Use of glycoprotein IIb/IIIa antagonists to prevent stent thrombosis in morphine-treated patients with ST-elevation myocardial infarction

Zwart, Bastiaan; Yazdani, Momina; Ow, Kok Weng; Richardson, J. David; Iqbal, Javaid; Gunn, Julian; Storey, Robert F.

doi:10.1080/09537104.2019.1665642

Cited by 19 publications

(16 citation statements)

References 15 publications

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“…A recent large retrospective study suggested that a short regimen of GPI was protective against stent thrombosis risk in morphine-treated patients with STEMI (who are potentially exposed to increased risk of acute stent thrombosis owing to delayed absorption of oral P2Y 12 inhibitors). 37 In recent years, the use of GPI has declined, mainly because of the perception that the ischemic benefits are counterbalanced by bleeding risks. 3 Yet, clinical data on GPI are mainly based on prolonged postbolus drug infusion and femoral access site at the time of intervention.…”

Section: Discussionmentioning

confidence: 99%

Cangrelor, Tirofiban, and Chewed or Standard Prasugrel Regimens in Patients With ST-Segment–Elevation Myocardial Infarction

et al. 2020

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Background: Standard administration of newer oral P2Y 12 inhibitors, including prasugrel or ticagrelor, provides suboptimal early inhibition of platelet aggregation (IPA) in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). We sought to investigate the effects of cangrelor, tirofiban and prasugrel, administered as chewed or integral loading dose, on IPA in patients undergoing primary PCI. Methods: The FABOLUS-FASTER is an investigator-initiated, multicenter, open-label, randomized study. A total of 122 P2Y 12 -naïve STEMI patients were randomly allocated (1:1:1) to cangrelor (n=40), tirofiban (n=40), both administered as bolus and 2h infusion followed by 60 mg of prasugrel, or 60 mg loading dose of prasugrel (n=42). The latter group underwent an immediate 1:1 sub-randomization to chewed (n=21), or integral (n=21) tablets administration. The trial was powered to test 3 hypotheses (non-inferiority of cangrelor compared with tirofiban using a non-inferiority margin of 9%, superiority of both tirofiban and cangrelor compared with chewed prasugrel and superiority of chewed prasugrel as compared with integral prasugrel; each with alpha of 0.016) for the primary endpoint that was 30-minute IPA at light transmittance aggregometry (LTA) in response to 20 μmol/L adenosine diphosphate (ADP). Results: At 30 min, cangrelor did not satisfy non-inferiority compared with tirofiban, which yielded superior IPA over cangrelor (IPA: 95.0±8.9 vs. 34.1±22.5; P<0.001); cangrelor or tirofiban were both superior to chewed prasugrel (IPA: 10.5±11.0, P<0.001 for both comparisons), which did not provide higher IPA over integral prasugrel (6.3±11.4; P=0.47), despite yielding higher prasugrel's active metabolite concentration (ng/ml; 62.3±82.6 vs 17.1±43.5; P=0.016). Conclusions: Cangrelor provided inferior IPA compared with tirofiban; both treatments yielded greater IPA compared with chewed prasugrel which led to higher active metabolite concentration but not greater IPA compared with integral prasugrel. Clinical Trial Registration: clinicaltrials.gov NCT02978040, and EudraCT 2017-001065-24

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Section: Discussionmentioning

confidence: 99%

Cangrelor, Tirofiban, and Chewed or Standard Prasugrel Regimens in Patients With ST-Segment–Elevation Myocardial Infarction

et al. 2020

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“…The U.S. FDA recommends consideration of a parenteral anti-platelet agent in acute coronary syndrome patients requiring co-administration of morphine or other opioid agonists because of the opioids' impact on the absorption of oral P2Y12 antagonists. In a recent study a routine GPI use in morphine-treated STEMI patients undergoing primary PCI appeared to protect against stent thrombosis (40).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Pre-Hospital Antiplatelet Therapy for STEMI Patients Undergoing Primary Percutaneous Coronary Intervention: What We Know and What Lies Ahead

et al. 2021

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Early recanalization of the infarct-related artery to achieve myocardial reperfusion is the primary therapeutic goal in patients with ST-elevation myocardial infarction (STEMI). In order to decrease the duration of ischemia, continuous efforts have been made to improve pre-hospital treatment and to target the early period after symptom onset, when the platelet content of the fresh coronary thrombus is maximal and the thrombi are dynamic, and thus more susceptible to powerful antiplatelet agents. There have been substantial advances in antiplatelet therapy in the last three decades with several classes of oral and intravenous antiplatelet agents with different therapeutic targets, pharmacokinetics, and pharmacodynamic properties. New parenteral drugs achieve immediate inhibition of platelet aggregation and fast and easy methods of administration may create the opportunity to bridge the initial gap in platelet inhibition observed with oral P2Y12 inhibitors. Moreover, potential future management of STEMI could directly involve select patients in the process with self-administered antiplatelet agents designed to achieve rapid reperfusion. However the potential anti-ischemic benefits of potent antiplatelet agents will need to be balanced against their risk of increased bleeding. This manuscript presents a comprehensive and updated review of pre-hospital antiplatelet therapy among STEMI patients undergoing primary percutaneous intervention and explores new therapies under development.

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“…However, early prehospital treatment with oral P2Y 12 antagonists, for example, to those with STEMI, has proved disappointing when compared to in-hospital dosing. One factor potentially reducing the benefits of pre-treatment is that absorption of oral P2Y 12 antagonists in the proximal small intestine is significantly delayed by the presence of opioid drugs, commonly administered in ACS [13]. SC-administered selatogrel, with its rapid onset even during ACS, therefore represents an additional option to be investigated with the possibility of preventing the early thrombotic propagation and hence reducing hemodynamic impact within a coronary artery.…”

Section: Early P2y 12 Inhibition In Acsmentioning

confidence: 99%

“…Similarly, whether oral P2Y 12 antagonists should be given before or after primary PCI (PPCI) for STEMI remains debated. Providing cover with a parenteral antiplatelet agent, such as a glycoprotein IIb/IIIa inhibitor, may reduce the risk of acute ischemic complications in those treated with opiates [13]. Use of selatogrel to achieve rapid P2Y 12 inhibition during PPCI, circumventing reduced enteral absorption related to morphine or other factors, might hypothetically reduce the need for additional parenteral antiplatelet agents, e.g.…”

Section: Use During Primary Percutaneous Coronary Interventionmentioning

confidence: 99%

Pharmacology and potential role of selatogrel, a subcutaneous platelet P2Y₁₂ receptor antagonist

Parker

Storey

2020

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Use of glycoprotein IIb/IIIa antagonists to prevent stent thrombosis in morphine-treated patients with ST-elevation myocardial infarction

Cited by 19 publications

References 15 publications

Cangrelor, Tirofiban, and Chewed or Standard Prasugrel Regimens in Patients With ST-Segment–Elevation Myocardial Infarction

Cangrelor, Tirofiban, and Chewed or Standard Prasugrel Regimens in Patients With ST-Segment–Elevation Myocardial Infarction

Pre-Hospital Antiplatelet Therapy for STEMI Patients Undergoing Primary Percutaneous Coronary Intervention: What We Know and What Lies Ahead

Pharmacology and potential role of selatogrel, a subcutaneous platelet P2Y₁₂ receptor antagonist

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Use of glycoprotein IIb/IIIa antagonists to prevent stent thrombosis in morphine-treated patients with ST-elevation myocardial infarction

Cited by 19 publications

References 15 publications

Cangrelor, Tirofiban, and Chewed or Standard Prasugrel Regimens in Patients With ST-Segment–Elevation Myocardial Infarction

Cangrelor, Tirofiban, and Chewed or Standard Prasugrel Regimens in Patients With ST-Segment–Elevation Myocardial Infarction

Pre-Hospital Antiplatelet Therapy for STEMI Patients Undergoing Primary Percutaneous Coronary Intervention: What We Know and What Lies Ahead

Pharmacology and potential role of selatogrel, a subcutaneous platelet P2Y12 receptor antagonist

Contact Info

Product

Resources

About

Pharmacology and potential role of selatogrel, a subcutaneous platelet P2Y₁₂ receptor antagonist