WASHINGTON –
The study CLEAR SYNERGY (OASIS 9)called “the largest ever trial of colchicine in acute myocardial infarction”, showed no sign of benefit compared to placebo over a period of 5 years, suggesting that the role of this drug after a myocardial infarction (MI) “is uncertain”, indicated the Dr Sanjit Jollyinterventional cardiologist at Hamilton Health Sciences and professor of medicine at McMaster University in Hamilton, Canada, at the Transcatheter Cardiovascular Therapeutics (TCT) 2024 conference.
Colchicine does not protect against major cardiovascular events after acute myocardial infarction, according to this multinational placebo-controlled trial of more than 7,000 patients. These results, which were surprising, could change current practice recommendations.
Regarding the primary composite endpoint – cardiovascular death, heart attack, stroke and revascularization due to ischemia – the event curves in the colchicine and placebo groups remained mostly overlapping during the 5 years of follow-up, with only one slight separation after 4 years. The hazard ratio for the primary endpoint showed a 1% difference in favor of colchicine (hazard ratio [HR]0,99 ; P = 0,93).
No significant differences were observed either on the evaluation criteria taken separately. Rates of cardiovascular death (3.3% vs. 3.2%) and stroke (1.4% vs. 1.2%) were numerically higher in the colchicine group than in the placebo group. The rates of MI (2.9% vs 3.1%) and ischemic revascularization (4.6% vs 4.7%) were numerically lower in the colchicine group.
No results approached the statistical threshold
No outcome, including all-cause death (4.6% vs 5.1%), approached the statistical threshold, with the exception of non-cardiovascular death (13.0% vs 1.9%, HR , 0.68; 95% CI, 0.46-0.99).
Adverse event rates (31.9% versus 31.7%; P = 0.86), serious adverse events (6.7% versus 7.4%; P = 0.22) and serious infections (2.5% versus 2.9%; P = 0.85) were similar in the colchicine and placebo groups, but diarrhea, a known side effect of colchicine, was higher in the colchicine group (10.2% vs. 6.6%; P 0,001).
Given these results, one panel member questioned the use of the word “uncertain” to describe the results during the closing session in which these results were presented.
“I think you underestimate yourself,” said the Dre J. Dawn Abbottdirector of the interventional cardiology training program at the Lifespan Cardiovascular Institute at Brown University (Providence, United States). Given the size and conduct of this trial, she called the results “definitive” and suggested that the recommendations be adjusted.
The OASIS 9 trial
In the OASIS 9 study, 3,528 patients were randomized to receive colchicine and 3,534 to receive placebo. These results will be presented at the next meeting of theAmerican Heart Association (AHA) 2024. Both analyzes will then be published in the New England Journal of MedicineDawn Jolly pointed out.
The study was conducted at 104 sites across Australia, Egypt, Europe, Nepal and North America. The follow-up rate in both groups was greater than 99%. Most patients had ST-segment elevation myocardial infarction (STEMI), but approximately 5% had non-ST-segment elevation myocardial infarction. Less than 10% of patients had already suffered a heart attack.
Less than 5% of patients were discharged with sodium-glucose cotransporter 2 treatment, and more than 95% with aspirin and a statin. Nearly 80% of patients received an angiotensin-converting enzyme inhibitor upon discharge, and most patients received an anticoagulant. More than 95% of patients received a drug-eluting stent.
At the third month, C-reactive protein levels were significantly lower in the colchicine group than in the placebo group. C-reactive protein is a biomarker of the anti-inflammatory effect which is considered the main mechanism of action of colchicine. An anti-inflammatory effect has been cited as a likely explanation for the positive results of the COLCOT and LODOCO2 trials, published in 2019 and 2020 respectively.
In the COLCOT study, which randomized 4,745 patients with an acute heart attack within the previous 30 days, colchicine was associated with a 23% reduction in a composite endpoint of major cardiovascular events versus to placebo (HR, 0.77; P = 0,02).
In the LODOCO2 study, which randomized 5,522 patients with chronic coronary artery disease, colchicine was associated with a 31% reduction in a composite endpoint of events (HR, 0.68; P
However, two more recent trials – CONVINCE and CHANCE-3 – showed no difference between colchicine and placebo for the endpoint of recurrent stroke at 90 days. CONVINCE, with approximately 3000 patients, was a relatively small trial, while CHANCE-3 randomized more than 8000 patients and showed no effect on stroke risk (HR, 0.98; 95% CI, 0.83-1.16).
New data challenges recommendations
Of these trials, COLCOT was the most similar to OASIS 9, according to Dawn Jolly. Among the differences, OASIS 9 launched earlier and was larger than the other trials, so it had more power to answer the study question.
Given the lack of benefit, Dawn Jolly said OASIS 9 could disrupt both the recommendations of the American College of Cardiology and the AHA, which have called for class 2b colchicine in 2023, and the guidelines of the European Society of Cardiology, who recommended colchicine in class 2a.
“It’s a shock to me,” said Ajay J. Kirtanedirector of the interventional cardiovascular care program at Columbia University in New York. As someone who now uses colchicine routinely, this data changed my opinion, he said.
Previous data supporting the use of colchicine “were only poor,” he said. “Today, I have good reasons” to give up the systematic use of this treatment.
Dawn Jolly said she started her own father on colchicine after an acute heart attack based on recommendations, but immediately stopped the treatment when data from the OASIS 9 study came to light.
“The only signal from this trial was an increased risk of diarrhea,” Dawn Jolly said. The results, at the very least, suggest that colchicine “is not for everyone” after an acute heart attack, although she stressed that these results do not rule out the potential benefits of anti-inflammatory therapy. . Ongoing trials, including one targeting interleukin 6, a cytokine associated with inflammation, remain of interest, she added.
This article was translated from Medscape.com using several editorial tools, including AI, in the process. The content was reviewed by the editorial staff before publication.
