Spironolactone for heart failure with preserved ejection fraction
Bertram Pitt, Marc A Pfeffer, Susan F Assmann, Robin Boineau, Inder S Anand, Brian Claggett, Nadine Clausell, Akshay S Desai, Rafael Diaz, Jerome L Fleg, Ivan Gordeev, Brian Harty, John F Heitner, Christopher T Kenwood, Eldrin F Lewis, Eileen O'Meara, Jeffrey L Probstfield, Tamaz Shaburishvili, Sanjiv J Shah, Scott D Solomon, Nancy K Sweitzer, Song Yang, Sonja M McKinlay, TOPCAT Investigators, Inder Anand, Susan Assmann, Robin Boineau, Akshay Desai, Jerome Fleg, David Lathrop, Eldrin Lewis, Sonja McKinlay, Maureen Montrond, Marc Pfeffer, Bertram Pitt, Scott Solomon, George Sopko, Nancy Sweitzer, Song Yang, Inder Anand, Robin Boineau, Nadine Clausell, Jerome Fleg, Sonja McKinlay, Eileen O'Meara, Marc Pfeffer, Bertram Pitt, Sanjiv Shah, Scott Solomon, Nancy Sweitzer, Song Yang, Barry Massie, Milton Packer, Bertram Pitt, Sanjeev Saksena, Edward Shapiro, Michael Zile, Michael Bristow, Bernard Gersh, Christine Grady, Barry Greenberg, Madeline Rice, Steven Singh, Ebrahim Barkoudah, Peter V Finn, Jacob Joseph, Eldrin F Lewis, Kayode Odutayo, Anne-Catherine Pouleur, Robin Boineau, Jerome Fleg, George Sopko, Julianna Keleti, A Caccavo, L Cartasegna, J Cuello, C Cuneo, A Fernandez, E Hasbani, M Hominal, H Luciardi, L Marquez, J Sala, A Sanchez, D Santos, P Schygiel, C Zaidman, J Abdalla Saad, D Albuquerque, D Almeida, R Botelho, J Braga, N Clausell, E Manenti, L Moura, S Rassi, G Reis, J Saraiva, R Tadeu Tumelero, R Amyot, M Arnold, M Boulianne, R Brossoit, H Comtois, J DeYoung, A Diaz, D Dion, N Giannetti, G Gosselin, H Haddad, T Huynh, S Lepage, S Mansour, D Manyari, R McKelvie, G Moe, E O'Meara, G Proulx, M Rajda, D Rupka, E Sabbah, D Saulnier, F Sestier, R Sheppard, M Shibata, B Sussex, G Syan, P Talbot, S Vizel, J Warnica, S Zieroth, G Chapidze, V Chumburidze, N Emukhvari, B Kobulia, Z Lominadze, M Mamatsashvili, I Megreladze, K Paposhvili, T Shaburishvili, G Arutyunov, M Balluzek, O Barbarash, D Belenky, V Berezin, N Bessonova, S Bondarev, M Butomo, G Chumakova, A Dembitskaya, L Ermoshkina, A Esayan, A Filippov, M Giorgadze, B Goloshchekin, I Gordeev, N Gratsiansky, O Khrustalev, E Kosmacheva, V Kostenko, V Markov, S Martsevich, A Masin, S Nedogoda, O Orlikova, A Panov, N Pikalova, V Popov, V Popova, V Shalnev, N Shilkina, Y Shvarts, V Simanenkov, A Timofeev, G Usova, A Vishnevsky, P Adamson, A Adler, T Albert, R Alimard, A Altschuller, R Alvarez, M Amidi, I Anand, J Aranda, L Arcement, M Ariani, R Baliga, M Balk, S Banerjee, M Berk, N Bhalodkar, S Bilazarian, R Birkhead, J Bisognano, J Blair, H Bolukoglu, W Bommer, R Bonita, P Campbell, S Cansino, T Cappola, W Carter, C Chambers, H Chapel, E Chung, W Colucci, C Corder, R Davidson, P Deedwania, V Desai, A Desai, A Deswal, M Donahue, M Drazner, S Dunlap, M Dunlap, S Eckrich, J Ellis, R Engelmeier, J Fang, F Fein, J Felicetta, H Fesniak, D Fox, B Frandsen, J Furiasse, E Gillespie, B Gitler, M Goldschmidt, S Gottlieb, S Graham, F Gredler, M Greenberg, S Hankins, S Hearne, J Heitner, J Herre, S Hummel, C Hunter, S Hutchins, M Iacona, M Imburgia, J Islam, A Jansujwicz, F Johnson, M Kesselbrenner, A Kfoury, G Khera, W Khoury, D Kitzman, P Kosolcharoen, K Kurrelmeyer, E Lader, W Leimbach, G Mallis, P Marcovitz, F McGrew, W McKenzie, J McNamara, J Mehta, T Meyer, S Meymandi, K Miller, F Mody, V Nadar, A Naftilan, K Newman, T O'Brien, A Onwuanyi, R Oren, A Pavlides, E Popjes, R Prasad, K Ramanathan, P Ramappa, T Retta, A Riba, A Ross, J Ryan, M Saklayen, J Samaha, H Samar, D Seidensticker, S Shah, K Sheikh, D Singal, M Slawsky, R Small, P Sood, T Stamos, J Stehlik, N Sweitzer, J Tallaj, U Thadani, C Thaik, T Tolleson, L Tsao, H Ventura, D Villarreal, M Vossler, J Walia, M Walsh, N Wenger, M Widmer, M Yamani, Bertram Pitt, Marc A Pfeffer, Susan F Assmann, Robin Boineau, Inder S Anand, Brian Claggett, Nadine Clausell, Akshay S Desai, Rafael Diaz, Jerome L Fleg, Ivan Gordeev, Brian Harty, John F Heitner, Christopher T Kenwood, Eldrin F Lewis, Eileen O'Meara, Jeffrey L Probstfield, Tamaz Shaburishvili, Sanjiv J Shah, Scott D Solomon, Nancy K Sweitzer, Song Yang, Sonja M McKinlay, TOPCAT Investigators, Inder Anand, Susan Assmann, Robin Boineau, Akshay Desai, Jerome Fleg, David Lathrop, Eldrin Lewis, Sonja McKinlay, Maureen Montrond, Marc Pfeffer, Bertram Pitt, Scott Solomon, George Sopko, Nancy Sweitzer, Song Yang, Inder Anand, Robin Boineau, Nadine Clausell, Jerome Fleg, Sonja McKinlay, Eileen O'Meara, Marc Pfeffer, Bertram Pitt, Sanjiv Shah, Scott Solomon, Nancy Sweitzer, Song Yang, Barry Massie, Milton Packer, Bertram Pitt, Sanjeev Saksena, Edward Shapiro, Michael Zile, Michael Bristow, Bernard Gersh, Christine Grady, Barry Greenberg, Madeline Rice, Steven Singh, Ebrahim Barkoudah, Peter V Finn, Jacob Joseph, Eldrin F Lewis, Kayode Odutayo, Anne-Catherine Pouleur, Robin Boineau, Jerome Fleg, George Sopko, Julianna Keleti, A Caccavo, L Cartasegna, J Cuello, C Cuneo, A Fernandez, E Hasbani, M Hominal, H Luciardi, L Marquez, J Sala, A Sanchez, D Santos, P Schygiel, C Zaidman, J Abdalla Saad, D Albuquerque, D Almeida, R Botelho, J Braga, N Clausell, E Manenti, L Moura, S Rassi, G Reis, J Saraiva, R Tadeu Tumelero, R Amyot, M Arnold, M Boulianne, R Brossoit, H Comtois, J DeYoung, A Diaz, D Dion, N Giannetti, G Gosselin, H Haddad, T Huynh, S Lepage, S Mansour, D Manyari, R McKelvie, G Moe, E O'Meara, G Proulx, M Rajda, D Rupka, E Sabbah, D Saulnier, F Sestier, R Sheppard, M Shibata, B Sussex, G Syan, P Talbot, S Vizel, J Warnica, S Zieroth, G Chapidze, V Chumburidze, N Emukhvari, B Kobulia, Z Lominadze, M Mamatsashvili, I Megreladze, K Paposhvili, T Shaburishvili, G Arutyunov, M Balluzek, O Barbarash, D Belenky, V Berezin, N Bessonova, S Bondarev, M Butomo, G Chumakova, A Dembitskaya, L Ermoshkina, A Esayan, A Filippov, M Giorgadze, B Goloshchekin, I Gordeev, N Gratsiansky, O Khrustalev, E Kosmacheva, V Kostenko, V Markov, S Martsevich, A Masin, S Nedogoda, O Orlikova, A Panov, N Pikalova, V Popov, V Popova, V Shalnev, N Shilkina, Y Shvarts, V Simanenkov, A Timofeev, G Usova, A Vishnevsky, P Adamson, A Adler, T Albert, R Alimard, A Altschuller, R Alvarez, M Amidi, I Anand, J Aranda, L Arcement, M Ariani, R Baliga, M Balk, S Banerjee, M Berk, N Bhalodkar, S Bilazarian, R Birkhead, J Bisognano, J Blair, H Bolukoglu, W Bommer, R Bonita, P Campbell, S Cansino, T Cappola, W Carter, C Chambers, H Chapel, E Chung, W Colucci, C Corder, R Davidson, P Deedwania, V Desai, A Desai, A Deswal, M Donahue, M Drazner, S Dunlap, M Dunlap, S Eckrich, J Ellis, R Engelmeier, J Fang, F Fein, J Felicetta, H Fesniak, D Fox, B Frandsen, J Furiasse, E Gillespie, B Gitler, M Goldschmidt, S Gottlieb, S Graham, F Gredler, M Greenberg, S Hankins, S Hearne, J Heitner, J Herre, S Hummel, C Hunter, S Hutchins, M Iacona, M Imburgia, J Islam, A Jansujwicz, F Johnson, M Kesselbrenner, A Kfoury, G Khera, W Khoury, D Kitzman, P Kosolcharoen, K Kurrelmeyer, E Lader, W Leimbach, G Mallis, P Marcovitz, F McGrew, W McKenzie, J McNamara, J Mehta, T Meyer, S Meymandi, K Miller, F Mody, V Nadar, A Naftilan, K Newman, T O'Brien, A Onwuanyi, R Oren, A Pavlides, E Popjes, R Prasad, K Ramanathan, P Ramappa, T Retta, A Riba, A Ross, J Ryan, M Saklayen, J Samaha, H Samar, D Seidensticker, S Shah, K Sheikh, D Singal, M Slawsky, R Small, P Sood, T Stamos, J Stehlik, N Sweitzer, J Tallaj, U Thadani, C Thaik, T Tolleson, L Tsao, H Ventura, D Villarreal, M Vossler, J Walia, M Walsh, N Wenger, M Widmer, M Yamani
Abstract
Background: Mineralocorticoid-receptor antagonists improve the prognosis for patients with heart failure and a reduced left ventricular ejection fraction. We evaluated the effects of spironolactone in patients with heart failure and a preserved left ventricular ejection fraction.
Methods: In this randomized, double-blind trial, we assigned 3445 patients with symptomatic heart failure and a left ventricular ejection fraction of 45% or more to receive either spironolactone (15 to 45 mg daily) or placebo. The primary outcome was a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure.
Results: With a mean follow-up of 3.3 years, the primary outcome occurred in 320 of 1722 patients in the spironolactone group (18.6%) and 351 of 1723 patients in the placebo group (20.4%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.77 to 1.04; P=0.14). Of the components of the primary outcome, only hospitalization for heart failure had a significantly lower incidence in the spironolactone group than in the placebo group (206 patients [12.0%] vs. 245 patients [14.2%]; hazard ratio, 0.83; 95% CI, 0.69 to 0.99, P=0.04). Neither total deaths nor hospitalizations for any reason were significantly reduced by spironolactone. Treatment with spironolactone was associated with increased serum creatinine levels and a doubling of the rate of hyperkalemia (18.7%, vs. 9.1% in the placebo group) but reduced hypokalemia. With frequent monitoring, there were no significant differences in the incidence of serious adverse events, a serum creatinine level of 3.0 mg per deciliter (265 μmol per liter) or higher, or dialysis.
Conclusions: In patients with heart failure and a preserved ejection fraction, treatment with spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. (Funded by the National Heart, Lung, and Blood Institute; TOPCAT ClinicalTrials.gov number, NCT00094302.).
Source: PubMed