@article{MTMT:32662628,
	title = {Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome},
	url = {https://m2.mtmt.hu/api/publication/32662628},
	author = {Schwartz, Gregory G and Steg, P Gabriel and Szarek, Michael and Bhatt, Deepak L and Bittner, Vera A and Diaz, Rafael and Edelberg, Jay M and Goodman, Shaun G and Hanotin, Corinne and Harrington, Robert A and Jukema, J Wouter and Lecorps, Guillaume and Mahaffey, Kenneth W and Moryusef, Angèle and Pordy, Robert and Quintero, Kirby and Roe, Matthew T and Sasiela, William J and Tamby, Jean-François and Tricoci, Pierluigi and White, Harvey D and Zeiher, Andreas M},
	doi = {10.1056/NEJMoa1801174},
	journal-iso = {NEW ENGL J MED},
	journal = {NEW ENGLAND JOURNAL OF MEDICINE},
	volume = {379},
	unique-id = {32662628},
	issn = {0028-4793},
	abstract = {Patients who have had an acute coronary syndrome are at high risk for recurrent ischemic cardiovascular events. We sought to determine whether alirocumab, a human monoclonal antibody to proprotein convertase subtilisin-kexin type 9 (PCSK9), would improve cardiovascular outcomes after an acute coronary syndrome in patients receiving high-intensity statin therapy.We conducted a multicenter, randomized, double-blind, placebo-controlled trial involving 18,924 patients who had an acute coronary syndrome 1 to 12 months earlier, had a low-density lipoprotein (LDL) cholesterol level of at least 70 mg per deciliter (1.8 mmol per liter), a non-high-density lipoprotein cholesterol level of at least 100 mg per deciliter (2.6 mmol per liter), or an apolipoprotein B level of at least 80 mg per deciliter, and were receiving statin therapy at a high-intensity dose or at the maximum tolerated dose. Patients were randomly assigned to receive alirocumab subcutaneously at a dose of 75 mg (9462 patients) or matching placebo (9462 patients) every 2 weeks. The dose of alirocumab was adjusted under blinded conditions to target an LDL cholesterol level of 25 to 50 mg per deciliter (0.6 to 1.3 mmol per liter). The primary end point was a composite of death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization.The median duration of follow-up was 2.8 years. A composite primary end-point event occurred in 903 patients (9.5%) in the alirocumab group and in 1052 patients (11.1%) in the placebo group (hazard ratio, 0.85; 95% confidence interval [CI], 0.78 to 0.93; P<0.001). A total of 334 patients (3.5%) in the alirocumab group and 392 patients (4.1%) in the placebo group died (hazard ratio, 0.85; 95% CI, 0.73 to 0.98). The absolute benefit of alirocumab with respect to the composite primary end point was greater among patients who had a baseline LDL cholesterol level of 100 mg or more per deciliter than among patients who had a lower baseline level. The incidence of adverse events was similar in the two groups, with the exception of local injection-site reactions (3.8% in the alirocumab group vs. 2.1% in the placebo group).Among patients who had a previous acute coronary syndrome and who were receiving high-intensity statin therapy, the risk of recurrent ischemic cardiovascular events was lower among those who received alirocumab than among those who received placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; ODYSSEY OUTCOMES ClinicalTrials.gov number, NCT01663402 .).},
	year = {2018},
	eissn = {1533-4406},
	pages = {2097-2107},
	orcid-numbers = {Merkely, Béla Péter/0000-0001-6514-0723; Ungi, Imre/0000-0002-2011-0069}
}

@article{MTMT:32750826,
	title = {Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients},
	url = {https://m2.mtmt.hu/api/publication/32750826},
	author = {Ridker, Paul M and Revkin, James and Amarenco, Pierre and Brunell, Robert and Curto, Madelyn and Civeira, Fernando and Flather, Marcus and Glynn, Robert J and Gregoire, Jean and Jukema, J Wouter and Karpov, Yuri and Kastelein, John J P and Koenig, Wolfgang and Lorenzatti, Alberto and Manga, Pravin and Masiukiewicz, Urszula and Miller, Michael and Mosterd, Arend and Murin, Jan and Nicolau, Jose C and Nissen, Steven and Ponikowski, Piotr and Santos, Raul D and Schwartz, Pamela F and Soran, Handrean and White, Harvey and Wright, R Scott and Vrablik, Michal and Yunis, Carla and Shear, Charles L and Tardif, Jean-Claude},
	doi = {10.1056/NEJMoa1701488},
	journal-iso = {NEW ENGL J MED},
	journal = {NEW ENGLAND JOURNAL OF MEDICINE},
	volume = {376},
	unique-id = {32750826},
	issn = {0028-4793},
	abstract = {Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk.In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months.At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P=0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P=0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P=0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001).In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients. (Funded by Pfizer; SPIRE-1 and SPIRE-2 ClinicalTrials.gov numbers, NCT01975376 and NCT01975389 .).},
	year = {2017},
	eissn = {1533-4406},
	pages = {1527-1539}
}

@article{MTMT:33282814,
	title = {Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes.},
	url = {https://m2.mtmt.hu/api/publication/33282814},
	author = {Cannon, Christopher P and Blazing, Michael A and Giugliano, Robert P and McCagg, Amy and White, Jennifer A and Theroux, Pierre and Darius, Harald and Lewis, Basil S and Ophuis, Ton Oude and Jukema, J Wouter and De Ferrari, Gaetano M and Ruzyllo, Witold and De Lucca, Paul and Im, KyungAh and Bohula, Erin A and Reist, Craig and Wiviott, Stephen D and Tershakovec, Andrew M and Musliner, Thomas A and Braunwald, Eugene and Califf, Robert M},
	doi = {10.1056/NEJMoa1410489},
	journal-iso = {NEW ENGL J MED},
	journal = {NEW ENGLAND JOURNAL OF MEDICINE},
	volume = {372},
	unique-id = {33282814},
	issn = {0028-4793},
	abstract = {Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known.We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. The median follow-up was 6 years.The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (P<0.001). The Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group, as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P=0.016). Rates of prespecified muscle, gallbladder, and hepatic adverse effects and cancer were similar in the two groups.When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit. (Funded by Merck; IMPROVE-IT ClinicalTrials.gov number, NCT00202878.).},
	year = {2015},
	eissn = {1533-4406},
	pages = {2387-2397},
	orcid-numbers = {Simonyi, Gábor/0000-0002-5205-3820}
}

@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}
}