Shelley Wood

May 21, 2014

PARIS, FRANCE — Use of morphine in patients undergoing primary PCI for STEMI may delay the onset of action with novel oral antiplatelet agents, potentially exposing patients to risk, a new analysis suggests.

Dr Guido Parodi (Careggi Hospital, Florence, Italy), reporting the results of a meta-analysis here at EuroPCR 2014 , stressed that his study looked only at platelet reactivity, not hard clinical events. Nevertheless, he says, physicians should be aware of the potential interaction with the new P2Y12 inhibitors and restrict morphine use to patients with the greatest need.

Parodi and colleagues first identified morphine as an independent predictor of high posttreatment platelet reactivity (HPPR) in the Rapid Activity of Platelet Inhibitor Drugs , looking specifically at prasugrel (Effient, Lilly/Daiichi-Sankyo) and ticagrelor (Brilinta, AstraZeneca) loading doses in STEMI patients, as reported by heartwire . In an interview with heartwire , Parodi explained that he and his colleagues, intrigued by this finding, expanded their analysis to include an additional four studies, all of which collected data on morphine use and platelet reactivity following use of the new oral antiplatelet drugs.

Using the five studies combined, Parodi et al were able to compare HPPR in a total of 300 patients, 95 of whom had also received morphine.

According to data Parodi showed Tuesday, residual platelet reactivity dropped more steeply in the no-morphine patients than in the morphine-treated patients, a difference that reaches statistical significance within the first hour and remains statistically distinct at the two- and four-hour mark. By eight hours, however, platelet reactivity converges for both groups. A plausible explanation is vomiting, Parodi noted, since nausea and vomiting are common side effects of morphine; however, the association between morphine use and high platelet reactivity persisted, even among patients who did not experience vomiting. Morphine is also known to delay GI transit time, and this may be one explanation for the delayed effects of antiplatelet drugs.

Of note, Parodi and colleagues saw no difference in the effects of morphine on patients treated with ticagrelor vs prasugrel. After adjustment for multiple factors, morphine use was associated with a more-than-threefold increase in HPPR two hours after antiplatelet loading dose (p=0.0001).

Morphine, ticagrelor, and prasugrel are all class 1 indications in the 2012 ESC guidelines for the management AMI in STEMI, yet there is no mention of potential drug-drug interactions.

Clinically Important?

During the question-and-answer session following his presentation, Dr Jean-Philippe Collet (Groupe Hospitalier Pitié-Salpêtrière, Paris, France) asked Parodi whether the solution in these patients is to promote a strategy of earlier P2Y12-inhibitor use, at first contact, given that the HPPR curves converge again after eight hours, or even whether this phenomenon is "very clinically important," given that other antiplatelet and anticoagulant drugs are also frequently used in this window of time.

In response, Parodi said it depends on which drugs are in use. "Of course, if you have a strategy of bivalirudin monotherapy, these data may be important," he said. "We note that we may have an increased risk of stent thrombosis within the very first hours [of STEMI], as the EuroMAX and HORIZONS trials have shown. If we perform a different strategy in the cath lab using unfractionated heparin and IV GP IIb/IIIa inhibitors, this may not be as important an effect."

To heartwire , Collet stressed that he would like to see bigger studies, with clinical end points, but believed that it is plausible that morphine use could be an additional risk factor "that we should pay attention to."

Parodi agreed that larger studies are warranted but points out that morphine is widely used to reduce chest pain, in as many as one-third to one-half of patients, he estimates. And that may not always be warranted, particularly if it is depleting the effects of antiplatelet drugs.

In his institution, they have started to limit their morphine use unless absolutely necessary.

"I think physicians should know that this is an interaction," he said. "And of course, the most effective way to relieve pain is to reperfuse, to reopen the artery by PCI and stenting."

Parodi disclosed being a consultant for AstraZeneca, Bayer Healthcare, Eli Lilly, and the Medicines Company.

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