ArticleArthritis & rheumatology (Hoboken, N.J.)2018
New Perspectives in Rheumatology: Implications of the Cardiovascular Safety of Febuxostat and Allopurinol in Patients With Gout and Cardiovascular Morbidities Trial and the Associated Food and Drug Administration Public Safety Alert.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 102 citations in OpenAlex.
- Colchicine linked with risk reduction for myocardial infarction in gout patients: systematic review and meta-analysis.Zeitschrift fur Rheumatologie · 2022Pooled it
- Uric acid in CKD: has the jury come to the verdict?Journal of nephrology · 2020Pooled it
- Efficacy and safety of the urate-lowering agent febuxostat in chronic heart failure patients with hyperuricemia: results from the LEAF-CHF study.Heart and vessels · 2025Trial
- Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy.European heart journal · 2019Trial
- Article
- Pentagalloyl glucose inhibits monosodium urate-induced inflammation and NLRP3 inflammasome formation via TAK1.American journal of physiology. Cell physiology · 2025Article
- Impact of Urate-Lowering Agents on Renal Outcomes in Chronic Kidney Disease: A Systematic Review.Cureus · 2025Review
- Efficacy and safety of Jinhuang ointment in treating acute gouty arthritis: a retrospective cohort study.Frontiers in pharmacology · 2025Article
- Advances in Gouty Arthritis Management: Integration of Established Therapies, Emerging Treatments, and Lifestyle Interventions.International journal of molecular sciences · 2024Review
- Mechanism and use strategy of uric acid-lowering drugs on coronary heart disease.International journal of cardiology. Heart & vasculature · 2024Review
- Past, present and future of xanthine oxidase inhibitors: design strategies, structural and pharmacological insights, patents and clinical trials.RSC medicinal chemistry · 2023Review
- Emerging Urate-Lowering Drugs and Pharmacologic Treatment Strategies for Gout: A Narrative Review.Drugs · 2023Review
- The Hong Kong Society of Rheumatology consensus recommendations for the management of gout.Clinical rheumatology · 2023Review
- Bioactivity and Component Analysis of Water Extract ofFoods (Basel, Switzerland) · 2022Article
- Cardiovascular risk and mortality in patients with hyperuricemia treated with febuxostat or allopurinol: a retrospective nation-wide cohort study in Austria 2014-2017.Rheumatology international · 2022Article
- Article
- U-shaped association of uric acid to overall-cause mortality and its impact on clinical management of hyperuricemia.Redox biology · 2022Review
- Comparative Effectiveness of Allopurinol and Febuxostat in Gout Management.NEJM evidence · 2022Article
- Excess comorbidities in gout: the causal paradigm and pleiotropic approaches to care.Nature reviews. Rheumatology · 2022Review
- Association of Mutations Identified in Xanthinuria with the Function and Inhibition Mechanism of Xanthine Oxidoreductase.Biomedicines · 2021Review
Corrections and comments
Authors and funding
5 authors at 5 institutions in 2 countries.
Funding
Abstract
Recently, the US Food and Drug Administration (FDA) issued a public safety alert, responding to the results of the now-published Cardiovascular Safety of Febuxostat and Allopurinol in Patients With Gout and Cardiovascular Morbidities (CARES) trial. The CARES trial showed no significant difference between allopurinol and febuxostat in the primary composite end point of cardiovascular (CV) events in subjects with gout and established CV comorbidities at baseline. However, there was a significantly increased risk of CV and all-cause mortality with febuxostat. Urate-lowering therapy (ULT) is central to the long-term management of gout, and xanthine oxidoreductase inhibitor (XOI) therapy is the consensus first-line approach. Allopurinol is generally the first XOI used, but febuxostat is an effective XOI option, and is commonly used when allopurinol is not tolerated. These data are further relevant since CV comorbidities are common in gout. Here, we examine why the CARES trial was done, and discuss other, ongoing comparative studies of febuxostat and allopurinol whose results are awaited. We assess the strengths and limitations of the CARES trial, and appraise the robustness and biologic plausibility of the results. The CARES trial does not prove that febuxostat raises CV mortality risk, but suggests greater risk with febuxostat than allopurinol. The CARES trial results do not support first-line use of febuxostat ULT, and raise questions about febuxostat placement at various pharmacologic ULT decision tree branches. Alternatives to febuxostat that are frequently effective include allopurinol dose escalation and uricosuric therapy alone or combined with allopurinol. The FDA safety alert highlights the need for shared ULT medical decision-making with gout patients, including discussion of the CV safety of febuxostat.
Indexed as
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.