In-hospital outcomes in invasively managed acute myocardial infarction patients who receive morphine

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Abstract

<div class="section"> <a class="named-anchor" id="S1">  </a> <h5 class="section-title" id="d5244957e141">Objective</h5> <p id="P1">We aimed to analyze the association between morphine and in-hospital outcomes in invasively managed ST elevation myocardial infarction (STEMI) and non-ST elevation acute coronary syndrome (NSTE-ACS) patients. </p> </div><div class="section"> <a class="named-anchor" id="S2">  </a> <h5 class="section-title" id="d5244957e146">Background</h5> <p id="P2">Morphine is commonly used for analgesia in the setting of acute coronary syndromes (ACS), however, recently its utility in ACS has come under closer scrutiny. </p> </div><div class="section"> <a class="named-anchor" id="S3">  </a> <h5 class="section-title" id="d5244957e151">Methods</h5> <p id="P3">We identified all STEMI and NSTE-ACS patients undergoing coronary angiogram +/- percutaneous intervention between January 2009 and July 2016 in our center and recorded patient characteristics and inpatient outcomes. </p> </div><div class="section"> <a class="named-anchor" id="S4">  </a> <h5 class="section-title" id="d5244957e156">Results</h5> <p id="P4">Overall, 3027 patients were examined. Overall, STEMI patients who received morphine had no difference in in-hospital mortality [4.18% versus 7.54%, odds ratio (OR): 0.36, p=0.19], infarct size (mean troponin level 0.75 ng/ml versus 1.29 ng/ml, p=0.32) or length of hospital stay (p=0.61). The NSTE-ACS patients who received morphine had a longer hospital stay (mean 6.58 days versus 4.78 days, p<0.0001) and larger infarct size (mean troponin 1.16 ng/ml versus 0.90 ng/ml, p= 0.02). Comparing matched patients, the use of morphine was associated with larger infarct size (mean troponin 1.14±1.92 ng/ml versus 0.83±1.49 ng/ml, p=0.01), longer hospital stay (6.5±6.82 days versus 4.89±5.36 days, p=0.004) and a trend towards increased mortality (5% versus 2%, OR: 2.55, p=0.06) in NSTE-ACS patients but morphine did not affect outcomes in the propensity matched STEMI patients. </p> </div><div class="section"> <a class="named-anchor" id="S5">  </a> <h5 class="section-title" id="d5244957e161">Conclusion</h5> <p id="P5">In a large retrospective study, morphine was associated with larger infarct size, a longer hospital stay and a trend towards increased mortality in invasively managed NSTE-ACS patients even after adjustment for clinical characteristics. </p> </div>

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2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.

Patrick O'Gara, Frederick Kushner, Deborah D Ascheim … (2013)

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Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction: the randomized, double-blind, placebo-controlled IMPRESSION trial

Jacek Kubica, Piotr Adamski, Małgorzata Ostrowska … (2015)

Aims The currently available data indicate a drug–drug interaction between morphine and oral P2Y12 receptor inhibitors, when administered together. The aim of this trial was to assess the influence of infused morphine on pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite (AR-C124910XX) in patients with acute myocardial infarction. Methods and results In a single-centre, randomized, double-blind trial, patients were assigned in a 1:1 ratio to receive intravenously either morphine (5 mg) or placebo, followed by a 180 mg loading dose of ticagrelor. Pharmacokinetics was determined with liquid chromatography tandem mass spectrometry and ticagrelor antiplatelet effects were measured with up to three different platelet function tests: vasodilator-stimulated phosphoprotein phosphorylation assay, multiple electrode aggregometry and VerifyNow. The pharmacokinetic and pharmacodynamic assessment was performed in 70 patients (35 in each study group). Morphine lowered the total exposure to ticagrelor and its active metabolite by 36% (AUC(0–12): 6307 vs. 9791 ng h/mL; P = 0.003), and 37% (AUC(0–12): 1503 vs. 2388 ng h/mL; P = 0.008), respectively, with a concomitant delay in maximal plasma concentration of ticagrelor (4 vs. 2 h; P = 0.004). Multiple regression analysis showed that lower AUC(0–12) values for ticagrelor were independently associated with the administration of morphine (P = 0.004) and the presence of ST-segment elevation myocardial infarction (P = 0.014). All three methods of platelet reactivity assessment showed a stronger antiplatelet effect in the placebo group and a greater prevalence of high platelet reactivity in patients receiving morphine. Conclusions Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction. ClinicalTrials.gov Identifier: NCT02217878.

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Association of intravenous morphine use and outcomes in acute coronary syndromes: results from the CRUSADE Quality Improvement Initiative.

Charles V Pollack, R. Patel, Jeffrey Washam … (2005)

Although intravenous morphine is commonly used for the treatment of chest pain in patients presenting with non-ST-segment elevation acute coronary syndromes (NSTE ACS), its safety has not been evaluated. The CRUSADE Initiative is a nonrandomized, retrospective, observational registry enrolling patients with NSTE ACS to evaluate acute medications and interventions, inhospital outcomes, and discharge treatments. The study population comprised patients presenting with NSTE ACS at 443 hospitals across the United States from January 2001 through June 2003 (n = 57,039). Outcomes were evaluated in patients receiving morphine versus not and between patients treated with morphine versus intravenous nitroglycerin. A total of 17,003 patients (29.8%) received morphine within 24 hours of presentation. Patients treated with any morphine had a higher adjusted risk of death (odds ratio [OR] 1.48, 95% CI 1.33-1.64) than patients not treated with morphine. Relative to those receiving nitroglycerin, patients treated with morphine also had a higher adjusted likelihood of death (OR 1.50, 95% CI 1.26-1.78). Utilizing a propensity score matching method, the use of morphine was associated with increased inhospital mortality (OR 1.41, 95% CI 1.26-1.57). The increased risk of death in patients receiving morphine persisted across all measured subgroups. Use of morphine either alone or in combination with nitroglycerin for patients presenting with NSTE ACS was associated with higher mortality even after risk adjustment and matching on propensity score for treatment. This analysis raises concerns regarding the safety of using morphine in patients with NSTE ACS and emphasizes the need for a randomized trial.