Background/Purpose: Hyperuricemia and gout are associated with an increased risk of hypertension and cardiovascular disease (CVD) such as myocardial infarction (MI) and stroke. Xanthine oxidase inhibitors (XOI), allopurinol and febuxostat, are the main therapy to treat gout patients with hyperuricemia. Little is known whether treating hyperuricemia with a XOI has any effect on CVD risks. We examined the risk of CVD in gout patients initiating a XOI drug compared to untreated hyperuricemic patients.    

Methods: We conducted a population-based cohort study combining two U.S. commercial insurance claims databases (2003-2012). Among adult patients with a diagnosis of gout, initiators of XOIs were identified. Serum uric acid levels at baseline were available in 15% of XOI initiators. Patients with hyperuricemia defined as the serum uric acid level ≥6.8 mg/dl were identified as a reference. For both groups, patients were required to have no use of XOIs in the 180-day baseline period. Patients with a history of malignancy were excluded. For primary ‘as treated’ analysis, patients were followed from the index date, the first receipt of XOI or the first high uric acid level measured after the 180-day baseline period, up to 180 days. Secondary ‘as treated’ analyses included the entire follow-up time from the index date. We calculated incidence rates (IR) of CVD including MI, coronary revascularization, stroke, and heart failure, based on inpatient and/or outpatient diagnosis and procedure codes. To control for baseline demographic factors, comorbidities, medications, and health care utilization, a propensity score (PS) matching with a 1:1 ratio was used. Cox proportional hazards models stratified by the PS matched pair compared the risk of CVD in XOI initiators vs. the hyperuricemic group.

Results: There were a total of 43,269 PS-matched pairs. Baseline comorbidities, medication use, and health care utilization were well-balanced between the groups. Mean age was 52.5 years and 86% male for both groups. Common comorbidities include hypertension (56%), hyperlipidemia (50%), diabetes (19%), CVD (9%), obesity (7%) and chronic kidney disease (7%). Use of systemic steroids at baseline was common (20%). The mean (SD) serum uric acid level was 8.6 (1.7) mg/dl in XOI initiators and 8.1 (3.0) mg/dl in the hyperuricemia group. The IR per 1,000 person-years was 8.03 (95% CI 6.63-9.72) for MI and 57.69 (95% CI 53.70-61.98) for composite CVD in XOI initiators, 1.13 times higher compared with the hyperuricemia group (Table). In secondary analyses not limited to the first 180 days of follow-up, CVD risks in XOI initiators were increased similarly to the main results (Table).

Conclusion: Our study found an increased risk of CVD in gout patients initiating a XOI drug compared to patients with untreated hyperuricemia. Further research is needed on the long-term effect of XOI on CVD.   

 

Table.  Risk of cardiovascular diseases (CVD) associated with initiation of xanthine oxidase inhibitors: PS-matched ‘as treated’ analysis
Outcomes	Xanthine  oxidase inhibitor group (n=43,269)					Hyperuricemia group (n=43,269)
	Follow-up limited up to 180 days				Any follow-up time	Follow-up limited up to 180 days				Any follow-up time
	Cases	PY	IR * (95% CI)	HR (95% CI)	HR (95% CI)	Cases	PY	IR * (95% CI)	HR (95% CI)	HR (95% CI)
Myocardial infarction	105	13079.3	8.03 (6.63-9.72)	1.04 (0.76-1.43)	1.06 (0.80-1.40)	114	16712.8	6.82 (5.68-8.19)	Ref	Ref
Coronary revascularization	197	13060.2	15.08 (13.11-17.34)	0.91 (0.74-1.13)	1.04 (0.86-1.25)	235	16678.2	14.09 (12.40-16.01)	Ref	Ref
Stroke	140	13077.0	10.71 (9.08-12.64)	1.01 (0.77-1.32)	0.93 (0.73-1.17)	160	16700.0	9.58 (8.20-11.19)	Ref	Ref
Heart failure	468	13013.0	35.96 (32.85-39.37)	1.23 (1.06-1.43)	1.26 (1.10-1.45)	419	16640.9	25.18 (22.88-27.71)	Ref	Ref
Composite CVD	748	12965.7	57.69 (53.70-61.98)	1.13 (1.00-1.27)	1.14 (1.03-1.27)	733	16564.9	44.25 (41.16-47.57)	Ref	Ref
*1,000 Person-Years (PY), IR: incidence rate, HR: hazard ratio, CI, confidence interval

---

« Back to 2013 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/risk-of-cardiovascular-disease-and-use-of-xanthine-oxidase-inhibitors-for-gout/