Cardiovascular Risks of Probenecid Versus Allopurinol in Older Patients With Gout

J Am Coll Cardiol. 2018 Mar 6;71(9):994-1004. doi: 10.1016/j.jacc.2017.12.052.


Background: Patients with gout are at an increased risk of cardiovascular (CV) disease including myocardial infarction (MI), stroke, and heart failure (HF).

Objectives: The authors conducted a cohort study to examine comparative CV safety of the 2 gout treatments-probenecid and allopurinol-in patients with gout.

Methods: Among gout patients ≥65 years of age and enrolled in Medicare (2008 to 2013), those who initiated probenecid or allopurinol were identified. The primary outcome was a composite CV endpoint of hospitalization for MI or stroke. MI, stroke, coronary revascularization, HF, and mortality were assessed separately as secondary outcomes. The authors estimated the incidence rate and hazard ratio of the primary and secondary outcomes in the 1:3 propensity score-matched cohort of probenecid and allopurinol initiators.

Results: A total of 9,722 probenecid initiators propensity score-matched to 29,166 allopurinol initiators with mean age of 76 ± 7 years, and 54% males were included. The incidence rate of the primary composite endpoint of MI or stroke per 100 person-years was 2.36 in probenecid and 2.83 in allopurinol initiators with a hazard ratio of 0.80 (95% confidence interval: 0.69 to 0.93). In the secondary analyses, probenecid was associated with a decreased risk of MI, stroke, HF exacerbation, and mortality versus allopurinol. These results were consistent in the subgroup analyses of patients without baseline CV disease or those without baseline chronic kidney disease.

Conclusions: In this large cohort of 38,888 elderly gout patients, treatment with probenecid appears to be associated with a modestly decreased risk of CV events including MI, stroke, and HF exacerbation compared with allopurinol.

Keywords: allopurinol; cardiovascular disease; comparative safety research; gout; probenecid.

Publication types

  • Comparative Study
  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Allopurinol / therapeutic use*
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / epidemiology*
  • Cardiovascular Diseases / prevention & control
  • Cohort Studies
  • Female
  • Gout / diagnosis
  • Gout / drug therapy
  • Gout / epidemiology*
  • Gout Suppressants / therapeutic use*
  • Humans
  • Male
  • Medicare / trends*
  • Probenecid / therapeutic use*
  • Risk Factors
  • United States / epidemiology
  • Uricosuric Agents / therapeutic use


  • Gout Suppressants
  • Uricosuric Agents
  • Allopurinol
  • Probenecid