351. Empagliflozin and Cerebrovascular Events in Patients With Type 2 Diabetes Mellitus at High Cardiovascular Risk
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Zinman, Bernard, Inzucchi, Silvio E., Lachin, John M., Wanner, Christoph, Fitchett, David, Kohler, Sven, Mattheus, Michaela, Biomath, Dipl, Woerle, Hans J., Broedl, Uli C., Johansen, Odd Erik, Albers, Gregory W., Diener, Hans Christoph, Aizenberg, D., Ulla, M., Waitman, J., De Loredo, L., Farias, J., Fideleff, H., Lagrutta, M., Maldonado, N., Colombo, H., Ferre Pacora, F., Wasserman, A., Maffei, L., Lehman, R., Selvanayagam, J., d'Emden, M., Fasching, P., Paulweber, B., Toplak, H., Luger, A., Drexel, H., Prager, R., Schnack, C., Schernthaner, G., Fliesser-Goerzer, E., Kaser, S., Scheen, A., Van Gaal, L., Hollanders, G., Kockaerts, Y., Capiau, L., Chachati, A., Persu, A., Hermans, M., Vantroyen, D., Vercammen, C., Van de Borne, P., Mathieu, C., Benhalima, K., Lienart, F., Mortelmans, J., Strivay, M., Vereecken, G., Keymeulen, B., Lamkanfi, F., Chacra, A., Eliaschewitz, F., Zanella, M., Faludi, A., Bertolami, M., Hayashida, C., Nunes Salles, J., Monte, O., Dinato, M., Manenti, E., Rassi, N., Halpern, A., Lima Filho, M., Ayoub, J., Felicio, J., Borges, J., Gross, J., Sgarbi, J., Betti, R., Tiburcio, A., Purisch, S., Schmid, H., Takahashi, M., Castro, M., Rea, R., Hissa, M., Geloneze Neto, B., Saraiva, J., Henein, S., Lochnan, H., Imran, S. A., Clayton, D., Bayly, K., Berlingieri, J., Boucher, P., Chan, Y., Gupta, M., Chehayeb, R., Ouellett, A., Ur, E., Woo, V., Zinman, B., St Amour, E., Terront Lozano, M., Yupanqui Lozno, H., Urina, M., Lopez Jaramillo, P., Jaramillo, N., Sanchez, G., Perez, G., Tusek, S., Mirosevic, G., Goldoni, V., Jurisic-Erzen, D., Balasko, A., Balic, S., Drvodelic-Sunic, E., Varzic, S. Canecki, Machkova, M., Weiner, P., Lastuvka, J., Olsovsky, J., Krarup, T., Ridderstrale, M., Tarnow, L., Boesgaard, T. Wellov, Lihn, A. Saetre, Christensen, P., Juhl, H., Urhammer, S., Lund, P., Adojaan, B., Jakovlev, U., Lanno, R., Lubi, M., Marandi, T., Gouet, D., Courreges, J., Zaoui, P., Choukroun, G., Petit, C., Formagne, L., Estour, B., Mabire, P., Daugenet, C., Lemarie, B., Clavel, S., Aure, P., Remaud, P., Halimi, J., Hadjadj, S., Couffinhal, T., Glonti, S., Metreveli, D., Lominadze, Z., Giorgadze, E., Burtchuladze, T., Javashvili, L., Kurashvili, G., Kurashvili, R., Virsaladze, D., Nadareishvili, L., Khomasuridze, A., Cahill, T., Green, F., MacRury, S., Waldron, M., Middleton, A., McKnight, J., Pearson, E., Butler, M., Choksi, M., Caldwell, I., Farmer, I., Wyatt, N., Patrick, J., O'Brien, I., Devers, M., Bousboulas, S., Pappas, S., Piaditis, G., Vryonidou, A., Tentolouris, N., Karamitsos, K., Manes, C., Benroubi, M., Avramidis, I., Ozaki, R., Tan, K., Siu, S., Tsang, C., Dudas, M., Nagy, K., Salamon, C., Ip, T., Geroo, L., Patkay, J., Tabak, A., Juhasz, F., Szentpeteri, I., Tamas, G., Ghaisas, N., Bantwal, G., Mohan, V., Gupta, J., Sadhu, N., Kulkarni, A., Garg, N., Reddy, S., Deshpande, N., Gutlapalli, K., Pillai, M., Premchand, R., Badgandi, M., Jain, S., Aravind, S., Shamanna, P., Pandey, A., Gupta, S., Pramono, B., Saksono, H. Dante, Agung, P., Wahono, S. Djoko, Suastika, K., Tanggo, Y., Juwana, Y., Siswanto, B., Adawi, F., Efrati, S., Mazen, E., Bashkin, A., Herskovits, T., Jaffe, A., Schiff, E., Wainstein, J., Taddei, S., Aiello, A., Arca, M., Calabro, P., Cignarelli, M., Fioretto, P., Reggiani, G. Marchesini, Gnasso, A., Marchionni, N., Marsilii, A., Bucci, M., Mezzetti, A., Pozzilli, P., Colivicchi, F., Santini, M., Moro, E., Toscano, V., Fucili, A., Semplicini, A., Monno, S., Furui, K., Higashiue, S., Hiramatsu, N., Kawamitsu, K., Takenaka, T., Takahashi, H., Hojo, F., Onishi, Y., Izumino, K., Okubo, M., Wakida, Y., Kondo, Y., Hieshima, K., Jinnouchi, H., Suzuki, A., Ito, M., Park, S., Kim, Y., Hong, T., Park, H., Gwon, H., Kim, H., Kang, K., Jeong, M., Seung, K., Lim, D., Rha, S., Tahk, S., Yang, J., Yoon, J., Shin, M., Kim, D., Jeong, J., Ahmad, N. Nik, Mustafa, N., Mohamed, W. Wan, Fung, Y., Ghani, R. Abdul, Chandramouli, A., Chee, K., Kadir, K. Abdul, Ling, K., Abu Hassan, M., Foo, S., Lee, S., Garcia Hernandez, P., Aguilar-Salinas, C., Vidrio Velazquez, M., Flores, F., Alpizar Salazar, M., Micher Escalante, D., Garcia Soria, M., Cardona Munoz, E., Storms, G., Schaper, N., Kooy, A., Krekels, M., van Bemmel, T., Verhoeven, R., Mulder, H., Oldenburg-Ligtenberg, P., Gonkel, F., de Jong, A., van Soest, J., Viergever, P., Mevissen, H., Lochorn, G., Zwiers, G., Hoogslag, P., Ronner, E., Nierop, P., Al-Windy, N., Kragten, J., Dekelver, P., Benatar, J., Krebs, J., Scott, R., Heggen, E., Berz, A., Fossum, C., Hurtig, U., Langslet, G., Baranowski, M., Sparby, J., Karlsson, T., Karlsson, Thomas, Delgado Torres, C., Rodriguez Escudero, A., Lisson, R., Allemant Maldonado, A., Gallardo Rojas, W., Gonzales Bravo, L., Lema Osores, J., Farfan, J., Zapata, L., Godoy Junchaya, J., Roldan Concha, Y., Urquiaga Calderon, J., Sy, R., Tan, G., Aquitania, G., De Los Santos, G., Panelo, A., Roderos, O., Rosales, R., Toledo, R., Liwag, A., Ramoncito, H., Skokowska, E., Krzyzagorska, E., Ogorek, M., Wojnowski, L., Spyra, J., Konieczny, M., Piesiewicz, W., Kus, W., Ocicka-Kozakiewicz, A., Orlowska-Kunikowska, E., Zmuda, W., Duarte, S., Leitao, A., Monteiro, P., Rita, H., Salgado, V., Pinto, L., Queiros, J., Teixeira, J., Rogado, C., Duarte, R., Sobral do Rosario, F., Silva, A., Andrade, L., Velez, M., Brazao, M., Istratoaie, O., Lichiardopol, R., Catrinoiu, D., Militaru, C., Zetu, C., Barbonta, D., Cosma, D., Crisan, C., Pop, L., Esip, V., Khetagurova, F., Petrov, A., Arutyunov, G., Boyarkin, M., Agafyina, A., Vorokhobina, N., Petunina, N., Libov, I., Zalevskaya, A., Nikolaev, K., Barbarash, O., Potemkin, V., Bystrova, A., Krasilnikova, E., Barbarich, V., Chumakova, G., Tarasov, N., Meleshkevich, T., Zateyshchikov, D., Lantseva, O., Belenkiy, D., Obrezan, A., Rossolko, L., Fillipova, E., Yakhontova, P., Khokhlov, A., Tan, R., Sum, C., Chang, H., Distiller, L., Pretorius, M., Nortje, H., Mitha, E., Burgess, L., Blignaut, S., Venter, T., Moodley, R., Lombaard, J., Govind, U., Naidoo, V., Mookadam, M., Engelbrecht, J., Omar, M., Jurgens, J., Podgorski, G., Vawda, H., Naidoo, D., Emanuel, S., Roodt, A., Amod, A., Van Zyl, L., Segura, J., Brito, M., Fernandez-Cruz, A., Artola, S., Iglesias, R., Toural, E., Garcia-Ortiz, L., Saban, J., Mesa, J., Vidal, J., Linares, J., del Canizo, F., Rigla, M., Suarez, C., Llorente, I., Moreno, B., Antoli, A., Gomez Peralta, F., Iglesias, M., Pereg, V., de Teresa, L., Camafort, M., Trescoli, C., Satarasinghe, R., Somasundaram, N., Siyambalapitiya, S., Antonypillai, C., Bulugahapitiya, D., Medagama, U., Huang, C., Lu, Y., Hwang, J., Chiang, C., Wen, M., Chen, J., Lai, W., Chang, K., Wang, J., Yeh, H., Kriangsak, P., Deerochanawong, C., Suwanwalaikorn, S., Mangklabruks, A., Kaewsuwanna, P., Piyayotai, D., Iabluchanskyi, M., Samoylov, O., Godlevska, O., Kovalyova, O., Voloshyna, O., Tseluyko, V., Zotov, S., Vykhovanyuk, I., Dulgeroff, A., Mayfield, R., Zaniewski-Singh, M., Ullal, J., Aloi, J., De La Rosa, R., Mosely, J., Wittmer, B., Aronoff, S., Rosenfeld, J., Seidner, M., Warren, M., Fishman, N., Weiss, R., Arif, A., Sandberg, M., Lewis, D., Ball, E., Graf, R., Breton, C., Tamayo, R., Richards, R., Cefalu, W., Uwaifo, G., Zayour, D., Hoffman, J., Fitz-Patrick, D., Khan, B., Blaze, K., Bressler, P., Halpern, S., Chappell, D., Bergenstal, R., Cuddihy, R., Matfin, G., Freedman, Z., Gonzalez-Campoy, J., Lerman, S., Rendell, M., Sitar, S., Reeves, M., Howard, T., Soufer, J., Miranda-Palma, B., Laliotis, A., Shomali, M., Teltser, M., Hurley, D., Morawski, E., Cherlin, R., Houchin, V., Welch, M., Goytia-Leos, D., Syed, M., Kowaloff, E., Weinrauch, L., Peniston, J., Brockmyre, A., First, B., Feld, L., Huffman, D., Nassim, O., Gottschlich, G., Patel, A., Knopke, C., Hernandez, M., Diaz, J., Giugliano, G., Nicasio, J., Eagerton, D., Huntley, R., Reed, J., III, Magee, M., Hippert, R., Sofley, C., Jr., Alzohaili, O., Levins, P., Anspach, R., Shah, S., Brusco, O., Naidu, J., Lindenbaum, J., Jacks, R., Hammond, G., Arena, C., Saxman, K., Mach, M., Kerstein, H., Kereiakes, D., Wahlen, J., Wehmeier, K., Chaykin, L., Rothman, J., Fogelfeld, L., Stroger, John H., Jr., Bittar, N., Rosenstock, J., Kayne, D., Navarro, J., Colfer, H., Mokshagundam, S., Shandilya, L., Connery, L., Wysham, C., Dela Llana, A., Jardula, M., MacAdams, M., Flippo, G., Heurich, E., Curtis, C., Sanders, D., Rawls, R., Velazquez, F., Osea, E., Mahood, K., Feldman, G., Eder, F., Riley, E., Fowler, W., Jain, M., Shepard, M., Schear, M., Barker, B., Strout, C., Obiekwe, O., Shanik, M., Green, C., Blakney, E., Roberson, K., Bretton, E., Pish, R., Kaveh, K., Maynard, B., Barager, W., Soldyshev, R., Austin, B., Parmar, P., Simpson, R., Chauhan, A., Kasper, J., Burr, R., Patel, N., Mariano, H., Pluto, T., Bratcher, C., Juarez, M., Levinson, L., Awad, A., Longshaw, K., Hoffman, K., Richwine, R., Molter, D., Boscia, J., III, Kowalyk, S., Lemis, P., Liss, J., Orr, R., Riser, J., Wood, J., Ubani, A., Paine, W., Hassani, F., Miranda, F., Hansen, V., Hansen, Val R., Farris, N., Bowden, R., Ajani, D., Maw, K., Andersen, J., Bergman, B., Dunmyer, S., Brandon, D., Anderson, M., Bononi, P., Prawer, J., Seidman, B., Cruz, H., Wilks, K., DiSanto, L., Buynak, R., Christensen, T., Denker, P., Koppel, W., Stedman, M., Lewy-Alterbaum, L., Karim, S., Shapiro, J., Gardner, T., Oskin, T., Gabra, N., Malano, J., and EMPA REG OUTCOME Investigators
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riesgo ,compuestos de bencidrilo ,type 2 diabetes mellitus ,Original Contributions ,humanos ,Medizin ,030204 cardiovascular system & hematology ,blood pressure ,cardiovascular diseases ,hematocrit ,stroke ,0302 clinical medicine ,Glucosides ,glucósidos ,030212 general & internal medicine ,Myocardial infarction ,Stroke ,mediana edad ,anciano ,OUTCOMES ,Hazard ratio ,Middle Aged ,ISCHEMIC-STROKE ,Anesthesia ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Cardiology ,TRIAL ,Cardiology and Cardiovascular Medicine ,Life Sciences & Biomedicine ,Risk ,medicine.medical_specialty ,Clinical Sciences ,enfermedades cardiovasculares ,Clinical Neurology ,Placebo ,03 medical and health sciences ,Outcome Assessment (Health Care) ,Internal medicine ,medicine ,Empagliflozin ,Diabetes Mellitus ,Humans ,Hypoglycemic Agents ,accidente cerebrovascular ,Benzhydryl Compounds ,METAANALYSIS ,Aged ,Advanced and Specialized Nursing ,Science & Technology ,business.industry ,MORTALITY ,Type 2 Diabetes Mellitus ,medicine.disease ,Confidence interval ,Blood pressure ,hipoglicemiantes ,Peripheral Vascular Disease ,evaluación de resultados (asistencia sanitaria) ,Cardiovascular System & Cardiology ,Neurology (clinical) ,Neurosciences & Neurology ,business ,FOLLOW-UP - Abstract
Supplemental Digital Content is available in the text., Background and Purpose— In the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients), empagliflozin added to standard of care in patients with type 2 diabetes mellitus and high cardiovascular risk reduced the risk of 3-point major adverse cardiovascular events, driven by a reduction in cardiovascular mortality, with no significant difference between empagliflozin and placebo in risk of myocardial infarction or stroke. In a modified intent-to-treat analysis, the hazard ratio for stroke was 1.18 (95% confidence interval, 0.89–1.56; P=0.26). We further investigated cerebrovascular events. Methods— Patients were randomized to empagliflozin 10 mg, empagliflozin 25 mg, or placebo; 7020 patients were treated. Median observation time was 3.1 years. Results— The numeric difference in stroke between empagliflozin and placebo in the modified intent-to-treat analysis was primarily because of 18 patients in the empagliflozin group with a first event >90 days after last intake of study drug (versus 3 on placebo). In a sensitivity analysis based on events during treatment or ≤90 days after last dose of drug, the hazard ratio for stroke with empagliflozin versus placebo was 1.08 (95% confidence interval, 0.81–1.45; P=0.60). There were no differences in risk of recurrent, fatal, or disabling strokes, or transient ischemic attack, with empagliflozin versus placebo. Patients with the largest increases in hematocrit or largest decreases in systolic blood pressure did not have an increased risk of stroke. Conclusions— In patients with type 2 diabetes mellitus and high cardiovascular risk, there was no significant difference in the risk of cerebrovascular events with empagliflozin versus placebo. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01131676.
- Published
- 2017