More Evidence That Morphine Hampers Effects of Antiplatelet Therapy in STEMI

CHICAGO, IL—The use of morphine in patients with STEMI is associated with greater platelet reactivity and a weakened ability to clear thrombus, a small study shows. The negative effects appear to be resolved by 2 days, however.

The short-term impairment is believed to be related to morphine delaying gastric transit and slowing the absorption of antiplatelet medications, explained study author Nikolaos Spinthakis, MBBS (East & North Hertfordshire NHS Trust, England).

“Whether this reduced antiplatelet effect leads to an increased danger of thrombosis needs to be assessed further in large clinical studies,” he told TCTMD during a poster presentation today at the American College of Cardiology 2016 Scientific Sessions.

Morphine is recommended in guidelines as the drug of choice for pain relief in STEMI patients, but there is accumulating evidence that it may affect the absorption of oral medications, particularly antiplatelets. One study, for example, showed that morphine was associated with greater platelet reactivity in patients treated with prasugrel (Effient; Eli Lilly) or ticagrelor (Brilinta; AstraZeneca) before primary PCI, and another showed that the opioid reduced exposure to and delayed absorption of ticagrelor.

The results of the current study are supported by those findings, Spinthakis said.

He and his colleagues prospectively looked at 125 consecutive patients presenting with STEMI, of whom 101 were given morphine in the ambulance and 24 were not. All patients received a loading dose of aspirin 300 mg and either clopidogrel 600 mg or ticagrelor 180 mg before primary PCI.

Blood samples taken at admission and on the second day of the hospitalization were tested using the point-of-care Global Thrombosis Test, which provides both the time to form an occlusive platelet thrombus (occlusion time) and the time required to break up the thrombus with endogenous thrombolysis (lysis time).

At admission, morphine-treated patients had a shorter occlusion time (mean 358 vs 670 seconds; P < 0.001), indicating greater platelet reactivity, and a longer lysis time (median 1,392 vs 1,084 seconds; P = 0.006), indicating lower thrombolytic potential. Those differences, however, were no longer significant on day 2, which “may well suggest that this effect can be related to the prolonged gastric emptying [and] the reduced absorption of these antiplatelet medications [with morphine],” Spinthakis said.

There were no differences based on morphine use in terms of in-hospital clinical events, but the study was not powered to examine that issue, he noted.

Commenting on the study for TCTMD, Luke Kim, MD (NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY), said the findings are consistent with prior research, but pointed out some limitations.

There is selection bias because of the lack of randomization, he said, noting that patients treated with morphine were more likely to have LV impairment and to be treated with glycoprotein IIb/IIIa inhibitors. “Is it really that patients who are receiving morphine [are] more prothrombotic, or did they come with worse clinical presentation including higher burden of clot to begin with?” Kim asked.

He said, too, that much of the research looking at this issue has involved patients taking clopidogrel rather than newer platelet inhibitors like ticagrelor and prasugrel, which have better absorption. And IV cangrelor (Kengreal; The Medicines Company) is another option that has become available in recent years, he said.

“Physicians should be aware that morphine can affect the level of available Plavix, at least in the initial stage of ST-elevation MI presentation,” Kim said. But “we shouldn’t be as concerned as we were a decade ago,” he added, “given that we have a lot of other agents at our disposal now.”  

• Farag M, Spinthakis N, Srinivasan M, Gorog DA. Morphine use impairs thrombotic status in patients with STEMI undergoing PPCI. Presented at: American College Cardiology 2016 Scientific Sessions. April 2, 2016. Chicago, IL.

Disclosures:

• Spinthakis and Kim report no relevant conflicts of interest.

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