Allopurinol and the risk of ventricular arrhythmias in the elderly: a study using US Medicare data.
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.
Medicine Service, Birmingham VA Medical Center, Birmingham, AL, USA. jasvinder.md@gmail.com.|Department of Medicine at School of Medicine, and Division of Epidemiology at School of Public Health, University of Alabama at Birmingham (UAB), Birmingham, AL, USA. jasvinder.md@gmail.com.|Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA. jasvinder.md@gmail.com.|University of Alabama at Birmingham, Faculty Office Tower 805B, 510 20th Street S, Birmingham, AL, 35294, USA. jasvinder.md@gmail.com.
Jasvinder A
JA
Singh
Department of Medicine at School of Medicine, and Division of Epidemiology at School of Public Health, University of Alabama at Birmingham (UAB), Birmingham, AL, USA.|University of Alabama at Birmingham, Faculty Office Tower 805B, 510 20th Street S, Birmingham, AL, 35294, USA.
John
J
Cleveland
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000493:Allopurinol / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000453:epidemiology* / Q000209:etiology; D015897:Comorbidity; D005260:Female; D006073:Gout / Q000188:drug therapy* / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D008297:Male; D006278:Medicare / Q000706:statistics & numerical data; D008875:Middle Aged; D012307:Risk Factors; D013997:Time Factors; D014481:United States / Q000453:epidemiology
D000493:Allopurinol
Allopurinol; Elderly; Medicare; Risk factor; Ventricular arrhythmias