Allopurinol Use In Concomitant Gout and Diabetes Lowers Cardiovascular Event Risk

Evidence for a potential cardiovascular protective effect of allopurinol in patients with gout and diabetes.
Evidence for a potential cardiovascular protective effect of allopurinol in patients with gout and diabetes.
TOPIC SERIES: CVD PREVENTION IN RHEUMATIC DISEASE

Current use of the urate-lowering therapy allopurinol by patients with gout and diabetes resulted in a reduced risk for the first incidence of hospitalized myocardial infarction (MI) or stroke, according to an analysis of claims data by researchers from the University of Alabama at Birmingham (UAB). Results were published recently in BMC Cardiovascular Disorders.1

The research team, led by UAB professor of medicine and epidemiology Jasvinder Singh, MD, MPH, derived their conclusions using data from the Multi-Payer Claims Database (MPCD), an aggregation of medical records information from patients with Medicare, Medicaid, or United Healthcare coverage. Current use of allopurinol was defined for the purposes of the study as a newly filled prescription. In their analysis of 2,053,185 person-days of current allopurinol use and 1,671,583 person-days of prior allopurinol use in patients with gout and concomitant diabetes, the investigators found 158 incident acute cardiovascular (CV) events in current allopurinol users and 151 CV events in prior allopurinol users.

High-Yield Data Summary

  • Allopurinol use was independently associated with a lower risk for incident stroke or MI in patients with gout and diabetes, which may indicate evidence for a potential cardioprotective effect in this high-risk group. However, future studies are needed to explore the factors that mediate this effect.

In multivariable-adjusted Cox proportional hazards models, hazards of incident acute CV events were significantly lower in current allopurinol users (hazard ratio [HR] 0.67, 95% CI, 0.53, 0.84). Compared with previous allopurinol use, current allopurinol use resulted in a 33% hazard reduction of incident stroke or MI. Adjustment for colchicine use or the presence of autoimmune disease yielded essentially the same results. Statistically significant associations with the risk of CV events were not seen with the use of colchicine (95% CI, 0.55, 1.18) or the presence of autoimmune disease (95% CI, 0.78, 1.37).

Previous studies that aimed in a similar manner to determine whether allopurinol is associated with better cardiac outcomes produced conflicting results. However, Dr. Singh and colleagues pointed out several methodological issues with prior research, including the frequent use of a prevalent-user design, which mixes ongoing users with new users in the same analysis.

Summary and Clinical Applicability 

“In conclusion, in robust analyses of data from a representative sample of Americans, we found that current allopurinol use was independently associated with a lower risk of incident stroke or MI in patients with gout and diabetes,” the investigators wrote. 

“Our findings provide evidence for a potential cardiovascular protective effect of allopurinol in patients with gout and diabetes, a group of patients at high risk for cardiovascular events. Future studies need to explore the factors that mediate this protective effect, and examine what proportion of variability in this protective effect is explained by serum urate reduction and/or anti-oxidant effect of allopurinol.”

Study Limitations

  • The use of ICD-9-CM codes to identify patients who had been diagnosed with acute CV events may have led to misclassification bias.
  • The investigators were unable to determine whether the association between allopurinol use and CV events may have mediated by reduced serum urate levels, as these measurements were not available for most patients in the database.
  • Important covariates/risk factors for MI and stroke, such as body mass index, smoking, diet and exercise, over-the-counter aspirin use, and family history of CV disease were not available in the database.
  • Current allopurinol users may be more likely to engage in other behaviors beneficial to CV outcomes, including healthier lifestyles and adherence to other medications.

Disclosures

Dr Singh has received research grants from Takeda and Savient and consultant fees from Savient, Takeda, Regeneron, Merz, Bioiberica, Crealta and Allergan Pharmaceuticals, WebMD, UBM LLC and the American College of Rheumatology. He also serves as the principal investigator for an investigator-initiated study funded by Horizon pharmaceuticals through a grant to DINORA, Inc., a 501 (c)(3) entity. Dr Curtis has received research grant funding and consulting fees for unrelated work from Abbvie, Amgen, BMS, Janssen, Pfizer, Roche, and UCB.

Reference

Singh JA, Ramachandaran R, Yu S, Curtis JR. Allopurinol use and the risk of acute cardiovascular events in patients with gout and diabetes. BMC Cardiovasc Disord. 2017;17:76. doi:10.1186/s12872-017-0513-6

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