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Abstract Number: 2844

Risk of Cardiovascular Events in Older Patients with Gout Initiating Febuxostat Versus Allopurinol: A Population-Based Cohort Study

MaryAnn Zhang1, Jun Liu2, Eun Ha Kang3, Rishi J. Desai4, Tuhina Neogi5, Daniel H. Solomon1 and Seoyoung C. Kim1, 1Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, 2Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Boston, MA, 3Division of Rheumatology, Department of Internal Medicine, Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea, Republic of (South), 4Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital, Boston, MA, 5Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, MA

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Allopurinol, Cardiovascular disease, Epidemiologic methods, febuxostat and gout

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Session Information

Date: Tuesday, November 7, 2017

Session Title: Metabolic and Crystal Arthropathies I: Gout Risk of Disease Activity, Cardiovascular Disease and Mortality

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: Gout, a disorder of uric acid deposition, is commonly treated with xanthine oxidase inhibitors like febuxostat and allopurinol.  While it is well-known that patients with gout are at increased risk of cardiovascular (CV) disease, little evidence is available with regard to comparative CV safety of febuxostat and allopurinol in the general older population.

Methods: Using claims data from U.S. Medicare (2008-2013), we conducted a cohort study among gout patients aged ≥65 initiating febuxostat versus allopurinol. All patients were continuously enrolled in Medicare parts A/B/D for ≥1 year free of a given drug prior to the 1st dispensing date (index date). The primary outcome was a composite CV endpoint of myocardial infarction (MI) or stroke.  Secondary outcomes comprised MI, stroke, coronary revascularization, and new and recurrent heart failure (HF) requiring hospitalization.  Follow-up time began the day after index date to the earliest day of the following: drug discontinuation, insurance disenrollment, occurrence of outcome, death, nursing home admission or last day of the study period. To adjust for ≥55 baseline covariates and index year, we used propensity score (PS) matching with a 1:3 ratio. Cox proportional hazards regression compared the risk of primary and secondary outcomes in the PS-matched cohorts of febuxostat and allopurinol initiators.

Results: We included 24,900 febuxostat initiators PS-matched on 74,700 allopurinol initiators.  The median age was 76 years, 52% were male, and 32% had CV disease at baseline. During the mean (SD) follow-up time of 1.1 (1.1) years among febuxostat initiators and 1.2 (1.2) years among allopurinol initiators, the incidence rate (IR) per 100 person-years for the primary endpoint (MI or stroke) was 3.45 (95% CI, 3.24-3.68) in febuxostat and 3.34 (95% CI, 3.23-3.46) in allopurinol initiators.  Hazard ratios (HR) for MI or stroke were 1.02 (95% CI, 0.95-1.10) in the febuxostat versus allopurinol groups. The risk of developing secondary outcomes was also similar in both groups (Table).  For new-onset HF hospitalization, the IR in the febuxostat group was 5.72 (95% CI, 5.39-6.08) per 100 person-years with a HR of 1.04 (95% CI, 0.97-1.12) compared to allopurinol.  Among patients with baseline HF, the IR of first-time HF exacerbation was 42.66 (95% CI, 41.12-44.26) per 100 person-years among febuxostat initiators with a HR of 0.95 (95% CI, 0.91-0.99) versus allopurinol.

Conclusion: Among 99,600 older patients with gout enrolled in Medicare, there was no difference in CV risk (including MI, stroke, coronary revascularization and new/recurrent HF) between patients initiating febuxostat compared to allopurinol.

 

 

Table. Risk of overall cardiovascular events and heart failure (HF) in febuxostat initiators versus allopurinol:

1:3 fixed ratio PS-matched

 

Febuxostat

(n=24,900)

Allopurinol

(n=74,700)

 

Outcome

Event (n)

Person-years

IR *

(95% CI)

Event (n)

Person-years

IR *

(95% CI)

HR

(95% CI)

Primary:

MI or stroke

941

27,261

3.45

(3.24-3.68)

3,081

92,192

3.34

(3.23-3.46)

1.02

(0.95-1.10)

Secondary:

MI

601

27,450

2.19

(2.02-2.37)

1,966

98,861

2.12

(2.03-2.21)

1.02

(0.93-1.12)

Stroke

372

27,630

1.35

(1.22-1.49)

1,217

93,507

1.30

(1.23-1.38)

1.03

(0.91-1.15)

Coronary revascularization

723

27,225

2.66

(2.47-2.86)

2,493

91,821

2.72

(2.61-2.82)

0.97

(0.89-1.05)

New-onset HF a

1,057

18,472

5.72

(5.39-6.08)

3,463

63,594

5.45

(5.27-5.63)

1.04

(0.97-1.12)

HF exacerbation b

2,848

6,676

42.66

(41.12-44.26)

9,407

21,306

44.15

(43.27-45.05)

0.95

(0.91-0.99)

PS matched covariates included demographic factors, medical comorbidities, use of gout-related medications, use of cardiovascular drugs, and markers of healthcare utilization intensity (i.e. number of emergency room visits).

* IR is per 100 person-years

a among the subgroup of patients with no baseline history of HF

b among the subgroup of patients with baseline history of HF, with HF as the primary diagnosis

 

 


Disclosure: M. Zhang, None; J. Liu, None; E. H. Kang, None; R. J. Desai, None; T. Neogi, None; D. H. Solomon, AstraZeneca, 2; S. C. Kim, Pfizer Inc, 2,Bristol-Myers Squibb, 2,Roche/Genentech, 2,AstraZeneca, 2,Merck Human Health, 2.

To cite this abstract in AMA style:

Zhang M, Liu J, Kang EH, Desai RJ, Neogi T, Solomon DH, Kim SC. Risk of Cardiovascular Events in Older Patients with Gout Initiating Febuxostat Versus Allopurinol: A Population-Based Cohort Study [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/risk-of-cardiovascular-events-in-older-patients-with-gout-initiating-febuxostat-versus-allopurinol-a-population-based-cohort-study/. Accessed July 2, 2022.
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