Review: Colchicine helpful in stable CAD, but long-term safety unknown
Click Here to Manage Email Alerts
Colchicine may be considered for the secondary prevention of CV events in chronic coronary disease; however, its long-term safety remains unknown, according to a review published in the European Heart Journal.
The CANTOS trial
In the research summary written on behalf of the LoDoCo2 Steering Committee, researchers said the self-assembly of free cholesterol into its crystalline form may drive the inflammatory cascade in atherosclerotic plaque, and agents that reduce the availability of free cholesterol may hold the potential to alter the atherosclerotic process.
The CANTOS trial demonstrated that selective cytokine inhibition with canakinumab (Ilaris, Novartis) to modulate inflammation resulted in clinical benefit with good safety.
As Healio previously reported, individuals with prior MI and elevated high-sensitivity C-reactive protein treated with canakinumab had reduced recurrent CV events compared with those treated with placebo.
“Colchicine is an ancient drug with broad anti-inflammatory effects,” Aernoud T.L. Fiolet, MD, from the department of cardiology at the University Medical Center Utrecht in the Netherlands, and colleagues wrote. “It is avidly taken up by leukocytes, affects tubulin binding, inhibits the interleukin-6 expression and alters crystal-induced inflammasome activity. Long-term use of the drug is used for gout prophylaxis, in pericarditis and familial Mediterranean fever. Chronic exposure in these patients appears to be safe.”
COLCOT and LoDoCo2 trials
In the COLCOT trial, colchicine 0.5 mg daily in addition to standard care after recent MI reduced the likelihood of an ischemic CV event over 2 years.
As Healio previously reported, CV death, resuscitated cardiac arrest, MI, stroke or hospitalization for angina leading to coronary revascularization were observed in 5.5% of the colchicine arm and 7.1% of the placebo arm (HR = 0.77; 95% CI, 0.61-0.96).
In addition, the LoDoCo2 trial compared colchicine plus optimal medical therapy vs. optimal medical therapy alone for chronic coronary disease and further confirmed the inflammation hypothesis of COLCOT.
As Healio previously reported, the risk for the primary endpoint of CV death, spontaneous MI, ischemic stroke or ischemia-driven coronary revascularization was lower among patients treated with low-dose colchicine compared with placebo, at a median of 28.6 months follow-up (HR = 0.69; 95% CI, 0.57-0.83).
“In both trials, the benefits of colchicine appeared soon after initiation and continued to accrue over time and were seen in addition to other established secondary prevention therapies including high-dose statins,” the researchers wrote. “Notably, both trials recruited patients in a pragmatic manner without selecting for inflammatory phenotype. Both trials excluded patients with manifest heart failure and severe renal failure. Prespecified analyses showed the efficacy of treatment to be consistent among relevant clinical subgroups.”
The researchers stated the following should be taken into consideration when interpreting the results of the COLCOT and LoDoCo2 trials:
- Neither were designed to assess the long-term safety of colchicine.
- The mean age of participants was 60 to 65 years.
- None of the patients had advanced cardiorenal failure.
- Colchicine interacts with strong CYP3A4 substrates.
- Colchicine should not be used concomitant with clarithromycin, antifungal or immunosuppressive therapy.
“The apparent efficacy of colchicine demonstrated so far add to the relevance of addressing the inflammatory driver in this regard. The effect estimates that were observed in acute and chronic coronary disease represent a clinically meaningful treatment benefit,” the researchers wrote. “Hence, the introduction of the drug as secondary preventive strategy in patients without extensive cardiovascular comorbidity could be considered. Evidence from long-term use in coronary disease will provide additional insight in the magnitude of relevant but yet undetermined safety signals.”
Collapse
Read more about
Click Here to Manage Email Alerts