Debra L. Beck and Eugene Braunwald, MD
Date Published: 17 Nov 2019
Multiple lines of evidence support the role of inflammation in atherosclerosis and its complications. Colchicine is an orally administered, potent anti-inflammatory medication that is indicated for the treatment of gout and pericarditis. The COLCOT trial was conducted in patients with recent myocardial infarction (MI) to evaluate the effects of colchicine on cardiovascular (CV) outcomes and its long-term safety and tolerability.
In this randomized, double-blind trial, 4745 patients were recruited within 30 days of an MI and were randomly assigned to receive either low-dose colchicine (0.5 mg once daily) or placebo. Patients were followed for a median of 23 months. Most (93%) underwent percutaneous coronary intervention for the index MI, and use of dual antiplatelet therapy and statins was 98% and 99%, respectively.
The primary efficacy endpoint was a composite of death from CV causes, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina leading to coronary revascularization. The primary endpoint rates were 5.5% for the colchicine group and 7.1% for the placebo group (hazard ratio [HR], 0.77; p=0.02).
The reduction in risk of the primary endpoint with colchicine was amplified (to 29%) in patients who adhered to protocol and took at least six months of treatment (per-protocol analysis), with event rates of 5.1% and 7.1% for colchicine and placebo, respectively (HR, 0.71; 95% confidence intervals [CI], 0.56 to 0.90).
The rate of total (first and recurrent) primary endpoint events was reduced by 34% with colchicine compared to placebo (HR, 0.66; 95% CI, 0.51 to 0.86).
Colchicine was generally well-tolerated, with no significant difference in the incidence of diarrhea (9.7% and 8.9%; p=0.35). Pneumonia was reported as a serious adverse event in 0.9% of the patients in the colchicine group and in 0.4% of the placebo group (p=0.03). Nausea and flatulence were uncommon but also more common with colchicine (1.8% vs. 1.0%; p=0.02 and 0.6% vs. 0.2%; p=0.02).
Summary
The researchers concluded that colchicine 0.5 mg/day significantly reduced the risk of first and total ischemic CV events by 23% and 34%, respectively, compared to placebo in patients with recent MI. Rates of adverse events were low, but included a small increase in pneumonia. Future research is needed to understand the longer-term risks and benefits of colchicine treatment in this group of patients.
Addendum
In a second late-breaking presentation, Dr. B Shah presented findings from the COLCHICINE-PCI trial, which tested the effects of colchicine versus placebo on peri-procedural myocardial injury (as measured by troponin and using the Universal Definition) and systemic inflammation. They tested a single dose of colchicine 1.8 mg given before PCI.
The trial showed that, compared to placebo, colchicine given before PCI did not lower the risk of PCI-related myocardial injury, although it did attenuate somewhat the increase in inflammation after PCI (hs-c-reactive protein compared to baseline).
Discussing the trials, Dr. S Verma concluded that more studies are needed that target residual inflammatory risk with acute and chronic treatment. One such trial is the ongoing OASIS 9 study, which will test colchicine with or without spironolactone and spironolactone alone in 4000 patients with ST-segment MI referred for PCI.
References
Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine features a unique update program by Dr. Braunwald, creating a “living textbook” by featuring weekly Hot off the Press, periodic Late-Breaking Clinical Trials (including links to authors’ presentation slides), and monthly Focused Reviews.
Learn more about Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine, 11th Edition. Download a free chapter here.
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