The online version of this article (doi:10.1186/s12916-017-0816-6) contains supplementary material, which is available to authorized users.
There are no published human studies investigating whether the use of allopurinol, the most commonly used medication for the treatment of hyperuricemia in gout, the most common type of inflammatory arthritis in adults, has any beneficial effects on ventricular electrophysiology. The objective of our study was to assess whether allopurinol use is associated with a reduction in the risk of ventricular arrhythmias (VA).
We used the 5% random sample of Medicare beneficiaries from 2006–2012 to examine new allopurinol use and the risk of incident VA. Multivariable Cox regression analyses were adjusted for demographics (age, race, sex), comorbidity, cardiac medications, and conditions associated with VA. We calculated hazard ratios (HR) and 95% confidence intervals (CI).
Of the 28,755 episodes of new allopurinol use, 2538 were associated with incident VA (8.8%). Among patients with incident VA, 54% were male, 78% were White, 75% had gout as the underlying diagnosis, and the mean Charlson–Romano comorbidity score was 4.8. The crude incidence of VA per 1,000,000 person-days declined as the duration of allopurinol use increased: 1–180 days, 151; 181 days to 2 years, 105; and > 2 years, 85. In multivariable-adjusted analyses, compared to non-use, allopurinol use was associated with lower HR of VA of 0.82 (95% CI, 0.76–0.90). Compared to allopurinol non-use, longer allopurinol use durations were significantly associated with lower multivariable-adjusted HR for VA: 1–180 days, 0.96 (95% CI, 0.85–1.08); 181 days to 2 years, 0.76 (95% CI, 0.68–0.85); and > 2 years, 0.72 (95% CI, 0.60–0.87). Multiple sensitivity analyses adjusting for cardiac conditions, anti-arrhythmic drugs and alternate definitions confirmed our findings with minimal/no attenuation of estimates.
Allopurinol use and use duration of more than 6 months were independently associated with a lower risk of VA. Future studies need to assess the pathophysiology of this potential benefit.
Additional file 1: Appendix 1. Crude incidence rate of ventricular arrhythmias with allopurinol exposure. Appendix 2. Sensitivity analysis 3: Main models run using a different set of ICD-9 codes for ventricular arrhythmias* based on the study by Hennessey et al. [ 38]. Appendix 3. Sensitivity analysis 4: Association of risk factors with hazard of ventricular arrhythmias in patients who received allopurinol including specific disease risk factors and three additional anti-arrhythmic medications* (mexilitine, propafenone and dofetilide). Appendix 4. Subgroup analysis by prior myocardial infarction (MI): Allopurinol use and duration of allopurinol use models by prior MI diagnosis. Appendix 5. Hazard ratios of ventricular arrhythmias by race and sex, adjusted for other factors. Appendix 6. Association of risk factors with hazard of ventricular fibrillation in patients who received allopurinol with no baseline ventricular fibrillation before the index date of allopurinol episode. Appendix 7. Sensitivity analysis by underlying diagnosis of gout versus non-gout: association of allopurinol with hazard of ventricular arrhythmias adjusted for specific disease risk factors for ventricular arrhythmias. Appendix 8. Sensitivity analysis limiting the cohort to patients not receiving any anti-arrhythmic or cardio-protective drugs: Association of allopurinol with hazard of ventricular arrhythmias adjusted for specific disease risk factors for ventricular arrhythmias. (DOCX 58 kb)
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- Allopurinol and the risk of ventricular arrhythmias in the elderly: a study using US Medicare data
Jasvinder A. Singh
- BioMed Central
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