Effects of morphine on P2Y12 platelet inhibitors in patients with acute myocardial infarction: A meta-analysis

https://doi.org/10.1016/j.ajem.2020.11.003Get rights and content

Abstract

Objective

To explore the effects of morphine on P2Y12 platelet inhibitors in patients with acute myocardial infarction (AMI).

Methods

PubMed, Embase, Cochrane Library, and Web of Science were used to retrieve literature through 11th May 2019. Standardized weighted mean difference (SMD) and relative risk (RR) with 95% confidence intervals (CI), P-value, and I2 value were used to assess the strength of the association in this meta-analysis. Outcomes included platelet reactivity, high residual platelet reactivity (HRPR), ticagrelor maximum concentration (Cmax), ticagrelor area under curve (AUC), death rate, reinfarction rate, stroke, stent thrombosis, thrombolysis in myocardial infarction (TIMI) hemorrhage, dyspnea, emesis, contrast-induced nephropathy, and pulmonary edema.

Results

A total of 13 articles were included in this study, containing 5688 patients (morphine group: n = 2014, control group: n = 3674). Results illustrated that the morphine group had a higher platelet reactivity (SMD: 0.834, 95%CI: 0.483–1.186, P < 0.001) and HRPR rate (RR: 1.994, 95%CI: 1.536–2.588, P < 0.001) than the control group, while the Cmax of ticagrelor (WMD: -481.838, 95%CI: −841.242–122.434, P = 0.009) was lower than that of the control group. The death rate of the morphine group was lower than that in the control group (RR: 0.561, 95%CI: 0.337–0.933, P = 0.026). The morphine group had a higher emesis rate than the control group (RR: 4.486, 95%CI: 2.263–8.891, P < 0.001).

Conclusion

Morphine effectively suppresses the inhibition effect of P2Y12 platelet inhibitors in patients with AMI.

Introduction

Acute coronary syndrome (ACS) occurs when the platelets clump together at the site of the ruptured or eroded atheromatous plaque and form local thrombus, causing a significant reduction or complete disruption of the coronary blood flow [1]. Considering the role of platelets activation in the formation of thrombus in ACS, pharmacologic treatments are focused on the inhibition of P2Y12ADP receptors of platelets [2]. P2Y12 inhibitors are commonly administrated with aspirin as a dual antiplatelet therapy, which plays an important role in the ACS treatment [[3], [4], [5]].

Morphine, an opioid analgesics, is commonly prescribed to patients with acute myocardial infarction (AMI) for pain management [6,7]. Unlike P2Y12 inhibitors, morphine is dispensable in ACS. The administration of morphine provides adequate pain relief and easing sympathetic drive [8]. Because of the strong analgesic and benefit hemodynamic properties, morphine has been recommended by the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) as a treatment for the nitrate resistant chest pain caused by AMI [9].

The growing prevalence of P2Y12 inhibitors use is urging the need to evaluate and assess the efficacy and safety of co-administrating morphine with P2Y12 inhibitors. Nimmo et al. found the ability of morphine to retard the absorption of orally administrated drugs by inhibiting gastric emptying, decreasing the peak plasma levels of oral drugs [10]. Moreover, recent studies revealed that morphine delayed and attenuated the maximal inhibition of oral antiplatelet agents [7,11].

Currently, the uncertainty of the interaction between P2Y12 inhibitors and morphine remains an obstacle in managing AMI. Hence, we conducted a meta-analysis of randomized/non-randomized controlled trials to investigate the effects of morphine on P2Y12 inhibitors.

Section snippets

Search strategy

PubMed, Embase, Cochrane Library, and Web of Science were used to retrieve the literature through 11th May 2019. Major search terms included were “myocardial infarction” OR “cardiovascular stroke” OR “heart attack” OR “myocardial infarct” OR “myocardial ischemia” OR “ischemic heart disease” OR “acute coronary syndrome” AND “morphia/morphine” AND “hydrochloride, prasugrel” OR “ticagrelor” OR “clopidogrel”.

Inclusion and exclusion criteria

Inclusion criteria were listed as follows: (1) randomized/non-randomized controlled trials;

Results

A total of 165 articles were retrieved according to search strategy from four databases, then all literature was screened by inclusion and exclusion criteria, and 8 high-quality and 5 low-quality articles were included finally (Fig. 1). In total, 5688 patients were enrolled in this study, of which 2014 subjects received morphine and 3674 subjects accepted placebo or no intervention. (Table 1).

Discussion

In this study, 8 high-quality and 5 low-quality articles were included. Patients were divided into the morphine group (n = 2014) and the control group (n = 3674). The main results of the meta-analysis are listed as follows: (1) The effect of P2Y12 platelet inhibitor diminished when the ingestion occurred after the administration of morphine; (2) The incidence of HRPR increased after the administration of morphine; (3) The use of morphine decreased the ticagrelor Cmax; (4) The death rate in the

Conclusion

This research observed a repressive impact of morphine on P2Y12 platelet inhibitors in patients with AMI. The application of morphine increases the platelet reactivity, HRPR rate, emesis, and decrease the death rate and efficacy of P2Y12 platelet inhibitors.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of Competing Interest

The authors declare that they have no competing interests.

Acknowledgements

None.

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