Allopurinol Not Associated With Increased All-Cause Mortality in Gout

Researchers evaluated the association between allopurinol use and mortality in patients with gout.

Allopurinol is not associated with increased risk for all-cause mortality in patients with gout, according to findings from a systematic review published in Arthritis Care & Research.

Investigators searched the Embase, Medline, CINAHL, and Cochrane Studies databases for full text articles reporting on the mortality risk estimates for adult patients with gout. Cohort studies were eligible for inclusion, and randomized clinical trials, case-control studies, and cross-sectional studies were excluded from the analysis. Study data were extracted by 2 independent reviewers. The primary outcomes were risk estimates for all-cause and cardiovascular mortality among patients receiving allopurinol. A random-effects meta-analysis model was used to pool mortality risk estimates. Study quality was appraised using the Newcastle-Ottawa Scale.

From 362 articles identified in the literature search, 4 were eligible for the study. Study populations were from Taiwan, United States, and the United Kingdom. All 4 studies reported mortality risk using hazard ratios (HRs). Study quality was high, with each article including a representative population, using validated outcome measures and propensity score matching, and avoiding confounding. The pooled adjusted HR for all-cause mortality was 0.80 (95% CI, 0.60-1.05) among patients receiving allopurinol vs those who were not. Heterogeneity was significant for this estimate (87.6%; P <.001), and 1 study was excluded based on the lack of risk stratification by allopurinol dose. Little data were available on cardiovascular outcomes to conduct a meta-analysis. One study suggested that cardiovascular-related mortality may increase with increasing allopurinol dose (unadjusted HR, 1.08; 95% CI, 0.97-1.21); however, in the fully adjusted model, this association was no longer significant (HR, 1.05; 95% CI, 0.92-1.20).

Results from a meta-analysis of 3 cohort studies suggested that allopurinol use does not increase risk for all-cause mortality in patients with gout. Conflicting evidence was available for the effect of allopurinol on cardiovascular-related mortality.

Study limitations included small sample size and between-study heterogeneity.

Researchers concluded that additional research is necessary to further explore the effect of allopurinol on mortality and cardiovascular outcomes.


Hay CA, Prior JA, Belcher J, Mallen CD, Roddy E. Mortality in patients with gout treated with allopurinol: a systematic review and meta-analysis [published online April 14, 2020]. Arthritis Care Res (Hoboken). doi:10.1002/acr.24205