Anti-inflammatory drug could reduce future heart attack risk

High levels of inflammation in blood vessels are linked to an increased risk of heart disease and heart attacks. After a heart attack, the body’s immune response can aggravate existing inflammation, causing more harm and increasing risk even further. However, NICE guidelines don’t currently recommend the use of any anti-inflammatory drugs to reduce future risk. 

Now, a team of researchers, led by Dr Joseph Cheriyan from Cambridge University Hospitals NHS Foundation Trust, have found that low doses of an anti-inflammatory drug called aldesleukin, injected under the skin of patients after a heart attack, significantly reduces inflammation in arteries.  

 

The researchers are currently following up patients to investigate the longer-term impact of this fall in inflammation. To date, in the two and a half years after their treatment, there have been no major adverse cardiac events - including heart attacks - in the group that received aldesleukin, compared to seven in the group that received the placebo. 

 

Professor Ziad Mallat, BHF Professor of Cardiovascular Medicine at the University of Cambridge who developed the trial, said: “We associate inflammation with healing – an inbuilt response that protects us from infection and injury. But it’s now clear that inflammation is a culprit in many cardiovascular conditions. 

 

“Early signs from our ongoing trial suggest that people treated with aldesleukin may have better long-term outcomes, including fewer heart attacks. If these findings are repeated in a larger trial, we’re hopeful that aldesleukin could become part of routine care after a heart attack within five to 10 years.”  

Aldesleukin is already used to treat kidney cancer, as high doses stimulate the immune system to attack cancer cells. The Cambridge team previously found that doses one thousand times lower than those used in cancer treatment increased the number regulatory T cells – a type of anti-inflammatory white blood cell – in patients’ blood compared to a placebo. 

 

In the current trial at Addenbrooke's Hospital and Royal Papworth Hospital in Cambridge, 60 patients admitted with a heart attack or unstable angina received either low dose aldesleukin or placebo. Patients received an injection once a day for the first five days, then once per week over the next seven weeks. Neither the participants or their doctors knew whether they had received the drug or placebo. 

 

At the end of their treatment Positron Emission Tomography (PET) scans showed that inflammation in the artery involved in patients’ heart attack or angina was significantly lower in the group treated with aldesleukin, compared to those who received the placebo.  

 

The anti-inflammatory effect of aldesleukin appeared even more striking in the most inflamed arteries, leading to a larger reduction in inflammation levels in these vessels and a bigger difference between the two groups by the end of the study. 

Dr Sonya Babu-Narayan, our Associate Medical Director and consultant cardiologist said: “Thanks to research, we have an array of effective treatments to help people avoid heart attacks and strokes and save lives. But, even after successful heart attack treatment, unwanted inflammation in the coronary arteries can remain, which can lead to life-threatening complications. 

 

“A treatment to reduce inflammation after a heart attack could be a game-changer. It would help doctors to interrupt the dangerous feedback loop that exacerbates inflammation and drives up risk. This research is an important step towards that treatment becoming a reality.” 

 

The study was predominantly funded by the Medical Research Council, with significant support from us and National Institute for Health and Care Research Cambridge Biomedical Research Centre (NIHR-BRC).