METoclopramide Administration as a Strategy to Overcome MORPHine-ticagrelOr Interaction in PatientS with Unstable Angina PectorIS—The METAMORPHOSIS Trial

Sikora, Joanna; Niezgoda, Piotr; Barańska, Malwina; Buszko, Katarzyna; Skibińska, Natalia; Sroka, Wiktor Dariusz; Pstrągowski, Krzysztof; Siller‐Matula, Jolanta M.; Jilma, Bernd; Gorog, Diana A.; Navarese, Eliano Pio; Marszałł, Michał Piotr; Kubica, Jacek

doi:10.1055/s-0038-1675605

Cited by 45 publications

(26 citation statements)

References 23 publications

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“…19 On the other hand, metoclopramide which increases gastrointestinal motility was effective in improving the antiplatelet effects of ticagrelor in the presence of morphine. 20 Alternatively, bridging with cangrelor, an intravenous P2Y12 inhibitor may be an effective strategy for tackling delayed bioavailability of oral P2Y12 inhibitors. 21 After adjustment for multiple comorbidities and hospital effect, each 1 mg of morphine equivalent was associated with a 1.4% increase in peak CK; however, this was no longer statistically significant after adjusting for TIMI flow pre-PCI.…”

Section: Resultsmentioning

confidence: 99%

Prehospital opioid dose and myocardial injury in patients with ST elevation myocardial infarction

et al. 2020

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ObjectiveTo characterise the relationship between opioid dose and myocardial infarct size in patients with ST elevation myocardial infarction (STEMI).MethodsPatients given opioid treatment by emergency medical services with confirmed STEMI were included in this secondary, retrospective cohort analysis of the Air versus Oxygen in Myocardial Infarction (AVOID) study. Patients with cardiogenic shock were excluded. The primary endpoint was comparison of cardiac biomarkers as a measure of infarct size based on opioid dose (low ≤8.75 mg, intermediate 8.76–15 mg and high >15 mg of intravenous morphine equivalent dose).Results422 patients were included in the analysis. There was a significantly higher proportion of patients with Thrombolysis in Myocardial Infarction (TIMI) 0 or 1 flow pre-percutaneous coronary intervention (PCI) (94% vs 81%, p=0.005) and greater use of thrombus aspiration catheters (59% vs 30%, p<0.001) in the high compared with low-dose opioid group. After adjustment for potential confounders, every 1 mg of intravenous morphine equivalent dose was associated with a 1.4% (95% CI 0.2%, 2.7%, p=0.028) increase in peak creatine kinase; however, this was no longer significant after adjustment for TIMI flow pre-PCI.ConclusionsOur study suggests no benefit of higher opioid dose and a dose-dependent signal between opioid dose and increased myocardial infarct size. Prospective randomised controlled trials are required to establish causality given that this may also be explained by patients with a greater ischaemic burden requiring higher opioid doses due to more severe pain. Future research also needs to focus on strategies to mitigate the opioid–P2Y12 inhibitor interaction and non-opioid analgesia to treat ischaemic chest pain.

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Section: Resultsmentioning

confidence: 99%

Prehospital opioid dose and myocardial injury in patients with ST elevation myocardial infarction

et al. 2020

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“…The PERSEUS (Platelet Inhibition After Pre‐hospital Ticagrelor Using Fentanyl Compared to Morphine in Patients With ST‐segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention) randomized trial (NCT02531165) will investigate the pharmacokinetics and pharmacodynamics of prehospital ticagrelor in patients with STEMI receiving either fentanyl or morphine. Coadministration of the antiemetic metoclopramide with morphine was recently shown to enhance ticagrelor absorption and platelet inhibition compared with morphine treatment alone in patients with unstable angina …”

Section: Discussionmentioning

confidence: 99%

Impact of Preadmission Morphine on Reinfarction in Patients With ST‐Elevation Myocardial Infarction Treated With Percutaneous Coronary Intervention: A Meta‐Analysis

Gue

Spinthakis

Farag

et al. 2020

Clin Pharma and Therapeutics

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Opiates are the traditional analgesics used in patients with ST‐elevation myocardial infarction (STEMI). Pharmacodynamic studies indicate that opiates delay the absorption of orally administered P2Y12 inhibitors and the onset of platelet inhibition. Whether these negative effects on platelet inhibition have an impact on clinical outcomes is unclear. A systematic review and meta‐analysis was performed searching PubMed, MEDLINE, and Cochrane Central Register of Controlled Trials to identify studies comparing morphine and no‐morphine treatment in STEMI patients undergoing primary percutaneous coronary intervention. The primary end point was the occurrence of in‐hospital myocardial infarction, and secondary end points were in‐hospital stroke and death. Four observational studies were identified, including 3,220 patients with STEMI. Morphine‐treated patients had a higher unadjusted rate of reinfarction compared with patients not receiving morphine (1.5% vs. 0.67%, odds ratio (OR) 2.41; 95% confidence interval (CI), 1.11–5.21; P = 0.03). Unadjusted mortality rate was lower in morphine‐treated patients (1.7% vs. 4.2%, OR 0.43, 95% CI, 0.23–0.81; P = 0.009). Exclusion of the study with baseline differences between groups showed more frequent reinfarction in the morphine group, but this was no longer statistically significant (1.3% vs. 0.5%, OR 2.02; 95% CI, 0.39–10.43; P = 0.40). There was no difference in stroke according to morphine treatment. Patients pretreated with morphine appear to have a higher rate of reinfarction than patients not receiving morphine. This may be attributable to opiate‐related delay in P2Y12 inhibitor absorption and resultant delay in onset of platelet inhibition. These concerning findings indicate the need for prospective, randomized trials to assess the impact of opiates on clinical outcomes in STEMI.

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“…So for patients with ACS without morphine usage at high ischemic risk, it is still a question how to increase the concentration of bioactive metabolites to accelerate the antiplatelet effect of ticagrelor. Recently Sikora observed that co-administration of metoclopramide overcame the delayed onset of P2Y 12 inhibitors caused by morphine among patients with unstable angina, but not for patients with STEMI [15]. The result was mainly caused by drug pharmacology of metoclopramide, which enhanced gastrointestinal tract motility and contractility.…”

Section: Discussionmentioning

confidence: 99%

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

Wang

Chen

et al. 2020

Adv Ther

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Introduction: 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. Methods: 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 12 h after 180 mg LD of ticagrelor. P2Y 12 reactivity units (PRU) and plasma concentrations of ticagrelor and its two metabolites were measured.

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METoclopramide Administration as a Strategy to Overcome MORPHine-ticagrelOr Interaction in PatientS with Unstable Angina PectorIS—The METAMORPHOSIS Trial

Cited by 45 publications

References 23 publications

Prehospital opioid dose and myocardial injury in patients with ST elevation myocardial infarction

Prehospital opioid dose and myocardial injury in patients with ST elevation myocardial infarction

Impact of Preadmission Morphine on Reinfarction in Patients With ST‐Elevation Myocardial Infarction Treated With Percutaneous Coronary Intervention: A Meta‐Analysis

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

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