Colchicine Treatment in Gout Does Not Increase Risk of Cardiovascular Events

The risk of revascularization, stroke, and myocardial infarction (MI) was not higher in patients with gout treated with colchicine compared with those who did not receive the drug, according to a meta-analysis published in IJC Heart & Vasculature.¹

Muhammad U Siddiqui, MD

Credit: Doximity.com

Although inflammation has been shown to significantly impact the pathogenesis and progression of coronary artery disease (CAD), treatment with anti-inflammatory drugs in CAD have historically revealed mixed results.²

“Scientists have been in search of a cost effective and safe anti-inflammatory therapy with favorable effects on the cardiovascular system,” wrote Muhammad U Siddiqui, MD, cardiologist at the Jefferson Heart Institute, Thomas Jefferson University Hospital, in Philadelphia, and colleagues. “Colchicine fits this profile and has been under study in recent years…Importantly, it acts not only against urate crystals in gouty joints, but also against cholesterol crystals in atherosclerotic coronary arteries.”

Investigators analyzed the impact of colchicine on cardiovascular outcomes in patients with gout, both with and without CAD, using a systematic search of Medline, Cochrane Central Register of Controlled Trials, and Web of Science. Keywords included gout, gouty arthritis, colchicine, myocardial infarction, coronary heart disease, coronary artery disease, and coronary atherosclerosis.

Primary outcomes included coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), and MI. Other outcomes of interest were stroke and all-cause mortality. The Modified Newcastle-Ottawa scale for observational studies, which evaluates outcome assessment, patient selection, and comparability, was used to determine the risk of bias.

Four observational studies were ultimately identified, comprised of 10,026 patients with gout. Of these patients, 6800 were being treated with colchicine and 3426 were not. Dosage was not mentioned in any of the studies and 3 provided information on the uric acid status.

No significant differences in the risk of MI were observed between groups (risk ratio [RR] .71; 95% confidence interval [CI], .36 – 1.39). Further, no differences in the need for CABG (RR 1.98; 95 % CI .70–5.58) or the need for PCI (RR .83; 95 % CI .53–1.29) were reported between those receiving the drug and those who were not. Of the 2 studies that included stroke as an outcome, pooled results did not report a statistical difference in the risk of stroke among patients in the colchicine cohort and the non-colchicine cohort (RR .51; 95 % CI .15–1.78).

Of the 3 studies that evaluated all-cause mortality, colchicine treatment was linked to a significantly lower risk of all-cause mortality (RR .58; 95% CI .43 – .79).

A high risk of selection bias was determined in all studies due to the lack of blinding and randomization. Two studies had a high risk of confounding bias because they did not adjust for confounders. Publication bias could not be evaluated due to the small number of studies included in the analysis, although there was no evidence of publication bias.

Investigators noted several factors that may have hindered the findings of the meta-analysis. Generalizability was limited as 2 studies did not include females. Additionally, the studies were heterogenous regarding the population studied, concomitant medications for the treatment of gout, and outcomes reported. Lastly, the dose of colchicine was not mentioned in any of the studies in the analysis.

“The studies included in our meta-analysis highlight the unclear utility of colchicine in reducing adverse cardiac outcomes in patients with gout,”¹ investigators concluded. “Despite the mixed results thus far, the utility of colchicine in improving cardiovascular outcomes in those with CAD remains of great interest.”

References

1. ^{Siddiqui MU, Junarta J, Sathyanarayanan S, Kochar K, Ullah W, Fischman DL. Risk of coronary artery disease in patients with gout on treatment with Colchicine: A systematic review and meta-analysis. Int J Cardiol Heart Vasc. 2023;45:101191. Published 2023 Mar 4. doi:10.1016/j.ijcha.2023.101191}
2. ^{D.D. Waters. Inflammation in cardiovascular disease: from basic concepts to clinical application Int. J. Cardiovascular Sci., 33 (2020), pp. 518-527}