What is the primary reason for administering morphine to a client with an mi?

Journal Article

Etienne Puymirat,

1

Department of Cardiology

,

European Hospital of Georges Pompidou, Assistance Publique des Hôpitaux de Paris [AP-HP]

,

15-20 rue Leblanc

,

Paris 75015

,

France

2

University Paris Descartes

,

Paris

,

France

3

INSERM U-970

,

Paris

,

France

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Revision received:

10 August 2015

Accepted:

04 October 2015

Published:

17 November 2015

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  Etienne Puymirat, Lionel Lamhaut, Nicolas Bonnet, Nadia Aissaoui, Patrick Henry, Guillaume Cayla, Simon Cattan, Gabriel Steg, Laurent Mock, Gregory Ducrocq, Patrick Goldstein, François Schiele, Eric Bonnefoy-Cudraz, Tabassome Simon, Nicolas Danchin, Correlates of pre-hospital morphine use in ST-elevation myocardial infarction patients and its association with in-hospital outcomes and long-term mortality: the FAST-MI [French Registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction] programme, European Heart Journal, Volume 37, Issue 13, 1 April 2016, Pages 1063–1071, //doi.org/10.1093/eurheartj/ehv567

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Abstract

Introduction

The use of opioids is recommended for pain relief, breathlessness, and anxiety in patients with acute myocardial infarction [AMI], although data from randomized controlled trials documenting its benefit or safety on hard outcomes are completely lacking.1,2 Beyond its analgesic benefit per se, the use of opioids appears justified because pain is associated with sympathetic activation that causes vasoconstriction and increased cardiac workload.2

In heathy volunteers, however, recent data have demonstrated a drug–drug interaction between morphine and clopidogrel: concomitant injection of morphine slows clopidogrel absorption, decreases plasma levels of its active metabolite, retards, and diminishes its pharmacologic effects, a mechanism which could lead to treatment failure at the acute stage of MI.3 Likewise, in ST-elevation myocardial infarction [STEMI] patients, inhibition of platelet reactivity by prasugrel and ticagrelor is delayed when morphine is co-administered.4 Recently, the Administration of Ticagrelor in the cathLab or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery [ATLANTIC] trial showed more frequent ST-segment resolution before percutaneous coronary intervention [PCI] in patients treated with ticagrelor in the ambulance when they did not receive pre-hospital morphine, whereas no such effect was observed in morphine-treated patients; there was no interaction between morphine use and infarct-related artery patency, however.5

The aim of this study was to assess the correlates of pre-hospital morphine use, and its relationship with clinical outcomes, in STEMI patients from the French Registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction [FAST-MI] 2010. Consistency of the results was assessed by replicating the analyses in STEMI patients from the FAST-MI 2005 registry. In this latter cohort, special consideration was given to the patients who had been pre-treated with clopidogrel, according to genetic polymorphisms of ABCB1 and CYP2C19 enzymes, which are involved in clopidogrel absorption and metabolism.6,7

Methods

Primary analysis

For the main analysis, we selected patients with STEMI or left bundle branch block [LBBB] from FAST-MI 2010, the methodology of which has been previously described in detail.8,9 Briefly, the primary objective was to evaluate practices for MI management in ‘real life’ and to measure their association with medium- and long-term outcomes in patients admitted to intensive care units [ICUs] with AMI. This registry results from a prospective multicentre [213 centres] study, including 4169 patients, recruited consecutively from ICUs over a period of 1 month, with a possible extension of recruitment up to one additional month. Participation in the study was offered to all French institutions, university teaching hospitals, general and regional hospitals, and private clinics with ICUs in the capacity to receive acute coronary syndrome [ACS] emergencies, and 76% participated.

We included men or women aged over 18 years, admitted within 48 h after symptom onset for an AMI characterized by the elevation of troponin or creatine phosphokinase myocardial band associated with at least one of the following elements—symptoms compatible with myocardial ischaemia, new pathological Q waves, ST-T changes compatible with myocardial ischaemia—and who agreed to take part in the study. For the present study, only patients presenting with persistent ST-elevation, presumed new Q waves, or presumed new LBBB were included.

The main exclusion criteria were [i] iatrogenic MI, defined as MI occurring within 48 h of a therapeutic procedure [bypass surgery, coronary angioplasty, or any other medical or surgical intervention]; [ii] ACS diagnosis invalidated in favour of another diagnosis; and [iii] patients with unstable angina and no increase in cardiac biomarkers.

The registry was conducted in compliance with Good Clinical Practice guidelines, French law, and the French data protection law. The protocol was reviewed and approved by the Committee for the Protection of Human Subjects of Saint-Louis University Hospital, and the data file of FAST-MI was declared to the Commission Nationale Informatique et Liberté. All patients gave informed consent for their participation in the study. Clinicaltrials.gov identifier: NCT01237418.

Baseline characteristics [demographics, risk factors, and medical history] were collected prospectively. All data were recorded on computerized case record forms by dedicated research technicians sent in each of the centres at least once a week. In-hospital complications [recurrent MI, stent thrombosis, bleeding, or transfusion] were collected. Recurrent MI was defined as recurrence of clinical symptoms or occurrence of ECG changes accompanied by a recurrent increase of cardiac markers. Stent thrombosis was defined as definite or probable according to the Academic Research Consortium definition.10 Bleeding was classified as major or minor according to the Thrombolysis in Myocardial Infarction [TIMI] criteria.11 Follow-up data were collected through contacts with the attending physicians, the patients, or their family. If missing, vital status was assessed from the civil registries of the patients' birthplaces. One-year follow-up was 99% complete.

Replication analysis

For assessing the robustness of the results, we repeated the analysis in patients [n = 1726] with STEMI or LBBB in the FAST-MI 2005 registry, which had been carried out 5 years before, using a similar methodology, and in which polymorphisms of CYP2C19 and ABCB1 had been assessed in 66% of the patients.6,12,13 Clinicaltrials.gov identifier: NCT00673036. In the 2005 registry, the only thienopyridine used was clopidogrel, and fewer patients had undergone primary PCI. The set of variables collected in 2005 was essentially similar to that collected in 2010, but some variables of interest, in particular stent thrombosis, had not been recorded in 2005.

Genetic testing in the FAST-MI 2005 cohort

Genomic DNA was extracted from whole-blood specimens with the use of a purifier [the MagNA Pure Compact Instrument, Roche] according to the manufacturer's recommendations. Genotyping for CYP2C19 and ABCB1 was performed with the use of an oligonucleotide ligation assay [SNPlex, Applied Biosystems] after initial amplification by means of a polymerase chain-reaction assay involving two primers for the major variant alleles CYP2C19*2 [rs4244285], CYP2C19*3 [rs4986893], and ABCB1 [rs1045642]. Genotyping for known variants of CYP2C19 with functional importance—CYP2C19*4 [rs28399504], CYP2C19*5, CYP2C19*17 [rs12248560]—was performed with the use of an allelic discrimination assay [Custom TaqMan] and a detection system [ABI prism 7900HT Sequence Detection System, Applied Biosystems]. Base numbering and allele definitions follow the nomenclature of the Human Cytochrome P450 [CYP] Allele Nomenclature Committee [www.cypalleles.ki.se].

Statistical analysis

Continuous variables are reported as means and standard deviations [SDs] or medians and interquartile ranges [IQRs], when appropriate. Discrete variables are described as counts and percentages. Comparisons were made with χ2 or Fisher's exact tests for discrete variables, and by unpaired t tests, Wilcoxon sign-rank tests, Mann–Whitney tests, or one-way analyses of variance for continuous variables. Backward binary logistic regression analysis, using pre-hospital morphine use, baseline characteristics, and therapeutic management as covariates, was used to determine independent correlates of in-hospital complications. In addition, a propensity score for getting morphine was calculated using multiple logistic regression [using baseline characteristics of the patients and concomitant pre-hospital medications received] and used to build two cohorts of patients [388 patients each] matched on the propensity score, using a greedy matching procedure; the C-statistic for the propensity score was 0.87, and the Hosmer–Lemeshow test was not significant [P = 0.32]. The differences between the two matched cohorts were assessed by calculating the absolute value of standardized differences, and were always ≤10%. The matched population would give an 80% power to detect an absolute 6% increase in 1-year mortality in the morphine group, based upon an expected 7% mortality in the control group. Survival curves were estimated using the Kaplan–Meier estimation and compared using log-rank tests. Multivariate analyses of predictors of in-hospital endpoints were made by using backward, stepwise multiple logistic regressions. Correlates of survival were determined using a multivariate backward stepwise Cox analysis, using baseline characteristics and early management data as covariates. Statistical analyses were performed using IBM SPSS 20.0 [IBM SPSS Inc.] and NCSS 9 [NCSS, LLC. Kaysville, UT, USA]. For all analyses, a two-sided P value of