By: Mathew Fontanez, PharmD Candidate c/o 2022

              What place does the familiar gout medication colchicine have in the fight against heart disease? Colchicine and its natural source, the autumn crocus plant, have been used to treat the “disease of kings”, or gout, for well over 2000 years. As a result of hyperuricemia, gout often occurs in those with a diet high in purine-containing foods and drinks such as alcohol, organ meats, spinach, lentils, and oatmeal to name a few. ⁶ These purines are broken down by the body and produce high levels of uric acid.⁵ As this build-up increases, uric acid may concentrate in certain areas of the body, namely various joints, and uric acid crystal formation occurs. Colchicine alleviates this by downregulating several inflammatory pathways that are triggered in response to the crystals building up in and around the joint space.⁵ It is here that we find a great deal of promise in the age-old gout therapy as a new avenue for heart disease treatment.

Cardiologist Dr. Mark Nidorf from Genesis Care, Australia, one of the largest providers of cancer and cardiac care services in Australia, postulates that low dose colchicine has a means of preventing cardiovascular events in patients with coronary artery disease. In his study, 5522 patients with stable chronic coronary disease were pre-treated with colchicine 0.5 mg daily in a 30-day open-label run-in phase to ensure tolerance. The patients were followed for a median 30-month period. ¹ The standard regimen for acute gout flares is 1.2 mg orally on Day 1 and 0.6 mg once or twice daily on Day 2 until the flare resolves. Some experts continue for 2-3 days after the flare resolves. ² As one might guess from the name, Dr. Nidorf’s “LoDoCo” trials 1 and 2 utilized a low dose of colchicine at 0.5 mg once daily. The primary endpoint was a composite of cardiovascular death which included myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization. Colchicine’s downregulation of various inflammatory pathways includes those that are known to contribute heavily to atherosclerosis. ³ The LoDoCo 2 trial provided credibility to the possibility of colchicine use as a means for secondary prevention for heart disease as the primary endpoint occurred in 187 (6.8%) patients in the colchicine group and 264 (9.6%) patients in the placebo group with a calculated hazard ratio of 0.69, a 95% confidence interval 0.57-0.83 and a p-value <0.001. This represents a statistically significant reduction in cardiovascular death, myocardial infarction, ischemic stroke, and ischemic coronary revascularization. ¹

With over 90% of the initial test population being able to tolerate colchicine during the open-label phase, this initial screening speaks to this medication’s potential as a viable option to a large number of those affected with heart disease. When considering the sample population used in the study, the variation in disease states strengthens the argument that the medication may have a wider use in clinical practice. That said, the clinics involved in the study were based in only two countries, with the Netherlands clinics (N = 3618) providing almost twice the number of patients as the Australian clinics (N = 1904), which may skew results when compared to practice across other countries. ⁴ Beyond a tolerance for the medication, key among the findings was the low incidence of adverse effects, with serious effects such as neutropenia occurring at comparable rates between the test group and control group. No issues were reported when administered with high dose statin therapy, a vital result to have as colchicine would be used in patients already on preventative therapies. Finally, most encouraging was the statistically significant primary endpoint revealing that composite death occurred less frequently in the colchicine group than the placebo group. ⁴

This study and its findings do not immediately cement colchicine’s place amongst other heart disease therapies. It does however provide more proof of its promise as a new option to be explored when considering how best to provide long-term preventative coronary disease care. It is these attempts at unconventional approaches to care that may open even more doors for utilizing previously marketed drugs for new indications.

References:

1. Antipolis S. Gout drug repurposed to fight heart disease. Escardio.org. https://www.escardio.org/The-ESC/Press-Office/Press-releases/Gout-drug-repurposed-to-fight-heart-disease. Published 08/31/2020. Accessed October 14, 2020.
2. Colchicine. Lexi-Drugs. Hudson, OH: Lexi-Comp, Inc. Updated October 1, 2020. Accessed October 14, 2020.
3. Leung YY, Yao Hui LL, Kraus VB. Colchicine–Update on mechanisms of action and therapeutic uses. Semin Arthritis Rheum.2015;45(3):341-50. doi: 10.1016/j.semarthrit.2015.06.013. Accessed October, 2020.
4. Nidorf SM, Fiolet ATL, Eikelboom JW ,et al. The effect of low-dose colchicine inpatients with stable coronary artery disease: The LoDoCo2 trial rationale, design, and baseline characteristics. Am Heart J.2019;218:46-56. doi: 10.1016/j.ahj.2019.09.011. Accessed October,2020
5. Nuki, G., Simkin, P.A. A concise history of gout and hyperuricemia and their treatment. Arthritis Res Ther 8,S1 (2006). https://doi.org/10.1186/ar1906. Accessed October, 2020.
6. Zhang Y, Chen C, Choi H, et al. Purine-rich foods intake and recurrent gout attacks. Ann RheumDis. 2012;71(9):1448-1453.doi:10.1136/annrheumdis-2011-201215. Accessed October,2020

Published by Rho Chi Post