Format

Send to

Choose Destination
N Engl J Med. 2018 Mar 29;378(13):1200-1210. doi: 10.1056/NEJMoa1710895. Epub 2018 Mar 12.

Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout.

Collaborators (518)

Aggarwal N, Bell A, Belle Isle J, Brown J, Cividino A, Dion D, Dzongowski P, Kelly A, Luton R, Misik K, Morin F, O'Mahony W, Pesant Y, Toma A, Van den Berg L, Wilderman I, Abud Mendoza C, Aguilera Real M, Alcocer Gamba MA, Aldrete‐Velasco J, Alpizar Salazar M, Avila Zapata F, Carmona Furusho L, Carrillo Vazquez SM, Chavez Paez JG, De la Garza Ramos E, Enkerlin Pauwells HL, Esquivel Valerio J, Fajardo Campos P, Garcia Olivera I, Garcia Reza R, Lopez Ruiz OM, Luna Ceballos RI, Maldonado Hernandez H, Del Rosario Marrufo M, Miracle Lopez S, Montano Gonzalez E, Montes Cruz E, Nevarez Ruiz L, Ramos Lopez G, Rodriguez Briones I, Sanchez Mijangos H, Sanchez Vazquez JC, Silveira Torre LH, Solis Morales L, Stobschinski de Alba CA, Vazquez Mellado Cervantes NJ, Vega Elguezabal JF, Villeda Espinosa E, Violante R, Zazueta Montiel BE, Abalos‐Galito M, Abboy C, Abraham W, Adams M, Aelion J, Alvarado O, Alwine L, Amin K, Anderson A, Anderson C, Andrawis N, Archuleta M, Arif A, Azorr M, Babich J, Baraf H, Barag S, Barker B, Barksdale W, Barreto A, Bartkowiak A, Batongmalaque J, Bays H, Bedel G, Berg I, Bernstein R, Bertsch J, Bhat A, Bland V, Bornfreund J, Bowling B, Box E, Branum R, Brewer M, Bright C, Britt D, Broker R, Bruce T, Buchanan P, Burack D, Burbano De Lara J, Burke D, Buynak R, Byars W, Bybee K, Campbell J, Canlas D, Canosa R, Captain A, Carlos E, Carpenter K, Carter M, Cauthen B, Cha G, Chang K, Chaykin L, Cheung D, Chilito A, Chiong R, Chipman H, Choi S, Christensen J, Chuang R, Claassen D, Clark G, Clower J, Coburn NJ, Collins H, Corder C, Cox R, Crawford P, Cunnar J, Davila W, Davit R, Dayon D, DeBusk C, Delgado J, Delmont J, DeMatteo D, Demetry K, Dennis D, DeSantis D, Diab I, Diener C, Dobrusin R, Dodd J, Drummond W, Dulgeroff A, Durrence H, Mari Elacion J, Ellison W, Elzi W, Escalante D, Ettlinger R, Fakih F, Fandino A, Fang M, Farooq O, Farrington C, Farris N, Feinman M, Feld L, Ferro F, Fields H, First B, Fitz‐Patrick D, Flint K, Flippo G, Folkerth S, Fowler F, Fox D, Frandsen B, Freeman J, Freyne B, Fritzhand M, Fung E, Funk G, Gabra N, Gagianas P, Gamarra L, Gaona R, Garcia R, Garner A, Gaston P, Ghanekar H, Ghosh C, Gladstein G, Goldfischer E, Gorman T, Gottschlich G, Grant D, Gray J, Green C, Green B, Gregory D, Griffin R, Guice M, Gupta R, Hahn G, Halter D, Halter M, Hansen V, Harris A, Harris M, Headley D, Hejeebu S, Hendrix E, Herman L, Herrera C, Herring C, Herrod J, Ho G, Hole S, Hollister R, Holt P, Hopkins J, Horton K, Howard T, Howell M, Huff J, Huffman C, Huling R, Hyers T, Hymowitz R, Ibraheem M, Idarraga S, Iranmanesh A, Isakov T, Jack D, Jacks R, Jackson R, Jackson R, Jackson B, Jain M, Janovitz R, Jeereddi P, Johary A, Johnson C, Johnson W, Johnson C, Jones S, Jones R, Jordan R, June J, Kafka S, Kalen V, Karl J, Kaufmann R, Kavanaugh A, Kaveh K, Keane J, Kerzner B, Khan J, Kidokoro Y, Kirstein J, Kivitz A, Klein S, Klein T, Knight H, Knutson T, Koch S, Koilpillai R, Kolettis E, Koontz D, Kopp J, Koshy N, Kotek L, Krause R, LaFata J, Lang C, Lano M, Lasala G, Lawless A, Lee K, Lee D, Lefebvre G, Lester F, Levins P, Lewis D, Lieberman D, Lillestol M, Lillo J, Littlefield R, Lockwood M, Lohr K, Look M, Lorch D, Ludivico C, Luna B, Lutskiy M, Mabaquiao A, Maggiacomo F, Makam S, Maletz L, Malik A, Martin E, Martinez J, Marx P, May P, Maynard K, McConnehey D, McConnehey B, McGettigan J, McGuire M, McIlwain H, McKenzie W, McLean B, McNeil D, Mehta D, Meisner C, Meli J, Metyas S, Metzger F, Meyers P, Michlin B, Mihills C, Miller K, Miller A, Minton S, Mohart A, Montenegro C, Montgomery R, Morelli J, Morin D, Morita C, Morris F, Mortensen S, Movafagh S, Multani P, Murphy D, Muse D, Myerson G, Nagrani M, Naidu J, Natividad MB, Neutel J, Nolen T, Nussbaum A, Olson R, Ong S, Osborne J, Pace M, Paez H, Palatnik M, Palmer W, Pappas J, Paster Z, Patel M, Patel M, Patel B, Patton W, Pema K, Peniston J, Peppin G, Petit C, Phillips C, Phillips A, Piatek M, Pick M, Pillinger M, Pogue B, Posey M, Poss G, Preston K, Prupas H, Pullman J, Raikhel M, Randall W, Rangaraj M, Rapo S, Rapoport R, Rastogi P, Reddy J, Reddy R, Reed L, Reeves M, Reiff M, Reynolds M, Rhee M, Rhudy J, Richter R, Ries D, Roberson K, Roberts D, Robinson D, Rock K, Roer D, Rosen R, Rosenblum G, Rosenfeld J, Rosenthal A, Ross D, Rothberg M, Rubino J, Rudolph L, Ruoff G, Ryan E, Sadler C, Samson M, Sanders R, Scarsella A, Schmidt J, Schoenwalder M, Schreiber A, Schreiman R, Schultz D, Schwartz A, Sensenbrenner J, Serfer G, Seshadri N, Severa L, Shah S, Shanes J, Sharma M, Sharpe C, Shergy W, Sherman H, Shlotzhauer T, Shoffner S, Shore K, Sims J, Singh H, Smallow S, Smith MT, Snyder B, Soo A, Sprague A, Stamps H, Stearns P, Sudano D, Sugimoto D, Suleman A, Sunkureddi P, Tan R, Tan A, Tannenbaum A, Tawney K, Teixeira G, Teltser M, Torres A, Tran C, Trapp R, Trevino M, Tsai Y, Tuan W, Vaid B, Valente R, Van Camp K, Van Ginkel E, Varano S, Vaughn M, Velderman P, Viera E, Vijay N, Vincent S, Von Feldt J, Vora K, Vora S, Vukotic G, Waller P, Walton M, Wayne J, Weinstein D, Weiss D, Weiss E, Whitlock L, Wiesenhutter C, Williams R, Williams T, Williams D, Wilson S, Wolfe S, Wombolt D, Wood J, Yarows S, Yetman C, Yiannias C, Yood R, Young VL, Young D, Zuzarte K, Gibofsky A, Carson PE, Lakatos E, Ryan LM, Waikar SS, Morris DD, Jackson R, McLean L, Qin Y, Kisfalvi K, MacDonald P, Palmer R, Yang T, Tsymbalov S, Alkawass N, Keeter K, Koziol M, Schickedanz B, Evans B, Chefo S, Xie B, Song E, Dong X, Zhang W, Chen Y, Loke R, Li D, Li X, Max E, Dabholkar A, Makaratzi M, Schulz P, Khursheed M, Marcinak J, Geiger C, Henning E, Harrigan P, Ludwig P, Idemoto C, Bronson C, Gans J, Kennedy JE, Villinski A, Koehler L, Parker J, Desai E.

Abstract

BACKGROUND:

Cardiovascular risk is increased in patients with gout. We compared cardiovascular outcomes associated with febuxostat, a nonpurine xanthine oxidase inhibitor, with those associated with allopurinol, a purine base analogue xanthine oxidase inhibitor, in patients with gout and cardiovascular disease.

METHODS:

We conducted a multicenter, double-blind, noninferiority trial involving patients with gout and cardiovascular disease; patients were randomly assigned to receive febuxostat or allopurinol and were stratified according to kidney function. The trial had a prespecified noninferiority margin of 1.3 for the hazard ratio for the primary end point (a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or unstable angina with urgent revascularization).

RESULTS:

In total, 6190 patients underwent randomization, received febuxostat or allopurinol, and were followed for a median of 32 months (maximum, 85 months). The trial regimen was discontinued in 56.6% of patients, and 45.0% discontinued follow-up. In the modified intention-to-treat analysis, a primary end-point event occurred in 335 patients (10.8%) in the febuxostat group and in 321 patients (10.4%) in the allopurinol group (hazard ratio, 1.03; upper limit of the one-sided 98.5% confidence interval [CI], 1.23; P=0.002 for noninferiority). All-cause and cardiovascular mortality were higher in the febuxostat group than in the allopurinol group (hazard ratio for death from any cause, 1.22 [95% CI, 1.01 to 1.47]; hazard ratio for cardiovascular death, 1.34 [95% CI, 1.03 to 1.73]). The results with regard to the primary end point and all-cause and cardiovascular mortality in the analysis of events that occurred while patients were being treated were similar to the results in the modified intention-to-treat analysis.

CONCLUSIONS:

In patients with gout and major cardiovascular coexisting conditions, febuxostat was noninferior to allopurinol with respect to rates of adverse cardiovascular events. All-cause mortality and cardiovascular mortality were higher with febuxostat than with allopurinol. (Funded by Takeda Development Center Americas; CARES ClinicalTrials.gov number, NCT01101035 .).

PMID:
29527974
DOI:
10.1056/NEJMoa1710895
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center