Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Magyarországi adatok a koszorúér-betegség másodlagos megelőzésének helyzetéről és a változás főbb jellemzői (EUROASPIRE 1995–2005) = Data on secondary prevention of coronary artery disease in Hungary and some changes in the last ten years (EUROASPIRE 1995–2005)

Az Európai Kardiológus Társaság EUROASPIRE I–II–III néven vizsgálatsorozatot kezdeményezett a másodlagos prevenció európai helyzetének felmérésére. Magyarország ugyanazon két kardiológiai centrum bevonásával részt vett ebben a jelentős epidemiológiai vizsgálatsorozatban. A szerzők az elmúlt 10 év hazai adatait elemzik. Összesen 1627 – 70 évesnél fiatalabb – koszorúérbeteg kórházi és utánvizsgálati adatait dolgozták fel standardizált módszerekkel. Az ischaemiás szívbetegség miatt kezelt betegek között csökkent a férfiak, és nőtt a nőbetegek, valamint a 60 évnél idősebbek aránya. A vizsgált rizikófaktorok kórházi dokumentálása jelentősen javult: az utolsó adatfelvétel időpontjában a betegek 89–99%-ában ezen adatok rögzítése a kórlapban megtörtént. A vizsgálati időpontokban csökkent a szisztolés és a diasztolés vérnyomás átlagértéke, valamint a harmadik vizsgálati időpontban 0,4 mmol/L-rel alacsonyabb volt az össz- és az LDL-koleszterin átlagértéke, mint a vizsgálat kezdetén. A HDL-koleszterin átlagértéke nem változott, a triglicerid esetén pedig az átlag növekedését figyelték meg. A tíz év alatt folyamatosan és jelentősen nőtt (23%-ról 49%-ra) a súlyosan elhízottak, valamint a diabetesesek aránya (27%-ról 45%-ra). A hypertoniások száma csak az első és második vizsgálati időpont között csökkent, a harmadik időpontban a megvizsgáltak 44%-ában 140/90 Hgmm feletti vérnyomásértéket mértek. A dohányzó betegek aránya a második és a harmadik adatfelvételi időpont között 8%-kal csökkent, a vizsgálat lezárásakor az aktív dohányosok aránya 18% volt. Jelentősen csökkent (60%-ról 24%-ra) az 5,5 mmol/L feletti összkoleszterin-értékkel bíró betegek aránya, ugyanakkor az összkoleszterin jelenlegi célértékét (4,5 mmo/L) a betegek 57%-a nem érte el. A másodlagos prevenció területén az elmúlt 10 évben kétségtelen javulás igazolható, de még mindig nem sikerült megfelelően csökkenteni a magas vérnyomást, a koleszterinszintet, a dohányzók arányát, és aggasztó az elhízottak és a cukorbetegek számának növekedése. A szerzők – a helyzet javítása érdekében – fontosnak tartják a prevenció fontosságának hangsúlyozását az orvosképzésben és az orvos-továbbképzésben, valamint az együttműködés javítását a kórházi orvosok, a családorvosok és a betegek között. Orv. Hetil., 2010, 43, 1776–1782. | In year 1995 the European Society of Cardiology started an epidemiological study EUROASPIRE to evaluate the results of secondary prevention in some European countries. The first study period was in 1995, the second in 1999-2000 and the third in 2007. From Hungary the same study centers participated in EUROASPIRE I–II–III investigation. Authors present the Hungarian data and changes occurring the last ten years. During the three studies, 1627 coronary patients- younger than 70 years – were evaluated, using standardized methods. In the two Hungarian study centers, the proportion of women and patients older than 60 years increased. The hospital documentation of risk factors improved, at the time of EUROASPIRE III necessary data were found in 89%–99% of patient’s records. Mean systolic and diastolic blood pressure continuously decreased between the first and second study period, but at the time of the third study 44% of the patients had elevated blood pressure (>140/90 mmHg). Prevalence of smoking decreased by 8% between second and third study period, however, at the time of the last study, 18% of coronary patients were smokers. The mean of total cholesterol was lower in the last study period comparing to the first investigation (5.6 vs. 5.2 mmol/l). HDL cholesterol level was unchanged and increasing triglyceride values were observed. During the study period the prevalence of obesity continuously increased from 23% to 49%. Prevalence of patients with total cholesterol level 5.5 mmol/l or higher has decreased from 60% to 24%, however 57% of patients did not reach the target level (4.5 mmol/l) although 80% of patients were treated with lipid lowering drugs: 76% of them received statins. Authors say that some part of secondary prevention improved during the last ten years, but many patients did not reach the target blood pressure and cholesterol level and it is embarrassing the prevalence of obesity and diabetes. The published data are not representative for whole Hungary; most probably the general situation is worse. Authors emphasize the importance of secondary prevention in the graduate and postgraduate education. For improving the secondary prevention, better cooperation is needed between hospital staff and patients and general practitioners as well. Orv. Hetil., 2010, 43, 1776–1782

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)