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Рабочая группа по реваскуляризации миокарда Европейского общества кардиологов (esc) и Европейской ассоциации кардиоторакальных хирургов (eActs) Разработаны с участием Европейской ассоциации по чрескожным сердечно-сосудистым вмешательствам (eApcI) Авторы/члены Рабочей группы: stephan Windecker* (Председатель esc) (Швейцария), philippe Kolh* (Председатель eActs) (Бельгия), Fernando Alfonso (Испания), Jean-philippe collet (Франция), Jochen cremer (Германия), Volkmar Falk (Швейцария), Gerasimos Filippatos (Греция), christian Hamm (Германия), stuart J. Head (Нидерланды), peter Jüni (Швейцария), A. pieter Kappetein (Нидерланды), Adnan Kastrati (Германия), Juhani Knuuti (Финляндия), Ulf Landmesser (Швейцария), Günther Laufer (Австрия), Franz-Josef Neumann (Германия), Dimitrios J. Richter (Греция), patrick schauerte (Германия), Miguel sousa Uva (Португалия), Giulio G. stefanini (Швейцария), David paul taggart (Соединённое Королевство), Lucia torracca (Италия), Marco Valgimigli (Италия), William Wijns (Бельгия), and Adam Witkowski (Польша). В подготовке данных рекомендаций приняли участие следующие подразделе-ния esc: Ассоциации esc: Ассоциация специалистов по острой сердечно-сосудистой помощи (Acute cardiovascular care Association; AccA), Европейская ассоциа-ция специалистов по методам визуализации сердечно-сосудистой системы (european Association of cardiovascular Imaging; eAcVI), Европейская ассоциа-ция специалистов по сердечно-сосудистой профилактике и реабилитации (european Association for cardiovascular prevention & Rehabilitation; eAcpR), Европейская ассоциация аритмологов (european Heart Rhythm Association; eHRA), Ассоциация специалистов по сердечной недостаточности (Heart Failure Association; HFA). КомитетРабочие группы esc: Сердечно-сосудистая клеточная электрофизиология, Магнитная резонансная томография сердечно-сосудистой системы, Сер-дечно-сосудистая фармакология и медикаментозная терапия, Сердечно-сосудистая хирургия, Коронарная патофизиология и микроциркуляция, Ядер-ная кардиология и КТ сердца, Периферическая циркуляция, Тромбоз, Коро-нарная болезнь сердца.Советы esc: Кардиологическая практика, Первичная сердечно-сосудистая помощь, Уход за сердечно-сосудистыми больными, Смежные профессии.Содержание данных рекомендаций, подготовленных Европейским Общест-вом Кардиологов (european society of cardiology, esc) опубликовано исклю-чительно для использования в личных и образовательных целях. Не допуска-ется коммерческое использование содержания рекомендаций. Рекомендации esc не могут быть переведены на другие языки либо воспроизведены, полно-стью или частично, без письменного согласия esc. Для получения данного согласия письменная заявка должна быть направлена в oxford University press -организацию, издающую european Heart Journal и официально упол-номоченную esc, рассматривать подобные заявки.Отказ от ответственности. Рекомендации esc отражают взгляды esc и осно-ваны на тщательном анализе научных данных, доступных во время подготовки данных рекомендаций. Медицинским работникам следует придер живаться данных реко...

AimsTo establish the safety, tolerability and most promising regimen of darexaban (YM150), a novel, oral, direct factor Xa inhibitor, for prevention of ischaemic events in acute coronary syndrome (ACS).MethodsIn a 26-week, multi-centre, double-blind, randomized, parallel-group study, 1279 patients with recent high-risk non-ST-segment or ST-segment elevation ACS received one of six darexaban regimens: 5 mg b.i.d., 10 mg o.d., 15 mg b.i.d., 30 mg o.d., 30 mg b.i.d., or 60 mg o.d. or placebo, on top of dual antiplatelet treatment. Primary outcome was incidence of major or clinically relevant non-major bleeding events. The main efficacy outcome was a composite of death, stroke, myocardial infarction, systemic thromboembolism, and severe recurrent ischaemia.ResultsBleeding rates were numerically higher in all darexaban arms vs. placebo (pooled HR: 2.275; 95% CI: 1.13–4.60, P = 0.022). Using placebo as reference (bleeding rate 3.1%), there was a dose–response relationship (P = 0.009) for increased bleeding with increasing darexaban dose (6.2, 6.5, and 9.3% for 10, 30, and 60 mg daily, respectively), which was statistically significant for 30 mg b.i.d. (P = 0.002). There was no decrease (indeed a numerical increase in the 30 and 60 mg dose arms) in efficacy event rates with darexaban, but the study was underpowered for efficacy. Darexaban showed good tolerability without signs of liver toxicity.ConclusionsDarexaban when added to dual antiplatelet therapy after ACS produces an expected dose-related two- to four-fold increase in bleeding, with no other safety concerns but no signal of efficacy. Establishing the potential of low-dose darexaban in preventing major cardiac events after ACS requires a large phase III trial.ClinicalTrials.gov Identifier: NCT00994292

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IMPORTANCE p38 Mitogen-activated protein kinase (MAPK)-stimulated inflammation is implicated in atherogenesis, plaque destabilization, and maladaptive processes in myocardial infarction (MI). Pilot data in a phase 2 trial in non-ST elevation MI indicated that the p38 MAPK inhibitor losmapimod attenuates inflammation and may improve outcomes. OBJECTIVE To evaluate the efficacy and safety of losmapimod on cardiovascular outcomes in patients hospitalized with an acute myocardial infarction. DESIGN, SETTING, AND PATIENTS LATITUDE-TIMI 60, a randomized, placebo-controlled, double-blind, parallel-group trial conducted at 322 sites in 34 countries from June 3, 2014, until December 8, 2015. Part A consisted of a leading cohort (n = 3503) to provide an initial assessment of safety and exploratory efficacy before considering progression to part B (approximately 22 000 patients). Patients were considered potentially eligible for enrollment if they had been hospitalized with an acute MI and had at least 1 additional predictor of cardiovascular risk. INTERVENTIONS Patients were randomized to either twice-daily losmapimod (7.5 mg; n = 1738) or matching placebo (n = 1765) on a background of guideline-recommended therapy. Patients were treated for 12 weeks and followed up for an additional 12 weeks. MAIN OUTCOMES AND MEASURES The primary end point was the composite of cardiovascular death, MI, or severe recurrent ischemia requiring urgent coronary revascularization with the principal analysis specified at week 12. RESULTS In part A, among the 3503 patients randomized (median age, 66 years; 1036 [29.6%] were women), 99.1% had complete ascertainment for the primary outcome. The primary end point occurred by 12 weeks in 123 patients treated with placebo (7.0%) and 139 patients treated with losmapimod (8.1%; hazard ratio, 1.16; 95% CI, 0.91-1.47; P = .24). The on-treatment rates of serious adverse events were 16.0% with losmapimod and 14.2% with placebo. CONCLUSIONS AND RELEVANCE Among patients with acute MI, use of losmapimod compared with placebo did not reduce the risk of major ischemic cardiovascular events. The results of this exploratory efficacy study did not justify proceeding to a larger efficacy trial in the existing patient population.

NCT01176968.

IMPORTANCE The optimal anticoagulant for patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) managed with an invasive strategy remains controversial.OBJECTIVE To compare the clinical efficacy and safety of otamixaban, a novel intravenous direct factor Xa inhibitor, with that of unfractionated heparin plus downstream eptifibatide in patients with NSTE-ACS undergoing a planned early invasive strategy. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, active-controlled superiority trial that enrolled 13 229 patients with NSTE-ACS and a planned early invasive strategy, at 568 active sites in 55 countries and conducted between April 2010 and February 2013. A planned interim analysis was conducted for otamixaban dose selection.INTERVENTIONS Eligible participants were randomized to otamixaban (bolus and infusion, at 1 of 2 doses) or unfractionated heparin plus, at the time of percutaneous coronary intervention, eptifibatide. The otamixaban dose selected at interim analysis was an intravenous bolus of 0.080 mg/kg followed by an infusion of 0.140 mg/kg per hour. MAIN OUTCOMES AND MEASURESThe primary efficacy outcome was the composite of all-cause death or new myocardial infarction through day 7.RESULTS Rates of the primary efficacy outcome were 5.5% (279 of 5105 patients) randomized to receive otamixaban and 5.7% (310 of 5466 patients) randomized to receive unfractionated heparin plus eptifibatide (adjusted relative risk, 0.99 [95% CI, 0.85-1.16]; P = .93). There were no differences for the secondary end points, including procedural thrombotic complications. The primary safety outcome of Thrombosis in Myocardial Infarction major or minor bleeding through day 7 was increased by otamixaban (3.1% vs 1.5%; relative risk, 2.13 [95% CI, 1.63-2.78]; P < .001). Results were consistent across prespecified subgroups.CONCLUSIONS AND RELEVANCE Otamixaban did not reduce the rate of ischemic events relative to unfractionated heparin plus eptifibatide but did increase bleeding. These findings do not support the use of otamixaban for patients with NSTE-ACS undergoing planned early percutaneous coronary intervention.

Aims To assess the proportion of patients with heart failure and reduced ejection fraction (HFrEF) who are eligible for sacubitril/valsartan (LCZ696) based on the European Medicines Agency/Food and Drug Administration (EMA/FDA) label, the PARADIGM‐HF trial and the 2016 ESC guidelines, and the association between eligibility and outcomes. Methods and results Outpatients with HFrEF in the ESC‐EORP‐HFA Long‐Term Heart Failure (HF‐LT) Registry between March 2011 and November 2013 were considered. Criteria for LCZ696 based on EMA/FDA label, PARADIGM‐HF and ESC guidelines were applied. Of 5443 patients, 2197 and 2373 had complete information for trial and guideline eligibility assessment, and 84%, 12% and 12% met EMA/FDA label, PARADIGM‐HF and guideline criteria, respectively. Absent PARADIGM‐HF criteria were low natriuretic peptides (21%), hyperkalemia (4%), hypotension (7%) and sub‐optimal pharmacotherapy (74%); absent Guidelines criteria were LVEF>35% (23%), insufficient NP levels (30%) and sub‐optimal pharmacotherapy (82%); absent label criteria were absence of symptoms (New York Heart Association class I). When a daily requirement of ACEi/ARB ≥ 10 mg enalapril (instead of ≥ 20 mg) was used, eligibility rose from 12% to 28% based on both PARADIGM‐HF and guidelines. One‐year heart failure hospitalization was higher (12% and 17% vs. 12%) and all‐cause mortality lower (5.3% and 6.5% vs. 7.7%) in registry eligible patients compared to the enalapril arm of PARADIGM‐HF. Conclusions Among outpatients with HFrEF in the ESC‐EORP‐HFA HF‐LT Registry, 84% met label criteria, while only 12% and 28% met PARADIGM‐HF and guideline criteria for LCZ696 if requiring ≥ 20 mg and ≥ 10 mg enalapril, respectively. Registry patients eligible for LCZ696 had greater heart failure hospitalization but lower mortality rates than the PARADIGM‐HF enalapril group.