BACKGROUND:
Disorders of mineral metabolism, including secondary hyperparathyroidism, are thought to contribute to extraskeletal (including vascular) calcification among patients with chronic kidney disease. It has been hypothesized that treatment with the calcimimetic agent cinacalcet might reduce the risk of death or nonfatal cardiovascular events in such patients.
METHODS:
In this clinical trial, we randomly assigned 3883 patients with moderate-to-severe secondary hyperparathyroidism (median level of intact parathyroid hormone, 693 pg per milliliter [10th to 90th percentile, 363 to 1694]) who were undergoing hemodialysis to receive either cinacalcet or placebo. All patients were eligible to receive conventional therapy, including phosphate binders, vitamin D sterols, or both. The patients were followed for up to 64 months. The primary composite end point was the time until death, myocardial infarction, hospitalization for unstable angina, heart failure, or a peripheral vascular event. The primary analysis was performed on the basis of the intention-to-treat principle.
RESULTS:
The median duration of study-drug exposure was 21.2 months in the cinacalcet group, versus 17.5 months in the placebo group. The primary composite end point was reached in 938 of 1948 patients (48.2%) in the cinacalcet group and 952 of 1935 patients (49.2%) in the placebo group (relative hazard in the cinacalcet group vs. the placebo group, 0.93; 95% confidence interval, 0.85 to 1.02; P=0.11). Hypocalcemia and gastrointestinal adverse events were significantly more frequent in patients receiving cinacalcet.
CONCLUSIONS:
In an unadjusted intention-to-treat analysis, cinacalcet did not significantly reduce the risk of death or major cardiovascular events in patients with moderate-to-severe secondary hyperparathyroidism who were undergoing dialysis. (Funded by Amgen; EVOLVE ClinicalTrials.gov number, NCT00345839.).
Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis / EVOLVE Trial, Investigators; Chertow, Gm; Block, Ga; Correa Rotter, R; Drüeke, Tb; Floege, J; Goodman, Wg; Herzog, Ca; Kubo, Y; London, Gm; Mahaffey, Kw; Mix, Tc; Moe, Sm; Trotman, Ml; Wheeler, Dc; Collaborators Chertow G, Parfrey P. S.; Parfrey, P; Block, G; Correa Rotter, R; Drüeke, T; Floege, J; Goodman, W; Herzog, C; London, G; Mahaffey, K; Moe, S; Wheeler, D; Hennekens, C; Baigent, C; Brown, W; O'Brien, P; Anderson, S; Hoel, J; Mahaffey, K; Szczech, L; Patel, U; Wampole, J; Pun, P; Felker, M; Inrig, J; Shah, S; Hernandez, A; Patel, C; Brennan, M; Albizem, M; Capper, E; Cauchi, L; Cheng, S; Dehmel, B; Dhami, K; Durham, C; Francioni, M; Gadd, S; Goodman, B; Guimaraes, L; Grey, N; Hamlin, R; Harris, C; Harris, E; Heavey, S; Heiges, T; Heiser, D; Jaeger, P; James, M; James, P; Karimi, S; Kewalramani, R; Kraszewski, A; Kubo, Y; Liang, J; Maguire, J; Mccormick, K; Mcfarlane, K; Mix, C; Modafferi, D; Prathikanti, R; Ryan, C; Santiago, N; Schumacher, J; Seder, C; Shahinfar, S; Soares, B; Stolman, D; Tisher, C; Trotman, M; Tseng, S; Ulias, G; Unger, P; Vyshenskaya, A; Walsh, L; White, C; Wilde, K; Santos, J; Zarazaga, C; Marin, I; Garrote, N; Cusumano, A; Penalba, N; Del Valle, E; Juncos, L; 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 Braun, 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; de Oliveira, J; Burdmann, E; Garcia, V; Thome, F; Deboni, L; Bregman, R; Lugon, J; Araújo, S; Ferreira Filho, S; Daher Ede, F; Baptista, M; Carvalho, A; D'Avila, D; Moyses Neto, M; Yu, L; Bastos, M; Lacativa, P; Jorgetti, V; Romão Ede, A; da Costa, Jc; Pecoits Filho, R; Gordan, P; Salgado, N; Araújo, M; Coelho, S; Oliveira, I; Moysés, R; Vasconcellos, L; Batista, P; 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; 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; Floege, J; Passauer, J; Hübel, E; Frischmuth, N; Liebl, R; Fiedler, R; Schwenger, V; Voßkühler, A; Kunzendorf, U; Renders, L; Rattensberger, D; Rump, L; Ketteler, M; Neumayer, H; Zantvoort, F; Stahl, R; Ladanyi, E; Braun, B; Kulcsar, I; Mezei, I; Csiky, B; Rikker, C; Arkossy, O; Berta, K; Braun, B; Szegedi, J; Major, L; Ferenczi, S; Fekete, A; Szabo, T; Zakar, G; Wagner, G; 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; Frascà, G; Cappelli, Gianni; 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; Correa Rotter, J; Verástegui, F; Peña, J; Wong, A; Cruz Valdez, J; Zamora, M; Solis, M; Diaz, M; Flores, M; Sandoval, E; van den Dorpel, M; Brink, H; Van Kuijk, W; Vermeij, C; 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; García, J; Ribes, E; Piera, E; Lucas, M; Galicia, M; Prados, M; González, M; Romero, R; de Francisco, Ám; Montenegro, J; Santiago, C; García, F; de La Ossa, J; Arrieta, J; Pons, J; Martín Malo, A; Amigó, J; Cases, A; Sterner, G; Jensen, G; Wikström, B; Jacobson, S; Lund, U; Weiss, L; Ståhl, A; von Albertini, B; Burnier, M; Meier, P; Martin, P; Uehlinger, D; Dickenmann, M; Yaqoob, M; Zehnder, D; Kalra, P; Wheeler, D; 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; Brown, C; 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; Cheng, J; Pogue, V; Block, G; 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; 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.. - In: THE NEW ENGLAND JOURNAL OF MEDICINE. - ISSN 0028-4793. - STAMPA. - 367:26(2012), pp. 2482-2494. [10.1056/NEJMoa1205624]
Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis
EVOLVE Trial Investigators; Chertow GM; Block GA; Correa Rotter R; Drüeke TB; Floege J; Goodman WG; Herzog CA; Kubo Y; London GM; Mahaffey KW; Mix TC; Moe SM; Trotman ML; Wheeler DC; Parfrey P.S. Collaborators Chertow G; Parfrey P; Block G; Correa Rotter R; Drüeke T; Floege J; Goodman W; Herzog C; London G; Mahaffey K; Moe S; Wheeler D; Hennekens C; Baigent C; Brown W; O'Brien P; Anderson S; Hoel J; Mahaffey K; Szczech L; Patel U; Wampole J; Pun P; Felker M; Inrig J; Shah S; Hernandez A; Patel C; Brennan M; Albizem M; Capper E; Cauchi L; Cheng S; Dehmel B; Dhami K; Durham C; Francioni M; Gadd S; Goodman B; Guimaraes L; Grey N; Hamlin R; Harris C; Harris E; Heavey S; Heiges T; Heiser D; Jaeger P; James M; James P; Karimi S; Kewalramani R; Kraszewski A; Kubo Y; Liang J; Maguire J; McCormick K; McFarlane K; Mix C; Modafferi D; Prathikanti R; Ryan C; Santiago N; Schumacher J; Seder C; Shahinfar S; Soares B; Stolman D; Tisher C; Trotman M; Tseng S; Ulias G; Unger P; Vyshenskaya A; Walsh L; White C; Wilde K; Santos J; Zarazaga C; Marin I; Garrote N; Cusumano A; Penalba N; Del Valle E; Juncos L; 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 Braun 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; de Oliveira J; Burdmann E; Garcia V; Thome F; Deboni L; Bregman R; Lugon J; Araújo S; Ferreira Filho S; Daher Ede F; Baptista M; Carvalho A; d'Avila D; Moyses Neto M; Yu L; Bastos M; Lacativa P; Jorgetti V; Romão Ede A; da Costa JC; Pecoits Filho R; Gordan P; Salgado N; Araújo M; Coelho S; Oliveira I; Moysés R; Vasconcellos L; Batista P; 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; 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; Floege J; Passauer J; Hübel E; Frischmuth N; Liebl R; Fiedler R; Schwenger V; Voßkühler A; Kunzendorf U; Renders L; Rattensberger D; Rump L; Ketteler M; Neumayer H; Zantvoort F; Stahl R; Ladanyi E; Braun B; Kulcsar I; Mezei I; Csiky B; Rikker C; Arkossy O; Berta K; Braun B; Szegedi J; Major L; Ferenczi S; Fekete A; Szabo T; Zakar G; Wagner G; 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; Frascà G; CAPPELLI, Gianni ;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; Correa Rotter J; Verástegui F; Peña J; Wong A; Cruz Valdez J; Zamora M; Solis M; Diaz M; Flores M; Sandoval E; van den Dorpel M; Brink H; Van Kuijk W; Vermeij C; 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; García J; Ribes E; Piera E; Lucas M; Galicia M; Prados M; González M; Romero R; de Francisco ÁM; Montenegro J; Santiago C; García F; de La Ossa J; Arrieta J; Pons J; Martín Malo A; Amigó J; Cases A; Sterner G; Jensen G; Wikström B; Jacobson S; Lund U; Weiss L; Ståhl A; von Albertini B; Burnier M; Meier P; Martin P; Uehlinger D; Dickenmann M; Yaqoob M; Zehnder D; Kalra P; Wheeler D; 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; Brown C; 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; Cheng J; Pogue V; Block G; 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; 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.
2012
Abstract
BACKGROUND:
Disorders of mineral metabolism, including secondary hyperparathyroidism, are thought to contribute to extraskeletal (including vascular) calcification among patients with chronic kidney disease. It has been hypothesized that treatment with the calcimimetic agent cinacalcet might reduce the risk of death or nonfatal cardiovascular events in such patients.
METHODS:
In this clinical trial, we randomly assigned 3883 patients with moderate-to-severe secondary hyperparathyroidism (median level of intact parathyroid hormone, 693 pg per milliliter [10th to 90th percentile, 363 to 1694]) who were undergoing hemodialysis to receive either cinacalcet or placebo. All patients were eligible to receive conventional therapy, including phosphate binders, vitamin D sterols, or both. The patients were followed for up to 64 months. The primary composite end point was the time until death, myocardial infarction, hospitalization for unstable angina, heart failure, or a peripheral vascular event. The primary analysis was performed on the basis of the intention-to-treat principle.
RESULTS:
The median duration of study-drug exposure was 21.2 months in the cinacalcet group, versus 17.5 months in the placebo group. The primary composite end point was reached in 938 of 1948 patients (48.2%) in the cinacalcet group and 952 of 1935 patients (49.2%) in the placebo group (relative hazard in the cinacalcet group vs. the placebo group, 0.93; 95% confidence interval, 0.85 to 1.02; P=0.11). Hypocalcemia and gastrointestinal adverse events were significantly more frequent in patients receiving cinacalcet.
CONCLUSIONS:
In an unadjusted intention-to-treat analysis, cinacalcet did not significantly reduce the risk of death or major cardiovascular events in patients with moderate-to-severe secondary hyperparathyroidism who were undergoing dialysis. (Funded by Amgen; EVOLVE ClinicalTrials.gov number, NCT00345839.).
Citazione
Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis / EVOLVE Trial, Investigators; Chertow, Gm; Block, Ga; Correa Rotter, R; Drüeke, Tb; Floege, J; Goodman, Wg; Herzog, Ca; Kubo, Y; London, Gm; Mahaffey, Kw; Mix, Tc; Moe, Sm; Trotman, Ml; Wheeler, Dc; Collaborators Chertow G, Parfrey P. 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[10.1056/NEJMoa1205624]
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