Drug Protects Heart Patients from Attacks

A study by our Cell Therapeutics Group has revealed that an anti-inflammatory medication used to treat gout can also improve heart health in people who have suffered a heart attack or other major heart event.

The discovery, published in the prestigious Journal of the American Heart Association, paves the way for a new treatment regime that could protect thousands of Canadian heart patients from future attacks that will kill or further damage the heart.

"Excitingly, we've been able to prove that this low-cost and widely available drug is both safe and profoundly effective in reducing local cardiac inflammation," says Dr Sanjay Patel, group leader of the Cell Therapeutics Group at the HRI. "If we're able to prove its success in larger studies, we'll have a brand new therapy that will considerably brighten the outlook for people who suffer heart attacks."

Dr Patel and his team investigated new treatments for acute coronary syndrome, a sudden and life-threatening condition in which the coronary blood vessel is blocked, triggering a heart attack or severe chest pain associated with unstable angina.

The condition, most commonly caused by atherosclerosis or thickened arteries, is often diagnosed on the operating table following a major heart event. Patients are closely managed in hospital but new treatments are still desperately needed to reduce the risk of future attacks.

Dr Patel hypothised that the drug colchicine, with its anti-inflammatory qualities, could combat the inflammation that plays a strong role in cardiovascular disease. HRI collaborated with researchers from Royal Prince Alfred Hospital and the University of Sydney (Australia), Catholic University School of Medicine, (Chile), the Paris-Cardiovascular Research Centre (France) and the University of Cambridge (UK) to test out the hypothesis in 83 patients.

Two doses of the drug were given the day before a coronary angiogram, a common procedure to investigate the state of a patient's heart vessels. When the angiogram was carried out the researchers tested levels of key inflammatory cytokines, substances that drive inflammation and disease progression.

"Patients with acute coronary syndrome will have higher levels of these cytokines that work to trigger the dangerous inflammation around the heart," Dr Patel explains. "We discovered that colchicine has a striking ability to suppress the release of these cytokines, effectively stopping inflammation in its tracks."

Specifically, researchers saw a rapid and significant drop in levels of interleukin-1 and interleukin-18 within the coronary arteries, as well as a drop in interleukin-6, a key downstream cytokine strongly associated with artery-thickening inflammation.

"This is an exciting finding as IL-6 is precursor to C-reactive protein, or CRP, which is significantly associated with the incidence of future cardiovascular events in patients with atherosclerosis," Dr Patel says.

Exactly how colchicine inhibits the production of inflammatory cytokines is not completely understood but the team believes the drug works by blocking the NLRP3 inflammasome, a protein complex within immune cells responsible for the production of active IL-1 and IL-18.

This is the first time the effects of colchicine on cardiac cytokine release have been studied in humans or animals, making the findings all the more important.

"The next step will be to prove clinical effect through rigorous multi-centre clinical trials,” explains Dr Patel.  "If it works we have a cheap yet potent treatment with very important therapeutic implications for heart patients."

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