Lidocaine Less Likely Than Fentanyl to Blunt P2Y12 Inhibitors in the Cath Lab

More data are backing up recent claims that fentanyl, which is widely used in US cath labs, interferes with the absorption and early antiplatelet effects of ticagrelor. The Australian study also suggests that lidocaine may be a better analgesic option.

In the LOCAL study, randomization to lignocaine (also known as lidocaine) resulted in significantly less blunting of ticagrelor’s effects after angiography or PCI compared with fentanyl. At 2 hours after the loading dose, levels of plasma ticagrelor were 1008 ng/mL in the lignocaine group versus 598 ng/mL in the fentanyl group (P = 0.014). Previously, the PACIFY study similarly showed that fentanyl delayed both the early absorption of P2Y12 inhibitors and platelet inhibition.

“The LOCAL study provides clear confirmation of the findings of the PACIFY study, with both trials highlighting significant interference of opioids on the bioavailability of ticagrelor,” said senior study author Dion Stub, MBBS, PhD (Alfred Hospital, Melbourne, Australia). “Our study went one step further by highlighting an alternative nonopioid analgesic in IV lignocaine, which does not interfere with ticagrelor absorption.”

Many long-held practices in medicine turn out to be questionable when rigorously tested with randomized controlled trials, Stub added. “Similar to the work we have previously done on the potential cardiac implications of routine oxygen in AMI, routine use of opioids should be avoided for cath lab procedural analgesia,” he said.

John William McEvoy, MB BCh (National University of Ireland, Galway), who was the lead investigator of PACIFY, agreed that the LOCAL trial is important, with some caveats.

“This study makes a stronger case against using routine fentanyl at all in the cath lab than it does for using lignocaine as an alternative,” he said in an email. McEvoy added that while LOCAL shows that lignocaine does not have the “Achilles’ heel” that opiates have in delaying absorption of antiplatelets, the study is too small to determine if lignocaine is safe in the cath lab, or to assess whether it might have other side effects that could be problematic in cardiac patients.

A Potential Fentanyl Alternative

The LOCAL study was led by Himawan Fernando, MBBS (Alfred Hospital, Melbourne, Australia), who presented the results as an e-poster at the European Society of Cardiology Congress 2021. Published simultaneously online ahead of print in the European Heart Journal, LOCAL included 70 patients in Australia undergoing coronary angiography following ticagrelor loading. Patients randomized to fentanyl (n = 47) received a dose of 0.75 mg/kg at the start of the procedure if under age 70 years, or 0.5 mg/kg if over age 70. Boluses were given as needed during the procedure at the discretion of the operator. At the end of the case, IV fentanyl 0.5 mg/kg was given.

Those randomized to lignocaine (n = 43) received 1 mg/kg to a maximum dose of 100 mg as a slow IV push over 2 minutes at the start of the case. An addition dose of 0.5mg/kg was given at the discretion of the operator as needed for pain. Patients in whom lignocaine did not provide satisfactory analgesia crossed over to the fentanyl arm.

All patients had an indication for dual antiplatelet therapy and received ticagrelor at the end of the procedure. At 2 hours, the area under the plasma concentration time curves for ticagrelor was significantly lower in the fentanyl patients than in the lignocaine group (1,228 vs 2,753 ng h/mL; P < 0.001), as were plasma levels of the active metabolite of ticagrelor (201 vs 447 ng h/mL; P = 0.001).

Additionally, more patients who received fentanyl had high on-treatment platelet reactivity as assessed by Multiplate Analyzer (Roche Diagnostics International), VerifyNow (Accumetrics), and vasodilator-stimulated phosphoprotein (VASP) assay.

Pain scores were comparable in the lignocaine and fentanyl groups, and patient satisfaction was 94% in the fentanyl arm and 97% in the lignocaine arm (P = 0.56). There were only two instances of crossover from the lignocaine arm, both due to intolerable ischemic chest pain during the procedure despite administration of two doses of the drug.

“Our study demonstrated that pain scores in a stable population were relatively low and similar between patients receiving fentanyl and lignocaine when both agents were used as procedural analgesia,” Stub observed. “We are currently conducting the AVOID-2 RCT in STEMI patients, together with Ambulance Victoria,  to assess the role of IV lignocaine compared to fentanyl in a STEMI population with moderate-to-severe ischemic chest pain.”

McEvoy noted that in Europe most patients undergo coronary angiography and PCI under local anesthetic, without IV fentanyl, which is much more commonly used in the United States.

“I think the data are clear,” he said. “Opioids should only be used in the cath lab for patients undergoing PCI for breakthrough pain unresponsive to other analgesic approaches.”

And while IV lignocaine might be worth considering, McEvoy added, “this trial is not powered enough to determine the safety of IV lignocaine in the cath lab and, given the approach in most European patients to just provide local anesthetic, one wonders why this should not be the default approach, particularly in STEMI patients at higher risk for stent thrombosis.”