Cardiorenal End Points in a Trial of Aliskiren for Type 2 Diabetes
Por:
Parving, HH, Brenner, BM, McMurray, JJV, de Zeeuw, D, Haffner, SM, Solomon, SD, Chaturvedi, N, Persson, F, Desai, AS, Nicolaides, M, Richard, A, Xiang, ZH, Brunel, P, Pfeffer, MA, Juncos, L, Orias, M, Kuschnir, E, Rusculleda, M, Garcia, S, Farias, E, Lema, L, Hominal, M, Montana, O, Sala, J, Diaz, M, Piskorz, D, Vita, N, Litwak, L, Sinay, I, Marin, M, Massari, P, Majul, C, Aizemberg, D, Azize, GM, Bartolacci, I, Reboredo, A, Vico, M, Milesi, R, Sessa, H, Wassermann, A, Margulis, F, Zangroniz, P, Watschinger, B, Prager, R, Toplak, H, Paulweber, B, Drexel, H, Francesconi, C, Foeger, B, Mayer, G, Braun, RK, Brath, H, Gaal, LV, Niepen, PVD, Persu, A, Vercammen, C, Vriese, AD, Coucke, F, Mathieu, C, Fery, F, Treille, S, Meeus, G, Acker, KV, Scheen, A, Tits, J, Ruige, J, Krzesinski, JM, Hollanders, G, Lienart, F, Dendale, P, Quinonez, M, Arnouts, P, Vanuytsel, J, Zanella, M, Mion, D, Forti, A, Almeida, F, Cunha, R, de Paula, RB, Brandao, A, Rocha, J, Krieger, E, Feitosa, G, Saraiva, J, Hissa, MN, Schmid, H, Felicio, J, Sgarbi, J, Oigman, W, Bowering, K, Garceau, C, Berlingieri, JC, Weisnagel, SJ, Hardin, P, Powell, C, Turcot, R, Muirhead, N, Aronson, R, Barima, YT, Steele, AW, Pandey, S, Woo, V, Cha, J, Dattani, D, Godin, C, Gupta, M, Leiter, L, Saunders, K, Tellier, G, Ting, G, Tobe, S, Chouinard, G, Schlosser, R, Khandwala, H, Ekoe, JM, Harris, SB, Pichette, V, Lachance, P, Ooi, TC, Tildesley, H, Barrett, B, Cournoyer, S, Lu, J, Zhang, H, Liu, X, Yan, S, Qi, X, Li, H, Lv, X, Yang, J, Sun, N, Xia, W, Wang, N, Tong, N, Mei, C, Gu, S, Zhang, J, Chen, X, Li, L, Su, B, Wang, L, Qiu, M, Wu, X, Liu, Z, Jia, W, Xu, G, Dong, J, Zhu, D, Zhang, M, Yan, J, Liu, B, Chen, J, Fu, J, Yan, L, Zhan, X, Zhong, L, Yang, T, Ma, J, Xu, M, Xu, X, Shi, B, Ji, Q, Zhong, H, He, R, Yuan, Z, Zhou, Z, Lin, H, Yang, W, Ke, Y, Li, Q, Hong, T, Franco, C, Casas, L, Triana, A, Botero, R, Jaramillo, C, Hernandez, E, Barrera, C, Blanco, D, Stipal, R, Widimsky, P, Dohnalova, L, Komroskova, M, Kvapil, M, Belobradkova, J, Tesar, V, Cifkova, R, Vodnansky, P, Kocourkova, B, Christiansen, JS, Lervang, H, Perrild, H, Rossing, P, Oestergaard, O, Juhl, H, Thorsteinsson, B, Snorgaard, O, Urhammer, S, Egstrup, K, Tikkanen, T, Helin, K, Rinne, J, Lahtela, J, Strand, J, Valtonen, E, Saari, M, Kananen, K, Savela, K, Marre, M, Blacher, J, Aldigier, JC, Zaoui, P, Fauvel, JP, Gouet, D, Valensi, PE, Charpentier, G, Marechaud, R, Penfornis, A, Ovize, M, Kovalchuck, AA, Haller, H, Dellanna, F, Schoen, N, Groeschel, W, Eickhoff, F, Hanefeld, M, Merke, J, Rambausek, M, Zimmermann, U, Stuetz, W, Vosskuehler, A, Hevendehl, G, Schax, U, Lehmann, G, Haack, A, Hilgenberg, J, Klausmann, G, Adelberger, V, Gessner, S, Fiesselmann, A, Oerter, E, Hohenstatt, T, Groeschel, A, Behnke, T, Sisting, RT, Schoch, D, Bieler, T, Schleyer, S, Altes, U, Klepzig, G, Rudofsky, G, Mueller, G, Burkhardt, F, Reschke, K, Senftleber, I, Wiesweg, CK, Herrmann, HJ, Brandstetter, R, Segner, A, Nickenig, G, Schmitt, H, Rippert, R, Goebel, R, Schreibmueller, F, Pencz, I, Ott, P, Siamopoulos, K, Migdalis, I, Pappas, S, Pagkalos, E, Yalouris, A, Tsapas, A, Maltezos, E, Tentolouris, N, Papadakis, I, Ioannidis, G, Goumenos Guatemala, D, Corona, V, Gonzalez, R, Haase, F, Monterroso, V, Sanchez, V, Turcios, E, Wyss, F, Arango, JL, Bako, B, Deak, L, Domotor, E, Dudas, M, Fulop, T, Kiss, I, Koranyi, L, Lengyel, Z, Nyirati, G, Oroszlan, T, Aniko, S, Voros, P, Kapocsi, J, Wittmann, I, Paragh, G, Abraham, G, Tandon, N, Thomas, N, Mohan, V, Sahay, R, Sethi, B, Rao, V, Kumar, S, Chowdhury, S, Dharmalingam, M, Seshiah, V, Bantwal, G, Viswanathan, V, Yajnik, C, Adhikari, P, Hiremath, J, Bha Ittacharyya, A, Dani, S, Modi, KK, Glorioso, N, Morosetti, M, Veglio, F, Perticone, F, Dotta, F, Quarello, F, Sesti, G, Aiello, A, D'Ospina, A, Giordano, C, Novo, S, Ferri, C, Capuano, V, Trimarco, B, Tonolo, G, Villa, G, De Pellegrin, A, Zanette, G, Federici, M, Aucello, G, Piatti, P, Vinciguerra, A, Mannarino, E, Taddei, S, Filetti, S, Grandaliano, G, Marchionni, N, Lambiase, C, Locatelli, F, Scanferla, F, Lembo, G, Leotta, S, Mos, L, Calatola, P, Fogari, R, David, S, Pedrinelli, R, Pignone, AM, Cozzolino, D, Bevilacqua, MT, Catena, C, Del Prato, S, Cerasola, G, Frontoni, S, Falcone, C, Porta, A, Bonora, E, Cocchi, R, Fucili, A, Frisinghelli, A, Volpe, M, Carugo, S, Gambardella, S, Spagnuolo, V, Maglia, G, D'Angelo, AR, Corsi, A, Limone, PP, Guarnieri, A, Ghigo, E, Ronchi, E, Ravera, M, Scioli, GA, Sekiguchi, M, Aoki, S, Ogawa, Y, Seino, H, Onishi, Y, Tojo, A, Narimiya, M, Iwaita, Y, Takeda, H, Shimizu, H, Yamada, T, Kojima, S, Zushi, S, Kaneko, S, Matsumoto, A, Kajiyama, S, Fujita, H, Shikata, K, Tone, A, Matsubayashi, S, Tanaka, S, Sekigami, T, Tatsukawa, Y, Abe, N, Kawahara, K, Kasahara, H, Maeda, Y, Suzuki, Y, Okamoto, H, Tachi, K, Yamada, K, Uzu, T, Itou, T, Fukui, T, Cho, W, Kwak, I, Chae, D, Oh, H, Ha, S, Shin, Y, Cha, D, Kim, Y, Kim, S, Kang, S, Lim, C, Song, J, Kwon, Y, Badariene, J, Labutiniene, IP, Zabuliene, L, Poteliuniene, V, Miglinas, M, Kooy, A, van den Meiracker, AH, Smak Gregoor, PJH, Luik, AJ, Potter van Loon, BJ, Feenstra, HJ, Kaasjager, HAH, Viergever, PP, Woittiez, AJJ, van Bemmel, T, Lieverse, AG, Simsek, S, Gaillard, CAJM, van der Zwaan, C, Lok, DJA, Spiering, W, Nierop, PR, Baggen, MGA, Leendert, RJM, de Jong, A, Leurs, PB, Vincent, HH, Wins, EHR, Voors, AA, Ronner, E, Heeg, JE, van Hal, JMC, Boermans, T, Feis, WL, Mostard, G, Bakker, RC, Dunselman, PHJM, Jorde, R, Skeie, S, Istad, H, Skjelvan, G, Gronert, J, Tomala, T, Gudnason, S, Tarje Torvik, D, Risberg, K, Abedini, S, Cabrera, W, Medina, B, Medina, F, Herrada, B, Saavedra, A, Jorge Polonia, D, Luis Providencia, D, Carvalho, D, Vasconcelos, MP, da Silva, GF, Branco, P, Gil, DV, da Costa, AG, da Silva, PM, Arez, L, Martins, L, Birne, R, Dzuponova, J, Surovcikova, M, Culak, J, Dukat, A, Filipova, S, Andre, I, Stevlik, J, Uhliar, R, Fabryova, L, Benacka, J, Koleny, D, Szentivanyi, M, Spisak, V, Pella, D, Pastrnakova, E, Martinka, E, Chua, T, Wong, KS, Lau, T, Ng, TG, Yeoh, LY, Bhana, SA, Rayner, B, Wellmann, H, Amod, A, Ranjith, N, Ahmed, F, Rheeder, P, Makan, H, Naicker, P, Podgorski, G, De Teresa, E, Olivan, J, Fernandez, VL, Povedano, ST, Terns, M, Ricart, W, Gonzalez, JM, Fernandez, P, de Teresa Parreno, L, Redon, J, Parra, J, Calvo, C, Lopez, I, Puig, JG, Calle, A, Garcia, JCF, Lopez, JM, Jimenez, ML, Fraile, B, Perez, JS, Nadal, JJ, Guija, E, Calvino, J, Barrios, V, Iglesias, JN, Armario, P, Garcia, M, Aranda, P, Brotons, C, Ruilope, L, Gomez, P, Catelao, AM, Cusachs, AR, Sarro, M, Martinez, V, dell Valle, MH, Trias, F, Comas, A, Salvador, N, Martinez, F, Hernandez, F, Martinez, J, Mateos, C, Peral, JL, Tolosana, J, Sobrino, J, Isart, J, Vizcaino, J, Fernandez Vega, F, Zamorano, JL, Bacariza, M, Soubriet, A, Fernandez-Cruz, A, Querejeta, R, Munoz Leira, V, Calvo Iglesias, FE, Ibrik, O, Martin, D, Nanclares, MS, Mediavilla, JD, Galceran, JM, Lopez, A, Muros, T, Pascual, J, Casalla, F, Tornero, F, Fernandez, G, Weiss, L, Pettersson, P, Olsen, H, Franke, F, Stroembom, U, Furuland, H, Larnefelt, H, Allemann, Y, Krapf, R, Wuethrich, R, Gerber, P, Munger, R, Hayoz, D, Graf, HJ, Burnier, M, Petrillo, A, Batt, R, Constam, EN, Moccetti, T, Bianda, T, Rickli, H, Builliard, C, Wu, KD, Lin, SH, Wu, CJ, Huey-Herng Sheu, W, Su, SL, Chen, SC, Chou, CW, Lee, CT, Yang, TC, Chen, HC, Sritara, P, Sukonthasarn, A, Sriratanasathavorn, C, Eiam-Ong, S, Supasyndh, O, Chanchairujira, T, Kitiyakara, C, Comlekci, A, Arici, M, Usalan, C, Guneri, S, Koc, M, Kalender, B, Ates, K, Gurgun, C, Araz, M, Demirbas, B, Biernacki, W, Calvert, J, Eavis, P, Kerrane, J, Litchfield, J, Middleton, A, Roberts, J, Simpson, H, Charles, H, Jardine, A, Fisher, M, Banerjee, D, Gallen, I, Gnudi, L, Harvey, J, O'Hare, P, Vora, J, Winocour, P, Soran, H, Browne, D, Darko, D, Mancebo, JG, de Roa, ER, Antepara, N, Carrillo, E, Berrizbeitia, M, Guevara, L, Pernalete, N, Ontiveros, C, Zigrang, W, Blakney, E, Rosenblit, P, Weinstein, R, Klaff, L, Lipetz, R, Busick, E, Tung, P, Cooperman, M, Michael, S, Sun, CH, Hart, T, Maddux, A, Bowden, R, East, C, Arakaki, R, Villafuerte, B, Mamish, Z, Mendez, R, Connery, L, Nour, K, Wynne, A, Busch, R, Zamora, B, Sachson, R, Prasad, J, Lasala, G, Smith, M, Fitz-Patrick, D, Ruiz-Rivera, L, Barranco, E, Solomon, R, Woolley, A, Brown, C, Freedman, Z, Schmidt, S, Pollock, J, Ruddy, M, Toto, R, Kopyt, NP, Bazzi, A, Horowitz, B, Feng, W, Wahl, T, Duprez, D, Gilbert, J, Steigerwalt, S, Jacqmein, J, Gorton, S, Allison, J, Pino, J, Lock, J, Leimbach, W, Anderson, J, Beacom, M, Craig, W, Gorson, D, Kerstein, H, Lerman, S, Minehart, C, Agarwal, N, Verma, SI, Valitutto, M, Demetry, K, Mersey, J, Koeper, D, Fanti, P, Eng, G, Jamerson, K, Grimm, R, Fagan, T, Bajaj, M, Katz, L, Portnay, G, Altschuller, A, Desai, V, Bilazari, S, Ipp, E, Rodelas, R, Burstein, D, Berg, J, Velez, J, Lund, R, Rekhi, A, Martin, E, Martin, J, Robertson, D, Singh, N, Narayan, P, Moustafa, M, Lanier, D, Seidner, M, Phillips, A, Vaughters, B, Sprague, A, Swartz, S, Lopez, R, Kumar, J, Bressler, P, Sadler, L, Wise, J, Kilbane, A
Publicada:
6 dic 2012
Resumen:
BACKGROUND
This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both.
METHODS
In a double-blind fashion, we randomly assigned 8561 patients to aliskiren (300 mg daily) or placebo as an adjunct to an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker. The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation; nonfatal myocardial infarction; nonfatal stroke; unplanned hospitalization for heart failure; end-stage renal disease, death attributable to kidney failure, or the need for renal-replacement therapy with no dialysis or transplantation available or initiated; or doubling of the baseline serum creatinine level.
RESULTS
The trial was stopped prematurely after the second interim efficacy analysis. After a median follow-up of 32.9 months, the primary end point had occurred in 783 patients (18.3%) assigned to aliskiren as compared with 732 (17.1%) assigned to placebo (hazard ratio, 1.08; 95% confidence interval [CI], 0.98 to 1.20; P = 0.12). Effects on secondary renal end points were similar. Systolic and diastolic blood pressures were lower with aliskiren (between-group differences, 1.3 and 0.6 mm Hg, respectively) and the mean reduction in the urinary albumin-to-creatinine ratio was greater (between-group difference, 14 percentage points; 95% CI, 11 to 17). The proportion of patients with hyperkalemia (serum potassium level, = 6 mmol per liter) was significantly higher in the aliskiren group than in the placebo group (11.2% vs. 7.2%), as was the proportion with reported hypotension (12.1% vs. 8.3%) (P < 0.001 for both comparisons).
CONCLUSIONS
The addition of aliskiren to standard therapy with renin-angiotensin system blockade in patients with type 2 diabetes who are at high risk for cardiovascular and renal events is not supported by these data and may even be harmful. (Funded by Novartis; ALTITUDE ClinicalTrials.gov number, NCT00549757.)
Filiaciones:
Parving, HH:
Univ Copenhagen, Rigshosp, Dept Med Endocrinol, DK-2100 Copenhagen, Denmark
Aarhus Univ, Fac Hlth Sci, Aarhus, Denmark
Brenner, BM:
Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA
McMurray, JJV:
Univ Glasgow, Cardiovasc Res Ctr, British Heart Fdn, Glasgow, Lanark, Scotland
de Zeeuw, D:
Univ Groningen, Univ Med Ctr Groningen, Dept Clin Pharmacol, Groningen, Netherlands
Haffner, SM:
Univ Texas Hlth Sci Ctr San Antonio, Dept Med & Clin Epidemiol, San Antonio, TX 78229 USA
Solomon, SD:
Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA
Chaturvedi, N:
Univ London Imperial Coll Sci Technol & Med, London, England
Persson, F:
Steno Diabet Ctr, DK-2820 Gentofte, Denmark
Desai, AS:
Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA
Nicolaides, M:
Novartis Pharmaceut, Basel, Switzerland
Richard, A:
Novartis Pharmaceut, Basel, Switzerland
Xiang, ZH:
Novartis Pharmaceut, Basel, Switzerland
Brunel, P:
Novartis Pharmaceut, Basel, Switzerland
Pfeffer, MA:
Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA
Harvard Univ, Sch Med, Boston, MA USA.
Green Published
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