Targeting the immune system could prevent future heart attacks, clinical trial suggests

Regulatory T cells, a unique type of white blood cell, are important gatekeepers of our immune system, and their discovery was recently awarded the 2025 Nobel Prize in Physiology or Medicine. In the UK, someone is admitted to hospital every five minutes due to a heart attack. While seven out of ten people will survive a heart attack, many are left with damaged hearts, which can increase risk of further attacks. People who have had a heart attack typically have high inflammation in major blood vessels and this is a strong indicator that they are at risk of further attacks. Currently there is no approved treatment targeting inflammation in people following heart attacks. Results published today in Nature Medicine indicate that low-dose treatment with aldesleukin could prevent repeat heart attacks by reducing inflammation. The results arose from two related clinical trials known as IVORY and IVORY-FINALE, largely funded by the Medical Research Council. Sixty patients who had recently had heart attacks took part in IVORY. Each was either given a low dose of aldesleukin or a placebo. Of these, 55 patients then participated in up to five years of follow-up health monitoring, known as IVORY-FINALE. Participants had PET scans before and after treatment to assess inflammation in their blood vessels. On average, aldesleukin reduced inflammation by nearly 8%, with the greatest effect seen in blood vessels that initially had the highest levels of inflammation. After two years follow-up, all patients treated with aldesleukin had no further heart attacks, while 11% of those treated with the placebo did. Larger studies are needed to confirm these findings before aldesleukin can be safely approved for widespread treatment of heart attack patients. Chief Investigator Dr Joseph Cheriyan, consultant clinical pharmacologist at Cambridge University Hospitals NHS Foundation Trust and an affiliated associate professor at the University of Cambridge, said: “We are delighted that our early phase trial, which tested the very mechanism thought to be a game changer by the Nobel Prize committee, has demonstrated encouraging results which we hope to conclusively answer in larger trials.” Professor Ziad Mallat, BHF Professor of Cardiovascular Medicine at the University of Cambridge, who conceived the study, said: “For decades, we have known that inflammation contributes to heart disease, but effective treatments have remained elusive. Harnessing the body’s natural immune regulators to protect the heart represents a paradigm shift in cardiovascular medicine.” The trial was conducted primarily by Dr Rouchelle Sriranjan-Rothwell, Cardiology Specialist Registrar at Royal Papworth Hospital NHS Foundation Trust and NIHR clinical lecturer in cardiology, with a dedicated team of nurses. Dr Stephen Hoole, consultant interventional cardiologist and the principal investigator for the study at Royal Papworth Hospital, as well as affiliated associate professor at the University of Cambridge, said: “Whilst advances in heart attack treatment have improved patient outcomes in recent decades, 1 in 10 patients still die within the first 12 months and new treatments are still needed. Targeting inflammation, that often drives plaque vulnerability, rupture and subsequent cardiovascular events, is an exciting proposition to address this residual risk.” Professor James Rudd, professor of cardiovascular medicine at the University of Cambridge, who led the imaging aspects of the trial, added: “It is very satisfying to see this type of advanced imaging test being used to identify a new treatment that could help reduce the risk of heart attacks in the future. The IVORY and IVORY-FINALE trials were supported by the Medical Research Council, the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre, the NIHR Cambridge Clinical Research Facility and the British Heart Foundation. Reference Sriranjan-Rothwell, RS et al. Anti-inflammatory therapy with low-dose IL-2 in acute coronary syndromes: a randomized phase 2 trial. Nat Med; 8 Jan DOI: 10.1038/s41591-025-04090-y Adapted from a press release by Cambridge University Hospitals and Royal Papworth Hospitals NHS Foundation Trusts Cambridge researchers have discovered that an existing therapy which boosts protective immune cells in people who recently had heart attacks reduces blood vessel inflammation and may reduce the likelihood of future heart attacks. For decades, we have known that inflammation contributes to heart disease, but effective treatments have remained elusiveZiad MallatAndy_Art (Pixabay)Man clutching his chest (stock image)Mark Andrews, 59One patient to have participated in the IVORY trial is Mark Andrews, 59, from Fulbourn, in Cambridgeshire. In August 2022 he had a heart attack while cycling home from the gym. Despite being active, healthy and having no history of heart problems, tests at Addenbrooke’s Hospital confirmed that Mark was having a heart attack. He was rapidly transferred to Royal Papworth Hospital where a stent was fitted to hold open a narrowed artery, restoring blood flow to his heart. While still in hospital, Mark was invited to participate in the IVORY trial. He said: “I was keen to join the trial. It wasn’t just the possibility that the treatment could stop me from having another heart attack. It was knowing the team would be closely monitoring my health, so they would probably spot it early if anything started to go wrong.” Three years on from joining the trial, Mark has had no further heart attacks or symptoms. He works an IT specialist and still stays active including regular gym sessions. He added, “The teams at Royal Papworth and Addenbrooke’s were fantastic. It’s a slow road to recovery and the contact with the teams as well as the specialist cardio rehab really helped to keep me active and get back to normal.”
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