Hopes that colchicine could be re-purposed as a cheap anti-inflammatory for heart disease have been dashed by a pilot study showing it does not appear to significantly reduce hs-CRP levels after acute MI.
“We all know that atherosclerosis is an inflammatory disease and that inflammation plays a key role in all stages of atherosclerosis, from the initiation to development and growth of plaques and of course plaque rupture,” study co-author Professor Graham Hillis from the Royal Perth hospital in Western Australia told Cardiac Society of Australia and NZ (CSANZ) annual scientific meeting delegates in Adelaide.
He noted that the best evidence to date for the role of inflammation in coronary heart disease was from the CANTOS trial which showed that targeting the interleukin-1β innate immunity pathway with canakinumab led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering.
“But of course canakinumab has several disadvantages the major one is that it is a hugely expensive medication and of course there are some other side effects such as sepsis… so what if we could find an agent that was effective in targeting inflammation but that was much cheaper and hopefully safe,” he said.
“There has been a lot of data coming out in recent years regarding colchicine derived from the Colchicum autumnale crocus…it’s a drug that has been used to treat inflammation for thousands of years,” he told delegates.
The single centre study placebo controlled LoDoCo-MI trial involved 224 patients with acute MI (type 1) who were randomised to 0.5 mg of colchicine (n=111) or placebo (n=113).
At 30-day follow-up, 44% of patients treated with colchicine had a CRP level ≥2 mg/L compared to 50% of those randomised to placebo.
There were also no significant reductions in median levels or in absolute or relative changes from baseline and no significant reductions were seen in interleukin-6 levels
The drug was well tolerated and adverse events were similar in both patient groups.
Professor Hillis noted that several studies exploring the use of colchicine in stable coronary heart disease (LoDoCO-2), STEMI (CLEAR-SYNERGY) and ACS (COPS and COACs) were underway.
Another study led by Professor Anthony Keetch from the RPA in Sydney also had a funding application under review by the NHMRC that is looking at specifically targeting patients with residual inflammation and high CRP levels post MI.
“Hopefully we’ll have new data in this field in the relatively near future,” he added.