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2. Concordance between clinical outcomes in the Systolic Blood Pressure Intervention Trial and in the electronic health record.

Author

Beddhu, Srinivasan, Powell, James, Suarez, Maritza, Lash, James, McWilliams, Andrew, Whelton, Paul, Drawz, Paul, Pajewski, Nicholas, Ishani, Areef, Tuot, Delphine, Lenoir, Kristin, Rai, Nayanjot, Soman, Sandeep, Dwyer, Jamie, Rocco, Michael, Chu, Chi, and Agarwal, Anil

Subjects
Cardiovascular outcomes, Electronic health record, Outcome ascertainment, Pragmatic trial, Aged, Female, Humans, Male, Acute Coronary Syndrome, Antihypertensive Agents, Blood Pressure, Cardiovascular Diseases, Electronic Health Records, Heart Failure, Hypertension, Myocardial Infarction, Stroke, Treatment Outcome
Abstract

BACKGROUND: Randomized trials are the gold standard for generating clinical practice evidence, but follow-up and outcome ascertainment are resource-intensive. Electronic health record (EHR) data from routine care can be a cost-effective means of follow-up, but concordance with trial-ascertained outcomes is less well-studied. METHODS: We linked EHR and trial data for participants of the Systolic Blood Pressure Intervention Trial (SPRINT), a randomized trial comparing intensive and standard blood pressure targets. Among participants with available EHR data concurrent to trial-ascertained outcomes, we calculated sensitivity, specificity, positive predictive value, and negative predictive value for EHR-recorded cardiovascular disease (CVD) events, using the gold standard of SPRINT-adjudicated outcomes (myocardial infarction (MI)/acute coronary syndrome (ACS), heart failure, stroke, and composite CVD events). We additionally compared the incidence of non-CVD adverse events (hyponatremia, hypernatremia, hypokalemia, hyperkalemia, bradycardia, and hypotension) in trial versus EHR data. RESULTS: 2468 SPRINT participants were included (mean age 68 (SD 9) years; 26% female). EHR data demonstrated ≥80% sensitivity and specificity, and ≥ 99% negative predictive value for MI/ACS, heart failure, stroke, and composite CVD events. Positive predictive value ranged from 26% (95% CI; 16%, 38%) for heart failure to 52% (95% CI; 37%, 67%) for MI/ACS. EHR data uniformly identified more non-CVD adverse events and higher incidence rates compared with trial ascertainment. CONCLUSIONS: These results support a role for EHR data collection in clinical trials, particularly for capturing laboratory-based adverse events. EHR data may be an efficient source for CVD outcome ascertainment, though there is clear benefit from adjudication to avoid false positives.

Published
2023

5. Effect of Intensive versus Standard BP Control on AKI and Subsequent Cardiovascular Outcomes and Mortality: Findings from the SPRINT EHR Study.

Author

Drawz, Paul, Rai, Nayanjot, Lenoir, Kristin, Suarez, Maritza, Powell, James, Raj, Dominic, Beddhu, Srinivasan, Agarwal, Anil, Soman, Sandeep, Whelton, Paul, Lash, James, Rahbari-Oskoui, Frederic, Dobre, Mirela, Parkulo, Mark, Rocco, Michael, McWilliams, Andrew, Dwyer, Jamie, Thomas, George, Rahman, Mahboob, Oparil, Suzanne, Horwitz, Edward, Pajewski, Nicholas, and Ishani, Areef

Subjects
acute kidney injury, cardiovascular disease, hypertension, mortality, Acute Kidney Injury, Antihypertensive Agents, Blood Pressure, Cardiovascular Diseases, Creatinine, Electronic Health Records, Humans, Hypertension, Risk Factors, Treatment Outcome
Abstract

BACKGROUND: Adjudication of inpatient AKI in the Systolic Blood Pressure Intervention Trial (SPRINT) was based on billing codes and admission and discharge notes. The purpose of this study was to evaluate the effect of intensive versus standard BP control on creatinine-based inpatient and outpatient AKI, and whether AKI was associated with cardiovascular disease (CVD) and mortality. METHODS: We linked electronic health record (EHR) data from 47 clinic sites with trial data to enable creatinine-based adjudication of AKI. Cox regression was used to evaluate the effect of intensive BP control on the incidence of AKI, and the relationship between incident AKI and CVD and all-cause mortality. RESULTS: A total of 3644 participants had linked EHR data. A greater number of inpatient AKI events were identified using EHR data (187 on intensive versus 155 on standard treatment) as compared with serious adverse event (SAE) adjudication in the trial (95 on intensive versus 61 on standard treatment). Intensive treatment increased risk for SPRINT-adjudicated inpatient AKI (HR, 1.51; 95% CI, 1.09 to 2.08) and for creatinine-based outpatient AKI (HR, 1.40; 95% CI, 1.15 to 1.70), but not for creatinine-based inpatient AKI (HR, 1.20; 95% CI, 0.97 to 1.48). Irrespective of the definition (SAE or creatinine based), AKI was associated with increased risk for all-cause mortality, but only creatinine-based inpatient AKI was associated with increased risk for CVD. CONCLUSIONS: Creatinine-based ascertainment of AKI, enabled by EHR data, may be more sensitive and less biased than traditional SAE adjudication. Identifying ways to prevent AKI may reduce mortality further in the setting of intensive BP control.

Published
2022

6. Effect of Intensive Blood Pressure Control on Kidney Outcomes: Long-Term Electronic Health Record–Based Post-Trial Follow-Up of SPRINT

Author

Drawz, Paul E., Lenoir, Kristin M., Rai, Nayanjot Kaur, Rastogi, Anjay, Chu, Chi D., Rahbari-Oskoui, Frederic F., Whelton, Paul K., Thomas, George, McWilliams, Andrew, Agarwal, Anil K., Suarez, Maritza Marie, Dobre, Mirela, Powell, James, Rocco, Michael V., Lash, James P., Oparil, Suzanne, Raj, Dominic S., Dwyer, Jamie P., Rahman, Mahboob, Soman, Sandeep, Townsend, Raymond R., Pemu, Priscilla, Horwitz, Edward, Ix, Joachim H., Tuot, Delphine S., Ishani, Areef, and Pajewski, Nicholas M.

Published
2024
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7. Health Informatics Educational Offerings through ALA-Accredited LIS Programs

Author

Raszewski, Rebecca, Dwyer, Jamie, and Griffin, Tina

Abstract

Librarians who pursue a health sciences librarianship career may need an understanding of health informatics for their work with health-care professionals. Health sciences librarianship courses and degrees are available in most American Library Association (ALA)-accredited library and information science (LIS) programs, but health informatics educational offerings within LIS programs have not been previously examined in the LIS literature. ALA-accredited programs' websites were examined to determine the availability of health sciences librarianship and health informatics educational offerings (e.g., courses, degrees) because ALA accreditation is a globally recognized accreditation standard. The institutions' Carnegie Classifications and their programs' iSchools statuses were also included in the analysis for benchmarking purposes. LIS programs may use the data from this study for benchmarking against other programs to compare their programs to peers, if there are gaps in their educational offerings, or to examine opportunities for expanding their current health informatics educational offerings and meet professional competencies.

Published
2019

13. A pre-specified analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) randomized controlled trial on the incidence of abrupt declines in kidney function

Author

Heerspink, Hiddo J.L., Wheeler, David C., Chertow, Glenn, Correa-Rotter, Ricardo, Greene, Tom, Hou, Fan Fan, McMurray, John, Rossing, Peter, Toto, Robert, Stefansson, Bergur, Langkilde, Anna Maria, Maffei, L.E., Raffaele, P., Solis, S.E., Arias, C.A., Aizenberg, D., Luquez, C., Zaidman, C., Cluigt, N., Mayer, M., Alvarisqueta, A., Wassermann, A., Maldonado, R., Bittar, J., Maurich, M., Gaite, L.E., Garcia, N., Sivak, L., Ramallo, P.O., Santos, J.C., Garcia Duran, R., Oddino, J.A., Maranon, A., Maia, L.N., Avila, D.D., Barros, E.J.G., Vidotti, M.H., Panarotto, D., Noronha, I.D.L., Turatti, L.A.A., Deboni, L., Canziani, M.E., Riella, M.C., Bacci, M.R., Paschoalin, R.P., Franco, R.J., Goldani, J.C., St-Amour, E., Steele, A.W., Goldenberg, R., Pandeya, S., Bajaj, H., Cherney, D., Kaiser, S.M., Conway, J.R., Chow, S.S., Bailey, G., Lafrance, J., Winterstein, J., Cournoyer, S., Gaudet, D., Madore, F., Houlden, R.L., Dowell, A., Langlois, M., Muirhead, N., Khandwala, H., Levin, A., Hou, F., Xue, Y., Zuo, L., Hao, C., Ni, Z., Xing, C., Chen, N., Dong, Y., Zhou, R., Xiao, X., Zou, Y., Wang, C., Liu, B., Chen, Q., Lin, M., Luo, Q., Zhang, D., Wang, J., Chen, M., Wang, X., Zhong, A., Dong, J., Zhu, C., Yan, T., Luo, P., Ren, Y., Pai, P., Li, D., Zhang, R., Zhang, J., Xu, M., Zhuang, Y., Kong, Y., Yao, X., Peng, X., Persson, F.I., Hansen, T.K., Borg, R., Pedersen Bjergaard, U., Hansen, D., Hornum, M., Haller, H., Klausmann, G., Tschope, D., Kruger, T., Gross, P., Hugo, C., Obermuller, N., Rose, L., Mertens, P., Zeller-Stefan, H., Fritsche, A., Renders, L., Muller, J., Budde, K., Schroppel, B., Wittmann, I., Voros, P., Dudas, M., Tabak, G.A., Kirschner, R., Letoha, A., Balku, I., Hermanyi, Z., Zakar, G., Mezei, I., Nagy, G.G., Lippai, J., Nemeth, A., Khullar, D., Gowdaiah, P.K., Fernando Mervin, E., Rao, V.A., Dewan, D., Goplani, K., Maddi, V.S.K., Vyawahare, M.S., Pulichikkat, R.K., Pandey, R., Sonkar, S.K., Gupta, V.K., Agarwal, S., Asirvatham, A.J., Ignatius, A., Chaubey, S., Melemadathil, S., Alva, H., Kadam, Y., Shimizu, H., Sueyoshi, A., Takeoka, H., Abe, Y., Imai, T., Onishi, Y., Fujita, Y., Tokita, Y., Oura, M., Makita, Y., Idogaki, A., Koyama, R., Kikuchi, H., Kashihara, N., Hayashi, T., Ando, Y., Tanaka, T., Shimizu, M., Hidaka, S., Gohda, T., Tamura, K., Abe, M., Kamijo, Y., Imasawa, T., Takahashi, Y., Nakayama, M., Tomita, M., Hirano, F., Fukushima, Y., Kiyosue, A., Kurioka, S., Imai, E., Kitagawa, K., Waki, M., Wada, J., Uehara, K., Iwatani, H., Ota, K., Shibazaki, S., Katayama, K., Narita, I., Iinuma, M., Matsueda, S., Sasaki, S., Yokochi, A., Tsukamoto, T., Yoshimura, T., Kang, S., Lee, S., Lim, C.S., Chin, H., Joo, K.W., Han, S.Y., Chang, T.I., Park, S., Park, H., Park, C.W., Han, B.G., Cha, D.R., Yoon, S.A., Kim, W., Kim, S.W., Ryu, D., Correa Rotter, R., Irizar Santana, S.S., Hernandez Llamas, G., Valdez Ortiz, R., Secchi Nicolas, N.C., Gonzalez Galvez, G., Lazcano Soto, J.R., Bochicchio Riccardelli, T., Bayram Llamas, E.A., Ramos Ibarra, D.R., Melo, M.G.S., Gonzalez Gonzalez, J.G., Sanchez Mijangos, J.H., Madero Robalo, M., Garcia Castillo, A., Manrique, H.A., Farfan, J.C., Vargas, R., Valdivia, A., Dextre, A., Escudero, E., Calderon Ticona, J.R., Gonzales, L., Villena, J., Leon, L., Molina, G., Saavedra, A., Garrido, E., Arbanil, H., Vargas Marquez, S., Rodriguez, J., Isidto, R., Villaflor, A.J., Gumba, M.A., Tirador, L., Comia, R.S., Sy, R.A., Guanzon, M.L.V.V., Aquitania, G., De Asis, N.C., Silva, A.A., Romero, C.M., Lim, M.E., Danguilan, R.A., Nowicki, M., Rudzki, H., Landa, K., Kucharczyk-Bauman, I., Gogola-Migdal, B., Golski, M., Olech-Cudzik, A., Stompor, T., Szczepanik, T., Miklaszewicz, B., Sciborski, R., Kuzniewski, M., Ciechanowski, K., Wronska, D., Klatko, W., Mazur, S., Popenda, G., Myslicki, M., Bolieva, L.Z., Berns, S., Galyavich, A., Abissova, T., Karpova, I., Platonov, D., Koziolova, N., Kvitkova, L., Nilk, R., Medina, T., Rebrov, A., Rossovskaya, M., Sinitsina, I., Vishneva, E., Zagidullin, N., Novikova, T., Krasnopeeva, N., Magnitskaya, O., Antropenko, N., Batiushin, M., Escudero Quesada, V., Barrios Barrea, C., Espinel Garauz, E., Cruzado Garrit, J.M., Morales Portillo, C., Gorriz Teruel, J.L., Cigarran Guldris, S., Praga Terente, M., Robles Perez-Monteoliva, N.R., Tinahones Madueno, F.J., Soto Gonzalez, A., Diaz Rodriguez, C., Furuland, H., Saeed, A., Dreja, K., Spaak, J., Bruchfeld, A., Kolesnyk, M., Levchenko, O., Pyvovarova, N., Stus, V., Doretskyy, V., Korobova, N., Horoshko, O., Katerenchuk, I., Mostovoy, Y.M., Orynchak, M., Legun, O., Dudar, I., Bilchenko, O., Andreychyn, S., Levchenko, A., Zub, L., Tereshchenko, N., Topchii, I., Ostapenko, T., Bezuglova, S., Kopytsya, M., Turenko, O., Mark, P., Barratt, J., Bhandari, S., Fraser, D., Kalra, P., Kon, S.P., Mccafferty, K., Mikhail, A., Alvarado, O.P., Anderson, R., Andrawis, N.S., Arif, A., Benjamin, S.A., Bueso, G., Busch, R.S., Carr, K.W., Crawford, P., Daboul, N., De La Calle, G.M., Delgado, B., Earl, J., El-Shahawy, M.A., Graf, R.J., Greenwood, G., Guevara, A., Wendland, E.M., Mayfield, R.K., Montero, M., Morin, D.J., Narayan, P., Numrungroad, V., Reddy, A.C., Reddy, R., Samson, M.B., Trejo, R., Butcher, M.B., Wise, J.K., Zemel, L.R., Raikhel, M., Weinstein, D., Hernandez, P., Wynne, A., Khan, B.V., Sterba, G.A., Jamal, A., Ross, D., Rovner, S.F., Tan, A., Ovalle, F., Patel, R.J., Talano, J., Patel, D.R., Burgner, A., Aslam, N., Elliott, M., Goral, S., Jovanovich, A., Manley, J.A., Umanath, K., Waguespack, D., Weiner, D., Yu, M., Schneider, L., Jalal, D., Le, T., Nguyen, N., Nguyen, H., Nguyen, D., Nguyen, V., Do, T., Chu, P., Ta, D., Tran, N., Pham, B., Pfeffer, Marc A., Pocock, Stuart, Swedberg, Karl, Rouleau, Jean L., Chaturvedi, Nishi, Ivanovich, Peter, Levey, Andrew S., Christ-Schmidt, Heidi, Held, Claes, Christersson, Christina, Mann, Johannes, Varenhorst, Christoph, Cherney, David, Postmus, Douwe, Stefánsson, Bergur V., Chertow, Glenn M., Dwyer, Jamie P., Kosiborod, Mikhail, McMurray, John J.V., Sjöström, C. David, and Toto, Robert D.

Published
2022
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14. Improving the prognosis of patients with severely decreased glomerular filtration rate (CKD G4+): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Author

Eckardt, Kai-Uwe, Bansal, Nisha, Coresh, Josef, Evans, Marie, Grams, Morgan E, Herzog, Charles A, James, Matthew T, Heerspink, Hiddo JL, Pollock, Carol A, Stevens, Paul E, Tamura, Manjula Kurella, Tonelli, Marcello A, Wheeler, David C, Winkelmayer, Wolfgang C, Cheung, Michael, Hemmelgarn, Brenda R, Participants, Conference, Abu-Alfa, Ali K, Anand, Shuchi, Arici, Mustafa, Ballew, Shoshana H, Block, Geoffrey A, Burgos-Calderon, Rafael, Charytan, David M, Das-Gupta, Zofia, Dwyer, Jamie P, Fliser, Danilo, Froissart, Marc, Gill, John S, Griffith, Kathryn E, Harris, David C, Huffman, Kate, Inker, Lesley A, Jager, Kitty J, Jun, Min, Kalantar-Zadeh, Kamyar, Kasiske, Bertrand L, Kovesdy, Csaba P, Krane, Vera, Lamb, Edmund J, Lerma, Edgar V, Levey, Andrew S, Levin, Adeera, Mauro, Juan Carlos Julián, Nash, Danielle M, Navaneethan, Sankar D, O’Donoghue, Donal, Obrador, Gregorio T, Pecoits-Filho, Roberto, Robinson, Bruce M, Schäffner, Elke, Segev, Dorry L, Stengel, Bénédicte, Stenvinkel, Peter, Tangri, Navdeep, Tentori, Francesca, Tsukamoto, Yusuke, Turakhia, Mintu P, Vazquez, Miguel A, Wang, Angela Yee-Moon, and Williams, Amy W

Subjects
Heart Disease, Cardiovascular, Clinical Research, Kidney Disease, Management of diseases and conditions, 7.3 Management and decision making, Renal and urogenital, Good Health and Well Being, Clinical Decision-Making, Consensus, Evidence-Based Medicine, Glomerular Filtration Rate, Humans, Kidney, Nephrology, Prognosis, Renal Insufficiency, Chronic, Risk Factors, Severity of Illness Index, chronic kidney disease, kidney failure, prediction, prognosis, progression, supportive care, Conference Participants, Clinical Sciences, Urology & Nephrology
Abstract

Patients with severely decreased glomerular filtration rate (GFR) (i.e., chronic kidney disease [CKD] G4+) are at increased risk for kidney failure, cardiovascular disease (CVD) events (including heart failure), and death. However, little is known about the variability of outcomes and optimal therapeutic strategies, including initiation of kidney replacement therapy (KRT). Kidney Disease: Improving Global Outcomes (KDIGO) organized a Controversies Conference with an international expert group in December 2016 to address this gap in knowledge. In collaboration with the CKD Prognosis Consortium (CKD-PC) a global meta-analysis of cohort studies (n = 264,515 individuals with CKD G4+) was conducted to better understand the timing of clinical outcomes in patients with CKD G4+ and risk factors for different outcomes. The results confirmed the prognostic value of traditional CVD risk factors in individuals with severely decreased GFR, although the risk estimates vary for kidney and CVD outcomes. A 2- and 4-year model of the probability and timing of kidney failure requiring KRT was also developed. The implications of these findings for patient management were discussed in the context of published evidence under 4 key themes: management of CKD G4+, diagnostic and therapeutic challenges of heart failure, shared decision-making, and optimization of clinical trials in CKD G4+ patients. Participants concluded that variable prognosis of patients with advanced CKD mandates individualized, risk-based management, factoring in competing risks and patient preferences.

Published
2018

15. WCN24-1766 EFFECTS OF DAPAGLIFLOZIN IN PATIENTS WITH MEMBRANOUS NEPHROPATHY

Author

Heerspink, Hiddo J.L., primary, Wheeler, David C., additional, Correa-Rotter, Ricardo, additional, Dwyer, Jamie P., additional, Langkilde, Anna Maria, additional, Mark, Patrick B., additional, Nowicki, Michal, additional, Rossing, Peter, additional, Toto, Robert D., additional, Chertow, Glenn M., additional, and Jongs, Niels, additional

Published
2024
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16. Age-stratified and blood-pressure-stratified effects of blood-pressure-lowering pharmacotherapy for the prevention of cardiovascular disease and death: an individual participant-level data meta-analysis

Author

Rahimi, Kazem, Bidel, Zeinab, Nazarzadeh, Milad, Copland, Emma, Canoy, Dexter, Wamil, Malgorzata, Majert, Jeannette, McManus, Richard, Adler, Amanda, Agodoa, Larry, Algra, Ale, Asselbergs, Folkert W, Beckett, Nigel S, Berge, Eivind, Black, Henry, Boersma, Eric, Brouwers, Frank P J, Brown, Morris, Brugts, Jasper J, Bulpitt, Christopher J, Byington, Robert P, Cushman, William C, Cutler, Jeffrey, Devereaux, Richard B, Dwyer, Jamie P, Estacio, Ray, Fagard, Robert, Fox, Kim, Fukui, Tsuguya, Gupta, Ajay K, Holman, Rury R, Imai, Yutaka, Ishii, Masao, Julius, Stevo, Kanno, Yoshihiko, Kjeldsen, Sverre E, Kostis, John, Kuramoto, Kizuku, Lanke, Jan, Lewis, Edmund, Lewis, Julia B, Lievre, Michel, Lindholm, Lars H, Lueders, Stephan, MacMahon, Stephen, Mancia, Giuseppe, Matsuzaki, Masunori, Mehlum, Maria H, Nissen, Steven, Ogawa, Hiroshi, Ogihara, Toshio, Ohkubo, Takayoshi, Palmer, Christopher R, Patel, Anushka, Pfeffer, Marc Allan, Pitt, Bertram, Poulter, Neil R, Rakugi, Hiromi, Reboldi, Gianpaolo, Reid, Christopher, Remuzzi, Giuseppe, Ruggenenti, Piero, Saruta, Takao, Schrader, Joachim, Schrier, Robert, Sever, Peter, Sleight, Peter, Staessen, Jan A, Suzuki, Hiromichi, Thijs, Lutgarde, Ueshima, Kenji, Umemoto, Seiji, van Gilst, Wiek H, Verdecchia, Paolo, Wachtell, Kristian, Whelton, Paul, Wing, Lindon, Woodward, Mark, Yui, Yoshiki, Yusuf, Salim, Zanchetti, Alberto, Zhang, Zhen-Yu, Anderson, Craig, Baigent, Colin, Brenner, Barry Morton, Collins, Rory, de Zeeuw, Dick, Lubsen, Jacobus, Malacco, Ettore, Neal, Bruce, Perkovic, Vlado, Rodgers, Anthony, Rothwell, Peter, Salimi-Khorshidi, Gholamreza, Sundström, Johan, Turnbull, Fiona, Viberti, Giancarlo, Wang, Jiguang, Chalmers, John, Davis, Barry R, Pepine, Carl J, and Teo, Koon K

Published
2021
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18. Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARE–TIMI 58 randomised trial

Author

Mosenzon, Ofri, Wiviott, Stephen D, Cahn, Avivit, Rozenberg, Aliza, Yanuv, Ilan, Goodrich, Erica L, Murphy, Sabina A, Heerspink, Hiddo J L, Zelniker, Thomas A, Dwyer, Jamie P, Bhatt, Deepak L, Leiter, Lawrence A, McGuire, Darren K, Wilding, John P H, Kato, Eri T, Gause-Nilsson, Ingrid A M, Fredriksson, Martin, Johansson, Peter A, Langkilde, Anna Maria, Sabatine, Marc S, and Raz, Itamar

Published
2019
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20. Efficacy and safety of zibotentan and dapagliflozin in patients with chronic kidney disease: study design and baseline characteristics of the ZENITH-CKD trial.

Author

Heerspink, Hiddo J L, Greasley, Peter J, Ahlström, Christine, Althage, Magnus, Dwyer, Jamie P, Law, Gordon, Wijkmark, Emma, Lin, Min, Mercier, Anne-Kristina, Sunnåker, Mikael, Turton, Michelle, Wheeler, David C, and Ambery, Philip

Subjects
CHRONIC kidney failure, EMPAGLIFLOZIN, DAPAGLIFLOZIN, CHRONICALLY ill, SAFETY, GLOMERULAR filtration rate, TYPE 2 diabetes
Abstract

Background Sodium–glucose co-transporter 2 inhibitors (SGLT2is) are part of the standard of care for patients with chronic kidney disease (CKD), both with and without type 2 diabetes. Endothelin A (ETA) receptor antagonists have also been shown to slow progression of CKD. Differing mechanisms of action of SGLT2 and ETA receptor antagonists may enhance efficacy. We outline a study to evaluate the effect of combination zibotentan/dapagliflozin versus dapagliflozin alone on albuminuria and estimated glomerular filtration rate (eGFR). Methods We are conducting a double-blind, active-controlled, Phase 2b study to evaluate the efficacy and safety of ETA receptor antagonist zibotentan and SGLT2i dapagliflozin in a planned 415 adults with CKD (Zibotentan and Dapagliflozin for the Treatment of CKD; ZENITH-CKD). Participants are being randomized (1:2:2) to zibotentan 0.25 mg/dapagliflozin 10 mg once daily (QD), zibotentan 1.5 mg/dapagliflozin 10 mg QD and dapagliflozin 10 mg QD alone, for 12 weeks followed by a 2-week off-treatment wash-out period. The primary endpoint is the change in log-transformed urinary albumin-to-creatinine ratio (UACR) from baseline to Week 12. Other outcomes include change in blood pressure from baseline to Week 12 and change in eGFR the study. The incidence of adverse events will be monitored. Study protocol–defined events of special interest include changes in fluid-related measures (weight gain or B-type natriuretic peptide). Results A total of 447 patients were randomized and received treatment in placebo/dapagliflozin (n  = 177), zibotentan 0.25 mg/dapagliflozin (n  = 91) and zibotentan 1.5 mg/dapagliflozin (n  =  179). The mean age was 62.8 years, 30.9% were female and 68.2% were white. At baseline, the mean eGFR of the enrolled population was 46.7 mL/min/1.73 m2 and the geometric mean UACR was 538.3 mg/g. Conclusion This study evaluates the UACR-lowering efficacy and safety of zibotentan with dapagliflozin as a potential new treatment for CKD. The study will provide information about an effective and safe zibotentan dose to be further investigated in a Phase 3 clinical outcome trial. Clinical Trial Registration Number NCT04724837 [ABSTRACT FROM AUTHOR]

Published
2024
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22. Risk Assessment of Kidney Disease Progression and Efficacy of SGLT2 inhibition in Patients with Type 2 Diabetes

Author

Moura, Filipe A., primary, Berg, David D., primary, Bellavia, Andrea, primary, Dwyer, Jamie P., primary, Mosenzon, Ofri, primary, A. Scirica, Benjamin, primary, Wiviott, Stephen D., primary, Bhatt, Deepak L., primary, Raz, Itamar, primary, Feinberg, Mark W., primary, Braunwald, Eugene, primary, Morrow, David A., primary, and Sabatine, Marc S., primary

Published
2023
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24. Decentralized Clinical Trials in the Trial Innovation Network: Value, Strategies, and Lessons Learned

Author

Hanley, Daniel F., primary, Bernard, Gordon R., additional, Wilkins, Consuelo H., additional, Selker, Harry P., additional, Dwyer, Jamie P., additional, Dean, J. Michael, additional, Benjamin, Daniel Kelly, additional, Dunsmore, Sarah E., additional, Waddy, Salina P., additional, Wiley, Kenneth L., additional, Palm, Marisha E., additional, Mould, W. Andrew, additional, Ford, Daniel F., additional, Burr, Jeri S., additional, Huvane, Jacqueline, additional, Lane, Karen, additional, Poole, Lori, additional, Edwards, Terri L., additional, Kennedy, Nan, additional, Boone, Leslie R., additional, Bell, Jasmine, additional, Serdoz, Emily, additional, Byrne, Loretta M., additional, and Harris, Paul A., additional

Published
2023
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25. Medical Costs in Patients with Hyperkalemia on Long-Term Sodium Zirconium Cyclosilicate Therapy: The RECOGNIZE II Study

Author

Agiro,Abiy, Dwyer,Jamie P, Oluwatosin,Yemisi, Desai,Pooja, Agiro,Abiy, Dwyer,Jamie P, Oluwatosin,Yemisi, and Desai,Pooja

Abstract

Abiy Agiro,1 Jamie P Dwyer,2 Yemisi Oluwatosin,3 Pooja Desai3 1US Evidence, US Medical Affairs, AstraZeneca, Wilmington, DE, USA; 2Department of Internal Medicine, University of Utah Health, Salt Lake City, UT, USA; 3US Renal, US Medical Affairs, AstraZeneca, Wilmington, DE, USACorrespondence: Abiy Agiro, AstraZeneca, US Medical Affairs, 1800 Concord Pike, Wilmington, DE, 19850, USA, Tel +1 302-886-1898, Email abiy.agiro@astrazeneca.comPurpose: Hyperkalemia, defined as abnormally high serum potassium levels of ≥ 5.1 mmol/L, is associated with increased medical costs. This real-world study evaluated the impact of long-term sodium zirconium cyclosilicate (SZC) therapy on medical costs in patients with hyperkalemia.Patients and Methods: This retrospective, comparative study used claims data from IQVIA PharMetrics® Plus. Patients aged ≥ 18 years with hyperkalemia who had outpatient SZC fills (> 3-month supply over 6 months) between July 2019 and December 2021 and continuous insurance coverage 6 months before and 6 months after the first SZC fill were included. These patients (SZC cohort) were 1:1 exact- and propensity score-matched on baseline variables with patients with hyperkalemia who did not receive SZC (non-SZC cohort). The primary endpoint was hyperkalemia-related medical costs to payers over 6 months.Results: Each cohort included 661 matched patients. Mean per-patient hyperkalemia-related medical costs were reduced by 49.5% ($3728.47) for the SZC versus non-SZC cohort ($3798.04 vs $7526.51; P< 0.001), whereas mean all-cause medical costs were reduced by 21.0% ($5492.20; $20,722.23 vs $26,214.43; P< 0.01). A 39.8% ($3621.03) increase in all-cause pharmacy costs ($12,727.20 vs $9106.17; P< 0.01) was offset by the medical cost savings.Conclusion: This study demonstrated that long-term (> 3 months) outpatient treatment with SZC was associated with medical cost savings compared with no SZC therapy. Plain Langua

Published
2023

27. Change in Albuminuria and GFR Slope as Joint Surrogate End Points for Kidney Failure: Implications for Phase 2 Clinical Trials in CKD

Author

Heerspink, Hiddo J.L., Inker, Lesley A., Tighiouart, Hocine, Collier, Willem H., Haaland, Benjamin, Luo, Jiyu, Appel, Gerald B., Chan, Tak Mao, Estacio, Raymond O., Fervenza, Fernando, Floege, Jürgen, Imai, Enyu, Jafar, Tazeen H., Lewis, Julia B., Kam-Tao Li, Philip, Locatelli, Francesco, Maes, Bart D., Perna, Annalisa, Perrone, Ronald D., Praga, Manuel, Schena, Francesco P., Wanner, Christoph, Xie, Di, Greene, Tom, Schrier, Robert W., Hanratty, Rebecca, Maschio, Giuseppe, Carlo, Manno, Saddelli, Mauro, Brenner, Barry M., Lewis, Edmund, von Eynatten, Maximilian, de Jong, Paul E., van Essen, GG, Hou, Fan Fan, Chapman, Arlene, Torres, Vicente, Yu, Alan, Brosnahan, Godela, Chow, Kai-Ming, Szeto, Cheuk-Chun, Leung, Chi-Bon, Hunsicker, Lawrence G., Dwyer, Jamie, Pohl, Marc, Raz, Itamar, Del Vecchio, Lucia, Andrulli, Simeone, Pozzi, Claudio, Casartelli, Donatella, Malfait, Thomas, Vanacker, An, Caravaca-Fontán, Fernando, Trujillo, Hernando, Cavero, Teresa, Gutierrez, Eduardo, Beck, Gerald, Kusek, John, Eknoyan, Garabed, Ponticelli, Claudio, Montagnino, Giuseppe, Passerini, Patrizia, Moroni, Gabriella, Kobayashi, Fumiaki, Makino, Hirofumi, Ito, Sadayoshi, Chan, Juliana CN, Tang, Colin, Gaspari, Flavio, Lesti, Maria Domenica, Gherardi, Giulia, Gamba, Sara, Keane, William, Donadio, James, Rauen, Thomas, Seikrit, Claudia, Wied, Stefanie, Dwyer, Jamie, and Becker, Gavin J.

Published
2023
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28. Risk Assessment of Kidney Disease Progression and Efficacy of SGLT2 Inhibition in Patients With Type 2 Diabetes.

Author

Moura, Filipe A., Berg, David D., Bellavia, Andrea, Dwyer, Jamie P., Mosenzon, Ofri, Scirica, Benjamin M., Wiviott, Stephen D., Bhatt, Deepak L., Raz, Itamar, Feinberg, Mark W., Braunwald, Eugene, Morrow, David A., and Sabatine, Marc S.

Subjects
DISEASE risk factors, DAPAGLIFLOZIN, CANAGLIFLOZIN, TYPE 2 diabetes, DISEASE progression, CHRONIC kidney failure, SYSTOLIC blood pressure
Abstract

OBJECTIVE: To develop a risk assessment tool to identify patients with type 2 diabetes (T2D) at higher risk for kidney disease progression and who might benefit more from sodium–glucose cotransporter 2 (SGLT2) inhibition. RESEARCH DESIGN AND METHODS: A total of 41,204 patients with T2D from four Thrombolysis In Myocardial Infarction (TIMI) clinical trials were divided into derivation (70%) and validation cohorts (30%). Candidate predictors of kidney disease progression (composite of sustained ≥40% decline in estimated glomerular filtration rate [eGFR], end-stage kidney disease, or kidney death) were selected with multivariable Cox regression. Efficacy of dapagliflozin was assessed by risk categories (low: <0.5%; intermediate: 0.5 to <2%; high: ≥2%) in Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58. RESULTS: There were 695 events over a median follow-up of 2.4 years. The final model comprised eight independent predictors of kidney disease progression: atherosclerotic cardiovascular disease, heart failure, systolic blood pressure, T2D duration, glycated hemoglobin, eGFR, urine albumin-to-creatinine ratio, and hemoglobin. The c-indices were 0.798 (95% CI, 0.774–0.821) and 0.798 (95% CI, 0.765–0.831) in the derivation and validation cohort, respectively. The calibration plot slope (deciles of predicted vs. observed risk) was 0.98 (95% CI, 0.93–1.04) in the validation cohort. Whereas relative risk reductions with dapagliflozin did not differ across risk categories, there was greater absolute risk reduction in patients with higher baseline risk, with a 3.5% absolute risk reduction in kidney disease progression at 4 years in the highest risk group (≥1%/year). Results were similar with the 2022 Chronic Kidney Disease Prognosis Consortium risk prediction model. CONCLUSIONS: Risk models for kidney disease progression can be applied in patients with T2D to stratify risk and identify those who experience a greater magnitude of benefit from SGLT2 inhibition. [ABSTRACT FROM AUTHOR]

Published
2023
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29. The Trial Innovation Network Liaison Team: building a national clinical and translational community of practice

Author

Palm, Marisha E., primary, Thompson, Dixie D., additional, Edwards, Terri, additional, Swartz, Kitt, additional, Herzog, Keith A., additional, Bansal, Shweta, additional, Echalier, Benjamin, additional, DeHart, Kristen Clasen, additional, Denmark, Signe, additional, Wilson, Jurran L., additional, Nelson, Sarah, additional, Waddy, Salina P., additional, Dunsmore, Sarah E., additional, Atkinson, Jane C., additional, Wiley, Ken, additional, Hassani, Sara, additional, Dwyer, Jamie P., additional, Hanley, Daniel F., additional, Dean, J. Michael, additional, and Ford, Daniel E., additional

Published
2023
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30. Development, implementation, and dissemination of operational innovations across the trial innovation network

Author

Palm, Marisha E., primary, Edwards, Terri L., additional, Wieber, Cortney, additional, Kay, Marie T., additional, Marion, Eve, additional, Boone, Leslie, additional, Nanni, Angeline, additional, Jones, Michelle, additional, Pham, Eilene, additional, Hildreth, Meghan, additional, Lane, Karen, additional, McBee, Nichol, additional, Benjamin, Daniel K., additional, Bernard, Gordon R., additional, Dean, J. Michael, additional, Dwyer, Jamie P., additional, Ford, Daniel E., additional, Hanley, Daniel F., additional, Harris, Paul A., additional, Wilkins, Consuelo H., additional, and Selker, Harry P., additional

Published
2023
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31. The Phosphate Binder Ferric Citrate and Mineral Metabolism and Inflammatory Markers in Maintenance Dialysis Patients: Results From Prespecified Analyses of a Randomized Clinical Trial

Author

Van Buren, Peter N., Lewis, Julia B., Dwyer, Jamie P., Greene, Tom, Middleton, John, Sika, Mohammed, Umanath, Kausik, Abraham, Josephine D., Arfeen, Shahabul S., Bowline, Isai G., Chernin, Gil, Fadem, Stephen Z., Goral, Simin, Koury, Mark, Sinsakul, Marvin V., and Weiner, Daniel E.

Published
2015
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34. Dapagliflozin and prevention of kidney disease among patients with type 2 diabetes– post hoc analyses from the DECLARE-TIMI 58 trial

Author

Mosenzon, Ofri, primary, Raz, Itamar, primary, Wiviott, Stephen D., primary, Schechter, Meir, primary, Goodrich, Erica L., primary, Yanuv, Ilan, primary, Rozenberg, Aliza, primary, Murphy, Sabina A., primary, Zelniker, Thomas A., primary, Langkilde, Anna Maria, primary, Gause-Nilsson, Ingrid A.M., primary, Fredriksson, Martin, primary, Johansson, Peter A., primary, Wilding, John P.H., primary, McGuire, Darren K., primary, Bhatt, Deepak L., primary, Leiter, Lawrence A., primary, Cahn, Avivit, primary, Dwyer, Jamie P., primary, Heerspink, Hiddo J.L., primary, and Sabatine, Marc S., primary

Published
2022
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35. Kidney Disease, Hypertension Treatment, and Cerebral Perfusion and Structure

Author

Kurella Tamura, Manjula, primary, Gaussoin, Sarah, additional, Pajewski, Nicholas M., additional, Zaharchuk, Greg, additional, Freedman, Barry I., additional, Rapp, Stephen R., additional, Auchus, Alexander P., additional, Haley, William E., additional, Oparil, Suzanne, additional, Kendrick, Jessica, additional, Roumie, Christianne L., additional, Beddhu, Srinivasan, additional, Cheung, Alfred K., additional, Williamson, Jeff D., additional, Detre, John A., additional, Dolui, Sudipto, additional, Bryan, R. Nick, additional, Nasrallah, Ilya M., additional, Whelton, Paul, additional, Johnson, Karen C., additional, Snyder, Joni, additional, Bild, Diane, additional, Bonds, Denise, additional, Cook, Nakela, additional, Cutler, Jeffrey, additional, Fine, Lawrence, additional, Kaufmann, Peter, additional, Kimmel, Paul, additional, Launer, Lenore, additional, Moy, Claudia, additional, Riley, William, additional, Ryan, Laurie, additional, Tolunay, Eser, additional, Yang, Song, additional, Reboussin, David, additional, Williamson, Jeff, additional, Ambrosius, Walter T., additional, Applegate, William, additional, Evans, Greg, additional, Foy, Capri, additional, Kitzman, Dalane, additional, Lyles, Mary, additional, Pajewski, Nick, additional, Rapp, Steve, additional, Rushing, Scott, additional, Shah, Neel, additional, Sink, Kaycee M., additional, Vitolins, Mara, additional, Wagenknecht, Lynne, additional, Wilson, Valerie, additional, Perdue, Letitia, additional, Woolard, Nancy, additional, Craven, Tim, additional, Garcia, Katelyn, additional, Lovato, Laura, additional, Newman, Jill, additional, Lovato, James, additional, Lu, Lingyi, additional, McLouth, Chris, additional, Russell, Greg, additional, Amoroso, Bobby, additional, Davis, Patty, additional, Griffin, Jason, additional, Harris, Darrin, additional, King, Mark, additional, Lane, Kathy, additional, Roberson, Wes, additional, Steinberg, Debbie, additional, Ashford, Donna, additional, Babcock, Phyllis, additional, Chamberlain, Dana, additional, Christensen, Vickie, additional, Cloud, Loretta, additional, Collins, Christy, additional, Cook, Delilah, additional, Currie, Katherine, additional, Felton, Debbie, additional, Harpe, Stacy, additional, Howard, Marjorie, additional, Lewis, Michelle, additional, Nance, Pamela, additional, Puccinelli-Ortega, Nicole, additional, Russell, Laurie, additional, Walker, Jennifer, additional, Craven, Brenda, additional, Goode, Candace, additional, Troxler, Margie, additional, Davis, Janet, additional, Hutchens, Sarah, additional, Killeen, Anthony A., additional, Lukkari, Anna M., additional, Ringer, Robert, additional, Dillard, Brandi, additional, Archibeque, Norbert, additional, Warren, Stuart, additional, Sather, Mike, additional, Pontzer, James, additional, Taylor, Zach, additional, Soliman, Elsayed Z., additional, Zhang, Zhu-Ming, additional, Li, Yabing, additional, Campbell, Chuck, additional, Hensley, Susan, additional, Hu, Julie, additional, Keasler, Lisa, additional, Barr, Mary, additional, Taylor, Tonya, additional, Davatzikos, Christos, additional, Nasarallah, Ilya, additional, Desiderio, Lisa, additional, Elliott, Mark, additional, Borthakur, Ari, additional, Battapady, Harsha, additional, Erus, Guray, additional, Smith, Alex, additional, Wang, Ze, additional, Doshi, Jimit, additional, Wright, Jackson T., additional, Rahman, Mahboob, additional, Lerner, Alan J., additional, Still, Carolyn, additional, Wiggers, Alan, additional, Zamanian, Sara, additional, Bee, Alberta, additional, Dancie, Renee, additional, Thomas, George, additional, Schreiber, Martin, additional, Navaneethan, Sankar Dass, additional, Hickner, John, additional, Lioudis, Michael, additional, Lard, Michelle, additional, Marczewski, Susan, additional, Maraschky, Jennifer, additional, Colman, Martha, additional, Aaby, Andrea, additional, Payne, Stacey, additional, Ramos, Melanie, additional, Horner, Carol, additional, Drawz, Paul, additional, Raghavendra, Pratibha P., additional, Ober, Scott, additional, Mourad, Ronda, additional, Pallaki, Muralidhar, additional, Russo, Peter, additional, Raghavendra, Pratibha, additional, Fantauzzo, Pual, additional, Tucker, Lisa, additional, Schwing, Bill, additional, Sedor, John R., additional, Horwitz, Edward J., additional, Schellling, Jeffrey R., additional, O’Toole, John F., additional, Humbert, Lisa, additional, Tutolo, Wendy, additional, White, Suzanne, additional, Gay, Alishea, additional, Clark, Walter, additional, Hughes, Robin, additional, Dobre, Mirela, additional, Still, Carolyn H., additional, Williams, Monique, additional, Bhatt, Udayan, additional, Hebert, Lee, additional, Agarwal, Anil, additional, Murphy, Melissa Brown, additional, Ford, Nicole, additional, Stratton, Cynthia, additional, Baxter, Jody, additional, Lykins, Alicia A., additional, McKinley Neal Leena Hirmath, Alison, additional, Kwame, Osei, additional, Soe, Kyaw, additional, Miser, William F., additional, Sagrilla, Colleen, additional, Johnston, Jan, additional, Anaya, Amber, additional, Mintos, Ashley, additional, Howell, Angel A., additional, Rogers, Kelly, additional, Taylor, Sara, additional, Ebersbacher, Donald, additional, Long, Lucy, additional, Bednarchik, Beth, additional, Schnall, Adrian, additional, Smith, Jonathan, additional, Peysha, Lori, additional, Leach, Lisa, additional, Tribout, Megan, additional, Harwell, Carla, additional, Ellington, Pinkie, additional, Banerji, Mary Ann, additional, Ghody, Pranav, additional, Rambaud, Melissa Vahídeh, additional, Townsend, Raymond, additional, Cohen, Debbie, additional, Huan, Yonghong, additional, Duckworth, Mark, additional, Ford, Virginia, additional, Leshner, Juliet, additional, Davison, Ann, additional, Veen, Sarah Vander, additional, Gadegbeku, Crystal A., additional, Gillespie, Avi, additional, Paranjape, Anuradha, additional, Amoroso, Sandra, additional, Pfeffer, Zoe, additional, Quinn, Sally B., additional, He, Jiang, additional, Chen, Jing, additional, Lustigova, Eva, additional, Malone, Erin, additional, Krousel-Wood, Marie, additional, Deichmann, Richard, additional, Ronney, Patricia, additional, Muery, Susan, additional, Trapani, Donnalee, additional, Rocco, Michael, additional, Goff, David, additional, Rodriguez, Carlos, additional, Coker, Laura, additional, Hawfield, Amret, additional, Yeboah, Joseph, additional, Crago, Lenore, additional, Summerson, John, additional, Hege, Anita, additional, Diamond, Matt, additional, Mulloy, Laura, additional, Hodges, Marcela, additional, Collins, Michelle, additional, Weathers, Charlene, additional, Anderson, Heather, additional, Stone, Emily, additional, Walker, Walida, additional, McWilliams, Andrew, additional, Dulin, Michael, additional, Kuhn, Lindsay, additional, Standridge, Susan, additional, Lowe, Lindsay, additional, Everett, Kelly, additional, Preston, Kelry, additional, Norton, Susan, additional, Gaines, Silena, additional, Rizvi, Ali A., additional, Sides, Andrew W., additional, Herbert, Diamond, additional, Hix, Matthew M., additional, Whitmire, Melanie, additional, Arnold, Brittany, additional, Hutchinson, Philip, additional, Espiritu, Joseph, additional, Feinglos, Mark, additional, Kovalik, Eugene, additional, Gedon-Lipscomb, Georgianne, additional, Evans, Kathryn, additional, Thacker, Connie, additional, Zimmer, Ronna, additional, Furst, Mary, additional, Mason, MaryAnn, additional, Powell, James, additional, Bolin, Paul, additional, Zhang, Junhong, additional, Pinion, Mary, additional, Davis, Gail, additional, Bryant, Winifred, additional, Phelps, Presley, additional, Garris-Sutton, Connie, additional, Atkinson, Beatrice, additional, Contreras, Gabriele, additional, Suarez, Maritza, additional, Schulman, Ivonne, additional, Koggan, Don, additional, Vassallo, Jackie, additional, Peruyera, Gloria, additional, Whittington, Sheri, additional, Bethea, Cassandra, additional, Gilliam, Laura, additional, Pedley, Carolyn, additional, Zurek, Geraldine, additional, Baird, Miriam, additional, Herring, Charles, additional, Smoak, Mary Martha, additional, Williams, Julie, additional, Rogers, Samantha, additional, Gordon, Lindsay, additional, Kennedy, Erin, additional, Belle, Beverly, additional, McCorkle-Doomy, Jessica, additional, Adams, Jonathan, additional, Lopez, Ramon, additional, Janavs, Juris, additional, Rahbari-Oskoui, Frederic, additional, Chapman, Arlene, additional, Dollar, Allen, additional, Williams, Olubunmi, additional, Han, Yoosun, additional, Haley, William, additional, Fitzpatrick, Peter, additional, Blackshear, Joseph, additional, Shapiro, Brian, additional, Harrell, Anna, additional, Palaj, Arta, additional, Henderson, Katelyn, additional, Johnson, Ashley, additional, Gonzalez, Heath, additional, Robinson, Jermaine, additional, Tamariz, Leonardo, additional, Denizard, Jennifer, additional, Barakat, Rody, additional, Krishnamoorthy, Dhurga, additional, Greenway, Frank, additional, Monce, Ron, additional, Church, Timothy, additional, Hendrick, Chelsea, additional, Yoches, Aimee, additional, Sones, Leighanne, additional, Baltazar, Markee, additional, Pemu, Priscilla, additional, Jones, Connie, additional, Akpalu, Derrick, additional, Chelune, Gordon, additional, Childs, Jeffrey, additional, Gren, Lisa, additional, Randall, Anne, additional, Dember, Laura, additional, Soares, Denise, additional, Yee, Jerry, additional, Umanath, Kausik, additional, Ogletree, Naima, additional, Thaxton, Schawana, additional, Campana, Karen, additional, Sheldon, Dayna, additional, MacArthur, Krista, additional, Muhlestein, J. Brent, additional, Allred, Nathan, additional, Clements, Brian, additional, Dhar, Ritesh, additional, Meredith, Kent, additional, Le, Viet, additional, Miner, Edward, additional, Orford, James, additional, Riessen, Erik R., additional, Ballantyne, Becca, additional, Chisum, Ben, additional, Johnson, Kevin, additional, Peeler, Dixie, additional, Chertow, Glenn, additional, Tamura, Manju, additional, Chang, Tara, additional, Erickson, Kevin, additional, Shen, Jenny, additional, Stafford, Randall S., additional, Zaharchuk, Gregory, additional, Del Cid, Margareth, additional, Dentinger, Michelle, additional, Sabino, Jennifer, additional, Sahay, Rukmani, additional, Telminova, Ekaterina, additional, Weiner, Daniel E., additional, Sarnak, Mark, additional, Chan, Lily, additional, Civiletto, Amanda, additional, Heath, Alyson, additional, Kantor, Amy, additional, Jain, Priyanka, additional, Kirkpatrick, Bethany, additional, Well, Andrew, additional, Yuen, Barry, additional, Chonchol, Michel, additional, Farmer, Beverly, additional, Farmer, Heather, additional, Greenwald, Carol, additional, Malaczewski, Mikaela, additional, Lash, James, additional, Porter, Anna, additional, Ricardo, Ana, additional, Rosman, Robert T., additional, Cohan, Janet, additional, Barrera, Nieves Lopez, additional, Meslar, Daniel, additional, Meslar, Patricia, additional, Conroy, Margaret, additional, Unruh, Mark, additional, Hess, Rachel, additional, Jhamb, Manisha, additional, Thomas, Holly, additional, Fazio, Pam, additional, Klixbull, Elle, additional, Komlos-Weimer, Melissa, additional, Mandich, LeeAnne, additional, Vita, Tina, additional, Toto, Robert, additional, Van Buren, Peter, additional, Inrig, Julia, additional, Cruz, Martha, additional, Lightfoot, Tammy, additional, Wang, Nancy, additional, Webster, Lori, additional, Raphael, Kalani, additional, Stults, Barry, additional, Zaman, Tahir, additional, Simmons, Debra, additional, Lavasani, Tooran, additional, Filipowicz, Rebecca, additional, Wei, Guo, additional, Miller, Gracie Mary, additional, Harerra, Jenice, additional, Christensen, Jeff, additional, Giri, Ajay, additional, Chen, Xiaorui, additional, Anderton, Natalie, additional, Jensen, Arianna, additional, Lewis, Julia, additional, Burgner, Anna, additional, Dwyer, Jamie P., additional, Schulman, Gerald, additional, Herrud, Terri, additional, Leavell, Ewanda, additional, McCray, Tiffany, additional, McNeil-Simaan, Edwina, additional, Poudel, Munmun, additional, Reed, Malia, additional, Sika, Mohammed, additional, Woods, Delia, additional, Zirkenbach, Janice L., additional, Raj, Dominic S., additional, Cohen, Scott, additional, Patel, Samir, additional, Velasquez, Manuel, additional, Bastian, Roshni S., additional, Wing, Maria, additional, Roy-Chaudhury, Akshay, additional, Depner, Thomas, additional, Dalyrymple, Lorien, additional, Kaysen, George, additional, Anderson, Susan, additional, Nord, John, additional, Ix, Joachim H., additional, Goldenstein, Leonard, additional, Miracle, Cynthia M., additional, Forbang, Nketi, additional, Mircic, Maja, additional, Thomas, Brenda, additional, Tran, Tiffany, additional, Rastogi, Anjay, additional, Kim, Mihae, additional, Rashid, Mohamad, additional, Lizarraga, Bianca, additional, Hocza, Amy, additional, Sarmosyan, Kristine, additional, Norris, Jason, additional, Sharma, Tushar, additional, Chioy, Amanda, additional, Bernard, Eric, additional, Cabrera, Eleanore, additional, Lopez, Christina, additional, Nunez, Susana, additional, Riad, Joseph, additional, Schweitzer, Suzanne, additional, Sirop, Siran, additional, Thomas, Sarah, additional, Wada, Lauren, additional, Kramer, Holly, additional, Bansal, Vinod, additional, Taylor, Corliss E., additional, Segal, Mark S., additional, Hall, Karen L., additional, Kazory, Amir, additional, Gilbert, Lesa, additional, Owens, Linda, additional, Poulton, Danielle, additional, Whidden, Elaine, additional, Wiggins, Jocelyn, additional, Blaum, Caroline, additional, Nyquist, Linda, additional, Min, Lillian, additional, Gure, Tanya, additional, Lewis, Ruth, additional, Mawby, Jennifer, additional, Robinson, Eileen, additional, Lewis, Cora E., additional, Bradley, Virginia, additional, Calhoun, David, additional, Glasser, Stephen, additional, Jenkins, Kim, additional, Ramsey, Tom, additional, Qureshi, Nauman, additional, Ferguson, Karen, additional, Haider, Sumrah, additional, James, Mandy, additional, Jones, Christy, additional, Renfroe, Kim, additional, Seay, April, additional, Weigart, Carrie, additional, Thornley-Brown, Denyse, additional, Rizik, Dana, additional, Cotton, Bari, additional, Fitz-Gerald, Meredith, additional, Grimes, Tiffany, additional, Johnson, Carolyn, additional, Kennedy, Sara, additional, Mason, Chanel, additional, Rosato-Burson, Lesa, additional, Willingham, Robin, additional, Judd, Eric, additional, Breaux-Shropshire, Tonya, additional, Cook, Felice, additional, Medina, Julia, additional, Ghazi, Lama, additional, Bhatt, Hemal, additional, Lewis, James, additional, Brantley, Roman, additional, Brouilette, John, additional, Glaze, Jeffrey, additional, Hall, Stephanie, additional, Hiott, Nancy, additional, Tharpe, David, additional, Boddy, Spencer, additional, Mack, Catherine, additional, Womack, Catherine, additional, Asao, Keiko, additional, Griffin, Beate, additional, Hendrix, Carol, additional, Johnson, Karen, additional, Jones, Lisa, additional, Towers, Chelsea, additional, Punzi, Henry, additional, Cassidy, Kathy, additional, Schumacher, Kristin, additional, Irizarry, Carmen, additional, Colon, Ilma, additional, Colon-Ortiz, Pedro, additional, Colón-Hernández, Pedro J., additional, Carrasquillo-Navarro, Orlando J., additional, Carrasquillo, Merari, additional, Vazquez, Nivea, additional, Sosa-Padilla, Miguel, additional, Cintron-Pinero, Alex, additional, Ayala, Mayra, additional, Pacheco, Olga, additional, Rivera, Catalina, additional, Sotomayor-Gonzalez, Irma, additional, Claudio, Jamie, additional, Lazaro, Jose, additional, Arce, Migdalia, additional, Heres, Lourdes, additional, Perez, Alba, additional, Tavarez-Valle, Jose, additional, Arocho, Ferlinda, additional, Torres, Mercedes, additional, Vazquez, Melvaliz, additional, Aurigemma, Gerard P., additional, Takis-Smith, Rebecca, additional, Andrieni, Julia, additional, Bodkin, Noelle, additional, Chaudhary, Kiran, additional, Hu, Paula, additional, Kostis, John, additional, Cosgrove, Nora, additional, Bankowski, Denise, additional, Boleyn, Monica, additional, Casazza, Laurie, additional, Giresi, Victoria, additional, Patel, Tosha, additional, Squindo, Erin, additional, Wu, Yan, additional, Henson, Zeb, additional, Wofford, Marion, additional, Lowery, Jessica, additional, Minor, Deborah, additional, Harkins, Kimberley, additional, Auchus, Alexander, additional, Flessner, Michael, additional, Adair, Cathy, additional, Asher, Jordan, additional, Loope, Debbie, additional, Cobb, Rita, additional, Venegas, Reiner, additional, Bigger, Thomas, additional, Bello, Natalie, additional, Homma, Shunichi, additional, Donovan, Daniel, additional, Lopez-Jimenez, Carlos, additional, Tirado, Amilcar, additional, Getaneh, Asqual, additional, Tang, Rocky, additional, Durant, Sabrina, additional, Maurer, Mathew, additional, Teruya, Sergio, additional, Helmke, Stephen, additional, Alvarez, Julissa, additional, Campbell, Ruth, additional, Pisoni, Roberto, additional, Sturdivant, Rachel, additional, Brooks, Deborah, additional, Counts, Caroline, additional, Hunt, Vickie, additional, Spillers, Lori, additional, Brautigam, Donald, additional, Kitchen, Timothy, additional, Gorman, Timothy, additional, Sayers, Jessica, additional, Button, Sarah, additional, Chiarot, June, additional, Fischer, Rosemary, additional, Lyon, Melissa, additional, Resnick, Maria, additional, Hodges, Nicole, additional, Ferreira, Jennifer, additional, Cushman, William, additional, Wall, Barry, additional, Nichols, Linda, additional, Burns, Robert, additional, Martindale-Adams, Jennifer, additional, Berlowitz, Dan, additional, Clark, Elizabeth, additional, Walsh, Sandy, additional, Geraci, Terry, additional, Huff, Carol, additional, Shaw, Linda, additional, Servilla, Karen, additional, Vigil, Darlene, additional, Barrett, Terry, additional, Sweeney, Mary Ellen, additional, Johnson, Rebecca, additional, McConnell, Susan, additional, Salles, Khadijeh Shahid, additional, Watson, Francoise, additional, Schenk, Cheryl, additional, Whittington, Laura, additional, Maher, Maxine, additional, Williams, Jonathan, additional, Swartz, Stephen, additional, Conlin, Paul, additional, Alexis, George, additional, Lamkin, Rebecca, additional, Underwood, Patti, additional, Gomes, Helen, additional, Rosendorff, Clive, additional, Atlas, Stephen, additional, Khan, Saadat, additional, Gonzalez, Waddy, additional, Barcham, Samih, additional, Kwon, Lawrence, additional, Matar, Matar, additional, Adhami, Anwar, additional, Basile, Jan, additional, John, Joseph, additional, Ham, Deborah, additional, Baig, Hadi, additional, Saklayen, Mohammed, additional, Yap, Jason, additional, Neff, Helen, additional, Miller, Carol, additional, Zheng-Phelan, Ling, additional, Gappy, Saib, additional, Rau, Shiva, additional, Raman, Arathi, additional, Berchou, Vicki, additional, Jones, Elizabeth, additional, Olgren, Erin, additional, Marbury, Cynthia, additional, Yudd, Michael, additional, Sastrasinh, Sithiporn, additional, Michaud, Jennine, additional, Fiore, Jessica, additional, Kutza, Marianne, additional, Shorr, Ronald, additional, Mount, Rattana, additional, Dunn, Helen, additional, Stinson, Susan, additional, Hunter, Jessica, additional, Taylor, Addison, additional, Bates, Jeffery, additional, Anderson, Catherine, additional, Kirchner, Kent, additional, Stubbs, Jodi, additional, Hinton, Ardell, additional, Spencer, Anita, additional, Sharma, Santosh, additional, Wiegmann, Thomas, additional, Mehta, Smita, additional, Krause, Michelle, additional, Dishongh, Kate, additional, Childress, Richard, additional, Gyamlani, Geeta, additional, Niakan, Atossa, additional, Thompson, Cathy, additional, Moody, Janelle, additional, Gresham, Carolyn, additional, Whittle, Jeffrey, additional, Barnas, Gary, additional, Wolfgram, Dawn, additional, Cortese, Heidi, additional, Johnson, Jonette, additional, Roumie, Christianne, additional, Hung, Adriana, additional, Wharton, Jennifer, additional, Niesner, Kurt, additional, Katz, Lois, additional, Richardson, Elizabeth, additional, Brock, George, additional, Holland, Joanne, additional, Dixon, Troy, additional, Zias, Athena, additional, Spiller, Christine, additional, Baker, Penelope, additional, Felicetta, James, additional, Rehman, Shakaib, additional, Bingham, Kelli, additional, Watnick, Suzanne, additional, Cohen, David, additional, Weiss, Jessica, additional, Johnston, Tera, additional, Giddings, Stephen, additional, Yamout, Hala, additional, Klein, Andrew, additional, Rowe, Caroline, additional, Vargo, Kristin, additional, Waidmann, Kristi, additional, Papademetriou, Vasilios, additional, Elkhoury, Jean Pierre, additional, Gregory, Barbara, additional, Amodeo, Susan, additional, Bloom, Mary, additional, Goldfarb-Waysman, Dalia, additional, Treger, Richard, additional, Kashefi, Mehran, additional, Huang, Christina, additional, Knibloe, Karen, additional, Ishani, Areef, additional, Slinin, Yelena, additional, Olney, Christine, additional, Rust, Jacqueline, additional, Fanti, Paolo, additional, Dyer, Christopher, additional, Bansal, Shweta, additional, Dunnam, Monica, additional, Hu, Lih-Lan, additional, and Zarate-Abbott, Perla, additional

Published
2022
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36. A pre-specified analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) randomized controlled trial on the incidence of abrupt declines in kidney function

Author

Heerspink, Hiddo J L, Cherney, David, Postmus, Douwe, Stefánsson, Bergur V, Chertow, Glenn M, Dwyer, Jamie P, Greene, Tom, Kosiborod, Mikhail, Langkilde, Anna Maria, McMurray, John J V, Correa-Rotter, Ricardo, Rossing, Peter, Sjöström, C David, Toto, Robert D, Wheeler, David C, Christersson, Christina, Held, Claes, Heerspink, Hiddo J L, Cherney, David, Postmus, Douwe, Stefánsson, Bergur V, Chertow, Glenn M, Dwyer, Jamie P, Greene, Tom, Kosiborod, Mikhail, Langkilde, Anna Maria, McMurray, John J V, Correa-Rotter, Ricardo, Rossing, Peter, Sjöström, C David, Toto, Robert D, Wheeler, David C, Christersson, Christina, and Held, Claes

Abstract

This pre-specified analysis of DAPA-CKD assessed the impact of sodium-glucose cotransporter 2 inhibition on abrupt declines in kidney function in high-risk patients based on having chronic kidney disease (CKD) and substantial albuminuria. DAPA-CKD was a randomized, double-blind, placebo-controlled trial that had a median follow-up of 2.4 years. Adults with CKD (urinary albumin-to-creatinine ratio 200-5000 mg/g and estimated glomerular filtration rate 25-75 mL/min/1.73m2) were randomized to dapagliflozin 10 mg/day matched to placebo (2152 individuals each). An abrupt decline in kidney function was defined as a pre-specified endpoint of doubling of serum creatinine between two subsequent study visits. We also assessed a post-hoc analysis of investigator-reported acute kidney injury-related serious adverse events. Doubling of serum creatinine between two subsequent visits (median time-interval 100 days) occurred in 63 (2.9%) and 91 (4.2%) participants in the dapagliflozin and placebo groups, respectively (hazard ratio 0.68 [95% confidence interval 0.49, 0.94]). Accounting for the competing risk of mortality did not alter our findings. There was no heterogeneity in the effect of dapagliflozin on abrupt declines in kidney function based on baseline subgroups. Acute kidney injury-related serious adverse events were not significantly different and occurred in 52 (2.5%) and 69 (3.2%) participants in the dapagliflozin and placebo groups, respectively (0.77 [0.54, 1.10]). Thus, in patients with CKD and substantial albuminuria, dapagliflozin reduced the risk of abrupt declines in kidney function., HJLH and DC are co-primary authors. The DAPA-CKD Trial Committees and Investigators are listed in the Appendix.

Published
2022
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37. Antihypertensive drug effects on long-term blood pressure : an individual-level data meta-analysis of randomised clinical trials

Author

Canoy, Dexter, Copland, Emma, Nazarzadeh, Milad, Ramakrishnan, Rema, Pinho-Gomes, Ana-Catarina, Salam, Abdul, Dwyer, Jamie P., Farzadfar, Farshad, Sundström, Johan, Woodward, Mark, Davis, Barry R., Rahimi, Kazem, Canoy, Dexter, Copland, Emma, Nazarzadeh, Milad, Ramakrishnan, Rema, Pinho-Gomes, Ana-Catarina, Salam, Abdul, Dwyer, Jamie P., Farzadfar, Farshad, Sundström, Johan, Woodward, Mark, Davis, Barry R., and Rahimi, Kazem

Abstract

Objective: Evidence from randomised trials of pharmacological treatments on long-term blood pressure (BP) reduction is limited. We investigated the antihypertensive drug effects on BP over time and across different participant characteristics. Methods: We conducted an individual patient-level data meta-analysis of 52 large-scale randomised clinical trials in the Blood Pressure Lowering Treatment Trialists' Collaboration using mixed models to examine treatment effects on BP over 4 years of mean follow-up. Results: There were 363 684 participants (42% women), with baseline mean age=65 years and mean systolic/diastolic BP=152/87 mm Hg, and among whom 19% were current smokers, 49% had cardiovascular disease, 28% had diabetes and 69% were taking antihypertensive treatment at baseline. Drugs were effective in lowering BP showing maximal effect after 12 months and gradually attenuating towards later years. Based on measures taken >= 12 months postrandomisation, mean systolic/diastolic BP difference (95% CI) between more and less intense BP-lowering treatment was -11.1 (-11.3 to -10.8)/-5.6 (-5.7 to -5.4) mm Hg; between active treatment and placebo was -5.1 (-5.3 to -5.0)/-2.3 (-2.4 to -2.2) mm Hg; and between active and control arms for drug comparison trials was -1.4 (-1.5 to -1.3)/-0.6 (-0.7 to -0.6) mm Hg. BP reductions were observed across different baseline BP values and ages, and by sex, history of cardiovascular disease and diabetes and prior antihypertensive treatment use. Conclusion: These findings suggest that BP-lowering pharmacotherapy is effective in lowering BP, up to 4 years on average, in people with different characteristics. Appropriate treatment strategies are needed to sustain substantive long-term BP reductions.

Published
2022
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38. Effect of Intensive Versus Standard Clinic-Based Hypertension Management on Ambulatory Blood Pressure: Results From the SPRINT (Systolic Blood Pressure Intervention Trial) Ambulatory Blood Pressure Study

Author

Drawz, Paul E., Pajewski, Nicholas M., Bates, Jeffrey T., Bello, Natalie A., Cushman, William C., Dwyer, Jamie P., Fine, Lawrence J., Goff, David C., Jr, Haley, William E., Krousel-Wood, Marie, McWilliams, Andrew, Rifkin, Dena E., Slinin, Yelena, Taylor, Addison, Townsend, Raymond, Wall, Barry, Wright, Jackson T., and Rahman, Mahboob

Published
2017
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40. Antihypertensive drug effects on long-term blood pressure: an individual-level data meta-analysis of randomised clinical trials

Author

Canoy, Dexter, primary, Copland, Emma, additional, Nazarzadeh, Milad, additional, Ramakrishnan, Rema, additional, Pinho-Gomes, Ana-Catarina, additional, Salam, Abdul, additional, Dwyer, Jamie P, additional, Farzadfar, Farshad, additional, Sundström, Johan, additional, Woodward, Mark, additional, Davis, Barry R, additional, and Rahimi, Kazem, additional

Published
2022
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42. The Effect of Dapagliflozin on Albuminuria in DECLARE-TIMI 58

Author

Mosenzon, Ofri, primary, Wiviott, Stephen D., additional, Heerspink, Hiddo J.L., additional, Dwyer, Jamie P., additional, Cahn, Avivit, additional, Goodrich, Erica L., additional, Rozenberg, Aliza, additional, Schechter, Meir, additional, Yanuv, Ilan, additional, Murphy, Sabina A., additional, Zelniker, Thomas A., additional, Gause-Nilsson, Ingrid A.M., additional, Langkilde, Anna Maria, additional, Fredriksson, Martin, additional, Johansson, Peter A., additional, Bhatt, Deepak L., additional, Leiter, Lawrence A., additional, McGuire, Darren K., additional, Wilding, John P.H., additional, Sabatine, Marc S., additional, and Raz, Itamar, additional

Published
2021
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44. Dapagliflozin and Prevention of Kidney Disease Among Patients With Type 2 Diabetes: Post Hoc Analyses From the DECLARE-TIMI 58 Trial.

Author

Mosenzon, Ofri, Raz, Itamar, Wiviott, Stephen D., Schechter, Meir, Goodrich, Erica L., Yanuv, Ilan, Rozenberg, Aliza, Murphy, Sabina A., Zelniker, Thomas A., Langkilde, Anna Maria, Gause-Nilsson, Ingrid A.M., Fredriksson, Martin, Johansson, Peter A., Wilding, John P.H., McGuire, Darren K., Bhatt, Deepak L., Leiter, Lawrence A., Cahn, Avivit, Dwyer, Jamie P., and Heerspink, Hiddo J.L.

Subjects
MYOCARDIAL infarction complications, GLOMERULAR filtration rate, BENZENE, RESEARCH, SODIUM, RESEARCH methodology, GLYCOSIDES, EVALUATION research, TYPE 2 diabetes, COMPARATIVE studies, RANDOMIZED controlled trials, GLUCOSE, DIABETIC nephropathies, DISEASE complications
Abstract

Objective: In patients with moderate to severe albuminuric kidney disease, sodium-glucose cotransporter 2 inhibitors reduce the risk of kidney disease progression. These post hoc analyses assess the effects of dapagliflozin on kidney function decline in patients with type 2 diabetes (T2D), focusing on populations with low kidney risk.Research Design and Methods: In the Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58 (DECLARE-TIMI 58) trial, patients with T2D at high cardiovascular risk were randomly assigned to dapagliflozin versus placebo. Outcomes were analyzed by treatment arms, overall, and by Kidney Disease: Improving Global Outcomes (KDIGO) risk categories. The prespecified kidney-specific composite outcome was a sustained decline ≥40% in the estimated glomerular filtration rate (eGFR) to <60 mL/min/1.73 m2, end-stage kidney disease, and kidney-related death. Other outcomes included incidence of categorical eGFR decline of different thresholds and chronic (6 month to 4 year) or total (baseline to 4 year) eGFR slopes.Results: Most participants were in the low-moderate KDIGO risk categories (n = 15,201 [90.3%]). The hazard for the kidney-specific composite outcome was lower with dapagliflozin across all KDIGO risk categories (P-interaction = 0.97), including those at low risk (hazard ratio [HR] 0.54, 95% CI 0.38-0.77). Risks for categorical eGFR reductions (≥57% [in those with baseline eGFR ≥60 mL/min/1.73 m2], ≥50%, ≥40%, and ≥30%) were lower with dapagliflozin (HRs 0.52, 0.57, 0.55, and 0.70, respectively; P < 0.05). Slopes of eGFR decline favored dapagliflozin across KDIGO risk categories, including the low KDIGO risk (between-arm differences of 0.87 [chronic] and 0.55 [total] mL/min/1.73 m2/year; P < 0.0001).Conclusions: Dapagliflozin mitigated kidney function decline in patients with T2D at high cardiovascular risk, including those with low KDIGO risk, suggesting a role of dapagliflozin in the early prevention of diabetic kidney disease. [ABSTRACT FROM AUTHOR]

Published
2022
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46. Effect of Dapagliflozin on Cardiovascular Outcomes According to Baseline Kidney Function and Albuminuria Status in Patients With Type 2 Diabetes

Author

Zelniker, Thomas A., primary, Raz, Itamar, additional, Mosenzon, Ofri, additional, Dwyer, Jamie P., additional, Heerspink, Hiddo H. J. L., additional, Cahn, Avivit, additional, Goodrich, Erica L., additional, Im, Kyungah, additional, Bhatt, Deepak L., additional, Leiter, Lawrence A., additional, McGuire, Darren K., additional, Wilding, John P. H., additional, Gause-Nilsson, Ingrid, additional, Langkilde, Anna Maria, additional, Sabatine, Marc S., additional, and Wiviott, Stephen D., additional

Published
2021
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47. Sotagliflozin in patients with diabetes and chronic kidney disease

Author

Bhatt, Deepak L., Szarek, Michael, Pitt, Bertram, Cannon, Christopher P., Leiter, Lawrence A., McGuire, Darren K., Lewis, Julia B., Riddle, Matthew C., Inzucchi, Silvio E., Kosiborod, Mikhail N., Cherney, David Z.I., Dwyer, Jamie P., Scirica, Benjamin M., Bailey, Clifford J., Díaz, Rafael, Ray, Kausik K., Udell, Jacob A., Lopes, Renato D., Lapuerta, Pablo, Gabriel Steg, P., Bhatt, Deepak L., Szarek, Michael, Pitt, Bertram, Cannon, Christopher P., Leiter, Lawrence A., McGuire, Darren K., Lewis, Julia B., Riddle, Matthew C., Inzucchi, Silvio E., Kosiborod, Mikhail N., Cherney, David Z.I., Dwyer, Jamie P., Scirica, Benjamin M., Bailey, Clifford J., Díaz, Rafael, Ray, Kausik K., Udell, Jacob A., Lopes, Renato D., Lapuerta, Pablo, and Gabriel Steg, P.

Abstract

BACKGROUND: The efficacy and safety of sodium-glucose cotransporter 2 inhibitors such as sotagliflozin in preventing cardiovascular events in patients with diabetes with chronic kidney disease with or without albuminuria have not been well studied. METHODS: We conducted a multicenter, double-blind trial in which patients with type 2 diabetes mellitus (glycated hemoglobin level, ≥7%), chronic kidney disease (estimated glomerular filtration rate, 25 to 60 ml per minute per 1.73 m 2 of body-surface area), and risks for cardiovascular disease were randomly assigned in a 1:1 ratio to receive sotagliflozin or placebo. The primary end point was changed during the trial to the composite of the total number of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure. The trial ended early owing to loss of funding. RESULTS: Of 19,188 patients screened, 10,584 were enrolled, with 5292 assigned to the sotagliflozin group and 5292 assigned to the placebo group, and followed for a median of 16 months. The rate of primary end-point events was 5.6 events per 100 patient-years in the sotagliflozin group and 7.5 events per 100 patient-years in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.63 to 0.88; P<0.001). The rate of deaths from cardiovascular causes per 100 patient-years was 2.2 with sotagliflozin and 2.4 with placebo (hazard ratio, 0.90; 95% CI, 0.73 to 1.12; P = 0.35). For the original coprimary end point of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, the hazard ratio was 0.84 (95% CI, 0.72 to 0.99); for the original coprimary end point of the first occurrence of death from cardiovascular causes or hospitalization for heart failure, the hazard ratio was 0.77 (95% CI, 0.66 to 0.91). Diarrhea, genital mycotic infections, volume depletion, and diabetic ketoacidosis were more common with sotagliflozin than with placebo. CONCLUSIONS: In patie

Published
2021

48. Age-stratified and blood-pressure-stratified effects of blood-pressure-lowering pharmacotherapy for the prevention of cardiovascular disease and death:an individual participant-level data meta-analysis

Author

Rahimi, Kazem, Bidel, Zeinab, Nazarzadeh, Milad, Copland, Emma, Canoy, Dexter, Wamil, Malgorzata, Majert, Jeannette, McManus, Richard, Adler, Amanda, Agodoa, Larry, Algra, Ale, Asselbergs, Folkert W., Beckett, Nigel S., Berge, Eivind, Black, Henry, Boersma, Eric, Brouwers, Frank P.J., Brown, Morris, Brugts, Jasper J., Bulpitt, Christopher J., Byington, Robert P., Cushman, William C., Cutler, Jeffrey, Devereaux, Richard B., Dwyer, Jamie P., Estacio, Ray, Fagard, Robert, Fox, Kim, Fukui, Tsuguya, Gupta, Ajay K., Holman, Rury R., Imai, Yutaka, Ishii, Masao, Julius, Stevo, Kanno, Yoshihiko, Kjeldsen, Sverre E., Kostis, John, Kuramoto, Kizuku, Lanke, Jan, Lewis, Edmund, Lewis, Julia B., Lievre, Michel, Lindholm, Lars H., Lueders, Stephan, MacMahon, Stephen, Mancia, Giuseppe, Matsuzaki, Masunori, Mehlum, Maria H., Nissen, Steven, Ogawa, Hiroshi, Rahimi, Kazem, Bidel, Zeinab, Nazarzadeh, Milad, Copland, Emma, Canoy, Dexter, Wamil, Malgorzata, Majert, Jeannette, McManus, Richard, Adler, Amanda, Agodoa, Larry, Algra, Ale, Asselbergs, Folkert W., Beckett, Nigel S., Berge, Eivind, Black, Henry, Boersma, Eric, Brouwers, Frank P.J., Brown, Morris, Brugts, Jasper J., Bulpitt, Christopher J., Byington, Robert P., Cushman, William C., Cutler, Jeffrey, Devereaux, Richard B., Dwyer, Jamie P., Estacio, Ray, Fagard, Robert, Fox, Kim, Fukui, Tsuguya, Gupta, Ajay K., Holman, Rury R., Imai, Yutaka, Ishii, Masao, Julius, Stevo, Kanno, Yoshihiko, Kjeldsen, Sverre E., Kostis, John, Kuramoto, Kizuku, Lanke, Jan, Lewis, Edmund, Lewis, Julia B., Lievre, Michel, Lindholm, Lars H., Lueders, Stephan, MacMahon, Stephen, Mancia, Giuseppe, Matsuzaki, Masunori, Mehlum, Maria H., Nissen, Steven, and Ogawa, Hiroshi

Abstract

Background: The effects of pharmacological blood-pressure-lowering on cardiovascular outcomes in individuals aged 70 years and older, particularly when blood pressure is not substantially increased, is uncertain. We compared the effects of blood-pressure-lowering treatment on the risk of major cardiovascular events in groups of patients stratified by age and blood pressure at baseline. Methods: We did a meta-analysis using individual participant-level data from randomised controlled trials of pharmacological blood-pressure-lowering versus placebo or other classes of blood-pressure-lowering medications, or between more versus less intensive treatment strategies, which had at least 1000 persons-years of follow-up in each treatment group. Participants with previous history of heart failure were excluded. Data were obtained from the Blood Pressure Lowering Treatment Triallists' Collaboration. We pooled the data and categorised participants into baseline age groups (<55 years, 55–64 years, 65–74 years, 75–84 years, and ≥85 years) and blood pressure categories (in 10 mm Hg increments from <120 mm Hg to ≥170 mm Hg systolic blood pressure and from <70 mm Hg to ≥110 mm Hg diastolic). We used a fixed effects one-stage approach and applied Cox proportional hazard models, stratified by trial, to analyse the data. The primary outcome was defined as either a composite of fatal or non-fatal stroke, fatal or non-fatal myocardial infarction or ischaemic heart disease, or heart failure causing death or requiring hospital admission. Findings: We included data from 358 707 participants from 51 randomised clinical trials. The age of participants at randomisation ranged from 21 years to 105 years (median 65 years [IQR 59–75]), with 42 960 (12·0%) participants younger than 55 years, 128 437 (35·8%) aged 55–64 years, 128 506 (35·8%) 65–74 years, 54 016 (15·1%) 75–84 years, and 4788 (1·3%) 85 years and older. The hazard ratios for the risk of major cardiovascular events per 5 mm

Published
2021

49. The dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial : baseline characteristics

Author

Wheeler, David C., Stefansson, Bergur, V, Batiushin, Mikhail, Bilchenko, Oleksandr, Cherney, David Z., I, Chertow, Glenn M., Douthat, Walter, Dwyer, Jamie P., Escudero, Elizabeth, Pecoits-Filho, Roberto, Furuland, Hans, Gorriz, Jose Luis, Greene, Tom, Haller, Hermann, Hou, Fan Fan, Kang, Shin-Wook, Isidto, Rey, Khullar, Dinesh, Mark, Patrick B., McMurray, John J., V, Kashihara, Naoki, Nowicki, Michal, Persson, Frederik, Correa-Rotter, Ricardo, Rossing, Peter, Toto, Robert D., Umanath, Kausik, Van Bui, Pham, Wittmann, Istvan, Lindberg, Magnus, Sjostrom, C. David, Langkilde, Anna Maria, Heerspink, Hiddo J. L., Wheeler, David C., Stefansson, Bergur, V, Batiushin, Mikhail, Bilchenko, Oleksandr, Cherney, David Z., I, Chertow, Glenn M., Douthat, Walter, Dwyer, Jamie P., Escudero, Elizabeth, Pecoits-Filho, Roberto, Furuland, Hans, Gorriz, Jose Luis, Greene, Tom, Haller, Hermann, Hou, Fan Fan, Kang, Shin-Wook, Isidto, Rey, Khullar, Dinesh, Mark, Patrick B., McMurray, John J., V, Kashihara, Naoki, Nowicki, Michal, Persson, Frederik, Correa-Rotter, Ricardo, Rossing, Peter, Toto, Robert D., Umanath, Kausik, Van Bui, Pham, Wittmann, Istvan, Lindberg, Magnus, Sjostrom, C. David, Langkilde, Anna Maria, and Heerspink, Hiddo J. L.

Abstract

Background. The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD; NCT03036150) trial was designed to assess the effect of the sodium-glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin on kidney and cardiovascular events in participants with CKD with and without type 2 diabetes (T2D). This analysis reports the baseline characteristics of those recruited, comparing them with those enrolled in other trials. Methods. In DAPA-CKD, 4304 participants with a urinary albumin:creatinine ratio (UACR) <= 200mg/g and estimated glomerular filtration rate (eGFR) between 25 and 75mL/min/1.73m(2) were randomized to dapagliflozin 10mg once daily or placebo. Mean eGFR was 43.1mL/min/1.73m(2) and median UACR was 949 mg/g (108mg/mmol). Results. Overall, 2906 participants (68%) had a diagnosis of T2D and of these, 396 had CKD ascribed to a cause other than diabetes. The most common causes of CKD after diabetes (n = 2510) were ischaemic/hypertensive nephropathy (n = 687) and chronic glomerulonephritis (n = 695), of which immunoglobulin A nephropathy (n = 270) was the most common. A total of 4174 participants (97%) were receiving an angiotensinconverting enzyme inhibitor or angiotensin receptor blocker, 1882 (43.7%) diuretics, 229 (5.3%) mineralocorticoid receptor antagonists and 122 (2.8%) glucagon-like peptide 1 receptor agonists. In contrast to the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), the DAPA-CKD trial enrolled participants with CKD due to diabetes and to causes other than diabetes. The mean eGFR of participants in the DAPA-CKD trial was 13.1mL/min/1.73m(2) lower than in CREDENCE, similar to that in the Finerenone in Reducing Kidney Failure and Disease Progression in DKD (FIDELIO-DKD) trial and the Study Of diabetic Nephropathy with AtRasentan (SONAR). Conclusions. Participants with a wide range of underlying kidney diseases receiving renin-angiotensin system blocking therapy

Published
2020
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50. The dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial:baseline characteristics

Author

Wheeler, David C., Stefansson, Bergur V., Batiushin, Mikhail, Bilchenko, Oleksandr, Cherney, David Z.I., Chertow, Glenn M., Douthat, Walter, Dwyer, Jamie P., Escudero, Elizabeth, Pecoits-Filho, Roberto, Furuland, Hans, Górriz, José Luis, Greene, Tom, Haller, Hermann, Hou, Fan Fan, Kang, Shin Wook, Isidto, Rey, Khullar, Dinesh, Mark, Patrick B., McMurray, John J.V., Kashihara, Naoki, Nowicki, Michal, Persson, Frederik, Correa-Rotter, Ricardo, Rossing, Peter, Toto, Robert D., Umanath, Kausik, Van Bui, Pham, Wittmann, István, Lindberg, Magnus, Sjöström, C. David, Langkilde, Anna Maria, Heerspink, Hiddo J.L., Wheeler, David C., Stefansson, Bergur V., Batiushin, Mikhail, Bilchenko, Oleksandr, Cherney, David Z.I., Chertow, Glenn M., Douthat, Walter, Dwyer, Jamie P., Escudero, Elizabeth, Pecoits-Filho, Roberto, Furuland, Hans, Górriz, José Luis, Greene, Tom, Haller, Hermann, Hou, Fan Fan, Kang, Shin Wook, Isidto, Rey, Khullar, Dinesh, Mark, Patrick B., McMurray, John J.V., Kashihara, Naoki, Nowicki, Michal, Persson, Frederik, Correa-Rotter, Ricardo, Rossing, Peter, Toto, Robert D., Umanath, Kausik, Van Bui, Pham, Wittmann, István, Lindberg, Magnus, Sjöström, C. David, Langkilde, Anna Maria, and Heerspink, Hiddo J.L.

Abstract

BACKGROUND: The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD; NCT03036150) trial was designed to assess the effect of the sodium-glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin on kidney and cardiovascular events in participants with CKD with and without type 2 diabetes (T2D). This analysis reports the baseline characteristics of those recruited, comparing them with those enrolled in other trials. METHODS: In DAPA-CKD, 4304 participants with a urinary albumin:creatinine ratio (UACR) ≥200 mg/g and estimated glomerular filtration rate (eGFR) between 25 and 75 mL/min/1.73 m2 were randomized to dapagliflozin 10 mg once daily or placebo. Mean eGFR was 43.1 mL/min/1.73 m2 and median UACR was 949 mg/g (108 mg/mmol). RESULTS: Overall, 2906 participants (68%) had a diagnosis of T2D and of these, 396 had CKD ascribed to a cause other than diabetes. The most common causes of CKD after diabetes (n = 2510) were ischaemic/hypertensive nephropathy (n = 687) and chronic glomerulonephritis (n = 695), of which immunoglobulin A nephropathy (n = 270) was the most common. A total of 4174 participants (97%) were receiving an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, 1882 (43.7%) diuretics, 229 (5.3%) mineralocorticoid receptor antagonists and 122 (2.8%) glucagon-like peptide 1 receptor agonists. In contrast to the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), the DAPA-CKD trial enrolled participants with CKD due to diabetes and to causes other than diabetes. The mean eGFR of participants in the DAPA-CKD trial was 13.1 mL/min/1.73 m2 lower than in CREDENCE, similar to that in the Finerenone in Reducing Kidney Failure and Disease Progression in DKD (FIDELIO-DKD) trial and the Study Of diabetic Nephropathy with AtRasentan (SONAR). CONCLUSIONS: Participants with a wide range of underlying kidney diseases receiving renin-angiotensin system blocking thera

Published
2020

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