A retrospective cohort study suggests that regular use of the gout drug colchicine protects against heart attacks in people with gout.

“Judging efficacy of drugs from observational studies is a hazardous pursuit, but the authors have hit a home run here by convincingly demonstrating that those patients with gout who consistently filled colchicine prescriptions are less likely to experience coronary events,” said Eswar Krishnan, MD, assistant professor of medicine (immunology and rheumatology) at Stanford University, Stanford, Calif., who was not involved in the study. “This study provides real-world data to confirm the seminal Australian clinical trial that showed conclusively that colchicine can reduce acute coronary events.” In the Australian study, the LoDoCo (Low Dose Colchicine) trial (J Am Coll Cardiol 2013;61:404-410), the investigators documented a 71% lower risk for cardiovascular events among non-gout patients with heart disease who used colchicine (Colcrys, Takeda) 0.5 mg daily without lapses.

The new study, which was supported in part by Takeda, was presented in a poster at the American College of Rheumatology’s (ACR) 2013 annual meeting by D. Barry Crittenden, MD, and her colleagues. They identified 4,486 active patients with an International Classification of Diseases, Ninth Edition, code for gout and/or hyperuricemia, who were being treated at the VA New York Harbor Healthcare System between 2000 and 2009. Six hundred forty-four patients met the criteria for gout and had at least three months’ follow-up information available. This included 410 individuals with gout who had used colchicine for at least 30 days and 234 who had never used the medication. The latter formed the control group.

The patients who had taken colchicine had a total of 1,184 person-years of active use and 682 person-years of lapse. Dr. Crittenden, instructor of medicine at New York University School of Medicine, New York City, and her team defined “lapse” as any period of colchicine non-use beginning two weeks after medication cessation, to take into account the drug’s elimination time. The colchicine-use and control groups had similar baseline characteristics, including average ages of 66 and 67 years, respectively; 99.3% and 97.4%, respectively, being male; and 24.1% and 26.1%, respectively, having coronary artery disease.

The investigators found that the incidence rates of myocardial infarction (MI) were 0.7% among active colchicine users, 2% among individuals in a colchicine lapse, and 3% among colchicine-naive patients (P=0.041 vs. active use). Furthermore, the respective rates of MI per patient-year in the groups were 0.003, 0.012 (P=0.02 vs. active colchicine), 0.009 (P=0.04 vs. active colchicine) and 0.007. The rate of MI among individuals who had ever used colchicine was 0.006.

Dr. Crittenden and her co-investigators are analyzing data from an additional 3,333 individuals from the same cohort. She said it is striking that the interim results indicate there is an even greater risk for cardiovascular events in individuals who are in a lapse period than in people who have never used colchicine.

“Is there a rebound effect when coming off colchicine that increases MI risk? Is lack of compliance with colchicine a surrogate for lack of compliance with other important cardiac medications? These are some of the questions we will be considering in the final analysis,” Dr. Crittenden said. “Future plans for this work may include use of a larger database to confirm or refute our findings, additional mechanistic studies, and perhaps eventually a blinded prospective study of colchicine and cardiovascular risk modulation.”

 

Drs. Crittenden and Krishnan reported no relevant financial conflicts of interest.