cangrelor and ST-Elevation-Myocardial-Infarction

Topics: Acute Coronary Syndrome; Adenosine Monophosphate; Administration, Intravenous; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor

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 6 h 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.

Topics: Adenosine Monophosphate; Aged; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Infusions, Intravenous; Injections, Intravenous; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Tirofiban

Although P2Y12 receptor blockers have become a standard, adjunctive therapy in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), the optimal regimen has not been established. We performed a prospective, open-label, randomized study to investigate the effect of cangrelor administration on platelet function and inflammation in patients with primary PCI (PPCI). Twenty-two patients were randomized to receive either cangrelor and ticagrelor or ticagrelor alone (standard group) before PPCI. Platelet reactivity was evaluated at baseline (before PCI), 10 min and the end of the procedure. At baseline, there was no significant difference in platelet reactivity between both groups, whereas platelets were significantly inhibited at 10 min after initiating cangrelor vs. standard (adenosine-diphosphate-induced aggregation 102.2 ± 24.88 vs. 333.4 ± 63.3, P < 0.05 and thrombin-receptor-activating-peptide-induced aggregation 285.8 ± 86.1 vs. 624.8 ± 106.0, P < 0.05). Lower platelet aggregation in the cangrelor group persisted but the difference was reduced by the end of the procedure. Circulating inflammatory cells, pro-inflammatory cytokines, total elastase, and surrogates of neutrophil extracellular traps (total elastase-myeloperoxidase complexes) were significantly lower in the cangrelor compared to the standard therapy group at 6 h after randomization. There was a trend towards reduction in cardiac damage in the cangrelor group as reflected by the changes in late gadolinium enhancement between 48 h and 3 months after STEMI. Early administration of cangrelor in STEMI patients was associated with more effective platelet inhibition during PPCI and significantly dampened the deleterious inflammatory response compared to standard therapy (NCT03043274).

Topics: Adenosine Monophosphate; Contrast Media; Gadolinium; Humans; Pancreatic Elastase; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

In ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PPCI), current oral P2Y12 platelet inhibitors do not provide maximal platelet inhibition at the time of reperfusion. Furthermore, administration of cangrelor prior to reperfusion has been shown in pre-clinical studies to reduce myocardial infarct (MI) size. Therefore, we hypothesize that cangrelor administered prior to reperfusion in STEMI patients will reduce the incidence of microvascular obstruction (MVO) and limit MI size in STEMI patients treated with PPCI.. The platelet inhibition to target reperfusion injury (PITRI) trial, is a phase 2A, multi-center, double-blinded, randomized controlled trial, in which 210 STEMI patients will be randomized to receive either an intravenous (IV) bolus of cangrelor (30 μg/kg) followed by a 120-minute infusion (4 μg/kg/min) or matching saline placebo, initiated prior to reperfusion (NCT03102723).. The study started in October 2017 and the anticipated end date would be July 2020. The primary end-point will be MI size quantified by cardiovascular magnetic resonance (CMR) on day 3 post-PPCI. Secondary endpoints will include markers of reperfusion, incidence of MVO, MI size, and adverse left ventricular remodeling at 6 months, and major adverse cardiac and cerebrovascular events.. The aim of the PITRI trial is to assess whether cangrelor administered prior to reperfusion would reduce acute MI size and MVO, as assessed by CMR.

Topics: Adenosine Monophosphate; Adult; Aged; Aged, 80 and over; Coronary Circulation; Double-Blind Method; Female; Follow-Up Studies; Humans; Infusions, Intravenous; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Myocardial Reperfusion; Myocardial Reperfusion Injury; Myocardium; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Treatment Outcome; Ventricular Remodeling; Young Adult

To describe the characteristics and outcomes of patients receiving bailout glycoprotein IIb/IIIa inhibitors (GPI) for thrombotic complications of percutaneous coronary intervention (PCI) in a large, contemporary trial.. In the CHAMPION PHOENIX trial, the use of GPI was restricted to bailout for thrombotic complications. We describe the characteristics and outcomes of patients requiring bailout GPI compared to patients not receiving GPIs, with adjustment through propensity-score. A multivariable model was constructed to identify independent correlates associated with bailout GPI use. A total of 380 out of 10,942 patients received GPI (3.5%); GPI patients were younger, more frequently male, more likely to present with ST segment elevation myocardial infarction and less frequently treated with cangrelor. At 48 h, GPI patients experienced higher rates of the primary composite outcome of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis (ST) (19.2% vs 4.8%; adjusted OR: 5.65(4.08, 7.82), p < 0.0001) and a higher rate of GUSTO severe or moderate bleeding (2.6% vs 0.4% adjusted OR: 4.90 (1.98, 12.18), p = 0.0006) compared with non GPI patients. Independent correlates of GPI use were STEMI, use of unfractionated heparin, drug-eluting stents and longer procedure duration.. In a large contemporary trial, patients receiving bailout GPI for thrombotic complications of PCI experienced very high risks of both ischemic and bleeding complications, suggesting that prevention of periprocedural complications rather than bailout GPI may be preferable.. http://www.clinicaltrials.gov identifier: NCT01156571.

Topics: Adenosine Monophosphate; Aged; Double-Blind Method; Female; Heart Diseases; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; ST Elevation Myocardial Infarction; Thrombosis; Treatment Outcome

The platelet inhibitory effects induced by oral P2Y. This was a prospective, randomized, double-blind, placebo-controlled pharmacodynamic study conducted in patients undergoing primary percutaneous coronary intervention (n=50) who were randomized to treatment with either cangrelor or matching placebo (bolus followed by 2-hour infusion). All patients received ticagrelor 180-mg loading dose administered as crushed tablets at the time of cangrelor/placebo bolus administration. Pharmacodynamic analyses were performed at 8 time points. Pharmacodynamic effects were measured as P2Y. In patients undergoing primary percutaneous coronary intervention, cangrelor is an effective strategy to bridge the gap in platelet inhibition associated with the use of oral P2Y. URL: https://www.clinicaltrials.gov . Unique identifier: NCT03247738.

Topics: Adenosine Monophosphate; Aged; Biomarkers; Blood Platelets; Cell Adhesion Molecules; Double-Blind Method; Drug Therapy, Combination; Female; Florida; Humans; Male; Microfilament Proteins; Middle Aged; Percutaneous Coronary Intervention; Phosphoproteins; Platelet Aggregation Inhibitors; Prospective Studies; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; ST Elevation Myocardial Infarction; Ticagrelor; Time Factors; Treatment Outcome

Topics: Adenosine Monophosphate; Blood Platelets; Drug Therapy, Combination; Humans; Middle Aged; Percutaneous Coronary Intervention; Prospective Studies; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor

Myocardial reperfusion is the main target of treatment in patients with ST-segment elevation myocardial infarction (STEMI). The intracoronary administration of cangrelor bolus could favor a higher local drug concentration, favoring an earlier thrombotic resolution and a reduced distal micro-embolization.. Seventy-one patients undergoing primary percutaneous coronary intervention (PCI) for STEMI: 37 treated with intracoronary and 34 with intravenous bolus administration of cangrelor. The primary endpoint was ST-segment elevation resolution (STR) ≥ 50% after 30 min from the end of the PCI. Other explorative reperfusion indices investigated were: STR ≥ 50% at 24 hours, STR ≥ 70% at 30 min, Thrombolysis In Myocardial Infarction frame count and the QT dispersion. Moreover, acute and subacute stent thrombosis, bleeding events and 30-day mortality have been evaluated.. More frequent STR ≥ 50% was observed in the intravenous cangrelor bolus group as compared to the intracoronary administration at 30 min (71.9% vs. 45.5%; p = 0.033), the difference was maintained 24 hours after PCI (87.1% vs. 63.6%; p = 0.030). STR ≥ 70% at 30 min was statistically more frequent in the intravenous bolus administration cohort (66.7% vs. 28.6% p = 0.02). At multivariable analysis, intravenous cangrelor administration was significantly related to STR ≥ 50% (odds ratio: 3.586; 95% confidence interval: 1.134-11.335; p = 0.030). The incidence of Bleeding Academic Research Consortium 3-5 bleedings was 15.5% and mortality was 4.2% without any significant difference between the two groups.. In conclusion the results of the study do not show any advantages in the administration of intracoronary bolus of cangrelor in patients affected by STEMI and treated with primary PCI.

Topics: Hemorrhage; Humans; Myocardial Infarction; Myocardial Reperfusion; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Treatment Outcome

Topics: Adenosine Monophosphate; Humans; Platelet Aggregation; ST Elevation Myocardial Infarction; Treatment Outcome

Topics: Adenosine Monophosphate; Humans; Platelet Aggregation; ST Elevation Myocardial Infarction; Treatment Outcome

Topics: Adenosine Monophosphate; Aged; Anxiety; Chest Pain; Coronary Angiography; Coronary Occlusion; Drug Substitution; Drug-Eluting Stents; Drug-Related Side Effects and Adverse Reactions; Dyspnea; Electrocardiography; Humans; Inferior Wall Myocardial Infarction; Male; Percutaneous Coronary Intervention; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome; Withholding Treatment

Topics: Adenosine Monophosphate; Humans; Prasugrel Hydrochloride; ST Elevation Myocardial Infarction; Tirofiban

Topics: Adenosine Monophosphate; Humans; Prasugrel Hydrochloride; ST Elevation Myocardial Infarction; Tirofiban

To date, there are no real-world studies comparing cangrelor to glycoprotein IIb/IIIa inhibitors (GPI) during percutaneous coronary intervention (PCI). Thus, we performed this study to evaluate the safety and effectiveness of cangrelor compared to GPI during PCI.. We identified patients who underwent PCI at our institution who received either cangrelor or GPI during PCI. Patients already on GPI or cangrelor prior to PCI or who received both cangrelor and GPI were excluded. Baseline demographics and clinical outcomes were extracted. Major bleeding is defined as a composite of major hematoma >4 cm, hematocrit drop >15, and gastrointestinal bleeding.. A total of 2072 patients received adjunctive antiplatelet therapy during PCI (cangrelor [n=478]; GPI [n=1594]). Patients' mean age was 61±12 years. Most (66%) presented with acute coronary syndrome. Patients who received cangrelor were older and had a higher percentage of acute coronary syndrome and lower baseline hematocrit in comparison with patients who received GPI. Procedural success was achieved in 94% of patients, with no difference between groups. Major bleeding events (1.7% vs. 5.1%, P=.001), any vascular complication rates, and hospital length of stay were significantly lower in the cangrelor group. In-hospital ischemic events did not differ between groups. On regression analysis, patients on cangrelor were noted to have significantly lower major bleeding events (OR 0.23; 95% CI, 0.09-0.59).. Balancing ischemic and bleeding risks with adjunctive antiplatelet drugs is of prime importance during PCI. Our real-world analysis shows that cangrelor is safe and effective when compared to GPI during PCI.

Topics: Acute Coronary Syndrome; Adenosine Monophosphate; Female; Gastrointestinal Hemorrhage; Hematocrit; Hemorrhage; Humans; Length of Stay; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Purinergic P2Y Receptor Antagonists; Retrospective Studies; ST Elevation Myocardial Infarction

Topics: Adenosine Monophosphate; Adult; Angioplasty, Balloon, Coronary; Coronary Thrombosis; Drug-Eluting Stents; Humans; Hydroxyurea; Infusions, Intravenous; Male; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Recurrence; ST Elevation Myocardial Infarction; Thrombocythemia, Essential; Treatment Outcome

This nationwide study aimed to analyse the first 2 years of routine clinical use of cangrelor in all Swedish patients undergoing percutaneous coronary intervention (PCI).. This observational Swedish Coronary Angiography and Angioplasty Registry (SCAAR) study identified 915 cangrelor-treated patients. As 899 were ST-segment elevation myocardial infarction (STEMI)-patients undergoing primary PCI, we decided to exclude all non-STEMI patients (n = 16) from the following analysis. We then identified all primary PCI patients, January 2016 to January 2018 (n = 10 816). Excluding hospitals without cangrelor use, tailoring time frames from first cangrelor use per hospital, patients treated with cangrelor (n = 899) were compared with those without cangrelor treatment (n = 4614). A separate analysis was performed for cardiac arrest STEMI patients (n = 273). Cangrelor-use in primary PCI varied greatly between hospitals (4-36%, mean 16%). At variance with randomized trials, cangrelor was used nearly exclusively in STEMI, often with cardiac arrest (19%). Cangrelor was combined with ticagrelor in two-thirds of patients, among which >50% was prehospital. Cangrelor was used more frequently in high-risk patients: left main PCI, thrombus aspiration, and cardiac arrest. Despite cangrelor being used in more high-risk patients, crude definite stent thrombosis rates at 30 days were low and similar in cangrelor (0.7%) and non-cangrelor treated patients (0.8%).. Cangrelor was used nearly exclusively in primary PCI STEMI patients, predominantly with ticagrelor. Despite being used in very high-risk patients, often with cardiac arrest, cangrelor treatment was associated with low stent thrombosis rates.

Topics: Adenosine Monophosphate; Aged; Coronary Thrombosis; Drug Utilization; Female; Hemorrhage; Humans; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Practice Patterns, Physicians'; Purinergic P2Y Receptor Antagonists; Registries; Retrospective Studies; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Sweden; Time Factors; Treatment Outcome

Topics: Adenosine Monophosphate; Humans; Percutaneous Coronary Intervention; ST Elevation Myocardial Infarction; Ticagrelor