Colchicine Use and Major Adverse Cardiovascular Events in Male Patients with Gout and Established Coronary Artery Disease: A Veterans Affairs Nested Retrospective Cohort Study

Q: What are the key findings of this study?

Consistent colchicine use was associated with lower odds of major cardiovascular events compared to less consistent use in men with gout and CAD.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Gout and established coronary artery disease (n=355). Intervention: Consistent colchicine use (>70% of observation period, Quartile 4) vs. Inconsistent colchicine use (Quartiles 1-3, <50% of observation period) or nonuse. Primary outcome: First major adverse cardiovascular event (MACE: composite of non-fatal myocardial infarction, coronary artery bypass graft, non-fatal stroke, and all-cause mortality) (OR 0.35, 95% CI 0.13-0.93, p=0.03).

Q: What does this research mean for the field?

Consistent colchicine use is associated with a 65% reduction in the odds of major adverse cardiovascular events compared to inconsistent use in male patients with gout and established coronary artery disease. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.NEUTRAL.

Gary Ho; Michael Toprover; Daria B. Crittenden; Binita Shah; Michael H. Pillinger

doi:10.3390/gucdd1010003

March 15, 2023Gout Urate and Crystal Deposition DiseaseOpen Access

Colchicine Use and Major Adverse Cardiovascular Events in Male Patients with Gout and Established Coronary Artery Disease: A Veterans Affairs Nested Retrospective Cohort Study

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Key result

Consistent colchicine use linked to ~65% lower odds of major cardiovascular events in gout and CAD.

OR 0.35
95% CI 0.13-0.93
P=0.03
n=355

Figures

Why the study?

Despite proven efficacy in non-gout populations, the effects of colchicine on MACE risk among high-risk patients with gout remain to be determined.

Does regular or consistent colchicine use reduce the risk of major adverse cardiovascular events (MACE) in male patients with gout and established coronary artery disease?

Study Design

Type

Cohort (n=355)

Structured PICO

Does regular or consistent colchicine use reduce the risk of major adverse cardiovascular events (MACE) in male patients with gout and established coronary artery disease?

P

Population

355 male veterans aged 45-90 years with clinical gout and established coronary artery disease in the VA New York Harbor Healthcare System, followed for a mean of 48 to 61 months.

E

Exposure

Regular colchicine use (>30 continuous days prescription with at least 1 refill; 58.8% prescribed 0.6 mg once daily, 13% 0.6 mg twice daily, 9.7% <0.6 mg daily, 18.5% combination), evaluated both as any regular use and stratified by consistency of use (Quartile 4: mean 88.5% ± 9.9% of observation period on colchicine, >70% time).

C

Comparator

Colchicine nonusers (never filled a prescription for colchicine during the study period, n=116) in Part I; inconsistent colchicine users (Quartiles 1-3, <50% of observation period on colchicine, n=180) in Part II.

O

Outcome

First major adverse cardiovascular event (MACE), defined as a composite of non-fatal myocardial infarction (definite or probable), coronary artery bypass graft (CABG), non-fatal ischemic stroke, and all-cause mortality over a mean observation period of 61 ± 36 months (users) and 48 ± 36 months (nonusers).composite

Main Result

Odds Ratio: 0.35 (95% CI 0.13–0.93)

Absolute Event Rate: 1.5% vs 3.4%

p-value: p=0.03

In male patients with gout and preexisting coronary artery disease, consistent long-term colchicine use (>70% of observation time) was associated with a 65% reduction in the odds of MACE compared with inconsistent use, suggesting cardiovascular protection requires sustained active therapy.

Limitations

Relatively small final sample size (n=355) limiting statistical power and precision
Retrospective cohort design with imperfectly matched groups and potential residual confounding
Inability to guarantee medication adherence after prescriptions were filled
Not powered to assess differences in efficacy between different colchicine dosages
Cardiovascular events occurring outside the VA system were only captured if documented in VA physician notes
Exclusion of female patients limits generalizability to women
Relatively small final sample size that limited power to detect small differences and limited precision
Retrospective cohort design with imperfectly matched groups, differing baseline CV risks and observation periods, and potential residual confounding
Inability to guarantee medication adherence once prescriptions were filled from the VA pharmacy
Not powered to assess differences in efficacy between different dosages of colchicine, and variable total dosage exposure across patients
CV events occurring outside the VA system were only captured if documented in VA physician notes
Exclusion of female patients (only 0.6% of initial cohort) limits generalizability to women

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Answers are grounded in this paper and cite their sources.

Implication

Supports potential MACE reduction with sustained colchicine in gout and CAD; hypothesis-generating and requires RCTs before practice change.

Abstract

Background: Despite colchicine’s proven efficacy in the non-gout population, the effects of colchicine on the risk of major adverse cardiovascular events (MACE) among high-risk patients with gout remain to be determined. The purpose of this study is to evaluate the association between colchicine use and MACE in gout patients with preexisting coronary artery disease (CAD). Methods: This retrospective cohort study followed patients with gout and established CAD within the VA New York Harbor Healthcare System who did or did not use colchicine regularly (>30 continuous days prescription with at least 1 refill). The primary outcome was first MACE, defined as a composite of non-fatal myocardial infarction, coronary artery bypass graft, non-fatal stroke, and all-cause mortality. Part I of the primary analysis compared MACE between colchicine users and nonusers. Part II of the study compared MACE within the colchicine-use group, divided into quartiles based on consistency of colchicine use (i.e., percentage of time on colchicine). Results: Among 1638 patients with gout, 355 had established CAD (239 colchicine users and 116 nonusers). In this cohort, the odds of MACE were similar between any colchicine use compared to nonuse (OR 1.14; 95% CI (0.59–2.20)); however, colchicine users overall had a higher baseline cardiovascular risk profile than nonusers, suggesting that colchicine may have served to equilibrate risk between the two groups. Moreover, patients in the highest continuous colchicine-use quartile (>70% of observation period on colchicine) demonstrated lower odds of MACE compared to those in the lowest three quartiles (OR 0.35; 95% CI (0.13–0.93)), with no difference in baseline risk. Additionally, colchicine users had a numerically lower rate of MACE during periods of active use compared with periods of lapse. Kaplan–Meier analysis revealed a difference in cumulative MACE over time, favoring the subgroup with the most consistent colchicine use (plog-rank = 0.01). Conclusions: Despite higher CV risk, gout patients with CAD receiving colchicine had no higher rates of MACE than those not receiving colchicine. Among all patients with gout and CAD treated with colchicine, those with the most consistent colchicine use had lower odds of MACE, and event rates were lower during active use. Colchicine protection against cardiovascular events may require maintenance of colchicine bloodstream levels.

Discussion

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Cite This Study

Ho et al. (2023) conducted a cohort in Gout and established coronary artery disease (n=355). Consistent colchicine use (>70% of observation period, Quartile 4) vs. Inconsistent colchicine use (Quartiles 1-3, <50% of observation period) or nonuse was evaluated on First major adverse cardiovascular event (MACE: composite of non-fatal myocardial infarction, coronary artery bypass graft, non-fatal stroke, and all-cause mortality) (OR 0.35, 95% CI 0.13-0.93, p=0.03). Consistent colchicine use was associated with lower odds of major cardiovascular events compared to less consistent use in men with gout and CAD.

synapsesocial.com/papers/6a775f53cb17b32ad6bd6e0b https://doi.org/10.3390/gucdd1010003

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Colchicine Use and Major Adverse Cardiovascular Events in Male Patients with Gout and Established Coronary Artery Disease: A Veterans Affairs Nested Retrospective Cohort Study

Figures

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Colchicine Use and Major Adverse Cardiovascular Events in Male Patients with Gout and Established Coronary Artery Disease: A Veterans Affairs Nested Retrospective Cohort Study

Figures

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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