Table 3.
Treatment-Emergent Adverse Events (TEAE).
| Year | Study | Study Group (mg) | Serious TEAE | Cardiovascular Specific Events | Fatal Events | Ref |
|---|---|---|---|---|---|---|
| 2005 | Becker et al. | Placebo | 0% | – | 0% | [106] |
| Febuxostat | 3% (3/115) | – | 0% | |||
| 2005 | Becker et al. (FACT) | Allopurinol | 8% (19/253) | – | 0% | [111] |
| Febuxostat [80] | 4% (11/256) | – | <1% (2/256) | |||
| Febuxostat [120] | 8% (21/251) | – | <1% (2/251) | |||
| 2008 | Schumacher et al. | Placebo | 1% (2/134) | <1% (1/134) | 0% | [112] |
| Allopurinol | 4% (11/267) | 2% (5/267) | 0% | |||
| Febuxostat [80] | 3% (9/269) | 2% (5/269) | 0% | |||
| Febuxostat [120] | 4% (5/134) | <1% (1/134) | 0% | |||
| Febuxostat (240) | 3% (7/268) | <1% (1/268) | 0% | |||
| 2008 | Hare et al. (OPT-CHF) | Placebo | – | 2% (4/202)+ | 3% (6/202) | [102] |
| Oxypurinol (600) | – | 4% (8/203)+ | 5% (10/203) | |||
| 2009 | Schumacher et al. (FOCUS) | Febuxostat (40–120) | 18% (21/116) | 5% (6/116) | 0% | [107] |
| 2009 | Becker et al. | Allopurinol (300) | 21 events (12 per patient-year) | 5 events (3 per patient-year) | 0% | [114] |
| Febuxostat [80] | 165 events (11 per patient-year) | 46 events (3 per patient-year) | 7 (<1 per patient-year) | |||
| Febuxostat [120] | 73 events (9 per patient-year) | 17 events (2 per patient-year) | 3 (<1 per patient-year) | |||
| 2010 | Becker et al. (CONFIRMS) | Allopurinol (200/300) | 4.1% (31/756) | 0.4% (3/756) | 0.26% (2/756) | [113] |
| Febuxostat [40] | 2.5% (19/757) | 0% | 0% | |||
| Febuxostat [80] | 3.7% (28/756) | 0.4% (3/756) | 0% | |||
| 2010 | Goicoechea et al. | Allopurinol | 0% | 27% (15/56) | 4% (2/56) | [91] |
| Usual Treatment | 0% | 12% (7/57) | 0% | |||
| 2011 | Kao et al. | Placebo | 12% (3/26) | – | 0% | [100] |
| Allopurinol (300) | 11% (3/37) | – | 0% | |||
| 2012 | European Medicines Agency | Placebo | 11.6% (5/43) | 0% | 2.3% (1/43) | [133] |
| Pegloticase 8 mg every 4wks | 22.6% (19/84) | 3.6% (3/84) | 2.4% (2/84) | |||
| Pegloticase 8 mg every 2wks | 23.5% (20/85) | 4.7% (4/85) | 3.5% (3/85) | |||
| 2014 | Hosoya et al. | Placebo | 3% (2/60) | – | 0% | [134] |
| Topiroxostat [160] | 3% (2/62) | – | 0% | |||
| 2015 | Goicoechea et al. | Placebo | 43% (24/56)++ | 28% (16/57) | 0% | [92] |
| Allopurinol [100] | 16% (9/57)++ | 41% (23/56) | 0% | |||
| 2015 | Sircar et al. | Placebo | 0% | 0% | 0% | [108] |
| Febuxostat [40] | 0% | 0% | 0% | |||
| 2015 | Givertz et al. (EXACT-HF) | Placebo | 15% (19/125) | 2% (2/125) | 6% (7/125) | [101] |
| Allopurinol [60] | 20% (25/128) | 2% (2/128) | 6% (8/128) | |||
| 2016 | Xiao et al. | Control | 0% | 3.2% (2/63) | 1.6% (1/63) | [99] |
| Allopurinol (300) | 1.6% (1/62) | 8.1% (5/62) | 0% | |||
| 2016 | Saag et al. (CLEAR 1) | Placebo + Allopurinol | 5.5% (11/201) | 3.5% (7/201)+++ | 0% | [128] |
| Lesinurad (200) + Allopurinol | 4.5% (9/201) | 4.5% (9/201)+++ | 0.5% (1/201) | |||
| Lesinurad (400) + Allopurinol | 8% (16/201) | 4.0% (8/201)+++ | 0% | |||
| 2016 | Bardin et al. (CLEAR 2) | Placebo + Allopurinol | 3.9% (8/206) | 5.3% (11/206)+++ | 0% | [129] |
| Lesinurad (200) + Allopurinol | 4.4% (9/204) | 3.9% (8/204)+++ | 0% | |||
| Lesinurad (400) + Allopurinol | 9.5% (19/200) | 3.0% (6/200)+++ | 1% (2/200) | |||
| 2017 | Jalal et al. | Placebo | 0%^ | 0% | 0% | [98] |
| Allopurinol (300) | 0%^ | 2.6% (1/39) | 2.6% (1/39) | |||
| 2017 | Stamp et al. | Current Dose of Allopurinol | 27% (25/93) | 9% (8/93) | 5.4% (5/93) | [105] |
| Allopurinol Dose-Escalation | 24% (22/90) | 12% (11/90) | 5.6 (5/90) | |||
| 2017 | Tausche et al. (LIGHT) | Placebo | 3.7% (4/107) | 0.9% (1/107) | 0% | [130] |
| Lesinurad (400) | 8.4% (9/107) | 0.9% (1/107) | 0.9% (1/107) | |||
| 2017 | Dalbeth et al. (CRYSTAL) | Placebo + Febuxostat | 9.2% (10/109) | 1.8% (2/109) | 0% | [131] |
| Lesinurad (200) +Febuxostat | 5.7% (6/106) | 5.7% (6/106) | 0.9% (1/106) | |||
| Lesinurad (400) +Febuxostat | 8.3% (9/109) | 3.7% (4/109) | 0.9% (1/109) | |||
| 2018 | Kimura et al. (FEATHER) | Placebo | 16.7% (37/222) | 3.2% (7/222) | 0.5% (1/222) | [110] |
| Febuxostat | 21.9% (48/219) | 1.8% (4/219) | 0.5% (1/219) | |||
| 2018 | Coburn et al. | Current Dose of Allopurinol | – | 18.1 per 1,000 person-years+ | 38.7 per 1,000 person-years | [104] |
| Allopurinol Dose-Escalation | – | 19.8 per 1,000 person-years+ | 42.5 per 1,000 person-years | |||
| 2018 | Wada et al. (UPWARD) | Placebo | 9.1% (2/22) | – | 0% | [135] |
| Topiroxostat [160] | 7.0% (3/43) | 0% | ||||
| 2018 | White et al. (CARES) | Allopurinol (200–600) | 10.4% (321/3092) | 3.2% (100/3092)^^ | 6.4% (199/3092) | [116] |
| Febuxostat [[40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68], [69], [70], [71], [72], [73], [74], [75], [76], [77], [78], [79], [80]] | 10.8% (335/3098) | 4.3% (134/3098)^^ | 7.8% (243/3098) |
TEAE: Treatment-Emergent Adverse Event.
-Not reported by the study.
+Cardiovascular mortality reported.
++ Serious renal adverse events reported+++Includes both MACE and non-MACE (Major Adverse Cardiovascular Events).
^Total TEAEs (Study did not specify serious TEAEs).
^^Specifically Rate of Cardiovascular Death.