The association between urate‐lowering therapies and treatment‐related adverse events, liver damage, and major adverse cardiovascular events (MACE): A network meta‐analysis of randomized trials

Abstract

Purpose Hyperuricemia is a common disease that may lead to gout, renal damage, and cardiovascular events. Oral medication is the main treatment for hyperuricemia patients when lifestyle intervention fails. An evaluation of the safety of various urate‐lowering therapies (ULTs) is integral to clinical decision‐making. We constructed a network meta‐analysis (NMA) to evaluate the safety of oral ULTs. Methods MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched up to April 1, 2021, for randomized controlled trials that examined the safety of ULTs. The language restriction was English. The three outcomes used to assess the safety of uric acid lowering medications were treatment‐related adverse events, liver damage, and major adverse cardiovascular events (MACE). Results Thirty‐two trials enrolling 23,868 individuals were included in the study. In terms of treatment‐related adverse events, there were no statistically significant differences between five uric acid lowering medications and placebo: allopurinol (risk ratio (RR): 1.08; 95% credible interval (CrI): 0.91, 1.29), febuxostat (RR: 1.05; 95% CrI: 0.89, 1.25), lesinurad (RR: 1.19; 95% CrI: 0.85, 1.67), lesinurad combined with xanthine oxidase inhibitor (XOI, RR: 1.05; 95% CrI: 0.83, 1.32), and topiroxostat (RR: 1.01; 95% CrI: 0.83, 1.23). Topiroxostat likely increases risk of liver damage (RR: 2.65; 95%CI: 1.24, 5.70; NNH: 33.40) as compared with placebo. With regard to MACE, there were no statistically significant differences between three uric acid lowering medications and placebo: allopurinol (RR: 0.63; 95% CrI: 0.36, 1.34), febuxostat (RR: 0.69; 95% CrI: 0.38, 1.66), and lesinurad combined with XOI (RR: 0.56; 95% CrI: 0.23, 1.85). The rankings of different interventions were depicted by cumulative ranking curve (SUCRA). Conclusions Through NMA, we provide some evidence for the safety of ULTs. We found no statistically significant differences in their effects on treatment‐related adverse events and MACE. However, topiroxostat likely increases the risk of liver damage.

16S rRNA and Metagenomics Combined with UPLC-Q/TOF-MS Metabolomics Analysis Reveals the Potential Mechanism of Radix Astragali Against Hyperuricemia in Mice

“…In clinical practice, the first-line drugs typically used for hyperuricemia are associated with severe liver and kidney damage, thereby limiting their safe application. 6 Fortunately, RA is a natural medicinal and edible Chinese medicine with a long history of application in the treatment of metabolic disorders. 21 , 22 More importantly, contemporary pharmacological investigations have indicated that RA can be used to lower UA.…”

“… 4 Obviously, there are several only UA-lowering medicines in the clinic, such as allopurinol (ALL) and benzbromarone. 5 Unfortunately, these chemical drugs are not suitable for a long-term and effective therapeutic schedule due to the reported side effects, 6 especially hepatorenal toxicity. Hence, it is necessary to seek a safer and more valid strategy to treat hyperuricemia.…”

Major adverse cardiovascular events associated with testosterone treatment: a pharmacovigilance study of the FAERS database

“…MACEs were defined using International Classification of Diseases, Clinical Modification, Tenth Revision (ICD-10-CM) diagnosis codes, including cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke ( Bosco et al, 2021 ; Zhang et al, 2021 ), including acute myocardial infarction (AMI)-induced left heart failure (LHF), ventricular fibrillation (VF)-induced sudden death, and cordial arrhythmia induced by valvular diseases, myocardiopathy, and myocarditis. Thus, MACEs can be detailed as all of the preferred terms containing the keywords “card,” “heart,” “ventricular,” “cereb,” “brain” coupled with “infarction,” “stroke,” “death,” “itis,” “pathy,” “failure,” and “fibri,” which were determined by the Standardized MedDRA Query (version 23.0) terminology ( Katsuhara and Ikeda, 2021 ) ( Supplementary Table S1 , MACEs).…”

Are serum uric acid levels predictors of cardiovascular risk? An update

“…Regarding medication, a detailed overview of specific drugs for the management of elevated serum uric acid is beyond the scope of this review. Briefly, although uric acid lowering drugs can beneficially affect surrogate CVD markers, a recent meta-analysis showed that there were no statistically significant differences in CVD risk between three uric acid lowering medications (allopurinol, febuxostat and lesinurad combined with xanthine oxidase inhibitor) and placebo [21 ▪▪ ]. It is also worth mentioning that there are several drugs (e.g.…”