Morphine delays the onset of action of prasugrel in patients with prior history of ST-elevation myocardial infarction

2016 ◽  
Vol 116 (07) ◽  
pp. 96-102 ◽  
Author(s):  
Mark Thomas ◽  
Allison Morton ◽  
Rashed Hossain ◽  
Beining Chen ◽  
Lei Luo ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Light Transmission ◽  
Platelet Reactivity ◽  
Platelet Inhibition ◽  
St Elevation Myocardial Infarction ◽  
Prior History ◽  
Onset Of Action ◽  
Study Objective ◽  
History Of ◽  
St Elevation

SummaryDelays in the onset of action of prasugrel during primary percutaneous coronary intervention (PPCI) have been reported and could be related to the effects of morphine on gastric emptying and subsequent intestinal absorption. The study objective was to determine whether morphine delays the onset of action of prasugrel in patients with a prior history of ST-elevation myocardial infarction (STEMI) treated with PPCI. This was a crossover study of 11 aspirin-treated patients with prior history of STEMI treated with PPCI, for which prasugrel and morphine had been previously administered. Patients were randomised to receive either morphine (5 mg) or saline intravenously followed by 60 mg prasugrel. Blood samples were collected before randomised treatment and over 24 hours after prasugrel administration. The inhibitory effects of prasugrel on platelets were determined using the VerifyNow P2Y12 assay and light transmission aggregometry. Plasma levels of prasugrel and prasugrel active metabolite were measured. Platelet reactivity determined by VerifyNow PRU, VerifyNow % Inhibition and LTA was significantly higher at 30–120 minutes (min) when morphine had been co-administered compared to when saline had been co-administered. Morphine, compared to saline, significantly delayed adequate platelet inhibition after prasugrel administration (158 vs 68 min; p = 0.006). Patients with delayed onset of platelet inhibition also had evidence of delayed absorption of prasugrel. In conclusion, prior administration of intravenous morphine significantly delays the onset of action of prasugrel. Intravenous drugs may be necessary to reduce the risk of acute stent thrombosis in morphine-treated STEMI patients undergoing PPCI.

P6529Safety of emergency pretreatment regimen for contrast allergy before percutaneous coronary intervention for ST-elevation myocardial infarction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K Jha ◽  
A Berger ◽  
J Blankenship
Keyword(s):  
Myocardial Infarction ◽  
Percutaneous Coronary Intervention ◽  
Medical Center ◽  
Coronary Intervention ◽  
St Elevation Myocardial Infarction ◽  
Prior History ◽  
Percutaneous Coronary ◽  
History Of ◽  
St Elevation ◽  
Contrast Allergy

Abstract Background Primary percutaneous coronary intervention (PPCI) is the best treatment for ST-elevation myocardial infarction (STEMI). However, patients with prior contrast reactions may not receive PCI due to concern over a recurrent contrast reaction. Purpose To determine the clinical efficacy of emergency pretreatment regimens for contrast allergy in STEMI patients undergoing PPCI. Methods We retrospectively identified all individuals with a history of contrast allergy who presented with STEMI, were pretreated for contrast allergy, and underwent PPCI at our medical center between January 2005 to May 2018. Emergency pretreatment regimen included a combination of intravenous (IV) steroid, IV famotidine and IV diphenhydramine administered immediately before PCI. Laboratory records, inpatient notes, and discharge summaries were reviewed to confirm the severity of the original contrast allergy and identify any allergic breakthrough reaction after pretreatment with an emergency regimen. Reactions were characterized as mild, moderate, severe, or of unknown severity. Results During the study period 15,712 individuals underwent PCI, of which 176 patients presented with STEMI, had confirmed contrast allergy, and were pretreated before undergoing PCI. No patient with a history of contrast allergy underwent PPCI without pre-treatment. Mean age was 64 years, with 52% males, and all individuals were white. The majority had hypertension (77%), 67% had dyslipidemia, 29% had diabetes mellitus, and 20% patients had a prior history of MI. Intravenous steroids used in the emergency regimen included methylprednisone (n=100), hydrocortisone (n=70), and dexamethasone (n=6). The original allergic response to ICM was mild in 59% patients, moderate in 15%, severe in 20% and of unknown severity in 13% patients. Of the 176 patients only 10 (5.6%) developed a breakthrough reaction. Most of which were mild; none was fatal. Median length of hospital stays was three days and nine patients (10.8%) passed away within 30 days of hospital admission. Conclusions Patients with prior contrast allergy presenting with STEMI can safely undergo PPCI after emergency pretreatment. Breakthrough reactions are infrequent and mild.

scholarly journals Sex Differences in Platelet Reactivity in Patients With ST-Elevation Myocardial Infarction: A Sub-Analysis of the ON-TIME 3 Trial

2021 ◽  
Vol 8 ◽  
Author(s):  
Anne H. Tavenier ◽  
Renicus S. Hermanides ◽  
Jan Paul Ottervanger ◽  
Svetlana V. Belitser ◽  
Olaf H. Klungel ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Sex Differences ◽  
Platelet Reactivity ◽  
Plasma Concentrations ◽  
Multivariable Analysis ◽  
Platelet Inhibition ◽  
St Elevation Myocardial Infarction ◽  
Primary Pci ◽  
St Elevation ◽  
Male Patients

Background: Fast and adequate platelet inhibition is one of the cornerstones in the treatment of patients with ST-elevation myocardial infarction (STEMI). The aim of this analysis is to examine sex differences in platelet inhibition in the acute treatment of STEMI patients.Methods: Platelet reactivity units (PRU) and ticagrelor plasma concentrations of all patients in the ON-TIME 3 were compared according to sex. All patients were pre-treated with crushed ticagrelor, aspirin and heparin. Both univariable and multivariable analyses were performed.Results: In this sub-analysis of the ON-TIME 3 trial, 195 STEMI patients, of which 58 female patients (29.7%) and 137 male patients (70.3%), were analyzed. PRU-values immediately post-PCI were not different in females [median 135 (IQR 47-228)] compared to males [160 (IQR 40-219), P = 0.92]. Ticagrelor plasma concentrations were higher in the females at the start of primary PCI [141 ng/mL (IQR 25-491) vs. 76 ng/mL (IQR 15-245), P = 0.049] and at 6 hours post-primary PCI [495 ng/mL (IQR 283-661) vs. 321 ng/mL (IQR 196-537), P = 0.001] compared to males. However, immediately post-primary PCI and at 1-hour post-primary PCI no significant differences in ticagrelor concentrations were seen between sexes. In multivariable analysis, sex was significantly associated with ticagrelor concentration (P = 0.04), but not with PRU (P = 0.93).Conclusion: Effective platelet inhibition reached by crushed ticagrelor in STEMI patients was similar in both sexes. Females had similar or even higher ticagrelor plasma concentrations up to 6 hours post-primary PCI compared with males.

scholarly journals Impact of opioids on P2Y12 receptor inhibition in patients with ST-elevation myocardial infarction who are pre-treated with crushed ticagrelor: Opioids aNd crushed Ticagrelor In Myocardial infarction Evaluation (ON-TIME 3) trial

2020 ◽  
Author(s):  
Anne H Tavenier ◽  
Renicus S Hermanides ◽  
Jan Paul Ottervanger ◽  
Rudolf Tolsma ◽  
Antony van Beurden ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Pain Relief ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
St Elevation Myocardial Infarction ◽  
P2y12 Receptor ◽  
Primary Pci ◽  
Receptor Inhibition ◽  
St Elevation

Abstract Aims Platelet inhibition induced by P2Y12 receptor antagonists in patients with ST-elevation myocardial infarction (STEMI) can be affected by concomitant use of opioids. The aim of this trial was to examine the effect of intravenous (iv) acetaminophen compared with iv fentanyl on P2Y12 receptor inhibition in patients with STEMI. Methods and results The Opioids aNd crushed Ticagrelor In Myocardial infarction Evaluation (ON-TIME 3) trial randomized 195 STEMI patients who were scheduled to undergo primary percutaneous coronary intervention (PCI) and were pre-treated with crushed ticagrelor to iv acetaminophen (N = 98) or iv fentanyl (N = 97) in the ambulance. The primary endpoint, consisting of the level of platelet reactivity units (PRU) measured immediately after primary PCI, was not significantly different between the study arms [median PRU 104 (IQR 37–215) vs. 175 (63–228), P = 0.18]. However, systemic levels of ticagrelor were significantly higher in the acetaminophen arm at the start of primary PCI [151 ng/mL (32–509) vs. 60 ng/mL (13–206), P = 0.007], immediately after primary PCI [326 ng/mL (94–791) vs. 115 ng/mL (38–326), P = 0.002], and at 1 h after primary PCI [488 ng/mL (281–974) vs. 372 ng/mL (95–635), P = 0.002]. Acetaminophen resulted in the same extent of pain relief when compared with fentanyl [reduction of 3 points on 10-step-pain scale before primary PCI (IQR 1–5)] in both study arms (P = 0.67) and immediately after PCI [reduction of 5 points (3–7); P = 0.96]. Conclusion The iv acetaminophen in comparison with iv fentanyl was not associated with significantly lower platelet reactivity in STEMI patients but resulted in significantly higher ticagrelor plasma levels and was effective in pain relief.

Impact of vomiting on P2Y12 platelet inhibition in patients with ST-elevation myocardial infarction: A prespecified subanalysis of the ON-TIME 3 trial

2022 ◽  
Vol 243 ◽  
pp. 39-42
Author(s):  
Anne  H. Tavenier ◽  
Renicus  S. Hermanides ◽  
Jan  Paul. Ottervanger ◽  
Svetlana  V. Belitser ◽  
Olaf.  H. Klungel ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Platelet Inhibition ◽  
St Elevation Myocardial Infarction ◽  
St Elevation

Abstract 346: Platelet Reactivity to Aspirin and Clopidogrel in Patients with Acute ST Elevation Myocardial Infarction and its Correlation with High Sensitivity C- Reactive Protein

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Archana Rajdev ◽  
Oana Penciu ◽  
Jacqueline Bradley ◽  
Cristina Mihu ◽  
Alan Siqueros ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Platelet Reactivity ◽  
High Sensitivity ◽  
St Elevation Myocardial Infarction ◽  
Diabetic Patients ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Significant Difference ◽  
St Elevation ◽  
Hs Crp

INTRODUCTION Implantation of bare metal or drug eluting stents supported by dual antiplatelet therapy (DAPT) is standard treatment for the management of patients with ST elevation myocardial infarction (STEMI). Individual response to aspirin and clopidogrel is heterogeneous, and decreased response is associated with thrombotic events following stenting. We postulated that systemic inflammation at the time of STEMI would diminish responsiveness to DAPT. The aim of this study is to evaluate the correlation between elevated high-sensitivity C-reactive protein (hs-CRP) as a marker of inflammation and decreased platelet sensitivity to DAPT in STEMI. METHODS We recruited patients with STEMI undergoing percutaneous coronary intervention (PCI) who received oral clopidogrel 600 mg loading dose followed by 75 mg daily maintenance dose and aspirin 325 mg daily. Platelet reactivity and hs-CRP were measured within 72 hours of PCI and at 6 weeks. For patients receiving eptifibatide, blood samples were taken 48 hours after discontinuation. Platelet reactivity was assessed using the VerifyNow platelet function analyzer. A cut-off value of 208 platelet reaction units (PRU) was used to define high on-clopidogrel platelet reactivity (HCPR) and a value of 454 aspirin reaction units (ARU) was used to define high on-aspirin platelet reactivity (HAPR). RESULTS In 20 patients aged 31 to 85, in hospital and 6 weeks after STEMI, hs-CRP was 6.7 (SD 4.0) and 2.6 (SD 3.2) respectively, p< 0.01. Changes in ARU from 408.3 (SD 54.3) to 425.2 (SD 68.2) and PRU from 157.8 (SD 74.7) to 164.2 (SD 75) were not statistically significant. 2 patients had HAPR in hospital; 1 became sensitive at follow up. 2 patients developed HAPR and HCPR. We saw a trend towards higher PRU in diabetic patients and those prescribed statins. CONCLUSIONS Although we found a significant difference in hs-CRP levels between the first and second time point, no significant difference was found in on-aspirin and on-clopidogrel platelet reactivity between the time points.Thus, in this small series, the acute inflammatory state associated with STEMI did not appear to influence the on-DAPT reactivity at the dosages used. Trends among those with diabetics and prescribed statins will be discussed

Abstract 14004: Pharmacodynamic Profiles of Ticagrelor in Patients With ST-Elevation Myocardial Infarction: A Prospective Randomized Comparison of Escalating Loading Dose Regimens

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Francesco Franchi ◽  
Fabiana Rollini ◽  
Jung Rae Cho ◽  
Mona Bhatti ◽  
Christopher DeGroat ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Time Course ◽  
Peak Plasma ◽  
Platelet Reactivity ◽  
Randomized Study ◽  
Plasma Concentrations ◽  
St Elevation Myocardial Infarction ◽  
Reactivity Index ◽  
Loading Dose ◽  
St Elevation

Background: Pharmacodynamic (PD) studies have shown that in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI), ticagrelor is associated with suboptimal platelet inhibition and elevated rates of high on-treatment platelet reactivity (HPR) in the early hours after loading dose (LD) administration. Impaired absorption affecting drug pharmacokinetics (PK) has been hypothesized as a contributing factor suggesting increasing LD regimens to improve PK/PD profiles. To date there are no randomized studies which have investigated the PK/PD effects of escalating ticagrelor LD regimens in patients undergoing PPCI. Methods: In this prospective, randomized study, STEMI patients undergoing PPCI (n=52) were randomized 1:1:1 to receive 180mg, 270mg or 360mg LD of ticagrelor. PK and PD analysis were performed before and at 6 time points after LD. PD assessments included P2Y 12 reaction units (PRU) measured by VerifyNow P2Y12 and platelet reactivity index (PRI) measured by VASP. PK assessments included plasma concentrations of ticagrelor and its metabolite AR-C124910XX. Results: At baseline there were no differences in platelet reactivity between groups. At 2 hrs (primary endpoint), there were no differences in PRU between groups (p=0.54). There were no differences in PRU between groups during the overall study time course (p=0.17; Figure). Accordingly, HPR (PRU>208) at 2 hrs was observed in 30% of patients and was not reduced by escalating ticagrelor LD regimens. Consistent PD findings were observed with VASP-PRI. PK data tracked PD results, with a non-dose related delay in peak plasma concentrations of both ticagrelor and AR-C124910XX, particularly in HPR patients. Conclusions: In STEMI patients undergoing PPCI, increasing the LD regimen of ticagrelor did not translate into more prompt or potent P2Y 12 inhibition, which is attributed to impaired absorption in the early hours after drug administration.

Factors influencing patient decision delay in activation of emergency medical services for suspected ST-elevation myocardial infarction

2020 ◽  
pp. 147451512095373
Author(s):  
Ahmad Alrawashdeh ◽  
Ziad Nehme ◽  
Brett Williams ◽  
Karen Smith ◽  
Michael Stephenson ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Emergency Medical Services ◽  
Symptom Onset ◽  
St Elevation Myocardial Infarction ◽  
Medical Services ◽  
Factors Associated ◽  
Emergency Medical ◽  
History Of ◽  
St Elevation ◽  
At Home

Objective: The purpose of this study was to identify factors associated with time delay to emergency medical services for patients with suspected ST-elevation myocardial infarction. Methods: This observational study involved 1994 suspected ST-elevation myocardial infarction patients presenting to the emergency medical services in Melbourne, Australia, between October 2011–January 2014. Factors associated with delays to emergency medical services call of >1 h and emergency medical services self-referral were analyzed using multivariable logistic regression. Results: The time of symptom onset was reported for 1819 patients (91.2%), the median symptom onset-to-call time was 52 min (interquartile range=17–176). Of all emergency medical services calls, 17% were referred by healthcare professionals. Compared to self-referred patients, patients who presented to a general practitioner or hospital had higher odds of delay >1 h to emergency medical services activation (adjusted odds ratio 7.76; 95% confidence interval 5.10–11.83; and 8.02; 3.65–17.64, respectively). The other factors associated with emergency medical services call delays of >1 h were living alone, non-English speaking background, a history of substance abuse, less severe symptoms, symptom onset at home and at rest, and self-treatment. Emergency medical services self-referred patients were more likely to be older than 75 years, have a history of ischemic heart disease or revascularization, more severe symptoms, and symptom onset at home, with activity, during the weekends and out-of-hours. Conclusion: Almost one-fifth of emergency medical services calls for suspected ST-elevation myocardial infarction were healthcare referrals, and this was associated with increased delays. A wide range of factors could influence a patient’s decision to directly and rapidly seek emergency medical services. More efforts are needed to educate at-risk populations about early self-referral to the emergency medical services.

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