Ticagrelor interaction highlights need to avoid opioids in cardiac procedures

Opioids should be avoided for analgesia in cardiac procedures involving patients treated with oral PDY12 inhibitors, according to Australian researchers who have shown that a drug interaction reduces levels of the antiplatelet agent.

Victorian cardiologist Dr Himawan Fernando said the routine use of fentanyl in patients undergoing PCI during acute MI care should be reconsidered after findings from his study showed the opioid interfered with ticagrelor absorption.

His research, presented at the Cardiac Society Of Australia and NZ (CSANZ) annual scientific meeting, looked lignocaine as an alternative analgesic to mitigate the potentially harmful reliance on fentanyl in the cath lab.

Dr Fernando, from The Alfred hospital in Melbourne, said a previous systematic review carried out by his group revealed that all opioids impair the absorption of all oral P2Y12 inhibitors – an action that appears to occur through binding to receptors in the gut causing gastroparesis and delayed intestinal peristalsis.

While the clinical significance of the effect was difficult to determine, his group’s post hoc analysis of the AVOID trial uncovered a signal of harm with higher doses of opioids correlating to greater infarct size based on cardiac biomarker release, suggesting a dose-dependent relationship.

Meanwhile a second analysis found an association between intravenous morphine use and a higher rate of death in a cohort of patients with NSTEMI.

Dr Fernando said the findings provided an opportunity to consider alternative analgesics to opioids that could mitigate the potentially harmful interaction.

The Alfred clinical team turned to lignocaine – readily available in cath labs and ambulances and easy to administer. The local anaesthetic has safety data in coronary artery disease and has been shown to be comparable to opioids for a range of acute pain indications, noted Dr Fernando.

Its effect on the bioavailability and antiplatelet effect of ticagrelor  in patients with unstable angina and STEMI as well as its efficacy and safety was compared against the routinely used fentanyl in a randomised trial of 70 patients undergoing coronary angiography with an indication for ticagrelor.

Dr Fernando told meeting delegates that plasma ticagrelor levels at two hours post loading dose were significantly lower in the fentanyl compared to lignocaine treatment arm (476 vs. 792 ng/mL, p=0.02).

It was a finding that correlated with significantly higher platelet reactivity at 60 minutes based on several platelet function assays and at four hours with the VerifyNow assay (30% vs. 3%, p=0.003) in the fentanyl arm.

Meanwhile pain scores were low and comparable across the two groups, he added suggesting that lignocaine is an effective, well tolerated alternative agent to fentanyl for patients undergoing coronary angiography without ticagrelor.

Dr Fernando argued that the use of opioids for routine procedural analgesia should be questioned given the established interaction with all oral PDY12 inhibitors.

“I think [this is] an opportunity for us to consider not using routine analgesics for everyone. Certainly in Europe it seems to be far less common to use routine analgesia and I think that’s certainly one of the messages that comes out of this study – given this biochemical interaction perhaps we should avoid routine analgesics – and if we do need it, lignocaine seems to be an effective alternative,” he said.

The presentation was  awarded the prestigious Ralph Reader prize for clinical science at CSANZ 2021.

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