The future of febuxostat after the Cardiovascular Safety of Febuxostat and Allopurinol in Patients with Gout and Cardiovascular Morbidities (CARES) trial: who CARES?

Katsiki, Niki; Borghi, Claudio

doi:10.1080/14656566.2018.1532503

Cited by 9 publications

(5 citation statements)

References 35 publications

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“…In 2018, the FAST (Febuxostat versus Allopurinol Streamlined Trial) study, performed on 6128 gouty patients without prior CV events randomized to Allopurinol versus Febuxostat, found the non-inferiority of the latter with respect to the primary CV endpoint (a composite of hospitalization for non-fatal CV events and CV death) [ 74 ]. An extensive discussion about the differences between the two RCTs is beyond the purpose of this review, as a focused paper has been published on this topic [ 75 ]. However, the CARES trial presents many important biases; foremost, and also valid for the FAST trial, is that the absence of a control group disallows us to conclude whether Allopurinol reduces CV risk or Febuxostat raises it.…”

Section: The Second Open Question: Are Uric-acid-lowering Therapies Effective In Reducing the Risk Of Cardiovascular Events?mentioning

confidence: 99%

The Role of Uric Acid in Acute and Chronic Coronary Syndromes

Maloberti

Biolcati

Ruzzenenti

et al. 2021

JCM

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Uric acid (UA) is the final product of the catabolism of endogenous and exogenous purine nucleotides. While its association with articular gout and kidney disease has been known for a long time, new data have demonstrated that UA is also related to cardiovascular (CV) diseases. UA has been identified as a significant determinant of many different outcomes, such as all-cause and CV mortality, and also of CV events (mainly Acute Coronary Syndromes (ACS) and even strokes). Furthermore, UA has been related to the development of Heart Failure, and to a higher mortality in decompensated patients, as well as to the onset of atrial fibrillation. After a brief introduction on the general role of UA in CV disorders, this review will be focused on UA’s relationship with CV outcomes, as well as on the specific features of patients with ACS and Chronic Coronary Syndrome. Finally, two issues which remain open will be discussed: the first is about the identification of a CV UA cut-off value, while the second concerns the possibility that the pharmacological reduction of UA is able to lower the incidence of CV events.

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Section: The Second Open Question: Are Uric-acid-lowering Therapies Effective In Reducing the Risk Of Cardiovascular Events?mentioning

confidence: 99%

The Role of Uric Acid in Acute and Chronic Coronary Syndromes

Maloberti

Biolcati

Ruzzenenti

et al. 2021

JCM

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“…The Cardiovascular Safety of Febuxostat and Allopurinol in Patients with Gout and Cardiovascular Morbidities (CARES) trial showed that febuxostat was noninferior to allopurinol for the primary composite outcome of cardiovascular events; however, all-cause and cardiovascular mortality rates were higher in the febuxostat group ( White et al, 2018 ). The CARES trial outcomes are difficult to generalize due to the high discontinuation rate, loss to follow-up, lack of a placebo group, and suboptimal prescription rates of cardioprotective medications such as aspirin and beta blockers ( Katsiki and Borghi, 2018 ; Abeles and Pillinger, 2019 ). A cohort study of 99,744 patients showed that febuxostat and allopurinol had statistically similar risks of myocardial infarction, stroke, new-onset heart failure, need for coronary revascularization, and all-cause mortality, but those taking febuxostat for more than 3 years had higher though statistically insignificant risk of all-cause mortality ( Zhang et al, 2018 ).…”

Section: Resultsmentioning

confidence: 99%

Review of Urate-Lowering Therapeutics: From the Past to the Future

et al. 2022

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We reviewed all currently available ULT, as well as any medications in development using following databases: United States Food and Drug Administration (FDA), European Medicines Agency (EMA), Japanese Pharmaceutical and Medical Devices Agency (PMDA), and ClinicalTrials.gov. We identified a total of 36 drugs, including 10 approved drugs, 17 in clinical testing phases, and 9 in preclinical developmental phases. The 26 drugs currently undergoing testing and development include 5 xanthine oxidase inhibitors, 14 uricosurics, 6 recombinant uricases, and one with multiple urate-lowering mechanisms of action. Herein, we reviewed the benefit and risk of each drug summarizing currently available drugs. New trials of uricosuric agents are underway to develop the new indication. New drugs are going on to improve the potency of recombinant uricase and to develop the new route administration of such as oral formulation. This review will provide valuable information on the properties, indications, and limitations of ULTs.

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“…The Cardiovascular Safety of Febuxostat and Allopurinol in Participants with Gout and Cardiovascular Comorbidities (CARES) research found that gout patients who took febuxostat had a greater risk of cardiovascular-related death than those who took allopurinol, even though this study had several methodological flaws that were widely discussed [41,42].…”

Section: Febuxostatmentioning

confidence: 96%