry was performed. Selection criteria were the administration of a prehospital loading dose of ticagrelor or clopidogrel according to the ambulance STEMI treatment protocol and the presentation to a percutaneous coronary intervention–capable hospital in our region between January 2011 and December 2012. Follow-up was performed using the electronic patient files for the time period between the antiplatelet loading dose and hospital discharge. The data were analyzed using a primary bleeding end point (any bleeding) and a secondary thrombotic end point (all-cause mortality, spontaneous myocardial infarction, definite stent thrombosis, stroke, or transient ischemic attack). Results Data of 304 clopidogrel-treated and 309 ticagrelor-treated patients were available for analysis. No significant difference in bleeding rate was observed between both groups, using univariate (17.8 vs. 20.1%; p = 0.47; odds ratio, 1.16 [95% confidence interval, 0.78–1.74]) and multivariate ( p = 0.42) analysis. Also for the secondary thrombotic end point (6.3 vs. 4.9%, p = 0.45), no significant differences were observed. Conclusion In this real-world registry, no significant differences in bleeding or thrombotic event rate were found between ticagrelor and clopidogrel after prehospital initiation of treatment.