@article{MTMT:31969727, title = {Sotagliflozin in patients with diabetes and recent worsening heart failure}, url = {https://m2.mtmt.hu/api/publication/31969727}, author = {Bhatt, D.L. and Szarek, M. and Gabriel, Steg P. and Cannon, C.P. and Leiter, L.A. and McGuire, D.K. and Lewis, J.B. and Riddle, M.C. and Voors, A.A. and Metra, M. and Lund, L.H. and Komajda, M. and Testani, J.M. and Wilcox, C.S. and Ponikowski, P. and Lopes, R.D. and Verma, S. and Lapuerta, P. and Pitt, B.}, doi = {10.1056/NEJMoa2030183}, journal-iso = {NEW ENGL J MED}, journal = {NEW ENGLAND JOURNAL OF MEDICINE}, volume = {384}, unique-id = {31969727}, issn = {0028-4793}, year = {2021}, eissn = {1533-4406}, pages = {117-128}, orcid-numbers = {Benedek, Imre-Sándor/0000-0003-0051-4047; Merkely, Béla Péter/0000-0001-6514-0723; Pálinkás, Attila/0000-0003-4839-7150} } @article{MTMT:30804305, title = {2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD}, url = {https://m2.mtmt.hu/api/publication/30804305}, author = {Cosentino, Francesco and Grant, Peter J and Aboyans, Victor and Bailey, Clifford J and Ceriello, Antonio and Delgado, Victoria and Federici, Massimo and Filippatos, Gerasimos and Grobbee, Diederick E and Hansen, Tina Birgitte and Huikuri, Heikki V and Johansson, Isabelle and Jüni, Peter and Lettino, Maddalena and Marx, Nikolaus and Mellbin, Linda G and Östgren, Carl J and Rocca, Bianca and Roffi, Marco and Sattar, Naveed and Seferović, Petar M and Sousa-Uva, Miguel and Valensi, Paul and Wheeler, David C}, doi = {10.1093/eurheartj/ehz486}, journal-iso = {EUR HEART J}, journal = {EUROPEAN HEART JOURNAL}, volume = {41}, unique-id = {30804305}, issn = {0195-668X}, keywords = {diabetes mellitus; Risk Factors; PREVENTION; EPIDEMIOLOGY; cardiovascular diseases; GUIDELINES; impaired glucose tolerance; Revascularization; pharmacological treatment; patient-centred care; Patient management; Cardiovascular risk assessment}, year = {2020}, eissn = {1522-9645}, pages = {255-323}, orcid-numbers = {Lengyel, Csaba Attila/0000-0002-0434-0067} } @article{MTMT:31591917, title = {Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure}, url = {https://m2.mtmt.hu/api/publication/31591917}, author = {Packer, Milton and Anker, Stefan D. and Butler, Javed and Filippatos, Gerasimos and Pocock, Stuart J. and Carson, Peter and Januzzi, James and Verma, Subodh and Tsutsui, Hiroyuki and Brueckmann, Martina and Jamal, Waheed and Kimura, Karen and Schnee, Janet and Zeller, Cordula and Cotton, Daniel and Bocchi, Edimar and Böhm, Michael and Choi, Dong-Ju and Chopra, Vijay and Chuquiure, Eduardo and Giannetti, Nadia and Janssens, Stefan and Zhang, Jian and Gonzalez Juanatey, Jose R. and Kaul, Sanjay and Brunner-La Rocca, Hans-Peter and Merkely, Béla Péter and Nicholls, Stephen J. and Perrone, Sergio and Pina, Ileana and Ponikowski, Piotr and Sattar, Naveed and Senni, Michele and Seronde, Marie-France and Spinar, Jindrich and Squire, Iain and Taddei, Stefano and Wanner, Christoph and Zannad, Faiez}, doi = {10.1056/NEJMoa2022190}, journal-iso = {NEW ENGL J MED}, journal = {NEW ENGLAND JOURNAL OF MEDICINE}, volume = {383}, unique-id = {31591917}, issn = {0028-4793}, year = {2020}, eissn = {1533-4406}, pages = {1413-1424}, orcid-numbers = {Merkely, Béla Péter/0000-0001-6514-0723} } @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:33677430, title = {Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy}, url = {https://m2.mtmt.hu/api/publication/33677430}, author = {Perkovic, Vlado and Jardine, Meg J and Neal, Bruce and Bompoint, Severine and Heerspink, Hiddo J L and Charytan, David M and Edwards, Robert and Agarwal, Rajiv and Bakris, George and Bull, Scott and Cannon, Christopher P and Capuano, George and Chu, Pei-Ling and de Zeeuw, Dick and Greene, Tom and Levin, Adeera and Pollock, Carol and Wheeler, David C and Yavin, Yshai and Zhang, Hong and Zinman, Bernard and Meininger, Gary and Brenner, Barry M and Mahaffey, Kenneth W}, doi = {10.1056/NEJMoa1811744}, journal-iso = {NEW ENGL J MED}, journal = {NEW ENGLAND JOURNAL OF MEDICINE}, volume = {380}, unique-id = {33677430}, issn = {0028-4793}, abstract = {Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium-glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes.In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin-angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically.The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P = 0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P = 0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P = 0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture.In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years. (Funded by Janssen Research and Development; CREDENCE ClinicalTrials.gov number, NCT02065791.).}, year = {2019}, eissn = {1533-4406}, pages = {2295-2306}, orcid-numbers = {Rosivall, László/0000-0002-9809-3879; Keltai, Katalin/0000-0002-8294-9062} } @article{MTMT:30744468, title = {SGLT2 inhibitors in T2D and associated comorbidities - differentiating within the class}, url = {https://m2.mtmt.hu/api/publication/30744468}, author = {Schernthaner, Guntram and Drexel, Heinz and Moshkovich, Evgeny and Zilaitiene, Birute and Martinka, Emil and Czupryniak, Leszek and Várkonyi, Tamás and Janež, Andrej and Ducena, Kristine and Lalić, Katarina and Tankova, Tsvetalina and Prázný, Martin and Smirčić Duvnjak, Lea and Sukhareva, Olga and Sourij, Harald}, doi = {10.1186/s12902-019-0387-y}, journal-iso = {BMC ENDOCR DISORD}, journal = {BMC ENDOCRINE DISORDERS}, volume = {19}, unique-id = {30744468}, issn = {1472-6823}, abstract = {For patients with type 2 diabetes (T2D), cardiovascular disease (CVD) is the single most common cause of mortality. In 2008 and 2012, the Federal Drug Administration (FDA) and the European Medicines Agency (EMA) respectively mandated cardiovascular outcomes trials (CVOTs) on all new anti-diabetic agents, as prospective trials statistically powered to rule out excess cardiovascular risk in patients with T2D. Unexpectedly, some of these CVOTs have demonstrated not only cardiovascular safety, but also cardioprotective effects, as was first shown for the SGLT2 inhibitor empagliflozin in EMPA-REG OUTCOME.To debate newly available CVOT data and to put them into context, we convened as a group of medical experts from the Central and Eastern European Region. Here we describe our discussions, focusing on the conclusions we can draw from EMPA-REG OUTCOME and other SGLT2 inhibitor CVOTs, including when considered alongside real-world evidence.CVOTs investigating SGLT2 inhibitors have suggested benefits beyond glucose lowering that have been confirmed in real-world evidence studies.}, keywords = {cardiovascular disease; Type 2 diabetes; dapagliflozin; Empagliflozin; Canagliflozin; SGLT2 inhibitor}, year = {2019}, eissn = {1472-6823}, orcid-numbers = {Várkonyi, Tamás/0000-0001-6833-3563} } @article{MTMT:33698770, title = {Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.}, url = {https://m2.mtmt.hu/api/publication/33698770}, author = {Zinman, Bernard and Wanner, Christoph and Lachin, John M and Fitchett, David and Bluhmki, Erich and Hantel, Stefan and Mattheus, Michaela and Devins, Theresa and Johansen, Odd Erik and Woerle, Hans J and Broedl, Uli C and Inzucchi, Silvio E}, doi = {10.1056/NEJMoa1504720}, journal-iso = {NEW ENGL J MED}, journal = {NEW ENGLAND JOURNAL OF MEDICINE}, volume = {373}, unique-id = {33698770}, issn = {0028-4793}, abstract = {The effects of empagliflozin, an inhibitor of sodium-glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known.We randomly assigned patients to receive 10 mg or 25 mg of empagliflozin or placebo once daily. The primary composite outcome was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, as analyzed in the pooled empagliflozin group versus the placebo group. The key secondary composite outcome was the primary outcome plus hospitalization for unstable angina.A total of 7020 patients were treated (median observation time, 3.1 years). The primary outcome occurred in 490 of 4687 patients (10.5%) in the pooled empagliflozin group and in 282 of 2333 patients (12.1%) in the placebo group (hazard ratio in the empagliflozin group, 0.86; 95.02% confidence interval, 0.74 to 0.99; P=0.04 for superiority). There were no significant between-group differences in the rates of myocardial infarction or stroke, but in the empagliflozin group there were significantly lower rates of death from cardiovascular causes (3.7%, vs. 5.9% in the placebo group; 38% relative risk reduction), hospitalization for heart failure (2.7% and 4.1%, respectively; 35% relative risk reduction), and death from any cause (5.7% and 8.3%, respectively; 32% relative risk reduction). There was no significant between-group difference in the key secondary outcome (P=0.08 for superiority). Among patients receiving empagliflozin, there was an increased rate of genital infection but no increase in other adverse events.Patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, as compared with placebo, had a lower rate of the primary composite cardiovascular outcome and of death from any cause when the study drug was added to standard care. (Funded by Boehringer Ingelheim and Eli Lilly; EMPA-REG OUTCOME ClinicalTrials.gov number, NCT01131676.).}, year = {2015}, eissn = {1533-4406}, pages = {2117-2128}, orcid-numbers = {Gerő, László/0000-0002-7584-9338; Tabák, Ádám/0000-0002-6234-3936} }