Researchers from the School’s Centre for Cardiac Research and Education in Therapeutics (CCRET) have been building a body of work that challenges over 50 years of medical practice regarding the use of opioids to treat people experiencing myocardial ischaemic pain – pain caused by a blockage of blood supply to the heart.
A severe blockage can lead to heart attack, heart failure and abnormal heart rhythms.
Opioids are frequently used by doctors and paramedics to relieve pain distress with the long held belief that it leads to better outcomes. However, recent research has raised concerns regarding potential interactions between opioids and anti-platelet drugs called oral P2Y12 inhibitors, a cornerstone of therapy in managing heart attacks thanks to their anti-clotting actions that reduce the risk of death.
It’s thought that opioids may act in two ways: firstly by slowing down the stomach’s natural forward movement, thereby impairing gastric absorption of the inhibitors. This in turn is thought to contribute to a delay in the anti-platelet activity of the inhibitors.
Dr Himawan Fernando (pictured right) is a Cardiologist undertaking a 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. Over a series of trials and other studies, they’ve questioned 50 years of accepted practice and joined the search for alternative pain relief agents to opioids.
In 2020 along with colleagues they published a review in Pharmacology and Therapeutics exploring both the mechanisms underlying the drug interaction, and promising alternative pain relief agents.
Dr Fernando says, “It was clear to us following that review that there were very plausible theories on the nature of the drug interaction occurring, and a great need for clinical trials and other robust evaluations of alternative analgesics for use in this context.”
Together with cardiac researchers at the Alfred Hospital, Monash University & Ambulance Victoria they then led a secondary observational study exploring the association 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 comprised 638 patients suspected of having a heart attack between 2011 and 2014, and subsequently transferred to Percutaneous Coronary Intervention (PCI) capable hospitals in Melbourne, Australia, and questioned the accepted role of oxygen therapy in AMI.
“Pain relief in these patients has been enshrined in medical practice not only for patient comfort, but for the belief that pain reduction confers improved outcomes. Because of this, liberal doses of opioids are often used to achieve pain-free status. However, our investigation showed limited association between pain status and markers of heart damage, suggesting a more judicious use of opioids, with a focus on patient comfort, would be appropriate.”
From here, Dr Fernando and A/Prof Stub evaluated the association between pre-hospital opioid dose and clinical outcomes for patients experiencing acute coronary syndrome (ACS), a wide range of cardiac conditions featuring blocked blood vessels to the heart.
For this, they linked data housed within Ambulance Victoria and two clinical registries maintained by the Monash School of Public Health and Preventive Medicine – the Victorian Cardiac Outcomes Registry and Melbourne Interventional Group databases. Over 10,000 ACS patients were included in the study, all of whom were transported by emergency services to hospital where they underwent PCI from 2014 through to 2018.
A/Prof Stub says, “We found no significant association between opioid use and the number of major adverse cardiac events in these patients up to 30-days post hospital admission. So while it seems that opioids do have an interactive negative effect on P2Y12 inhibitors, the clinical outcomes may not be severely impacted. But what this study did do is lend credence to the fact that a really robust clinical trial is needed to compare opioids with alternatives.”
The LOCAL study is one study filling this gap. The alternative the researchers selected was the local anaesthetic lignocaine (lidocaine) which when given intravenously has systemic analgesic properties.
A/Prof Stub says, “We already know intravenous (IV) lignocaine is effective for ischaemic limb pain, acts quickly, and is generally well tolerated, including in patients with coronary artery disease. It’s exciting to think that a readily available, affordable option might in fact be a superior candidate to what’s in use.”
Published in the European Heart Journal in late 2021, the LOCAL study compared the effects of lignocaine and the opioid fentanyl on the bioavailability of the oral P2Y12 inhibitor ticagrelor, and its antiplatelet effects in patients with suspected heart blockages (as indicated by undergoing either coronary angiography or PCI). The study also evaluated the safety and efficacy of lignocaine compared to fentanyl as procedural analgesia in patients presenting with unstable angina (UA) and a type of heart attack called non-ST-elevation myocardial infarction (NSTEMI). NSTEMIs are often less damaging to the heart than their counterpart, STEMI.
They found that IV lignocaine avoided the biochemical impacts of IV fentanyl, leading to greater bioavailability of ticagrelor and comparable levels of pain relief. Patients reported good satisfaction with both drugs. They further recommended that routine procedural pain relief during PCI be reconsidered, and if performed, lignocaine is a beneficial alternative to fentanyl.
“These results indicate that lignocaine could be considered as a possible alternative to fentanyl in patients presenting with UA and NSTEMI. They also justify further research into lignocaine and other non-opioid agents for use in patients with acute ischaemic chest pain, such as STEMI,” says A/Prof Stub.
This point may be illuminated during the second half of 2022, when together with Ambulance Victoria the duo hope to publish results of a randomized clinical trial exploring lignocaine vs. fentanyl in a cohort of patients experiencing the more serious STEMI heart attacks.
Dr Fernando says, “No matter what these results reveal, it’s becoming clearer that safer alternatives to opioids need to be identified, and when that happens, it will revolutionise more than 50 years of medical practice around the world.”
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2022-07-11 06:11:41Z
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