Challenging 50 years of pain relief for heart attack management

11 July 2022

Researchers from the School’s Center for Cardiac Research and Education in Therapeutics (CCRET) have built a challenging work of more than 50 years of medical practice on the use of opioids to treat people with myocardial ischemic pain – pain caused by blood clots. supply to the heart.

Severe blockage can lead to a heart attack, heart failure, and abnormal heart rhythms.

Opioids are often used by doctors and paramedics to relieve pain pressure with the longstanding belief that it leads to better outcomes. However, recent studies have raised concerns regarding the potential interaction between opioids and an anti-platelet drug called P2Y. oral₁₂ inhibitors, the cornerstone of therapy in managing heart attacks thanks to its anti-clotting action which reduces the risk of death.

It is thought that opioids can act in two ways: first by slowing the natural forward movement of the stomach, thereby interfering with the absorption of gastric inhibitors. This in turn is thought to contribute to the delay in the anti-platelet activity of the inhibitor.

Dr Himawan Fernando (right image) is a Cardiologist doing PhD with CCRET, Alfred Health and Baker Heart and Diabetes Institute, under the supervision of A/Prof Dion Stub from CCRET and Prof Karlheinz Peter at the Baker Institute. During a series of trials and other studies, they questioned 50 years of accepted practice and joined the search for alternative pain relief agents to opioids.

In 2020 they together with colleagues published a review in Pharmacology and Therapeutics exploring the mechanisms underlying drug interactions, and promising alternative pain relief agents.

Dr Fernando said, “It became clear to us after that review that there is a very plausible theory about the nature of the drug interactions that occur, and a great need for clinical trials and other robust evaluations of alternative analgesics for use in this context.”

Together with cardiac researchers at Alfred Hospital, Monash University & Victoria Ambulance, they then led a secondary observational study exploring the relationship between reported pain levels and clinical biomarkers of myocardial injury (heart damage). They used a secondary analysis of the AVOID study for this. The AVOID study consisted of 638 patients who were suspected of having a heart attack between 2011 and 2014, and were subsequently transferred to a Percutaneous Coronary Intervention (PCI)-supporting hospital in Melbourne, Australia, and questioned the role of received oxygen therapy in AMI.

“Patient pain relief has been enshrined in medical practice not only for patient comfort, but also for the belief that pain reduction provides better outcomes. Therefore, liberal doses of opioids are often used to achieve pain-free status. However, our investigation demonstrated a limited association between pain status and markers of cardiac damage, suggesting prudent use of opioids, with a focus on patient comfort, would be appropriate.”

From here, Dr Fernando and A/Prof Stub evaluated the relationship between prehospital opioid doses and clinical outcomes for patients with acute coronary syndrome (ACS), a variety of heart conditions that feature blocked blood vessels to the heart.

For this, they linked data stored in Ambulance Victoria and two clinical registries maintained by the Monash School of Public Health and Preventive Medicine – the Victorian Cardiac Outcomes Registry and the Melbourne Interventional Group database. More than 10,000 ACS patients were included in the study, all of whom were transported by emergency services to the hospital where they underwent PCI from 2014 to 2018.

A/Prof Stub said, “We did not find a significant association between opioid use and the number of major cardiac adverse events in these patients up to 30 days after hospital admission. So although it appears that opioids do have an interactive negative effect on P2Y₁₂ inhibitors, clinical outcome may not be significantly affected. But what this study does is lend credence to the fact that very robust clinical trials are needed to compare opioids with alternatives.”

The LOCAL Study is one study that fills this gap. The alternative chosen by the researcher is the local anesthetic lignocaine (lidocaine), which when given intravenously has systemic analgesic properties.

A/Prof Stub said, “We have found that intravenous (IV) lignocaine is effective for ischemic leg pain, acts quickly, and is generally well tolerated, including in patients with coronary artery disease. It’s interesting to think that an available and affordable option might actually be a superior candidate to what is being used. ”

Published in the European Heart Journal in late 2021, the LOCAL study compared the effects of the opioid lignocaine and fentanyl on oral P2Y bioavailability.₁₂ ticagrelor inhibitors, and their antiplatelet effects in patients with suspected cardiac obstruction (as demonstrated by undergoing coronary angiography or PCI). This study also evaluated the safety and efficacy of lignocaine compared with fentanyl as procedural analgesia in patients with unstable angina (UA) and a type of heart attack called non-ST-elevation myocardial infarction (NSTEMI). NSTEMI are often less damaging to the heart than their counterpart, STEMI.

They found that IV lignocaine avoided the biochemical effects of IV fentanyl, leading to greater ticagrelor bioavailability and comparable levels of pain relief. Patients reported good satisfaction with both drugs. They further recommend that routine procedural pain relief during PCI be reconsidered, and if performed, lignocaine is a favorable alternative to fentanyl.

“These results suggest that lignocaine may be considered as a possible alternative to fentanyl in patients with UA and NSTEMI. They also warrant further research into lignocaine and other non-opioid agents for use in patients with acute ischemic chest pain, such as STEMI,” said A/Prof Stub.

This point can be explained during the second half of 2022, when together with Victoria Ambulance, the two hope to publish the results of a randomized clinical trial exploring lignocaine vs. fentanyl in a group of patients experiencing more serious STEMI cardiac arrest.

Dr Fernando said, “Whatever these results reveal, it is becoming increasingly clear that safer alternatives to opioids need to be identified, and when they do, they will revolutionize medical practice for over 50 years worldwide.”

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