Cardiovascular safety of febuxostat and allopurinol in patients with gout: A meta-analysis
Background: Gout is a common disease and is usually treated with uric acid-lowering drugs (the most commonly used of which are febuxostat and allopurinol). However, the cardiovascular safety of febuxostat and allopurinol is still controversial. The purpose of our study is to evaluate the cardiovascu...
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| Format: | Article |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.998441/full |
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| author | Xudong Guan Xudong Guan Shengzhao Zhang Jiayan Liu Fengbo Wu Lingyan Zhou Ying Liu Na Su Na Su |
| author_facet | Xudong Guan Xudong Guan Shengzhao Zhang Jiayan Liu Fengbo Wu Lingyan Zhou Ying Liu Na Su Na Su |
| author_sort | Xudong Guan |
| collection | DOAJ |
| description | Background: Gout is a common disease and is usually treated with uric acid-lowering drugs (the most commonly used of which are febuxostat and allopurinol). However, the cardiovascular safety of febuxostat and allopurinol is still controversial. The purpose of our study is to evaluate the cardiovascular safety of the two drugs in patients with gout using one-stage and two-stage meta-analysis.Methods: PubMed, Embase, CBM, CNKI, WanFang, Central, and VIP were searched from inception to 30 January 2022. Randomized controlled trials which evaluated the cardiovascular safety of febuxostat or allopurinol for treating patients with gout were included. Based on the Kaplan–Meier curves of the two studies, individual patient data (IPD) were extracted and reconstructed. We used time-varying risk ratios (RRs) to summarize time-to-event outcomes, and the RRs of MACE incidence, cardiovascular mortality, and all-cause mortality were calculated by a multi-level flexible hazard regression model in 1-stage meta-analyses. p values were calculated using a log-rank test. At the same time, using the reconstructed IPD, we performed 2-stage meta-analyses to inform the quantitative estimates of time-specific relative risks at the six time points (1 , 2, 3, 4, 5, and 6 years) based on a random-effects model.Results: Two RCTs with 12,318 participants were included. In the incidence of major adverse cardiovascular events between the two regimens, there was no significant difference [RR = 0.99 (95% CI, 0.89–1.11), p = 0.87]; at the same time, there was no significant difference in cardiovascular mortality [RR = 1.17 (95% CI, 0.98–1.40),p = 0.08] or all-cause mortality [RR = 1.03 (95% CI, 0.91–1.17),p = 0.62]. In terms of 2-stage meta-analyses, there was no significant difference in any outcomes at any time point (moderate-to low-certainty evidence).Conclusion: In patients without atherosclerotic disease, febuxostat likely has a similar cardiovascular profile to allopurinol. However, in patients with a history of cardiovascular disease, allopurinol treatment is associated with less cardiovascular mortality as compared with febuxostat.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/#loginpage, identifier PROSPERO, CRD42022325656. |
| first_indexed | 2024-04-12T16:58:20Z |
| format | Article |
| id | doaj.art-38d5abd35dee45d792f2cffd1c7b1ac5 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-12T16:58:20Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
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| spelling | doaj.art-38d5abd35dee45d792f2cffd1c7b1ac52022-12-22T03:24:08ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-09-011310.3389/fphar.2022.998441998441Cardiovascular safety of febuxostat and allopurinol in patients with gout: A meta-analysisXudong Guan0Xudong Guan1Shengzhao Zhang2Jiayan Liu3Fengbo Wu4Lingyan Zhou5Ying Liu6Na Su7Na Su8Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, ChinaWest China School of Pharmacy, Sichuan University, Chengdu, ChinaDepartment of Pharmacy, Karamay Central Hospital, Xinjiang, ChinaDepartment of Dermatology and Venereal Disease, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Pharmacy, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Pharmacy, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Pharmacy, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Pharmacy, West China Hospital, Sichuan University, Chengdu, ChinaWest China School of Pharmacy, Sichuan University, Chengdu, ChinaBackground: Gout is a common disease and is usually treated with uric acid-lowering drugs (the most commonly used of which are febuxostat and allopurinol). However, the cardiovascular safety of febuxostat and allopurinol is still controversial. The purpose of our study is to evaluate the cardiovascular safety of the two drugs in patients with gout using one-stage and two-stage meta-analysis.Methods: PubMed, Embase, CBM, CNKI, WanFang, Central, and VIP were searched from inception to 30 January 2022. Randomized controlled trials which evaluated the cardiovascular safety of febuxostat or allopurinol for treating patients with gout were included. Based on the Kaplan–Meier curves of the two studies, individual patient data (IPD) were extracted and reconstructed. We used time-varying risk ratios (RRs) to summarize time-to-event outcomes, and the RRs of MACE incidence, cardiovascular mortality, and all-cause mortality were calculated by a multi-level flexible hazard regression model in 1-stage meta-analyses. p values were calculated using a log-rank test. At the same time, using the reconstructed IPD, we performed 2-stage meta-analyses to inform the quantitative estimates of time-specific relative risks at the six time points (1 , 2, 3, 4, 5, and 6 years) based on a random-effects model.Results: Two RCTs with 12,318 participants were included. In the incidence of major adverse cardiovascular events between the two regimens, there was no significant difference [RR = 0.99 (95% CI, 0.89–1.11), p = 0.87]; at the same time, there was no significant difference in cardiovascular mortality [RR = 1.17 (95% CI, 0.98–1.40),p = 0.08] or all-cause mortality [RR = 1.03 (95% CI, 0.91–1.17),p = 0.62]. In terms of 2-stage meta-analyses, there was no significant difference in any outcomes at any time point (moderate-to low-certainty evidence).Conclusion: In patients without atherosclerotic disease, febuxostat likely has a similar cardiovascular profile to allopurinol. However, in patients with a history of cardiovascular disease, allopurinol treatment is associated with less cardiovascular mortality as compared with febuxostat.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/#loginpage, identifier PROSPERO, CRD42022325656.https://www.frontiersin.org/articles/10.3389/fphar.2022.998441/fullgoutallopurinolfebuxostatcardiovascular safetyan individual-patient data level META analysis |
| spellingShingle | Xudong Guan Xudong Guan Shengzhao Zhang Jiayan Liu Fengbo Wu Lingyan Zhou Ying Liu Na Su Na Su Cardiovascular safety of febuxostat and allopurinol in patients with gout: A meta-analysis Frontiers in Pharmacology gout allopurinol febuxostat cardiovascular safety an individual-patient data level META analysis |
| title | Cardiovascular safety of febuxostat and allopurinol in patients with gout: A meta-analysis |
| title_full | Cardiovascular safety of febuxostat and allopurinol in patients with gout: A meta-analysis |
| title_fullStr | Cardiovascular safety of febuxostat and allopurinol in patients with gout: A meta-analysis |
| title_full_unstemmed | Cardiovascular safety of febuxostat and allopurinol in patients with gout: A meta-analysis |
| title_short | Cardiovascular safety of febuxostat and allopurinol in patients with gout: A meta-analysis |
| title_sort | cardiovascular safety of febuxostat and allopurinol in patients with gout a meta analysis |
| topic | gout allopurinol febuxostat cardiovascular safety an individual-patient data level META analysis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.998441/full |
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