The effects of cinacalcet in older and younger patients on hemodialysis: The evaluation of cinacalcet HCL therapy to lower cardiovascular events (EVOLVE) trial

Parfrey, P.S.; Drueke, T.B.; Block, G.A.; Correa-Rotter, R.; Floege, J.; Herzog, C.A.; London, G.M.; Mahaffey, K.W.; Moe, S.M.; Wheeler, D.C.; Kubo, Y.; Dehmel, B.; Goodman, W.G.; Chertow, G.M.; Santos, J.; Najun Zarazaga, C.; Marin, I.; Garrote, N.; Cusumano, A.; Penalba, N.; Del Valle, E.; Juncos, L.; Martinez Saye, J.; Lef, L.; Altobelli, V.; Petraglia, G.; Rosa Diez, G.; Douthat, W.; Lobo, J.; Gallart, C.; Lafalla, A.; Diez, G.; Linares, B.; Lopez, N.; Ramirez, N.; Gonzalez, R.; Valtuille, R.; Beresan, H.; Hermida, O.; Rudolf, G.; Marchetta, N.; Rano, M.; Ramirez, M.; Garcia, N.; Gillies, A.; Jones, B.; Pedagogos, E.; Walker, R.; Talaulikar, G.; Bannister, K.; Suranyi, M.; Kark, A.; Roger, S.; Kerr, P.; Disney, A.; Mount, P.; Fraenkel, M.; Mathew, M.; Fassett, R.; Jose, M.; Hawley, C.; Lonergan, M.; Mackie, J.; Ferrari, P.; Menahem, S.; Sabto, J.; Hutchison, B.; Langham, R.; Pollock, C.; Holzer, H.; Oberbauer, R.; Arias, I.; Graf, H.; Mayer, G.; Lhotta, K.; Neyer, U.; Klauser, R.; Hoerl, W.; Horn, S.; Kovarik, J.; Kramar, R.; Eigner, M.; Dhaene, M.; Billiouw, J.; De Meester, J.; Warling, X.; Cambier-Dwelschauwers, P.; Evenepoel, P.; Daelemans, R.; Dratwa, M.; Maes, B.; Stolear, J.; Dejagere, T.; Vanwalleghem, J.; Bouman, K.; Jadoul, M.; Peeters, J.; Vanholder, R.; Tielemans, C.; Donck, J.; Almeida, F.; Picollo de Oliveira, J.; Burdmann, E.; Garcia, V.; Saldanha Thome, F.; Deboni, L.; Bregman, R.; Lugon, J.; Araujo, S.; Ferreira Filho, S.; de Francesco Daher, E.; Sperto Baptista, M.; Carvalho, A.; D'Avila, D.; Moyses Neto, M.; Yu, L.; Bastos, M.; Sampaio Lacativa, P.; Jorgetti, V.; de Almeida Romao, E.; Cardeal da Costa, J.; Pecoits Filho, R.; Gordan, P.; Salgado, N.; Teixeira Araujo, M.; Neiva Coelho, S.; Oliveira, I.; Moyses, R.; Vasconcellos, L.; Batista, P.; Luiz Gross, J.; Pedrosa, A.; Cournoyer, S.; Leblanc, M.; Chow, S.; Karunakaran, S.; Wong, G.; Tobe, S.; Desmeules, S.; Zimmerman, D.; Murphy, S.; Montambault, P.; Donnelly, S.; Macrae, J.; Culleton, B.; Soroka, S.; Rabbat, C.; Jindal, K.; Vasilevsky, M.; Michaud, M.; Wijeyesinghe, E.; Zacharias, J.; Lok, C.; Muirhead, N.; Verrelli, M.; Da Roza, G.; Sapir, D.; Olgaard, K.; Daugaard, H.; Brandi, L.; Jensen, P.; Boulechfar, H.; Ang, K.; Simon, P.; Rieu, P.; Brunet, P.; Touchard, G.; London, G.; Urena Torres, P.; Combe, C.; Durrbach, A.; Ortiz, J.; Hannedouche, T.; Vela, C.; Lionet, A.; Ryckelynck, P.; Zaoui, P.; Choukroun, G.; Fessi, H.; Lang, P.; Stroumza, P.; Joly, D.; Mousson, C.; Laville, M.; Dellanna, F.; Erley, C.; Braun, J.; Rambausek, M.; Riegel, W.; Klingberg, M.; Schwertfeger, E.; Wizemann, V.; Eckardt, K.; Reichel, H.; Passauer, J.; Hubel, E.; Frischmuth, N.; Liebl, R.; Fiedler, R.; Schwenger, V.; Vosskuhler, A.; Kunzendorf, U.; Renders, L.; Rattensberger, D.; Rump, L.; Ketteler, M.; Neumayer, H.; Zantvoort, F.; Stahl, R.; Ladanyi, E.; Kulcsar, I.; Mezei, I.; Csiky, B.; Rikker, C.; Arkossy, O.; Berta, K.; Szegedi, J.; Major, L.; Ferenczi, S.; Fekete, A.; Szabo, T.; Zakar, G.; Wagner, G.; Kazup Erdelyine, S.; Borbas, B.; Eustace, J.; Reddan, D.; Capasso, G.; Locatelli, F.; Villa, G.; Cozzolino, M.; Brancaccio, D.; Messa, P.; Bolasco, P.; Ricciardi, B.; Malberti, F.; Moriero, E.; Cannella, G.; Ortalda, V.; Stefoni, S.; Frasca, G.; Cappelli, G.; Albertazzi, A.; Zoccali, C.; Farina, M.; Elli, A.; Avella, F.; Ondei, P.; Mingardi, G.; Errico, R.; Losito, A.; Di Giulio, S.; Pertosa, G.; Schena, F.; Grandaliano, G.; Gesualdo, L.; Auricchio, M.; Bochicchio-Ricardelli, T.; Aranda Verastegui, F.; Pena, J.; Chew Wong, A.; Cruz-Valdez, J.; Torres Zamora, M.; Solis, M.; Sebastian Diaz, M.; Vital Flores, M.; Alvarez Sandoval, E.; van den Dorpel, M.; Brink, H.; Van Kuijk, W.; Vermeij, C.; Smak Gregoor, P.; Hagen, E.; van der Sande, F.; Klinger, M.; Nowicki, M.; Muszytowski, M.; Bidas, K.; Bentkowski, W.; Wiecek, A.; Ksiazek, A.; Marczewski, K.; Ostrowski, M.; Switalski, M.; Sulowicz, W.; Matuszkiewicz-Rowinska, J.; Mysliwiec, M.; Durlik, M.; Rutkowski, B.; Macario, F.; Carvalho, B.; Frazao, J.; Machado, D.; Weigert, A.; Andrusev, A.; Khrustalev, O.; Zemtchenkov, A.; Gurevich, K.; Staroselsky, K.; Khadikova, N.; Rozhinskaya, L.; Timokhovskaya, G.; Strokov, A.; Balkarova, O.; Ermolenko, V.; Kolmakova, E.; Komandenko, M.; Timofeev, M.; Shilo, V.; Shostka, G.; Smirnov, A.; Anashkin, V.; Volgina, G.; Domashenko, O.; Gurevich, A.; Perlin, D.; Martinez Garcia, J.; Andres Ribes, E.; Coll Piera, E.; Fernandez Lucas, M.; Galicia, M.; Prados, M.; Gonzalez, M.; Romero, R.; Martin de Francisco, A.; Montenegro, J.; Santiago, C.; Garcia, F.; Alcazar de La Ossa, J.; Arrieta, J.; Pons, J.; Martin-Malo, A.; Soler Amigo, J.; Cases, A.; Sterner, G.; Jensen, G.; Wikstrom, B.; Jacobson, S.; Lund, U.; Weiss, L.; Stahl, A.; von Albertini, B.; Burnier, M.; Meier, P.; Martin, P.; Uehlinger, D.; Dickenmann, M.; Yaqoob, M.; Zehnder, D.; Kalra, P.; Padmanabhan, N.; Roe, S.; Eadington, D.; Pritchard, N.; Hutchison, A.; Davies, S.; Wilkie, M.; Davies, M.; Pai, P.; Swift, P.; Kwan, J.; Goldsmith, D.; Tomson, C.; Stratton, J.; Dasgupta, I.; Sarkar, S.; Moustafa, M.; Gandhi, K.; Jamal, A.; Galindo-Ramos, E.; Tuazon, J.; Batlle, D.; Tucker, K.; Schiller-Moran, B.; Assefi, A.; Martinez, C.; Samuels, L.; Goldman, J.; Cangiano-Rivera, J.; Darwish, R.; Lee, M.; Topf, J.; Kapatkin, K.; Baer, H.; Kopelman, R.; Acharya, M.; Tharpe, D.; Bernardo, M.; Nader, P.; Guzman-Rivera, J.; Pergola, P.; Sekkarie, M.; Alas, E.; Zager, P.; Liss, K.; Navarro, J.; Roppolo, M.; Denu-Ciocca, C.; Kshirsagar, A.; El Khatib, M.; Kant, K.; Scott, D.; Murthyr, B.; Finkelstein, F.; Keightley, G.; Mccrary, R.; Pitone, J.; Cavalieri, T.; Tsang, A.; Pellegrino, B.; Schmidt, R.; Ahmad, S.; Brown, C.; Friedman, E.; Mittman, N.; Fadem, S.; Shapiro, W.; Reddy, M.; Goldberger, S.; Woredekal, Y.; Agarwal, A.; Anger, M.; Haque, M.; Chidester, P.; Kohli, R.; Rubinstein, S.; Newman, G.; Gladish, R.; Ayodeji, O.; Soman, S.; Sprague, S.; Hunt, N.; Gehr, T.; Rizk, D.; Warnock, D.; Polack, D.; Pahl, M.; Fischer, D.; Dreyer, P.; James, G.; Husserl, F.; Rogers, T.; Raff, A.; Sedor, J.; Silver, M.; Smith, M.; Steinberg, S.; Delgiorno, T.; Jones, E.; Cunha, P.D.; Cheng, J.; Pogue, V.; Blumenthal, S.; Brown, E.; Charytan, C.; Buerkert, J.; Cook, M.; Felsenfeld, A.; Tareen, N.; Gupta, A.; Herman, T.; Diamond, S.; Hura, C.; Laski, M.; Maclaurin, J.; Plumb, T.; Brosnahan, G.; Kumar, J.; Henriquez, M.; Poole, C.; Osanloo, E.; Matalon, A.; Sholer, C.; Arfeen, S.; Azer, M.; Belledonne, M.; Gross, M.; Dunnigan, E.; Mcconnell, K.; Becker, B.; Skinner, F.; Rigolosi, R.; Spiegel, D.; Stegman, M.; Patak, R.; Streja, D.; Ranjit, U.; Youell, T.; Wooldridge, T.; Stafford, C.; Cottiero, R.; Weinberg, M.; Schonefeld, M.; Shahmir, E.; Hazzan, A.; Ashfaq, A.; Bhandari, K.; Cleveland, W.; Culpepper, M.; Golden, J.; Lai, L.; Lien, Y.; Lorica, V.; Robertson, J.; Malireddi, K.; Morse, S.; Thakur, V.; Israelit, A.; Raguram, P.; Alfred, H.; Weise, W.; Al-Saghir, F.; El Shahawy, M.; Rastogi, A.; Nissenson, A.; Kopyt, N.; Lynn, R.; Lea, J.; Mcclellan, W.; Teredesai, P.; Ong, S.; Tolkan, S.; Sugihara, J.; Minga, T.; Mehrotra, R.; Minasian, R.; Bhatia, D.; Specter, R.; Capelli, J.; Sidhu, P.; Dalal, S.; Dykes, P.; Khan, M.; Rahim, F.; Saklayen, M.; Thomas, A.; Michael, B.; Torres, M.; Al-Bander, H.; Murray, B.; Abukurah, A.; Gupta, B.; Nosrati, S.; Raja, R.; Zeig, S.; Braun, M.; Amatya, A.; Endsley, J.; Sharon, Z.; Gupta, A.; Dolson, G.; Dumler, F.; Ntoso, K.; Rosansky, S.; Kumar, N.; Gura, V.; Thompson, N.; Goldfarb, D.; Halligan, R.; Middleton, J.; Widerhorn, A.; Arbeit, L.; Arruda, J.; Crouch, T.; Friedman, L.; Khokhar, S.; Mittleman, J.; Light, P.; Taparia, B.; West, C.; Cotton, J.; Dhingra, R.; Kleinman, L.; Arif, F.; Lew, S.; Nammour, T.; Sterrett, J.; Williams, M.; Ramirez, J.; Rubin, J.; Mccarthy, J.; Noble, S.; Chaffin, M.; Rekhi, A.

doi:10.2215/CJN.07730814

Background and objectives The calcimimetic cinacalcet reduced the risk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older (≥ 65 years, n=1005) and younger (<65 years, n=2878) patients. Design, setting, participants, & measurements Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified. ResultsOlder patients had higher baseline prevalence of diabetesmellitus and CV comorbidity. Annualized rates of kidney transplantation and parathyroidectomy were > 3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups. Conclusions In the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone.

The effects of cinacalcet in older and younger patients on hemodialysis: The evaluation of cinacalcet HCL therapy to lower cardiovascular events (EVOLVE) trial / P.S. Parfrey, T.B. Drueke, G.A. Block, R. Correa-Rotter, J. Floege, C.A. Herzog, G.M. London, K.W. Mahaffey, S.M. Moe, D.C. Wheeler, Y. Kubo, B. Dehmel, W.G. Goodman, G.M. Chertow, J. Santos, C. Najun Zarazaga, I. Marin, N. Garrote, A. Cusumano, N. Penalba, E. Del Valle, L. Juncos, J. Martinez Saye, L. Lef, V. Altobelli, G. Petraglia, G. Rosa Diez, W. Douthat, J. Lobo, C. Gallart, A. Lafalla, G. Diez, B. Linares, N. Lopez, N. Ramirez, R. Gonzalez, R. Valtuille, H. Beresan, O. Hermida, G. Rudolf, N. Marchetta, M. Rano, M. Ramirez, N. Garcia, A. Gillies, B. Jones, E. Pedagogos, R. Walker, G. Talaulikar, K. Bannister, M. Suranyi, A. Kark, S. Roger, P. Kerr, A. Disney, P. Mount, M. Fraenkel, M. Mathew, R. Fassett, M. Jose, C. Hawley, M. Lonergan, J. Mackie, P. Ferrari, S. Menahem, J. Sabto, B. Hutchison, R. Langham, C. Pollock, H. Holzer, R. Oberbauer, I. Arias, H. Graf, G. Mayer, K. Lhotta, U. Neyer, R. Klauser, W. Hoerl, S. Horn, J. Kovarik, R. Kramar, M. Eigner, M. Dhaene, J. Billiouw, J. De Meester, X. Warling, P. Cambier-Dwelschauwers, P. Evenepoel, R. Daelemans, M. Dratwa, B. Maes, J. Stolear, T. Dejagere, J. Vanwalleghem, K. Bouman, M. Jadoul, J. Peeters, R. Vanholder, C. Tielemans, J. Donck, F. Almeida, J. Picollo de Oliveira, E. Burdmann, V. Garcia, F. Saldanha Thome, L. Deboni, R. Bregman, J. Lugon, S. Araujo, S. Ferreira Filho, E. de Francesco Daher, M. Sperto Baptista, A. Carvalho, D. d'Avila, M. Moyses Neto, L. Yu, M. Bastos, P. Sampaio Lacativa, V. Jorgetti, E. de Almeida Romao, J. Cardeal da Costa, R. Pecoits Filho, P. Gordan, N. Salgado, M. Teixeira Araujo, S. Neiva Coelho, I. Oliveira, R. Moyses, L. Vasconcellos, P. Batista, J. Luiz Gross, A. Pedrosa, S. Cournoyer, M. LeBlanc, S. Chow, S. Karunakaran, G. Wong, S. Tobe, S. Desmeules, D. Zimmerman, S. Murphy, P. Montambault, S. Donnelly, J. MacRae, B. Culleton, S. Soroka, C. Rabbat, K. Jindal, M. Vasilevsky, M. Michaud, E. Wijeyesinghe, J. Zacharias, C. Lok, N. Muirhead, M. Verrelli, G. Da Roza, D. Sapir, K. Olgaard, H. Daugaard, L. Brandi, P. Jensen, H. Boulechfar, K. Ang, P. Simon, P. Rieu, P. Brunet, G. Touchard, G. London, P. Urena Torres, C. Combe, A. Durrbach, J. Ortiz, T. Hannedouche, C. Vela, A. Lionet, P. Ryckelynck, P. Zaoui, G. Choukroun, H. Fessi, P. Lang, P. Stroumza, D. Joly, C. Mousson, M. Laville, F. Dellanna, C. Erley, J. Braun, M. Rambausek, W. Riegel, M. Klingberg, E. Schwertfeger, V. Wizemann, K. Eckardt, H. Reichel, J. Passauer, E. Hubel, N. Frischmuth, R. Liebl, R. Fiedler, V. Schwenger, A. Vosskuhler, U. Kunzendorf, L. Renders, D. Rattensberger, L. Rump, M. Ketteler, H. Neumayer, F. Zantvoort, R. Stahl, E. Ladanyi, I. Kulcsar, I. Mezei, B. Csiky, C. Rikker, O. Arkossy, K. Berta, J. Szegedi, L. Major, S. Ferenczi, A. Fekete, T. Szabo, G. Zakar, G. Wagner, S. Kazup Erdelyine, B. Borbas, J. Eustace, D. Reddan, G. Capasso, F. Locatelli, G. Villa, M. Cozzolino, D. Brancaccio, P. Messa, P. Bolasco, B. Ricciardi, F. Malberti, E. Moriero, G. Cannella, V. Ortalda, S. Stefoni, G. Frasca, G. Cappelli, A. Albertazzi, C. Zoccali, M. Farina, A. Elli, F. Avella, P. Ondei, G. Mingardi, R. Errico, A. Losito, S. Di Giulio, G. Pertosa, F. Schena, G. Grandaliano, L. Gesualdo, M. Auricchio, T. Bochicchio-Ricardelli, F. Aranda Verastegui, J. Pena, A. Chew Wong, J. Cruz-Valdez, M. Torres Zamora, M. Solis, M. Sebastian Diaz, M. Vital Flores, E. Alvarez Sandoval, M. van den Dorpel, H. Brink, W. Van Kuijk, C. Vermeij, P. Smak Gregoor, E. Hagen, F. van der Sande, M. Klinger, M. Nowicki, M. Muszytowski, K. Bidas, W. Bentkowski, A. Wiecek, A. Ksiazek, K. Marczewski, M. Ostrowski, M. Switalski, W. Sulowicz, J. Matuszkiewicz-Rowinska, M. Mysliwiec, M. Durlik, B. Rutkowski, F. Macario, B. Carvalho, J. Frazao, D. Machado, A. Weigert, A. Andrusev, O. Khrustalev, A. Zemtchenkov, K. Gurevich, K. Staroselsky, N. Khadikova, L. Rozhinskaya, G. Timokhovskaya, A. Strokov, O. Balkarova, V. Ermolenko, E. Kolmakova, M. Komandenko, M. Timofeev, V. Shilo, G. Shostka, A. Smirnov, V. Anashkin, G. Volgina, O. Domashenko, A. Gurevich, D. Perlin, J. Martinez Garcia, E. Andres Ribes, E. Coll Piera, M. Fernandez Lucas, M. Galicia, M. Prados, M. Gonzalez, R. Romero, A. Martin de Francisco, J. Montenegro, C. Santiago, F. Garcia, J. Alcazar de La Ossa, J. Arrieta, J. Pons, A. Martin-Malo, J. Soler Amigo, A. Cases, G. Sterner, G. Jensen, B. Wikstrom, S. Jacobson, U. Lund, L. Weiss, A. Stahl, B. von Albertini, M. Burnier, P. Meier, P. Martin, D. Uehlinger, M. Dickenmann, M. Yaqoob, D. Zehnder, P. Kalra, N. Padmanabhan, S. Roe, D. Eadington, N. Pritchard, A. Hutchison, S. Davies, M. Wilkie, M. Davies, P. Pai, P. Swift, J. Kwan, D. Goldsmith, C. Tomson, J. Stratton, I. Dasgupta, S. Sarkar, M. Moustafa, K. Gandhi, A. Jamal, E. Galindo-Ramos, J. Tuazon, D. Batlle, K. Tucker, B. Schiller-Moran, A. Assefi, C. Martinez, L. Samuels, J. Goldman, J. Cangiano-Rivera, R. Darwish, M. Lee, J. Topf, K. Kapatkin, H. Baer, R. Kopelman, M. Acharya, D. Tharpe, M. Bernardo, P. Nader, J. Guzman-Rivera, P. Pergola, M. Sekkarie, E. Alas, P. Zager, K. Liss, J. Navarro, M. Roppolo, C. Denu-Ciocca, A. Kshirsagar, M. El Khatib, K. Kant, D. Scott, B. Murthyr, F. Finkelstein, G. Keightley, R. McCrary, J. Pitone, T. Cavalieri, A. Tsang, B. Pellegrino, R. Schmidt, S. Ahmad, C. Brown, E. Friedman, N. Mittman, S. Fadem, W. Shapiro, M. Reddy, S. Goldberger, Y. Woredekal, A. Agarwal, M. Anger, M. Haque, P. Chidester, R. Kohli, S. Rubinstein, G. Newman, R. Gladish, O. Ayodeji, S. Soman, S. Sprague, N. Hunt, T. Gehr, D. Rizk, D. Warnock, D. Polack, M. Pahl, D. Fischer, P. Dreyer, G. James, F. Husserl, T. Rogers, A. Raff, J. Sedor, M. Silver, M. Smith, S. Steinberg, T. DelGiorno, E. Jones, P.D. Cunha, J. Cheng, V. Pogue, S. Blumenthal, E. Brown, C. Charytan, J. Buerkert, M. Cook, A. Felsenfeld, N. Tareen, A. Gupta, T. Herman, S. Diamond, C. Hura, M. Laski, J. MacLaurin, T. Plumb, G. Brosnahan, J. Kumar, M. Henriquez, C. Poole, E. Osanloo, A. Matalon, C. Sholer, S. Arfeen, M. Azer, M. Belledonne, M. Gross, E. Dunnigan, K. McConnell, B. Becker, F. Skinner, R. Rigolosi, D. Spiegel, M. Stegman, R. Patak, D. Streja, U. Ranjit, T. Youell, T. Wooldridge, C. Stafford, R. Cottiero, M. Weinberg, M. Schonefeld, E. Shahmir, A. Hazzan, A. Ashfaq, K. Bhandari, W. Cleveland, M. Culpepper, J. Golden, L. Lai, Y. Lien, V. Lorica, J. Robertson, K. Malireddi, S. Morse, V. Thakur, A. Israelit, P. Raguram, H. Alfred, W. Weise, F. Al-Saghir, M. El Shahawy, A. Rastogi, A. Nissenson, N. Kopyt, R. Lynn, J. Lea, W. McClellan, P. Teredesai, S. Ong, S. Tolkan, J. Sugihara, T. Minga, R. Mehrotra, R. Minasian, D. Bhatia, R. Specter, J. Capelli, P. Sidhu, S. Dalal, P. Dykes, M. Khan, F. Rahim, M. Saklayen, A. Thomas, B. Michael, M. Torres, H. Al-Bander, B. Murray, A. Abukurah, B. Gupta, S. Nosrati, R. Raja, S. Zeig, M. Braun, A. Amatya, J. Endsley, Z. Sharon, A. Gupta, G. Dolson, F. Dumler, K. Ntoso, S. Rosansky, N. Kumar, V. Gura, N. Thompson, D. Goldfarb, R. Halligan, J. Middleton, A. Widerhorn, L. Arbeit, J. Arruda, T. Crouch, L. Friedman, S. Khokhar, J. Mittleman, P. Light, B. Taparia, C. West, J. Cotton, R. Dhingra, L. Kleinman, F. Arif, S. Lew, T. Nammour, J. Sterrett, M. Williams, J. Ramirez, J. Rubin, J. McCarthy, S. Noble, M. Chaffin, A. Rekhi. - In: CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY. - ISSN 1555-9041. - 10:5(2015), pp. 791-799.

The effects of cinacalcet in older and younger patients on hemodialysis: The evaluation of cinacalcet HCL therapy to lower cardiovascular events (EVOLVE) trial

Parfrey P. S.;Drueke T. B.;Block G. A.;Correa-Rotter R.;Floege J.;Herzog C. A.;London G. M.;Mahaffey K. W.;Moe S. M.;Wheeler D. C.;Kubo Y.;Dehmel B.;Goodman W. G.;Chertow G. M.;Santos J.;Najun Zarazaga C.;Marin I.;Garrote N.;Cusumano A.;Penalba N.;Del Valle E.;Juncos L.;Martinez Saye J.;Lef L.;Altobelli V.;Petraglia G.;Rosa Diez G.;Douthat W.;Lobo J.;Gallart C.;Lafalla A.;Diez G.;Linares B.;Lopez N.;Ramirez N.;Gonzalez R.;Valtuille R.;Beresan H.;Hermida O.;Rudolf G.;Marchetta N.;Rano M.;Ramirez M.;Garcia N.;Gillies A.;Jones B.;Pedagogos E.;Walker R.;Talaulikar G.;Bannister K.;Suranyi M.;Kark A.;Roger S.;Kerr P.;Disney A.;Mount P.;Fraenkel M.;Mathew M.;Fassett R.;Jose M.;Hawley C.;Lonergan M.;Mackie J.;Ferrari P.;Menahem S.;Sabto J.;Hutchison B.;Langham R.;Pollock C.;Holzer H.;Oberbauer R.;Arias I.;Graf H.;Mayer G.;Lhotta K.;Neyer U.;Klauser R.;Hoerl W.;Horn S.;Kovarik J.;Kramar R.;Eigner M.;Dhaene M.;Billiouw J.;De Meester J.;Warling X.;Cambier-Dwelschauwers P.;Evenepoel P.;Daelemans R.;Dratwa M.;Maes B.;Stolear J.;Dejagere T.;Vanwalleghem J.;Bouman K.;Jadoul M.;Peeters J.;Vanholder R.;Tielemans C.;Donck J.;Almeida F.;Picollo de Oliveira J.;Burdmann E.;Garcia V.;Saldanha Thome F.;Deboni L.;Bregman R.;Lugon J.;Araujo S.;Ferreira Filho S.;de Francesco Daher E.;Sperto Baptista M.;Carvalho A.;d'Avila D.;Moyses Neto M.;Yu L.;Bastos M.;Sampaio Lacativa P.;Jorgetti V.;de Almeida Romao E.;Cardeal da Costa J.;Pecoits Filho R.;Gordan P.;Salgado N.;Teixeira Araujo M.;Neiva Coelho S.;Oliveira I.;Moyses R.;Vasconcellos L.;Batista P.;Luiz Gross J.;Pedrosa A.;Cournoyer S.;LeBlanc M.;Chow S.;Karunakaran S.;Wong G.;Tobe S.;Desmeules S.;Zimmerman D.;Murphy S.;Montambault P.;Donnelly S.;MacRae J.;Culleton B.;Soroka S.;Rabbat C.;Jindal K.;Vasilevsky M.;Michaud M.;Wijeyesinghe E.;Zacharias J.;Lok C.;Muirhead N.;Verrelli M.;Da Roza G.;Sapir D.;Olgaard K.;Daugaard H.;Brandi L.;Jensen P.;Boulechfar H.;Ang K.;Simon P.;Rieu P.;Brunet P.;Touchard G.;London G.;Urena Torres P.;Combe C.;Durrbach A.;Ortiz J.;Hannedouche T.;Vela C.;Lionet A.;Ryckelynck P.;Zaoui P.;Choukroun G.;Fessi H.;Lang P.;Stroumza P.;Joly D.;Mousson C.;Laville M.;Dellanna F.;Erley C.;Braun J.;Rambausek M.;Riegel W.;Klingberg M.;Schwertfeger E.;Wizemann V.;Eckardt K.;Reichel H.;Passauer J.;Hubel E.;Frischmuth N.;Liebl R.;Fiedler R.;Schwenger V.;Vosskuhler A.;Kunzendorf U.;Renders L.;Rattensberger D.;Rump L.;Ketteler M.;Neumayer H.;Zantvoort F.;Stahl R.;Ladanyi E.;Kulcsar I.;Mezei I.;Csiky B.;Rikker C.;Arkossy O.;Berta K.;Szegedi J.;Major L.;Ferenczi S.;Fekete A.;Szabo T.;Zakar G.;Wagner G.;Kazup Erdelyine S.;Borbas B.;Eustace J.;Reddan D.;Capasso G.;Locatelli F.;Villa G.;M. Cozzolino;Brancaccio D.;P. Messa;Bolasco P.;Ricciardi B.;Malberti F.;Moriero E.;Cannella G.;Ortalda V.;Stefoni S.;Frasca G.;Cappelli G.;Albertazzi A.;Zoccali C.;Farina M.;Elli A.;Avella F.;Ondei P.;Mingardi G.;Errico R.;Losito A.;Di Giulio S.;Pertosa G.;Schena F.;Grandaliano G.;Gesualdo L.;Auricchio M.;Bochicchio-Ricardelli T.;Aranda Verastegui F.;Pena J.;Chew Wong A.;Cruz-Valdez J.;Torres Zamora M.;Solis M.;Sebastian Diaz M.;Vital Flores M.;Alvarez Sandoval E.;van den Dorpel M.;Brink H.;Van Kuijk W.;Vermeij C.;Smak Gregoor P.;Hagen E.;van der Sande F.;Klinger M.;Nowicki M.;Muszytowski M.;Bidas K.;Bentkowski W.;Wiecek A.;Ksiazek A.;Marczewski K.;Ostrowski M.;Switalski M.;Sulowicz W.;Matuszkiewicz-Rowinska J.;Mysliwiec M.;Durlik M.;Rutkowski B.;Macario F.;Carvalho B.;Frazao J.;Machado D.;Weigert A.;Andrusev A.;Khrustalev O.;Zemtchenkov A.;Gurevich K.;Staroselsky K.;Khadikova N.;Rozhinskaya L.;Timokhovskaya G.;Strokov A.;Balkarova O.;Ermolenko V.;Kolmakova E.;Komandenko M.;Timofeev M.;Shilo V.;Shostka G.;Smirnov A.;Anashkin V.;Volgina G.;Domashenko O.;Gurevich A.;Perlin D.;Martinez Garcia J.;Andres Ribes E.;Coll Piera E.;Fernandez Lucas M.;Galicia M.;Prados M.;Gonzalez M.;Romero R.;Martin de Francisco A.;Montenegro J.;Santiago C.;Garcia F.;Alcazar de La Ossa J.;Arrieta J.;Pons J.;Martin-Malo A.;Soler Amigo J.;Cases A.;Sterner G.;Jensen G.;Wikstrom B.;Jacobson S.;Lund U.;Weiss L.;Stahl A.;von Albertini B.;Burnier M.;Meier P.;Martin P.;Uehlinger D.;Dickenmann M.;Yaqoob M.;Zehnder D.;Kalra P.;Padmanabhan N.;Roe S.;Eadington D.;Pritchard N.;Hutchison A.;Davies S.;Wilkie M.;Davies M.;Pai P.;Swift P.;Kwan J.;Goldsmith D.;Tomson C.;Stratton J.;Dasgupta I.;Sarkar S.;Moustafa M.;Gandhi K.;Jamal A.;Galindo-Ramos E.;Tuazon J.;Batlle D.;Tucker K.;Schiller-Moran B.;Assefi A.;Martinez C.;Samuels L.;Goldman J.;Cangiano-Rivera J.;Darwish R.;Lee M.;Topf J.;Kapatkin K.;Baer H.;Kopelman R.;Acharya M.;Tharpe D.;Bernardo M.;Nader P.;Guzman-Rivera J.;Pergola P.;Sekkarie M.;Alas E.;Zager P.;Liss K.;Navarro J.;Roppolo M.;Denu-Ciocca C.;Kshirsagar A.;El Khatib M.;Kant K.;Scott D.;Murthyr B.;Finkelstein F.;Keightley G.;McCrary R.;Pitone J.;Cavalieri T.;Tsang A.;Pellegrino B.;Schmidt R.;Ahmad S.;Brown C.;Friedman E.;Mittman N.;Fadem S.;Shapiro W.;Reddy M.;Goldberger S.;Woredekal Y.;Agarwal A.;Anger M.;Haque M.;Chidester P.;Kohli R.;Rubinstein S.;Newman G.;Gladish R.;Ayodeji O.;Soman S.;Sprague S.;Hunt N.;Gehr T.;Rizk D.;Warnock D.;Polack D.;Pahl M.;Fischer D.;Dreyer P.;James G.;Husserl F.;Rogers T.;Raff A.;Sedor J.;Silver M.;Smith M.;Steinberg S.;DelGiorno T.;Jones E.;Cunha P. D.;Cheng J.;Pogue V.;Blumenthal S.;Brown E.;Charytan C.;Buerkert J.;Cook M.;Felsenfeld A.;Tareen N.;Gupta A.;Herman T.;Diamond S.;Hura C.;Laski M.;MacLaurin J.;Plumb T.;Brosnahan G.;Kumar J.;Henriquez M.;Poole C.;Osanloo E.;Matalon A.;Sholer C.;Arfeen S.;Azer M.;Belledonne M.;Gross M.;Dunnigan E.;McConnell K.;Becker B.;Skinner F.;Rigolosi R.;Spiegel D.;Stegman M.;Patak R.;Streja D.;Ranjit U.;Youell T.;Wooldridge T.;Stafford C.;Cottiero R.;Weinberg M.;Schonefeld M.;Shahmir E.;Hazzan A.;Ashfaq A.;Bhandari K.;Cleveland W.;Culpepper M.;Golden J.;Lai L.;Lien Y.;Lorica V.;Robertson J.;Malireddi K.;Morse S.;Thakur V.;Israelit A.;Raguram P.;Alfred H.;Weise W.;Al-Saghir F.;El Shahawy M.;Rastogi A.;Nissenson A.;Kopyt N.;Lynn R.;Lea J.;McClellan W.;Teredesai P.;Ong S.;Tolkan S.;Sugihara J.;Minga T.;Mehrotra R.;Minasian R.;Bhatia D.;Specter R.;Capelli J.;Sidhu P.;Dalal S.;Dykes P.;Khan M.;Rahim F.;Saklayen M.;Thomas A.;Michael B.;Torres M.;Al-Bander H.;Murray B.;Abukurah A.;Gupta B.;Nosrati S.;Raja R.;Zeig S.;Braun M.;Amatya A.;Endsley J.;Sharon Z.;Gupta A.;Dolson G.;Dumler F.;Ntoso K.;Rosansky S.;Kumar N.;Gura V.;Thompson N.;Goldfarb D.;Halligan R.;Middleton J.;Widerhorn A.;Arbeit L.;Arruda J.;Crouch T.;Friedman L.;Khokhar S.;Mittleman J.;Light P.;Taparia B.;West C.;Cotton J.;Dhingra R.;Kleinman L.;Arif F.;Lew S.;Nammour T.;Sterrett J.;Williams M.;Ramirez J.;Rubin J.;McCarthy J.;Noble S.;Chaffin M.;Rekhi A.

2015

Abstract

Background and objectives The calcimimetic cinacalcet reduced the risk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older (≥ 65 years, n=1005) and younger (<65 years, n=2878) patients. Design, setting, participants, & measurements Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified. ResultsOlder patients had higher baseline prevalence of diabetesmellitus and CV comorbidity. Annualized rates of kidney transplantation and parathyroidectomy were > 3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups. Conclusions In the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone.

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	Parole chiave
	
			CKD; cardiovascular disease; hemodialysis; hyperparathyroidism; mineral metabolism; Adult; Age Factors; Aged; Aged, 80 and over; Calcimimetic Agents; Cardiovascular Diseases; Cinacalcet; Female; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Parathyroidectomy; Renal Dialysis; Severity of Illness Index
		
	Settori scientifico-disciplinari dell'articolo
	
			Settore MED/14 - Nefrologia
		
	Data di pubblicazione
	
			2015
		
	Rivista in ANCE
	
			CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
		
	DOI
	
			https://dx.doi.org/10.2215/CJN.07730814
		
	Tipologia
	
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			01 - Articolo su periodico

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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/802498

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