@article{MTMT:30828891,
	title = {Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction.},
	url = {https://m2.mtmt.hu/api/publication/30828891},
	author = {McMurray, John J V and Solomon, Scott D and Inzucchi, Silvio E and Køber, Lars and Kosiborod, Mikhail N and Martinez, Felipe A and Ponikowski, Piotr and Sabatine, Marc S and Anand, Inder S and Bělohlávek, Jan and Böhm, Michael and Chiang, Chern-En and Chopra, Vijay K and de Boer, Rudolf A and Desai, Akshay S and Diez, Mirta and Drozdz, Jaroslaw and Dukát, Andrej and Ge, Junbo and Howlett, Jonathan G and Katova, Tzvetana and Kitakaze, Masafumi and Ljungman, Charlotta E A and Merkely, Béla Péter and Nicolau, Jose C and O'Meara, Eileen and Petrie, Mark C and Vinh, Pham N and Schou, Morten and Tereshchenko, Sergey and Verma, Subodh and Held, Claes and DeMets, David L and Docherty, Kieran F and Jhund, Pardeep S and Bengtsson, Olof and Sjöstrand, Mikaela and Langkilde, Anna-Maria},
	doi = {10.1056/NEJMoa1911303},
	journal-iso = {NEW ENGL J MED},
	journal = {NEW ENGLAND JOURNAL OF MEDICINE},
	volume = {381},
	unique-id = {30828891},
	issn = {0028-4793},
	abstract = {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.).},
	year = {2019},
	eissn = {1533-4406},
	pages = {1995-2008},
	orcid-numbers = {Merkely, Béla Péter/0000-0001-6514-0723}
}

@article{MTMT:31089317,
	title = {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},
	url = {https://m2.mtmt.hu/api/publication/31089317},
	author = {Packer, Milton and Butler, Javed and Filippatos, Gerasimos S. and Jamal, Waheed and Salsali, Afshin and Schnee, Janet and Kimura, Karen and Zeller, Cordula and George, Jyothis and Brueckmann, Martina and Anker, Stefan D. and Zannad, Faiez and Perrone, Sergio and Nicholls, Stephen and Janssens, Stefan and Bocchi, Edmar and Giannetti, Nadia and Verma, Subodh and Jian, Zhang and Spinar, Jindrich and Seronde, Marie-France and Boehm, Michael and Merkely, Béla Péter and Chopra, Vijay and Senni, Michele and Taddei, Stefano and Tsutsui, Hiroyuki and Choi, Dong-Ju and Chuquiure, Eduardo and La Rocca, Hans Pieter Brunner and Ponikowski, Piotr and Gonzalez Juanatey, Jose Ramon and Squire, Iain and Butler, Javed and Januzzi, James and Pina, Ileana and Pocock, Stuart J. and Carson, Peter and Doehner, Wolfram and Miller, Alan and Haas, Markus and Pehrson, Steen and Komajda, Michel and Anand, Inder and Teerlink, John and Rabinstein, Alejandro and Steiner, Thorsten and Kamel, Hooman and Tsivgoulis, Georgios and Lewis, James and Freston, James and Kaplowitz, Neil and Mann, Johannes and Petrie, Mark and Bernstein, Richard and Cheung, Alfred and Green, Jennifer and Januzzi, James and Kaul, Sanjay and Ping, Carolyn Lam Su and Lip, Gregory and Marx, Nikolaus and McCullough, Peter and Mehta, Cyrus and Ponikowski, Piotr and Rosenstock, Julio and Sattar, Naveed and Scirica, Benjamin and Tsutsui, Hiroyuki and Verma, Subodh and Wanner, Christoph and Welty, Francine K. and Parhofer, Klaus G. and Clayton, Tim and Pedersen, Terje R. and Lees, Kennedy R. and Konstam, Marvin A. and Greenberg, Barry and Palmer, Mike},
	doi = {10.1002/ejhf.1536},
	journal-iso = {EUR J HEART FAIL},
	journal = {EUROPEAN JOURNAL OF HEART FAILURE},
	volume = {21},
	unique-id = {31089317},
	issn = {1388-9842},
	abstract = {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.},
	keywords = {heart failure; Diabetes; REDUCED EJECTION FRACTION; Trial design; SGLT2 inhibitors},
	year = {2019},
	eissn = {1879-0844},
	pages = {1270-1278},
	orcid-numbers = {Merkely, Béla Péter/0000-0001-6514-0723}
}

@article{MTMT:3257329,
	title = {Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes.},
	url = {https://m2.mtmt.hu/api/publication/3257329},
	author = {Neal, B and Perkovic, V and Mahaffey, KW and de Zeeuw, D and Fulcher, G and Erondu, N and Shaw, W and Law, G and Desai, M and Matthews, DR},
	doi = {10.1056/NEJMoa1611925},
	journal-iso = {NEW ENGL J MED},
	journal = {NEW ENGLAND JOURNAL OF MEDICINE},
	volume = {377},
	unique-id = {3257329},
	issn = {0028-4793},
	abstract = {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.).},
	keywords = {Aged; Female; Middle Aged; Male; Humans; DISEASE PROGRESSION; Albuminuria/complications; Hypoglycemic Agents/adverse effects/*therapeutic use; Amputation/statistics & numerical data; Glomerular Filtration Rate/drug effects; Hospitalization/statistics & numerical data; Foot/surgery; Cardiovascular Diseases/epidemiology/mortality/*prevention & control; Kidney Diseases/*etiology/mortality; Diabetes Mellitus, Type 2/complications/*drug therapy/physiopathology; Canagliflozin/adverse effects/*therapeutic use},
	year = {2017},
	eissn = {1533-4406},
	pages = {644-657}
}