Colchicine does not improve outcomes in patients getting PCI after acute heart attack
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Key takeaways:
- In patients referred for PCI after acute heart attack, colchicine did not improve heart-related outcomes vs. placebo.
- The findings contradict a previous study that had impact on clinical practice.
WASHINGTON — Contradicting previous research, in a large trial of patients referred for PCI after acute MI, colchicine did not improve CV outcomes compared with placebo, according to the CLEAR SYNERGY (OASIS-9) trial presented at TCT 2024.
As Healio previously reported, in the COLCOT trial of 4,745 adults recruited 30 days after acute MI, colchicine reduced risk for CV death, resuscitated cardiac arrest, MI, stroke or hospitalization for angina leading to coronary revascularization by 23%. But in CLEAR SYNERGY (OASIS-9), consisting of 7,062 patients who underwent randomization within 72 hours of PCI for acute STEMI or acute large non-STEMI, there was no difference in the primary outcome of CV death, MI, stroke or ischemia-driven revascularization, Sanjit Jolly, MD, MSc, interventional cardiologist and professor of medicine at McMaster University in Hamilton, Ontario, Canada, said during a press conference.
“I was a believer in colchicine; I believed the data,” Jolly said during the press conference. “My father had an MI. I put him on colchicine. And I have just taken him off colchicine.”
COLCOT and LoDoCo2, a positive trial of colchicine in patients with stable CAD, “changed guidelines and had some influence on practice,” he said, noting that the CONVINCE and CHANCE-3 trials showed no effect of colchicine on stroke.
The results “should give clinicians pause,” Jolly said during the press conference. “We didn’t see an effect on cardiovascular outcomes, and unfortunately there was a side effect of diarrhea.”
CLEAR SYNERGY (OASIS-9) was a 2x2 factorial trial in which patients were also randomly assigned to spironolactone or placebo, and the spironolactone results will be presented in November at the American Heart Association Scientific Sessions, Jolly said.
The mean age of the patient population was 61 years, and 20% were women, 95% had STEMI, 18% had diabetes and 9% had prior MI, Jolly said. Most patients in the colchicine group received 0.5 mg once daily after the results of COLCOT, which used that dose, were released, but some patients enrolled early received a higher dose, he said.
At 3 months, C-reactive protein level was reduced in the colchicine group compared with the placebo group, indicating that colchicine was working as expected (mean difference, –1.3 mg/L; 95% CI, –1.8 to –0.7), he said.
The incidence of the primary outcome was almost identical between the groups over long-term follow-up (colchicine, 9.1%; placebo, 9.3%; HR = 0.99; 95% CI, 0.85-1.13; P = .93), Jolly said during the press conference.
There were also no differences between the groups in the individual components of the primary outcome, all-cause death or CV death/MI/stroke, he said, noting that the incidence of non-CV death was slightly lower in the colchicine group, “but we think that’s likely a play of chance, given that the totality of the data was actually going in the opposite direction. Probably the truth is that there is no difference.”
The on-treatment analysis was similar to the intention-to-treat analysis except that the difference in non-CV death was no longer significant, and the results were consistent across all prespecified subgroups, he said.
There were no differences between the groups in serious or overall adverse events, and as expected, there was a higher rate of diarrhea in the colchicine group than in the placebo group (10.2% vs. 6.6%; P < .001), Jolly said.
“Colchicine can be a challenging drug to take; it does cause diarrhea,” Jolly said during the press conference.
“The CLEAR trial is the largest trial of colchicine in acute MI, actually in any CAD, and it has substantially more events than prior trials,” he said. “We believe, based on this large trial, the role of colchicine post-MI and long term, is uncertain.”
COLCOT had about 300 events compared with 649 for CLEAR SYNERGY (OASIS-9), and in that trial, there was no difference between the groups in hard outcomes, and the results were driven by reduced risk for urgent hospitalization for angina, Jolly said during the press conference.
“We can’t rule out a smaller treatment effect, but the truth is that there may be no effect or a very modest effect,” he said.
The results of CLEAR SYNERGY (OASIS-9) will be published in The New England Journal of Medicine in the near future, Jolly said during the press conference.
Reference:
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Jolly S, et al. Late-breaking clinical trials: Session II, in collaboration with The Lancet. Presented at: TCT Scientific Symposium; Oct. 27-30, 2024; Washington, D.C. (hybrid meeting).
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