PHILADELPHIA – The proof of concept shown by the CANTOS study in 2017 that an anti-inflammatory drug could cut the incidence of cardiovascular events has now been replicated in a study with more than 4,700 post-MI patients who received the much more affordable oral anti-inflammatory drug colchicine.
Daily treatment with a single, 0.5-mg/day colchicine tablet cut cardiovascular disease events by a statistically significant 23%, compared with placebo patients during nearly 20 months on treatment when colchicine was added on top of a regimen that included aspirin, a second antiplatelet drug, a statin, and in many patients a beta-blocking drug, Jean-Claude Tardif, MD, said at the American Heart Association scientific sessions.
Adding colchicine to the treatment of patients within 30 days of having a MI led to an absolute reduction in the study’s primary endpoint of 1.6% during a median 19.6 months on treatment. In a secondary analysis that looked at total cardiovascular events and not just first events, adding colchicine to background therapy was associated with a relative 34% decline, said, professor of medicine at the University of Montreal and director of the Research Centre at the Montreal Heart Institute. In addition to his report at the meeting, the results also appeared concurrently in an article published online (N Engl J Med. 2019 Nov 16. ).
The dramatic efficacy and overall safety shown by colchicine in(Colchicine Cardiovascular Outcomes Trial) appeared to replicate the benefit seen with the relatively expensive monoclonal antibody canakinumab (Ilaris) in (Canakinumab Anti-Inflammatory Thrombosis Outcome Study), where a canakinumab injection every 3 months led to a 15% reduction in the incidence of cardiovascular events, compared with placebo, during a median 3.7 years of follow-up in a study with just over 10,000 post-MI patients ( ).
“One of the limitations of CANTOS was that canakinumab is a very expensive, injectable drug. We followed in the footsteps of CANTOS with a less expensive, oral drug,” Dr. Tardif explained during a press briefing. “Colchicine is a known, potent anti-inflammatory drug,” and as of November 2019, the average U.S. cost of a 30-day supply of 0.6-mg capsules was. The colchicine formulation used in COLCOT delivered a 0.5-mg daily dose to patients, a formulation that’s not currently on the U.S. market.
“Having a safe drug that’s easily available; it will be hard to hold this one back,” commented, professor and chairman of preventive medicine at Northwestern University in Chicago. “What the guidelines will need to wrestle with is there are five drugs” already recommended to use after an MI; “is colchicine number six?” The existing guideline-directed drugs for post-MI patients include aspirin, a second antiplatelet agent, a statin, a beta-blocker, and an angiotensin-converting enzyme inhibitor, Dr. Lloyd-Jones noted. The incremental benefit from adding colchicine to background regimen was “modest, but statistically significant,” he said, and “importantly, this was not an industry-sponsored trial.” Dr. Lloyd-Jones said that he has recently heard from a patient of his in the Chicago area who takes colchicine for gout that the monthly cost for the drug has risen to as high as $270. By comparison, the price in Montreal is less than $9/month, Dr. Tardif said.
COLCOT enrolled 4,745 patients at a median of about 13.5 days following an acute MI at 167 centers in 12 countries. The study’s primary endpoint was the combination of death from cardiovascular causes, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina leading to coronary revascularization in a time-to-event analysis. The combined endpoint occurred in 5.5% of the patients on colchicine and 7.1% of those on placebo during a median of nearly 20 months on treatment. The adverse effects data showed generally similarly rates among patients on colchicine and in the control group, including their rates of gastrointestinal effects. The one exception was the rate of serious pneumonias, which were more than double in the colchicine recipients, a statistically significant difference.
COLCOT received no commercial support. Dr. Tardif has received honoraria from Amarin, DalCor, Sanofi, and Servier; he has an ownership interest in DalCor; and he has received research funding from Amarin, AstraZeneca, DalCor, Esperion, Ionis, RegenxBio, Sanofi, and Servier. Dr. Lloyd-Jones had no disclosures.
SOURCE: Tardif J-C et al. AHA 2019, .