Beware! Morphine together with clopidogrel in MI may increase ischemic events, says JACC study

US: Morphine has been widely used to alleviate chest pain and anxiety of patients suffering from an acute MI. It has long been recommended for management of acute chest pain in patients with ACS and is currently endorsed by all guidelines for such use, although no randomized trial has been conducted so far to assess its clinical safety.

Previous studies have shown that morphine can delay gastric emptying and reduce the absorption of other important oral medications like ADP-receptor antagonists such as clopidogrel given to prevent stent thrombosis and reinfarction. Mechanistic studies have shown that morphine blunts the antiplatelet effects of clopidogrel and another oral adenosine diphosphates (ADP) receptor blockers like prasugrel and ticagrelor

New data have added more concerns about using morphine and clopidogrel together in patients presenting with non-ST-segment elevation ACS (NSTEACS).

Now a new study among patients presenting with a high-risk, invasively managed NSTEACS has shown concomitant morphine use with clopidogrel pretreatment to be associated with a higher risk for short-term cardiac ischemic events compared with patients receiving clopidogrel without morphine. The experts feel that this interaction has important clinical implications.

The researchers had a large patient population and conducted several statistical adjustments to account for potential confounders. They found that when the patients received both morphine and clopidogrel this lead to an early increase in [myocardial infarction (MI)]," They suggested that it is time to take action and not to give these two agents together.

The findings of the study have been published online in the Journal of the American College of Cardiology.

This study sought to explore the association between morphine and ischemic events in 5,438 patients treated with concomitant clopidogrel presenting with non-ST-segment elevation acute coronary syndromes (NSTEACS) in the EARLY ACS (Early Glycoprotein IIb/IIIa Inhibition in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome) trial. Patients not treated with clopidogrel (n = 3,462) were used as negative controls.Out of total patients enrolled 11.3% of patients were administered morphine early on.

Results showed that, in patients pretreated with clopidogrel, morphine use was associated with higher rates of ischemic events at 96 hours (adjusted odds ratio [OR], 1.40; P = .026), and there was also a trend for higher rates of death or MI at 30 days (adjusted OR, 1.29; P = .072).

The trial also included 3462 patients who were not pretreated with clopidogrel, and in this group, the use of morphine was not associated with increased ischemic events at 96 hours or any increase in death or MI at 30 days.

The researchers concluded that when used concomitantly with clopidogrel pre-treatment, morphine was associated with higher rates of ischemic events in patients with NSTEACS. (EARLY ACS: Early Glycoprotein IIb/IIIa Inhibition in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome; NCT00089895)

"Our results provide important new information for both society NSTEACS guidelines and regulatory agencies," the researchers add.

"Given the paucity of effective non-narcotic options for pain management in NSTEACS, our results are intended to encourage new investigation on alternative treatments," the authors say. Replacing morphine with other opioids may be a reasonable approach, they suggest.

For more details click on the link: DOI: 10.1016/j.jacc.2019.11.035