Comparison of the effect of Morphine and Fentanyl in patients with acute coronary syndrome receiving Ticagrelor - The COMET (Comparison Morphine, Fentanyl and Ticagrelor) randomized controlled trial

Senguttuvan, Nagendra Boopathy; Suman, Febe Renjitha; Paneerselvam, TamilAnbu; Malepati, Balakrishna; Sankaran, Ramesh; Vallivedu, Mano Vikash; Badimela, Phalgun; Ramadoss, Mahalakshmi; Iyer, Meena; Krishnamurthy, Preetam; Balakrishnan, Vinodkumar; Balasubramaniyan, Jayanthy Venkata; Sadhanandham, Shanmugasundram; Rathinasamy, Jebaraj; Panchanatham, Manokar; Muralidharan, T.R.; Murthy, Jyotsna; Thanikachalam, Sadagopan; Krishnamoorthy, Parasuram; Baber, Usman; Karthikeyan, Ganesan

doi:10.1016/j.ijcard.2021.02.037

Cited by 5 publications

(6 citation statements)

References 24 publications

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“…A robust body of randomized evidence suggests that platelet inhibition induced by potent orally administered P2Y 12 receptor antagonists is affected by the concomitant use of opioids in the setting of STEMI ( 5 , 6 , 18 , 19 , 23 ). Intravenous opioids have been shown to delay gastro-intestinal drug absorption of oral P2Y 12 inhibitors during the management of STEMI ( 24 – 26 ), which results in higher platelet reactivity and an increased risk for adverse ischemic and thrombotic events ( 4 , 27 , 28 ).…”

Section: Discussionmentioning

confidence: 99%

“…Third, we categorized patients who were randomized in the PERSEUS trial into different small subgroups according to low vs. high doses of opioids received. Considering the initial small sample size of the PERSEUS trial, this may have further reduced statistical power to compare individual ouctomes between treatment groups and prevented from analyzing other relevant outcomes investigated in the main analysis and in similar studies, such as the proportion of patients with HTPR, achievement of Thrombolysis In Myocardial Infarction grade 3 flow in the infarct-related artery prior to PCI, or ≥70% ST-segment elevation resolution after primary PCI ( 5 , 15 , 18 , 21 , 23 ). Finally, the results of this analysis may not be applicable to other oral P2Y 12 receptor inhibitors than ticagrelor.…”

Section: Discussionmentioning

confidence: 99%

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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

Garin,

Degrauwe,

Carbone

et al. 2024

Front. Cardiovasc. Med.

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IntroductionAmong 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.Materials and methodsWe 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.Results38 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.ConclusionIn 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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Garin,

Degrauwe,

Carbone

et al. 2024

Front. Cardiovasc. Med.

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“…For the treatment of acute coronary syndrome, the majority of colleagues provide morphine (85.7%). Although textbooks and numerous studies refer to a beneficial effect of morphine in ACS, an advantage of morphine over other potent opioids for this indication has not been proven [ 24 – 26 ].…”

Section: Discussionmentioning

confidence: 99%

Application of analgesics in emergency services in Germany: a survey of the medical directors

Vilcane,

Scharonow,

Weilbach

et al. 2023

BMC Emerg Med

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Abstrac Background Treatment of acute pain is an essential element of pre-hospital care for injured and critically ill patients. Clinical studies indicate the need for improvement in the prehospital analgesia. Objective The aim of this study is to assess the current situation in out of hospital pain management in Germany regarding the substances, indications, dosage and the delegation of the use of analgesics to emergency medical service (EMS) staff. Material and methods A standardized survey of the medical directors of the emergency services (MDES) in Germany was carried out using an online questionnaire. The anonymous results were evaluated using the statistical software SPSS (Chi-squared test, Mann-Whitney-U test). Results Seventy-seven MDES responsible for 989 rescue stations and 397 EMS- physician bases in 15 federal states took part in this survey. Morphine (98.7%), Fentanyl (85.7%), Piritramide (61%), Sufentanil (18.2%) and Nalbuphine (14,3%) are provided as opioid analgesics. The non-opioid analgesics (NOA) including Ketamine/Esketamine (98,7%), Metamizole (88.3%), Paracetamol (66,2%), Ibuprofen (24,7%) and COX-2-inhibitors (7,8%) are most commonly available. The antispasmodic Butylscopolamine is available (81,8%) to most rescue stations. Fentanyl is the most commonly provided opioid analgesic for treatment of a traumatic pain (70.1%) and back pain (46.8%), Morphine for visceral colic-like (33.8%) and non-colic pain (53.2%). In cases of acute coronary syndrome is Morphine (85.7%) the leading analgesic substance. Among the non-opioid analgesics is Ketamine/Esketamine (90.9%) most frequently provided to treat traumatic pain, Metamizole for visceral colic-like (70.1%) and non-colic (68.6%) as well as back pain (41.6%). Butylscopolamine is the second most frequently provided medication after Metamizole for “visceral colic-like pain” (55.8%). EMS staff (with or without a request for presence of the EMS physician on site) are permitted to use the following: Morphine (16.9%), Piritramide (13.0%) and Nalbuphine (10.4%), and of NOAs for (Es)Ketamine (74.1%), Paracetamol (53.3%) and Metamizole (35.1%). The dosages of the most important and commonly provided analgesic substances permitted to independent treatment by the paramedics are often below the recommended range for adults (RDE). The majority of medical directors (78.4%) of the emergency services consider the independent application of analgesics by paramedics sensible. The reason for the relatively rare authorization of opioids for use by paramedics is mainly due to legal (in)certainty (53.2%). Conclusion Effective analgesics are available for EMS staff in Germany, the approach to improvement lies in the area of application. For this purpose, the adaptations of the legal framework as well as the creation of a guideline for prehospital analgesia are useful.

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“…This leads to administration of significant opioid doses in the prehospital setting. The latter is of significant concern given there is now very convincing biochemical evidence that opioid analgesia impairs the bioavailability and subsequent antiplatelet effect of all oral P2Y 12 inhibitors [4] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [35] . This exacerbates the delayed onset of platelet inhibition seen in patients with ST elevation myocardial infarction where therapeutic inhibition may only occur 4 or more hours after oral loading of P2Y 12 inhibitors [21] , [22] , [23] .…”

Section: Discussionmentioning

confidence: 99%

Association between pre-hospital chest pain severity and myocardial injury in ST elevation myocardial infarction: A post-hoc analysis of the AVOID study

Fernando

Nehme

Peter

et al. 2021

IJC Heart & Vasculature

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Comparison of the effect of Morphine and Fentanyl in patients with acute coronary syndrome receiving Ticagrelor - The COMET (Comparison Morphine, Fentanyl and Ticagrelor) randomized controlled trial

Cited by 5 publications

References 24 publications

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

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

Application of analgesics in emergency services in Germany: a survey of the medical directors

Association between pre-hospital chest pain severity and myocardial injury in ST elevation myocardial infarction: A post-hoc analysis of the AVOID study

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