Urate lowering therapy is associated with a lower risk of heart failure hospitalisation or mortality in hyperuricaemic patients with heart failure: a comparative effectiveness study
Authors: Kiddle S.J , Abdul-Sultan A , Andersson Sundell K , Nolan S , Perl S , Bjursell M 
Published: October 2021

Abstract

Background
There is a strong association between hyperuricemia (elevated serum uric acid) and the risk of heart failure. However, it remains unclear whether prescribing urate lowering therapies have any bearing on long term clinical outcomes.

Purpose
In this study, we assessed the impact of urate lowering therapy treatment on the risk of adverse health outcomes (hospitalisation for heart failure and all-cause mortality) in patients with hyperuricemia and heart failure.

Methods
We utilised data from Clinical Practice Research Datalink (CPRD) GOLD, a UK-based primary care database linked to secondary care (Hospital Episode Statistics) and mortality data (Office of National Statistics). The study population included patients with a first record of hyperuricemia (serum uric acid &gt;7 mg/dl for men and &gt;6 mg/dl for women or a gout diagnosis) between 1990 and 2019 with a history of heart failure. Incident urate lowering therapy users were identified post hyperuricemia diagnosis. To account for potential confounding variables and potential treatment paradigm changes over the study period, a propensity score matched cohort was constructed for urate lowering therapy initiators and non-initiators within 6 month accrual blocks. Adverse health outcomes were compared between matched treatment groups using Cox regression analysis adjusted for the same variables used in the propensity score. Due to extensive treatment switching and discontinuation, on-treatment analysis was the main analysis.

Results
A total of 2,174 propensity score matched pairs were identified. We found that urate lowering therapy was associated with a 43% lower risk of all-cause mortality or hospitalization for heart failure (Figure 1, adjusted hazard ratio 0.57, 95% confidence interval 0.51–0.65), and a 19% lower risk of cardiovascular mortality or hospitalization for heart failure (Figure 2, adjusted hazard ratio 0.81, 95% confidence interval 0.71–0.92) within five years compared to those not on therapy (on-treatment analysis). In an intention-to-treat sensitivity analysis, urate lowering therapy was associated with a 17% lower risk of all-cause mortality or hospitalization for heart failure (adjusted hazard ratio 0.83, 95% confidence interval 0.76–0.91), and a 11% lower risk of cardiovascular mortality or hospitalization for heart failure (adjusted hazard ratio 0.89, 95% confidence interval 0.81–0.98) within five years compared to those not on urate lowering therapy. Adjusted and non-adjusted hazard ratios were consistent for all outcomes.

Conclusion
We found that urate lowering therapy was associated with a lower risk of adverse outcomes in hyperuricemia or gout patients with a history of heart failure. These results are consistent with the hypothesis that uric acid lowering may lead to improved outcome in patients with heart failure and hyperuricemia, emphasizing the need to investigate the potential benefits of intense uric acid lowering in prospective randomized controlled trials.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): AstraZeneca Figure 1 (HF = heart failure)Figure 2 (CV = cardiovascular)