Format

Send to

Choose Destination
JAMA. 2014 Apr 16;311(15):1515-25. doi: 10.1001/jama.2014.3321.

Effect of aleglitazar on cardiovascular outcomes after acute coronary syndrome in patients with type 2 diabetes mellitus: the AleCardio randomized clinical trial.

Collaborators (723)

Vico ML, Conde DG, Botta CE, Gelersztein E, Ramos H, Prado AD, Piombo A, Piredda A, Lorente C, Canella JP, Guzman P, Avaca H, Maffei LE, Vita NA, Gorosito V, Cosman C, Caccavo A, Piskorz D, Jure HO, Fernandez RA, Toledo SS, Nul D, Marino JC, Estrada JL, Sztejfman L, Amerena J, Arnolda L, Yadav R, Garrahy P, Lo S, Brieger D, Nelson G, Arstall M, Worthley M, Colquhoun D, Wilson S, Dang TH, Prasan A, Kilian J, Collins N, Oqueli E, Carroll P, De Lima E Silva F, Dutra O, Franken M, Tumelero R, Pimentel P, Herdy A, Paiva MS, Frack CR, Rossi F, Maia L, Forti A, Saraiva JF, Bodanese L, Oliveira J, Rossi P, Gross J, Feitosa A, Wainstein M, Silva R, Silva D, Botelho R, Manenti E, de Arruda JA, Fortes JA, Ardito W, Dos Santos Filho R, Precoma DB, Saad J, Jatene JA, Hissa M, Junior A, Borges J, Sampaio C, Reis G, Issa A, Leaes PE, Kaiser SE, Savard D, Tardif JC, Sanaratne M, Syan G, Kouz S, Kornder J, Diaz A, Bourgeois R, Schampaert E, Lonn E, Nigro F, Degrace M, Mazza G, Robichaud P, Title L, Rupka D, Baril JF, Hatheway RJ, Roy A, Lavoie JP, Leung R, Tremblay G, Pouliot J, Hill L, Labonte R, Lavi S, Bergin P, Pesant Y, Phaneuf DC, Nogareda G, Smith S, Huynh T, Rolfe A, Conway J, Bertrand O, Chehayeb R, Pandey S, Petrella R, Lepage S, Nawaz S, Johri A, Abramson B, Fay D, Searles G, Chouinard G, Luterman M, Zadra R, Welsh R, Vizel S, Leduc C, Nault P, Beaudry P, Bakbak A, Shabani F, Berlingieri J, Yang X, Zhao R, Peng J, Hu H, Luo M, Ke Y, Yuan Z, Zhang Y, Lv X, Ma C, Ma G, Chen J, Li X, Li Z, Yan X, Gan X, Chen J, Zhao S, Chen Y, Li H, Li L, Huimin L, Guo Y, Hu T, Fang W, Wang X, Yang K, Bao X, Fu G, Li H, Yan J, Wang D, He B, Zhang F, Han Y, Liu J, Wei M, Ma H, Wu S, Li W, Shi H, Monhart Z, Solar M, Belohlavek J, Ferkl R, Kral R, Hutyra M, Novak M, Kettner J, Podpera I, Malik J, May O, Gohr T, Clemmensen P, Lomholdt J, Verges M, Agraou B, Montalescot G, Probst V, Galinier M, Roudaut R, Tropeano AI, Ovize M, Elhadad S, Belhassane A, Dhoudain F, Schiele F, Danchin N, Dutoiu T, Caussin C, Cottin Y, Münzel T, Voeller H, Neumann FJ, Edel K, Kamke W, vom Dahl J, Ali T, Schächinger V, Natour M, Kadel C, Löw A, Hamm C, Düngen HD, Eckert S, Hoffmann U, von Hodenberg E, Werner N, Laufs U, Voehringer HF, Reinecke H, Mügge A, Fleck E, Reuter H, Hensen J, Bergmann M, Tschoepe C, Kuehne U, Proskynitopoulos N, Michalko P, Kelm M, Edes I, Koranyi L, Papp A, Vertes A, Horvath I, Lupkovics G, Deak L, Benczur B, Sziliczei-Nemeth E, Hodi G, Csapo K, Dudas M, Somogyi A, Czuriga I, Nagy L, Parikh K, Sethi BK, Sahay RK, Premchand R, Bhattacharya A, Hiremath J, Ghosh S, Jawahirani A, Sharma K, Gadkari M, Dash A, Dani S, Kumar S, Khanna P, Deshpande N, Kumar H, Arneja J, Setthuraman S, Chowdhury S, Kumble Y, Jali M, Yerra S, Gandhi P, Mehrotra S, Bantwal G, Basavanagowdappa H, Kannampilly J, Pathanakayil R, Malpani G, Prasad G, Sarna M, Kapoor D, Adhikari P, Hardas S, Byrapaneni R, Suvarna T, Barton J, McAdam B, MacNeill BD, Maher VM, Sugrue D, Crean PA, Grassia V, Morocutti G, Tortorella G, Cosentino F, Bramucci E, Filardi PP, Mafrici A, Salvioni A, Ansani L, Pancaldi L, De Servi S, Cavallini C, Zanini R, Musumeci G, Roncon L, Moon KW, Shin ES, Kim HY, Jeong JO, Cha TJ, Kim DK, Jeon HK, Lim do S, Yoon JH, Park KS, Kang WC, Jeong MH, Lee NH, Kim SH, Park WJ, Hur SH, Park CG, Kim HS, Park JS, Tahk SJ, Lee SY, Chae JK, Kim SW, Kim SJ, Jeon DW, Hyon MS, Hong TJ, Ong TK, Ahmad WA, Ismail O, Ng KH, Mohamed M, Yahya M, Ali RM, Ghapar AK, Cervantes J, Gambe MA, Castillo AG, Riojas C, Benavides M, Llamas G, Pons JL, Rosas EL, Ramos G, De Los Rios M, Violante R, Mendoza E, Ruiz LN, Lechuga A, Alva JC, Cedeño R, Hernandez J, Cantu RQ, Fernandez LE, Velasco R, Lopez AG, Cardona E, Chavez J, Alpizar M, Arechavaleta R, Micher D, Bayram E, Sánchez RR, Herrera CH, Guerrero HG, Isunza JR, Sanchez H, Munoz L, Garza MG, Malpica EM, Hof AV, Herrman JP, Jukema JW, Bronzwaer P, Ten Holt W, ten Berg J, De Winter R, Basart D, de Graaf J, Gerdes VE, Bokern M, Troughton R, Fisher N, Wong S, Tang EW, Nirmalaraj KB, O'Meeghan T, Nowak J, Kusnierz B, Pieniazek P, Drozdz D, Zarebinski M, Ponikowski P, Kosmider M, Musial W, Zabowka M, Hamankiewicz M, Derlaga B, Piepiorka M, Kuc K, Janion M, Kuzniar J, Wierzykowski T, Serafin R, Kochman J, Pijanowski Z, Jaworska K, Szpajer M, Miekus P, Cwetsch A, Ochala A, Konieczny M, Hoffmann A, Kowalski J, Walczewska J, Krzeminska-Pakula M, Buszman P, Bryniarski L, Ogorek M, Dluzniewski M, Buszman P, Sciborski R, Miarka J, Hiczkiewicz J, Kleinrok A, Wysokinski A, Janiak B, Szczuka K, Lesiak M, Dryja T, Rynkiewicz A, Szwed H, Gorski J, Olszewski M, Buszman P, Benedek IS, Popa AR, Militaru C, Morosanu M, Constantinescu S, Tivadar S, Popescu A, Radoi M, Fruntelata AG, Veresiu IA, Dragulescu SI, Eryshev S, Baranova E, Yakovlev A, Gordeev I, Gorelov A, Lopez MG, Pinto X, Coronado JB, Muñoz CP, Acuna JG, Soriano FR, Navarro MJ, Sanz RR, Basilio EG, Cortada JB, Ros JA, Macaya CM, Juanatey CG, Torrent AJ, Recena JB, Botas J, Fernandez PA, Alegret J, Moll XG, Sanz E, Blázquez JC, Soldevila JG, Murga N, Bellido D, Plaza I, Mellbin L, Boberg G, Mooe T, Tyden P, Linder R, Luostarinen R, Axelkvist M, Pettersson T, Boman K, Jidbratt H, Lindgren M, Johanson P, Wongvipaporn C, Kuanprasert S, Srimahachota S, Siriwattana K, Ngamjanyaporn P, Tresukosol D, Promlikitchai P, Chotnoparatpat P, Taweesangsuksakul P, Thongsri T, Wongtheptian W, Sansanayudh N, Hutayanon P, Laksomya T, Sritara P, Price D, Aggarwal R, Purcell I, Davies C, Malik I, Violaris A, Game F, Harvey J, Robertson D, Kadr H, Trouton TG, Kaprielian R, Dutka D, Hildick-Smith D, Butler R, MacRury S, Millward BA, Purvis J, Reckless J, Ajjan R, Bruce D, Cox D, Malik I, Kooner J, Muir S, Hutchinson S, Gupta D, Weinstein D, Bieniarz M, Traina M, Lieber I, Mohart J, Prodafikas J, Laurion D, Oberoi M, Carlson E, Schmedtje J, Mayfield R, Chandler G, Modi K, Budoff M, Zelman R, Dalton R, Lee K, Gordon P, Ayenew W, Mathis C, Busch R, Schuchard T, Raisinghani A, Shepherd AM, Jaffrani N, Lee PV, Chandrashekhar Y, Mohammed A, Weisz G, Almassi H, Krantzler J, Quadrel M, Martin S, Brener S, Harris B, Eaton C, Nalluri C, Schwartz G, Gogia H, Colfer H, Doherty J, Dang N, Blonder R, Jacobson S, Rogers W Jr, Levin E, Isa G, Chandna H, Singh J, Forgosh L, Melucci M, Chilton R, El Hafi S, Way B, Lambert C, Korban E, Auerbach E, Hickey K, McKenzie M, Tandon N, Mahal S, Heitner S, O'Halloran D, Loh IK, Harris J, Gelormini J, Clavijo L, Klapholz M, Studeny M, Goswami R, Norris R, Busui RP, Cox SL, Tak T, Anan T, Taghizadeh T, Pompili V, Camp A, Khera A, Shah A, Frey A, Zakhary B, Humiston D, Griffin D, Herrington D, Perloff D, Kereiakes D, Christofides E, Dippel E, Fung G, Marais H, Dotani I, Fidelholtz J, Hermiller J, Naidu J, Gilbert J, El-Shahawy M, Mandviwala M, Rastogi P, Breaux P, Norwood P, Staab P, Fish R, Sanchez R, Gupta V, Herzog W, Rabinowitz A, Samal A, Kabour A, Lee D, Carlos E, Kosinski E, Portnay E, Rivera E, Madu IJ, Welker J, Fialkow J, Londono J, Martinez L, Pirwitz M, Ariani M, Saklayen M, Vijay N, Feldman R, Rosenson R, Steinhubl S, Srinivasan V, Nair V, Shalev Y, Bouchard A, Adolphe A, Miller A, Ahmad A, Omar B, Masri B, Iteld B, Gifford C, Scott C, Maislos F, Longo J, Rider J, Silverstein J, Miller M, Nanna M, Khan M, Schneider R, Bashir R, Evans R, Fierer R, Teniola S, Welka S, Singh V, Randall W, Rowe W, Salacata A, Bazzi A, Steinberg A, Mooss A, Tang A, Kahn B, Chandler B, Bayron C, Schmalfuss C, Hirsch C, Thompson C, Thompson C, Singal D, Lo E, Spivack E, Gopalakrishnan G, Lowe J, Talano J, Albu J, McClure J, McGettigan J, Hemphill J, Vora K, Solano Mdel P, Shoukfeh M, Best P, Thompson P, Borromeo S 3rd, Barringer T, Hilton T, Knickelbine T, Palmer W.

Abstract

IMPORTANCE:

No therapy directed against diabetes has been shown to unequivocally reduce the excess risk of cardiovascular complications. Aleglitazar is a dual agonist of peroxisome proliferator-activated receptors with insulin-sensitizing and glucose-lowering actions and favorable effects on lipid profiles.

OBJECTIVE:

To determine whether the addition of aleglitazar to standard medical therapy reduces cardiovascular morbidity and mortality among patients with type 2 diabetes mellitus and a recent acute coronary syndrome (ACS).

DESIGN, SETTING, AND PARTICIPANTS:

AleCardio was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial conducted in 720 hospitals in 26 countries throughout North America, Latin America, Europe, and Asia-Pacific regions. The enrollment of 7226 patients hospitalized for ACS (myocardial infarction or unstable angina) with type 2 diabetes occurred between February 2010 and May 2012; treatment was planned to continue until patients were followed-up for at least 2.5 years and 950 primary end point events were positively adjudicated.

INTERVENTIONS:

Randomized in a 1:1 ratio to receive aleglitazar 150 µg or placebo daily.

MAIN OUTCOMES AND MEASURES:

The primary efficacy end point was time to cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Principal safety end points were hospitalization due to heart failure and changes in renal function.

RESULTS:

The trial was terminated on July 2, 2013, after a median follow-up of 104 weeks, upon recommendation of the data and safety monitoring board due to futility for efficacy at an unplanned interim analysis and increased rates of safety end points. A total of 3.1% of patients were lost to follow-up and 3.2% of patients withdrew consent. The primary end point occurred in 344 patients (9.5%) in the aleglitazar group and 360 patients (10.0%) in the placebo group (hazard ratio, 0.96 [95% CI, 0.83-1.11]; P = .57). Rates of serious adverse events, including heart failure (3.4% for aleglitazar vs 2.8% for placebo, P = .14), gastrointestinal hemorrhages (2.4% for aleglitazar vs 1.7% for placebo, P = .03), and renal dysfunction (7.4% for aleglitazar vs 2.7% for placebo, P < .001) were increased.

CONCLUSIONS AND RELEVANCE:

Among patients with type 2 diabetes and recent ACS, use of aleglitazar did not reduce the risk of cardiovascular outcomes. These findings do not support the use of aleglitazar in this setting with a goal of reducing cardiovascular risk.

TRIAL REGISTRATION:

clinicaltrials.gov Identifier: NCT01042769.

PMID:
24682069
DOI:
10.1001/jama.2014.3321
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center