Effect of Uric Acid-Lowering Agents on Cardiovascular Outcome in Patients With Heart Failure: A Systematic Review and Meta-Analysis of Clinical Studies

Abstract

Several trials have been completed in patients with heart failure (HF) treated with uric acid (UA)-lowering agents with inconsistent results. We aimed to investigate whether lowering UA would have an effect on mortality and cardiovascular (CV) events in patients with HF in a systematic review and meta-analysis. The primary outcome measures were all-cause mortality, CV mortality, CV events, and CV hospitalization in patients with HF. We included 11 studies in our final analysis. Overall, allopurinol treatment was associated with a significant increase in the risk for all-cause mortality (hazard ratio [HR]: 1.24, 95% confidence interval [CI]: 1.04-1.49, P = .02). The trial heterogeneity is high (heterogeneity χ2 = 37.3, I2 = 73%, P < .001). With regard to CV mortality, allopurinol treatment was associated with a 42% increased risk of CV mortality (HR: 1.42, 95% CI: 1.11-1.81, P = .005). There was a trend toward increased CV hospitalization in the same group (HR: 1.21, 95% CI: 0.95-1.53, P = .12). Uric acid-lowering treatments increase all-cause and CV mortality but did not increase CV hospitalization significantly in this study.

Why Does Hyperuricemia Not Necessarily Induce Gout?

“…Furthermore, as some comorbidities such as chronic heart failure and diabetes mellitus are less influenced by SUA levels [47], UTL would not be favorable to them. In spite of UA infusion improving endothelial function [102], quickly lowering SUA could induce an acute gout flare [82], cardiovascular events [103], nerve dysfunction [104], the risk of all-cause death in hemodialysis [61], vertebral fracture [105], or heart failure in patients [106]. Additionally, it has been reported that in patients with gout SUA is usually lower during acute gouty attacks than during intercritical periods [11] possibly due to the slow systemic inflammatory response.…”

Heart rate at discharge in patients with acute decompensated heart failure is a predictor of mortality

“…Lastly, in regard to the observed significantly higher mortality in patients taking xanthine oxidase inhibitors, indeed, in a recent systematic review and meta-analysis of uric acid-lowering agents on cardiovascular outcome in patients with heart failure treatments, allopurinol treatment was associated with a significant increase in the risk for all-cause and cardiovascular mortality [33]. Whether the observed effect of an increased mortality in patients treated with a xanthine oxidase inhibitor in our study is due to a treatment effect or elevated uric acid levels leading to medical treatment characterizes a sicker heart failure population cannot be answered with the data presented.…”

Why Hyperuricemia Does Not Necessarily Induce Gout?

“…Furthermore, as some comorbidities such as chronic heart failure and diabetes mellitus are less influenced by SUA level [47], UTL would not be favorable to them. In spite of UA infusion could improve endothelial function [102], quickly lowing SUA could induce acute gout attack [82], cardiovascular events [103], nerve dysfunction [104], the risk of all-cause death in hemodialysis [61], vertebral fracture [105] or heart failure patients [106]. Additionally, it has been reported that in patients with gout SUA is usually lower during acute gouty attacks than during intercritical periods [11] possibly due to the slow systemic inflammatory response.…”