Effects of Colchicine Use on CVD, Mortality in Gout

TOPIC SERIES: CVD PREVENTION IN RHEUMATIC DISEASE

Researchers from the Brigham and Women’s Hospital in Boston have found that in a cohort study of electronic medical records (EMRs) linked with Medicare claims, colchicine exposure was associated with lower cardiovascular (CV) risk in patients with gout. The findings were published in Annals of the Rheumatic Diseases.

“Since gout and hyperuricemia are associated with an increased CV risk,^2-4 it is important to consider whether colchicine might have value as a CV prevention measure in patients with gout,” wrote Daniel H Solomon, MD, MPH, from Brigham and Women’s Hospital in Boston and colleagues.

The use of immunomodulators and anti-inflammatory medication to reduce systemic inflammation and reduce secondary CV events in the general population has been well-studied in the past. However, the use of colchicine to reduce systemic inflammation in gout, and any possible reductions in CV events, had not yet been rigorously studied.

To test their hypothesis that colchicine use would reduce the risk of CV events in patients with gout, the researchers examined 501 colchicine users from an EMR database linked with Medicare claims between 2006-2011, and matched them with 501 non-users. Both groups of participants were followed for a composite of myocardial infarction, stroke, or transient ischemic attack.

The researchers found that among colchicine users, there were 28 CV events during follow-up, and among non-users, there were 82 events. The incidence rate per 1000 person-years was 35.6 for users and 81.8 for non-users. 

After full adjustment, colchicine use was associated with a 49% lower risk (hazard ratio [HR] 0.51, 95% CI 0.30 to 0.88) of CV outcomes as well as a 73% reduction in all-cause mortality (HR 0.55, 95% CI 0.35 to 0.85, P = .007).

“Most patients with gout do not receive long-term colchicine, as it is indicated for acute attacks or while initiating uric-acid lowering treatments.⁵ However, some patients with frequent attacks use it long term. 

These results, along with those from prior studies, suggest that long-term colchicine may provide CV risk protection among patients with gout with and without known cardiovascular disease (CVD), a group known to experience a 30–60% increased risk of CV events,”⁴ the authors wrote.

The researchers also noted, however, that while there is a strong biological basis for these results, and that research thus far lends support to colchicine’s benefit,⁶ the results are based on hypothesis and should be interpreted with caution. These results may lend support for a  randomized controlled trial to examine whether colchicine reduces CV risk.

Summary & Clinical Applicability

Using data from an EMR database linked with Medicare claims from 2006-2011, researchers found that new use of colchicine was associated with lower CV risk in patients with gout.

“While we are unable to confirm a causal link in a non-randomized observational study, this study provides justification for a randomized controlled trial of colchicine to reduce CV risk among patients with gout. Such a trial might focus on secondary CV prevention,” the authors concluded.

They noted that because CV disease affects approximately 7%-14% of an estimated 8 million adults in the US with gout, and because colchicine is already familiar to many of these patients, the study has strong feasibility.

Limitations & Disclosures

• Differences between the 2 treatment groups suggest that colchicine may have been prescribed to patients more willing to use medications
• Increased all-cause mortality in non-users may suggest that clinicians were less likely to prescribe colchicine to sicker patients
• Lack of a clear gradient of colchicine’s effect according to duration of use could be viewed as evidence against a causal relationship
• Using an observational database may misclassify some patients’ use (ie, those prescribed colchicines who did not use it, or those without recent prescriptions who used samples or old prescriptions)

The study was partially funded by NIH K24 AR055989.

Daniel H. Solomon, MD, has disclosed the following relevant financial relationships: Receives salary support from unrelated grants to Brigham and Women‘s Hospital from Lilly, Pfizer and Amgen; received research funding from Astra Zeneca on gout medication

Seoyoung C. Kim, MD, has disclosed the following relevant financial relationships: Receives salary support from unrelated grants to Brigham and Women‘s Hospital from Lilly and Pfizer; received research funding from Astra Zeneca on gout medication

References

1. Solomon DH, Liu CC, Kuo IH, Zak A, Kim SC. Effects of colchicine on risk of cardiovascular events and mortality among patients with gout: a cohort study using electronic medical records linked with Medicare claims. Ann Rheum Dis. 2016;75(9):1674-9. doi:10.1136/annrheumdis-2015-207984.
2. Kim SY, Guevara JP, Kim KM, et al. Hyperuricemia and risk of stroke: a systematic review and meta-analysis.Arthritis Rheum. 2009;61:885–92.
3. Kim SY, Guevara JP, Kim KM, et al. Hyperuricemia and coronary heart disease: a systematic review and meta-analysis. Arthritis Care Res (Hoboken). 2010;62:170–80.
4. Choi HK, Curhan G. Independent impact of gout on mortality and risk for coronary heart disease. Circulation. 2007;116:894–900.
5. Nuki G. Colchicine: its mechanism of action and efficacy in crystal-induced inflammation. Curr Rheumatol Rep. 2008;10:218–27.
6. Nidorf SM, Eikelboom JW, Budgeon CA, et al. Low-dose colchicine for secondary prevention of cardiovascular disease. J Am Coll Cardiol. 2013;61:404–10.