Morphine in acute coronary syndrome: systematic review and meta-analysis

Abstract

ObjectiveMorphine is frequently used in acute coronary syndrome (ACS) due to its analgesic effect, it being recommended in the main cardiology guidelines in Europe and the USA. However, controversy exists regarding its routine use due to potential safety concerns. We conducted a systematic review of randomised-controlled trials (RCTs) and observational studies to synthesise the available evidence.DesignSystematic review and meta-analysis.Data sourcesCENTRAL, MEDLINE, EMBASE and trial registries.Eligibility criteria for selecting studiesWe included RCTs and observational studies evaluating the impact of morphine in cardiovascular outcomes or platelet reactivity measures.Data extraction and synthesisData were screened, extracted and appraised by two independent reviewers. The data were pooled results using a random-effects model. Outcomes included in-hospital mortality, major adverse cardiovascular events (MACE), platelet reactivity (using VerifyNow) and bleeding, reported as relative risk (RR) with 95% CI. We assessed the confidence in the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. We followed the Meta-analysis Of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.ResultsFive RCTs and 12 observational studies were included, enrolling 69 993 participants. Pooled results showed an increased risk of in-hospital mortality (RR 1.45 [95% CI 1.10 to 1.91], low GRADE confidence), MACE (RR 1.21, 95% CI 1.02 to 1.45) and an increased platelet reactivity at 1 and 2 hours (59.37 platelet reactivity units [PRU], 95% CI 36.04 to 82.71; 68.28 PRU, 95% CI 37.01 to 99.55, high GRADE confidence) associated with morphine. We found no significant difference in the risk of bleeding. We found no differences in subgroup analyses based on study design and ACS subtype.ConclusionsMorphine was associated with an increased risk of in-hospital mortality and MACE but the high risk of bias leads to low result confidence. There is high confidence that morphine decreases the antiplatelet effect of P2Y12 inhibitors.PROSPERO registration numberCRD42016036357.

Cardiogenic shock induced by a high dose of intravenous morphine

“…There are also reported cases of CS occurring after the administration of opioids different from morphine, such as tramadol [25] or dextropropoxyphene [26]. Moreover, there is a widely observed effect on mortality of the patients treated with morphine during acute heart failure or acute coronary syndromes [7][8][9][10][11], but because of the lack of randomized clinical trials and observational characteristics of the conducted studies, it is impossible to draw definite conclusions on that subject. However, the guidelines of the European Cardiovascular Society report the suspected effect on mortality and recommend not to use morphine routinely in acute heart failure with an exception of cases with severe dyspnea and pulmonary edema [7].…”

“…It is widely used as a medication, most often in chronic pain treatment [5], hemorrhagic shock [6], or acute heart failure accompanied by pulmonary edema with severe dyspnea [7]. Although it is clear that the therapeutic use of morphine has many positive effects, there are studies that bring up concerns about serious side effects and risks associated with its use, such as reported a higher mortality among the patients treated with morphine in acute heart failure or with acute coronary syndromes [7][8][9][10][11].…”

Management Therapy of ST-Segment Elevation Myocardial Infarction: A Literature Review

“…It reduces the sympathetic effect in the arteriolar and venous contraction, producing venous pooling which can reduce the cardiac output and arterial pressure [15]. However, some meta-analysis research concludes that morphine can reduce the antiplatelet effect of clopidogrel in the early onset of ACS symptoms, inhibiting the clopidogrel therapy effect [16].…”

“…Besides, it is more effective than fibrinolytics in opening a blockage in the coronary artery. Also, it has a good effect on the clinical result, either in the short or long term and can minimize the death risk, myocardial infarction, or repetitive stroke [16].…”

Nitrous oxide/oxygen plus acetaminophen versus morphine in ST elevation myocardial infarction: open-label, cluster-randomized, non-inferiority study

“…Opioids (most commonly morphine) are recommended, [2] although their efficacy and safety have not been fully evaluated in randomized trials. Recently, the deleterious effect of morphine on inhibition of platelet reactivity in STEMI patients treated with P2Y 12 inhibitors has been reported [3][4][5][6]. Studies have reported that morphine is associated with a delayed onset of action of oral antiplatelet drugs due to vomiting or delayed gastric emptying, which reduce the absorption of these drugs [4].…”