Colchicine for cardiovacular risk reduction in lower extremity peripheral artery disease

Abstract Introduction Although recent evidence from randomized trials suggests colchicine can reduce major adverse cardiovascular events (MACE) in patients with coronary artery disease, its effect in lower extremity peripheral artery disease (PAD) is not known.1,2 To make inferences about the effects of colchicine in PAD, we leveraged the variable prescribing practice of adding colchicine versus a non-steroidal anti-inflammatory (NSAID) to urate lowering therapy in patients with gout and PAD. Purpose Estimate the effect of colchicine therapy initiation on adverse cardiovascular and limb events in a real-world sample of high-risk patients with PAD and gout. Methods A pragmatic open-label target trial comparing colchicine initiators (treatment group) to NSAID initiators (control group) was emulated in PAD patients taking either drug in conjunction with initiation of urate lowering therapy. Patients were enrolled between July 2007 and December 2019 using electronic health records from a multi-hospital academic medical system linked to Medicare claims data. Patients with contraindications to colchicine or NSAIDs (e.g., severe kidney disease, hepatic failure) were excluded. Inverse probability of treatment weighting was used to create a pseudopopulation balanced with respect to risk factors for the outcomes. The primary outcome was a 5-year composite of major adverse limb events (MALE), MACE, and all-cause mortality. Secondary outcomes included MALE and death, MACE and death, and individual components of the primary outcome accounting for the competing event of death. Risks were estimated with the Kaplan-Meier estimator for the composite outcomes and the Aalen-Johansen estimator for the competing event outcomes. Percentile based 95% confidence intervals were generated using nonparametric bootstrapping. Results A total of 1,786 patients were enrolled; mean age was 77 years (SD 7), 33% were female, and 9% were non-white race (Table). Maximum absolute standardized mean difference in relevant covariates was 23% prior to weighting and 0.8% after weighting, indicating covariate balance. The risk of the primary composite outcome of MALE, MACE, and death at 5 years was 58% (95% CI 55%, 61%) in the colchicine group and 60% (95% CI 56%, 64%) in the control group, with a risk difference of -2% (-8%, 4%) and risk ratio of 0.96 (0.89, 1.04; Figure). Similar findings were noted in the secondary composite outcomes (Figure). In the analysis accounting for the competing risk of death, the cause-specific risk of MALE (9% colchicine vs. 9% control) and MACE (24% colchicine vs. 26% control) alone were similar at 5 years. Conclusions In a real-world sample of high-risk patients with PAD and gout, colchicine did not appear to reduce the risk of adverse cardiovascular or limb events. The cardiovascular benefits of colchicine in older populations with PAD and advanced systematic atherosclerosis remain uncertain.Table.Patient characteristics.Figure.Weighted Kaplan-Meier estimates.