Substituting acetaminophen for fentanyl feasible in PCI for STEMI
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In patients with STEMI given crushed ticagrelor before PCI, using IV acetaminophen instead of IV fentanyl as a painkiller did not increase pain levels or platelet reactivity and prevented delay of ticagrelor’s effects, researchers reported.
Patients in the acetaminophen group had higher levels of ticagrelor (Brilinta, AstraZeneca) in their system during and after the procedure compared with patients in the fentanyl group, according to the results of the investigator-initiated, randomized, open-label ON-TIME 3 trial that were presented at the virtual PCR e-Course.
“Platelet inhibitory affects induced by oral P2Y12 inhibitors are delayed in patients who undergo STEMI PCI, and this is mainly due to delayed intestinal absorption,” Anne H. Tavenier, MD, cardiologist at Isala Clinic in, Zwolle, the Netherlands, said during a presentation. “For years, STEMI patients were treated with morphine or morphine-like pain relievers ... however, these pain relievers appear to delay the intestinal absorption [of P2Y12 inhibitors]. Moreover, nausea and vomiting are more frequently observed in patients receiving morphine. IV acetaminophen, also known as paracetamol, may be an alternative to morphine or morphine-like pain relievers in these patients.”
Tavenier and colleagues randomly assigned 195 patients with STEMI who were treated with crushed ticagrelor, aspirin and heparin in the ambulance to IV acetaminophen or IV fentanyl, an opioid, as a painkiller in the ambulance. Each patient was analyzed for pain on a scale of 1 to 10, platelet reactivity measured by VerifyNow (Instrumentation Laboratory) and level of ticagrelor and its active metabolite before primary PCI, immediately after PCI, at 1 hour after PCI and at 6 hours after PCI.
Immediately after PCI, there was no significant difference between the median platelet reactivity units in each group (acetaminophen, 104; fentanyl, 175), Tavenier said.
However, she said, systemic levels of ticagrelor were higher in the acetaminophen group than the fentanyl group before PCI (151 ng/mL vs. 60 ng/mL; P = .007), immediately after PCI (326 ng/mL vs. 115 ng/mL; P = .002) and 1 hour after PCI (488 ng/mL vs. 372 ng/mL; P = .002).
Pain scores were similar at randomization (P = .45) and pain reduction did not differ between the groups before PCI (P = .67) or after it (P = .96), according to the researchers.
“The results of this trial may have implications for the prehospital treatment of STEMI patients in the future, but large, randomized trials will be needed to investigate the effects on clinical outcomes,” Tavenier said.
In a commentary after the presentation, Christoph K. Naber, MD, PhD, director of the cardiology and intensive care department at Klinikum Wilhelmshaven, Germany, said: “The open question that I have is, will these increased P2Y12 inhibitor levels translate into a measurable difference regarding clinical outcomes? We don’t always know if increased levels of ticagrelor ... makes a biological impact that can later be measured in a clinical endpoint.”
However, he said, “the risk of switching to acetaminophen instead of an opioid, if it works for the patient, is very low. This could be something that I might introduce in my practice.”
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Tavenier AH, et al. STEMI interventions: First-in-Man and novel pharmacological strategies. Presented at: PCR e-Course; June 25-27, 2020 (virtual meeting).
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