TY - JOUR AU - McMurray, John J V AU - Solomon, Scott D AU - Inzucchi, Silvio E AU - Køber, Lars AU - Kosiborod, Mikhail N AU - Martinez, Felipe A AU - Ponikowski, Piotr AU - Sabatine, Marc S AU - Anand, Inder S AU - Bělohlávek, Jan AU - Böhm, Michael AU - Chiang, Chern-En AU - Chopra, Vijay K AU - de Boer, Rudolf A AU - Desai, Akshay S AU - Diez, Mirta AU - Drozdz, Jaroslaw AU - Dukát, Andrej AU - Ge, Junbo AU - Howlett, Jonathan G AU - Katova, Tzvetana AU - Kitakaze, Masafumi AU - Ljungman, Charlotta E A AU - Merkely, Béla Péter AU - Nicolau, Jose C AU - O'Meara, Eileen AU - Petrie, Mark C AU - Vinh, Pham N AU - Schou, Morten AU - Tereshchenko, Sergey AU - Verma, Subodh AU - Held, Claes AU - DeMets, David L AU - Docherty, Kieran F AU - Jhund, Pardeep S AU - Bengtsson, Olof AU - Sjöstrand, Mikaela AU - Langkilde, Anna-Maria ED - Masszi, Gabriella / Collaborator TI - Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. JF - NEW ENGLAND JOURNAL OF MEDICINE J2 - NEW ENGL J MED VL - 381 PY - 2019 IS - 21 SP - 1995 EP - 2008 PG - 14 SN - 0028-4793 DO - 10.1056/NEJMoa1911303 UR - https://m2.mtmt.hu/api/publication/30828891 ID - 30828891 N1 - BHF Cardiovascular Research Centre, University of Glasgow, 126 University Pl., Glasgow, G128TA, United Kingdom Cardiovascular Division, TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, United States Section of Endocrinology, Yale University School of Medicine, New Haven, CT, United States Rigshospitalet Copenhagen University Hospital, Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark Department of Medicine, Saarland University Hospital, Homburg-Saar, Germany Saint Luke's Mid America Heart Institute, University of Missouri, Kansas City, United States National University of Cordoba, Cordoba, Spain Division of Cardiology, Instituto Cardiovascular de Buenos Aires, Buenos Aires, Argentina Wroclaw Medical University, Wroclaw, Poland Department of Cardiology, Medical University of Lodz, Lodz, Poland Department of Cardiology, University of Minnesota, Minneapolis, United States 2nd Department of Internal Medicine, Department of Cardiovascular Medicine, General Teaching Hospital, 1st Faculty of Medicine, Charles University, Prague, Czech Republic Division of Cardiology, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan Department of Cardiology, Medanta, Gurgaon, India Department of Cardiology, University Medical Center, University of Groningen, Groningen, Netherlands 5th Department of Internal Medicine, Comenius University in Bratislava, Bratislava, Slovakia Department of Cardiology, Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, Shanghai, China Cumming School of Medicine, Libin Cardiovascular Institute, University of Calgary, Calgary, AB, Canada Department of Cardiology, Montreal Heart Institute, Montreal, Canada Clinic of Cardiology, National Cardiology Hospital, Sofia, Bulgaria Cardiovascular Division of Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan Department of Molecular and Clinical Medicine and Cardiology, Sahlgrenska Academy, AstraZeneca, Gothenburg, Sweden Department of Medical Sciences, Cardiology, Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden Heart and Vascular Center, Semmelweis University, Budapest, Hungary Instituto Do Coracao, Hospital das Clinicas, Faculdade de Medicina, Universidade de Saõ Paolo, Saõ Paolo, Brazil Department of Internal Medicine, Tan Tao University, Tan Duc, Viet Nam Department of Myocardial Disease and Heart Failure, National Medical Research Center of Cardiology, Moscow, Russian Federation Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, United States Division of Cardiac Surgery, St. Michael's Hospital, University of Toronto, Toronto, Canada Cited By :1420 Export Date: 6 October 2021 CODEN: NEJMA Correspondence Address: McMurray, J.J.V.; BHF Cardiovascular Research Centre, 126 University Pl., United Kingdom; email: john.mcmurray@glasgow.ac.uk Chemicals/CAS: dapagliflozin, 461432-26-8; digitalis, 8031-42-3, 8053-83-6; sacubitril plus valsartan, 936623-90-4; glucoside, 50986-29-3; glycosylated hemoglobin, 9062-63-9; 2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol; Benzhydryl Compounds; Cardiovascular Agents; Glucosides; Glycated Hemoglobin A; Sodium-Glucose Transporter 2 Inhibitors AB - In patients with type 2 diabetes, inhibitors of sodium-glucose cotransporter 2 (SGLT2) reduce the risk of a first hospitalization for heart failure, possibly through glucose-independent mechanisms. More data are needed regarding the effects of SGLT2 inhibitors in patients with established heart failure and a reduced ejection fraction, regardless of the presence or absence of type 2 diabetes.In this phase 3, placebo-controlled trial, we randomly assigned 4744 patients with New York Heart Association class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either dapagliflozin (at a dose of 10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of worsening heart failure (hospitalization or an urgent visit resulting in intravenous therapy for heart failure) or cardiovascular death.Over a median of 18.2 months, the primary outcome occurred in 386 of 2373 patients (16.3%) in the dapagliflozin group and in 502 of 2371 patients (21.2%) in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P<0.001). A first worsening heart failure event occurred in 237 patients (10.0%) in the dapagliflozin group and in 326 patients (13.7%) in the placebo group (hazard ratio, 0.70; 95% CI, 0.59 to 0.83). Death from cardiovascular causes occurred in 227 patients (9.6%) in the dapagliflozin group and in 273 patients (11.5%) in the placebo group (hazard ratio, 0.82; 95% CI, 0.69 to 0.98); 276 patients (11.6%) and 329 patients (13.9%), respectively, died from any cause (hazard ratio, 0.83; 95% CI, 0.71 to 0.97). Findings in patients with diabetes were similar to those in patients without diabetes. The frequency of adverse events related to volume depletion, renal dysfunction, and hypoglycemia did not differ between treatment groups.Among patients with heart failure and a reduced ejection fraction, the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dapagliflozin than among those who received placebo, regardless of the presence or absence of diabetes. (Funded by AstraZeneca; DAPA-HF ClinicalTrials.gov number, NCT03036124.). LA - English DB - MTMT ER - TY - JOUR AU - Packer, Milton AU - Butler, Javed AU - Filippatos, Gerasimos S. AU - Jamal, Waheed AU - Salsali, Afshin AU - Schnee, Janet AU - Kimura, Karen AU - Zeller, Cordula AU - George, Jyothis AU - Brueckmann, Martina AU - Anker, Stefan D. AU - Zannad, Faiez AU - Perrone, Sergio AU - Nicholls, Stephen AU - Janssens, Stefan AU - Bocchi, Edmar AU - Giannetti, Nadia AU - Verma, Subodh AU - Jian, Zhang AU - Spinar, Jindrich AU - Seronde, Marie-France AU - Boehm, Michael AU - Merkely, Béla Péter AU - Chopra, Vijay AU - Senni, Michele AU - Taddei, Stefano AU - Tsutsui, Hiroyuki AU - Choi, Dong-Ju AU - Chuquiure, Eduardo AU - La Rocca, Hans Pieter Brunner AU - Ponikowski, Piotr AU - Gonzalez Juanatey, Jose Ramon AU - Squire, Iain AU - Butler, Javed AU - Januzzi, James AU - Pina, Ileana AU - Pocock, Stuart J. AU - Carson, Peter AU - Doehner, Wolfram AU - Miller, Alan AU - Haas, Markus AU - Pehrson, Steen AU - Komajda, Michel AU - Anand, Inder AU - Teerlink, John AU - Rabinstein, Alejandro AU - Steiner, Thorsten AU - Kamel, Hooman AU - Tsivgoulis, Georgios AU - Lewis, James AU - Freston, James AU - Kaplowitz, Neil AU - Mann, Johannes AU - Petrie, Mark AU - Bernstein, Richard AU - Cheung, Alfred AU - Green, Jennifer AU - Januzzi, James AU - Kaul, Sanjay AU - Ping, Carolyn Lam Su AU - Lip, Gregory AU - Marx, Nikolaus AU - McCullough, Peter AU - Mehta, Cyrus AU - Ponikowski, Piotr AU - Rosenstock, Julio AU - Sattar, Naveed AU - Scirica, Benjamin AU - Tsutsui, Hiroyuki AU - Verma, Subodh AU - Wanner, Christoph AU - Welty, Francine K. AU - Parhofer, Klaus G. AU - Clayton, Tim AU - Pedersen, Terje R. AU - Lees, Kennedy R. AU - Konstam, Marvin A. AU - Greenberg, Barry AU - Palmer, Mike TI - Evaluation of the effect of sodium-glucose co-transporter 2 inhibition with empagliflozin on morbidity and mortality of patients with chronic heart failure and a reduced ejection fraction: rationale for and design of the EMPEROR-Reduced trial JF - EUROPEAN JOURNAL OF HEART FAILURE J2 - EUR J HEART FAIL VL - 21 PY - 2019 IS - 10 SP - 1270 EP - 1278 PG - 9 SN - 1388-9842 DO - 10.1002/ejhf.1536 UR - https://m2.mtmt.hu/api/publication/31089317 ID - 31089317 AB - Drugs that inhibit the sodium-glucose co-transporter 2 (SGLT2) have been shown to reduce the risk of hospitalizations for heart failure in patients with type 2 diabetes. In populations that largely did not have heart failure at the time of enrolment, empagliflozin, canagliflozin and dapagliflozin decreased the risk of serious new-onset heart failure events by approximate to 30%. In addition, in the EMPA-REG OUTCOME trial, empagliflozin reduced the risk of both pump failure and sudden deaths, the two most common modes of death among patients with heart failure. In none of the three trials could the benefits of SGLT2 inhibitors on heart failure be explained by the actions of these drugs as diuretics or anti-hyperglycaemic agents. These observations raise the possibility that SGLT2 inhibitors could reduce morbidity and mortality in patients with established heart failure, including those without diabetes. The EMPEROR-Reduced trial is enrolling approximate to 3600 patients with heart failure and a reduced left ventricular ejection fraction (<= 40%), half of whom are expected not to have diabetes. Patients are being randomized to placebo or empagliflozin 10 mg daily, which is added to all appropriate treatment with inhibitors of the renin-angiotensin system and neprilysin, beta-blockers and mineralocorticoid receptor antagonists. The primary endpoint is the time-to-first event analysis of the combined risk of cardiovascular death and hospitalization for heart failure, but the trial will also evaluate the effects of empagliflozin on renal function, cardiovascular death, all-cause mortality, and recurrent hospitalization events. By adjusting eligibility based on natriuretic peptide levels to the baseline ejection fraction, the trial will preferentially enrol high-risk patients. A large proportion of the participants is expected to have an ejection fraction < 30%, and the estimated annual event rate is expected to be at least 15%. The EMPEROR-Reduced trial is well-positioned to determine if the addition of empagliflozin can add meaningfully to current approaches that have established benefits in the treatment of chronic heart failure with left ventricular systolic dysfunction. LA - English DB - MTMT ER - TY - JOUR AU - Neal, B AU - Perkovic, V AU - Mahaffey, KW AU - de Zeeuw, D AU - Fulcher, G AU - Erondu, N AU - Shaw, W AU - Law, G AU - Desai, M AU - Matthews, DR ED - Gaszner, Balázs / Collaborator TI - Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. JF - NEW ENGLAND JOURNAL OF MEDICINE J2 - NEW ENGL J MED VL - 377 PY - 2017 IS - 7 SP - 644 EP - 657 PG - 14 SN - 0028-4793 DO - 10.1056/NEJMoa1611925 UR - https://m2.mtmt.hu/api/publication/3257329 ID - 3257329 AB - Background Canagliflozin is a sodium-glucose cotransporter 2 inhibitor that reduces glycemia as well as blood pressure, body weight, and albuminuria in people with diabetes. We report the effects of treatment with canagliflozin on cardiovascular, renal, and safety outcomes. Methods The CANVAS Program integrated data from two trials involving a total of 10,142 participants with type 2 diabetes and high cardiovascular risk. Participants in each trial were randomly assigned to receive canagliflozin or placebo and were followed for a mean of 188.2 weeks. The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Results The mean age of the participants was 63.3 years, 35.8% were women, the mean duration of diabetes was 13.5 years, and 65.6% had a history of cardiovascular disease. The rate of the primary outcome was lower with canagliflozin than with placebo (occurring in 26.9 vs. 31.5 participants per 1000 patient-years; hazard ratio, 0.86; 95% confidence interval [CI], 0.75 to 0.97; P<0.001 for noninferiority; P=0.02 for superiority). Although on the basis of the prespecified hypothesis testing sequence the renal outcomes are not viewed as statistically significant, the results showed a possible benefit of canagliflozin with respect to the progression of albuminuria (hazard ratio, 0.73; 95% CI, 0.67 to 0.79) and the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate, the need for renal-replacement therapy, or death from renal causes (hazard ratio, 0.60; 95% CI, 0.47 to 0.77). Adverse reactions were consistent with the previously reported risks associated with canagliflozin except for an increased risk of amputation (6.3 vs. 3.4 participants per 1000 patient-years; hazard ratio, 1.97; 95% CI, 1.41 to 2.75); amputations were primarily at the level of the toe or metatarsal. Conclusions In two trials involving patients with type 2 diabetes and an elevated risk of cardiovascular disease, patients treated with canagliflozin had a lower risk of cardiovascular events than those who received placebo but a greater risk of amputation, primarily at the level of the toe or metatarsal. (Funded by Janssen Research and Development; CANVAS and CANVAS-R ClinicalTrials.gov numbers, NCT01032629 and NCT01989754 , respectively.). LA - English DB - MTMT ER -