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

National Registry of Hypertension. Epidemiological Characteristics of Hypertension in Argentina. The RENATA 2 study

Background: Hypertension is the main risk factor for cardiovascular disease and cardiovascular mortality. As the prevalence of hypertension is increasing, it is necessary to know the updated information in Argentina. Objective: The aim of this study was to evaluate the prevalence, awareness, treatment and control of hypertension in Argentina. Methods: A cross-sectional study was conducted including subjects ≥ 18 years from 25 cities in Argentina. The participants were surveyed and blood pressure was measured using validated automated sphygmomanometers. Results: A total of 5.931 subjects were surveyed. Mean age was 43.5±17.1 years. The prevalence of hypertension was 36.3% (95% CI, 35.1-37.6), was higher in men (43.7% vs. 30.4%; p < 0.0001), and increased with age in both sexes. Among subjects with hypertension, 38.8% were unaware of their condition while 5.7% knew it but were not receiving treatment. In 55.5% of cases, subjects were receiving therapy, and only 24.2% were well controlled, particularly women. In treated subjects, 73.4% were receiving monotherapy and hypertension was controlled in only 43.6%. Patients who adhered to treatment had better blood pressure control than those who did not (46.9% vs. 40.1%; p=0.01). Conclusions: The prevalence of hypertension in Argentina is 36.3%, in agreement with the reports of the World Health Organization for the region. In 38.8% of cases, participants were unaware of their condition. Half of the subjects with hypertension were receiving drug therapy and only 25% were controlled. Three out of four patients treated were receiving monotherapy. Blood pressure control was associated with better adherence to treatment.Introducción: La hipertensión arterial es el principal factor de riesgo para enfermedad y muerte cardiovascular. Su prevalencia va en aumento, lo cual hace necesario conocer los datos actualizados en la Argentina. Objetivo: Evaluar la prevalencia, el conocimiento, el tratamiento y el control de la hipertensión arterial en la Argentina. Material y métodos: Estudio de corte transversal que incluyó individuos ≥ 18 años de 25 ciudades argentinas. Los participantes fueron encuestados y se midió la presión arterial con presurómetros automáticos validados. Resultados: Se encuestaron 5.931 individuos, con una edad promedio de 43,5 ± 17,1 años. La prevalencia de hipertensión arterial fue del 36,3% (IC 95% 35,1-37,6), siendo mayor en varones (43,7% vs. 30,4%; p < 0,0001). La prevalencia aumentó con la edad en ambos sexos. El 38,8% de los hipertensos desconocían su enfermedad y el 5,7% la conocían pero no recibían tratamiento. El 55,5% estaban tratados y solo el 24,2% se encontraban controlados, observándose más control en las mujeres. El 73,4% de los hipertensos tratados recibían monoterapia y solo el 43,6% estaban controlados. Los pacientes adherentes al tratamiento tuvieron mejor control de la presión arterial que los no adherentes (46,9% vs. 40,1%; p = 0,01). Conclusiones: La prevalencia de hipertensión arterial en la Argentina es del 36,3%, en coincidencia con los reportes de la Organización Mundial de la Salud para la región. El 38,8% de los participantes desconocían su enfermedad. La mitad de los hipertensos recibían tratamiento farmacológico y solo la cuarta parte estaban controlados. Tres de cada cuatro pacientes tratados recibían monoterapia. El control de la presión arterial se relacionó con mejor adherencia al tratamiento

Evaluación de la calidad de la atención en un Centro de Hipertensión Arterial de un Hospital Universitario

Introducción: La Hipertensión Arterial (HTA) constituye uno de los motivos más frecuentes de consulta y prescripción de medicamentos. Afecta al 30 al 35% de la población mundial; número que está en aumento debido al envejecimiento poblacional (1). Más aún, esta enfermedad constituye el principal factor de riesgo para desarrollar enfermedad coronaria, insuficiencia cardíaca, insuficiencia renal, enfermedad vascular periférica, inclusive accidentes cerebrovasculares (2). Recientemente se ha realizado un registro para evaluar la prevalencia de HTA en Argentina (RENATA: REgistro NAcional de HiperTensión Arterial 2008/2009). Este estudio con características de encuesta, incluyó 4006 sujetos de la población general con una edad promedio de 43.7 ± 17.0 años, de los cuales el 48.3% fueron hombres. Los hallazgos del mismo mostraron que el 33.5% de la población general presentó hipertensión siendo más prevalente en hombres (44.6% en hombres vs. 25.9% en mujeres; p<O,OOl). Se observó que dentro de los pacientes con HTA, el 37.2% desconocía que tenía esta patología y un 6.6% de los mismos a pesar de conocer que eran hipertensos no realizaban tratamiento alguno..

Morning Hypertension and Non-dipper Behavior in Pregnant Women with White Coat Syndrome

Background: White coat syndrome (WCS) is common during pregnancy, although little is known about its clinical outcomeduring gestation. Morning hypertension and the non-dipper behavior, measured by ambulatory blood pressure monitoring(ABPM), are associated with greater risk of cardiovascular events. However, there are few studies during pregnancy.Objectives: The primary aim of the study was to evaluate morning hypertension and the non-dipper behavior in pregnantwomen with WCS versus a control normotensive group. A secondary objective was to evaluate whether WCS, morning hypertensionand the non-dipper behavior in the second trimester of pregnancy were associated with greater hypertension inthe third trimester.Methods: This prospective study included 95 primiparae in the 20th week of gestation, 50 with WCS and 45 as normotensivecontrol group. Routine lab tests, office blood pressure and ABPM at inclusion and in the 32th week of gestation were recorded.Morning hypertension and the non-dipper behavior were evaluated by ABPM.Results: Age, and baseline blood glucose level and daytime and nighttime blood pressure by ABPM were similar in both groups.Conversely, patients presenting WCS had significantly higher values of morning hypertension and non-dipper behavior, whichwere independently associated with sustained hypertension in the third trimester of pregnancy.Conclusions: Pregnant women with WCS in the 20th week of gestation presented greater morning hypertension and non-dipperbehavior and progressed more frequently to sustained hypertension than the control normotensive group.Antecedentes: la hipertensión de guardapolvo blanco (HGB) es común en el embarazo pero, su evolución clínica  es aun objeto de debate. Por otro lado, la presión al despertar  elevada (PDE)  y el comportamiento no dipper (CND)  medidos por monitoreo de presión arterial ambulatorio  (MAPA), se asocian a mayor riesgo de eventos cardiovasculares. Sin embargo, han sido poco estudiados en esta población.   Objetivo primario: evaluar  la PDE y el CND en embarazadas  con HGB respecto a un grupo control de normotensas (N).   Objetivo secundario: evaluar si la HGB, la PDE  y el CND  en etapa precoz del embarazo  se relacionan a mayor  hipertensión sostenida (HS) en la segunda mitad del embarazo. Métodos: estudio prospectivo, se incluyeron 198 primigestas en semana 20 de gestación, continuaron en seguimiento 50 con HGB y 45 con N. Se registró laboratorio de rutina, presión de consultorio (PC)  y MAPA en la inclusión y a las 32 semanas de gestación. La PDE  y CND fueron evaluadas por MAPA.   Resultados: Las variables: edad, glucemia, valores de presion por MAPA  diurnos y nocturnos fueron similares en el examen basal en ambos grupos. Por el contrario, las  con HGB presentaron valores significativamente superiores de PDE y CND, los cuales se asociaron en forma independiente con HS en la segunda mitad del embarazo.     Conclusion: Las gestantes con HGB presentaron mayor PDE y CND en semana 20 del embarazo, respecto a N. La evolucion a HS en la segunda mitad de gestacion , fue  mayor respecto a normotensas pero sin  valor estadistico significativo.Antecedentes: la hipertensión de guardapolvo blanco (HGB) es común en el embarazo pero, su evolución clínica  es aun objeto de debate. Por otro lado, la presión al despertar  elevada (PDE)  y el comportamiento no dipper (CND)  medidos por monitoreo de presión arterial ambulatorio  (MAPA), se asocian a mayor riesgo de eventos cardiovasculares. Sin embargo, han sido poco estudiados en esta población.   Objetivo primario: evaluar  la PDE y el CND en embarazadas  con HGB respecto a un grupo control de normotensas (N).   Objetivo secundario: evaluar si la HGB, la PDE  y el CND  en etapa precoz del embarazo  se relacionan a mayor  hipertensión sostenida (HS) en la segunda mitad del embarazo. Métodos: estudio prospectivo, se incluyeron 198 primigestas en semana 20 de gestación, continuaron en seguimiento 50 con HGB y 45 con N. Se registró laboratorio de rutina, presión de consultorio (PC)  y MAPA en la inclusión y a las 32 semanas de gestación. La PDE  y CND fueron evaluadas por MAPA.   Resultados: Las variables: edad, glucemia, valores de presion por MAPA  diurnos y nocturnos fueron similares en el examen basal en ambos grupos. Por el contrario, las  con HGB presentaron valores significativamente superiores de PDE y CND, los cuales se asociaron en forma independiente con HS en la segunda mitad del embarazo.     Conclusion: Las gestantes con HGB presentaron mayor PDE y CND en semana 20 del embarazo, respecto a N. La evolucion a HS en la segunda mitad de gestacion , fue  mayor respecto a normotensas pero sin  valor estadistico significativo

Hipertensión de guardapolvo blanco: evolución a hipertensión sostenida luego de 10 años de seguimiento

Background The long-term outcome of white coat hypertension (WCH) is still controversial despite the extensive information currently available. Objective To evaluate the cumulative incidence of sustained hypertension (SH) among patients with white coat hypertension compared to normotensive patients after 10 years of inclusion in the study. Methods Two hundred and fifty patients of both genders were prospectively included in the study with the following office blood pressure (OBP) and 24-hour ambulatory blood pressure monitoring (ABPM) values : WCH Hypertension Normal BP OBP (mm Hg) . 140 and/or 90 . 140 and/or 90 . 140 and/or 90 ABPM (mm Hg) . 135 and 85 . 135 and 85 . 135 and 85 The patients were divided into two groups: 129 patients with WCH and 121 normotensive patients, and were evaluated after 10 years of follow-up. Glucose blood level, lipid profile and left ventricular mass index (LVMI) were measured. Results Age, gender, smoking habits and glucose blood level were similar at baseline among normotensive patients and patients with white coat hypertension. However, body mass index, total cholesterol levels, lipid levels and LVMI were significantly greater in white-coat hypertensive patients. Sustained hypertension was developed by 48 patients with WCH and 21 normotensive patients. We found an independent association between WCH and SH at 10 years of follow-up [OR: 2.5 (95% CI 1.2-4.2)]. Conclusion Progression to sustained hypertension was greater in patients with white coat hypertension compared to normotensive patients.Introducción No obstante la amplia información en la bibliografía sobre la caracterización de la hipertensión de guardapolvo blanco (HGB), su evolución alejada es hasta el presente tema de controversia. Objetivo Evaluar la incidencia acumulada de hipertensión sostenida (HS) en hipertensos de guardapolvo blanco respecto de normotensos a los 10 años de su inclusión en el estudio. Material y métodos Se incorporaron en forma prospectiva 250 pacientes de ambos sexos, según los siguientes valores de presión de consultorio (PC) y de monitoreo ambulatorio de la presión arterial (MAPA) de 24 horas: Se conformaron dos grupos: 129 hipertensos de guardapolvo blanco y 121 normotensos, los cuales fueron evaluados nuevamente a los 10 años de seguimiento. Se midieron la glucemia, el perfil lipídico y el índice de masa ventricular izquierda (IMVI). Resultados Las variables edad, sexo, tabaquismo y glucemia de normotensos e hipertensos de guardapolvo blanco fueron similares en el examen basal. Los hipertensos de guardapolvo blanco, por el contrario, presentaron valores significativamente superiores en IMC, colesterol total, hipertrigliceridemia e IMVI. Cuarenta y ocho hipertensos de guardapolvo blanco y 21 normotensos originales evolucionaron a HS. La HGB se asoció en forma independiente con HS a los 10 años de seguimiento [OR: 2,5 (IC 95% 1,2-4,2)]. Conclusión La evolución a hipertensión sostenida fue mayor en los hipertensos de guardapolvo blanco que en los normotensos

La preeclampsia es precedida por alteración de la función cardiovascular

Background: Preeclampsia (PE) is associated with changes in cardiovascular function (CVF), but whether these changes precede and persist in the clinical phase of the disease is still unknown. Objectives: The aim of this study was to evaluate the differences in CVF during 22 weeks of gestation and one year after delivery in patients who developed PE vs. those with normotension (N). The association between CVF on 22 weeks of gestation and the development of PE was also analyzed. Methods: We conducted a prospective study including 260 normotensive primiparous women. Routine laboratory tests, 24-hour urine protein and blood pressure (BP) were measured on 22 weeks and one year after delivery. Cardiac index (CI) systemic vascular resistance index (SVRI) and pulse wave velocity (PWV) were measured by impedance cardiography. The population was divided into three groups according to the outcome during pregnancy: PE: G1, gestational hypertension (GH): G2 and normotension: G3. The results are presented as mean ± SD, ANOVA and post hoc test, p < 0.05. Results: Twelve patients evolved to PE, 18 to GH and 220 remained with N. In G1, CI was lower and BP, SVRI and PWV were higher than in G3 on 22 weeks and one year after delivery. In G2, values were always intermediate between G1 and G3. PWV and SVRI measured on 22 weeks resulted predictors of PE. Conclusions: Patients who developed PE had different CVF in the early stage of pregnancy than those with normotension. The early diagnosis of those changes could predict PE and thus contribute to prevent its complications.Introducción: La preeclampsia (PE) se acompaña de cambios en la función cardiovascular (FCV). Sin embargo, es desconocido si los cambios preceden y persisten a la manifestación clínica de PE. Objetivos: Evaluar las diferencias en la FCV, en la semana 22 de gestación (22sg) y un año posterior al parto (1app) en las pacientes que evolucionaron a la PE vs. a la normotensión (N). También, la asociación entre la FCV en 22sg y la evolución a PE. Material y métodos: Estudio prospectivo, que incluyó 260 primíparas normotensas. Se midió en la semana 22sg y a 1app: laboratorio de rutina, proteinuria de 24horas, presión arterial (PA). Por cardiografía por impedancia: índice cardíaco (IC) y de resistencia vascular sistémica (IRVS), velocidad de onda de pulso (VOP). Se formaron 3 grupos según la evolución a: PE, G1, HTA gestacional (HG) G2, y N, G3. Los resultados se presentan como media ± DS, ANOVA y test post hoc, p < 0,05. Resultados: 12 pacientes evolucionaron a PE, 18 a HG y 220 a N. El G1 presentó en los dos tiempos de medición, valores inferiores de IC y superiores de PA, IRP y VOP comparados al G3. El G2 presentó valores intermedios entre el G1 y el G3. La VOP y el IRP en la 22sg de gestación resultaron predictores de PE. Conclusiones: Las pacientes que evolucionaron a PE presentaron en fase temprana del embarazo diferente FCV respecto a las normotensas. El diagnóstico temprano de estos cambios contribuiría a predecir la PE y prevenir sus complicaciones

Cardiorenal End Points in a Trial of Aliskiren for Type 2 Diabetes

BACKGROUND: This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both. METHODS: In a double-blind fashion, we randomly assigned 8561 patients to aliskiren (300 mg daily) or placebo as an adjunct to an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker. The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation; nonfatal myocardial infarction; nonfatal stroke; unplanned hospitalization for heart failure; end-stage renal disease, death attributable to kidney failure, or the need for renal-replacement therapy with no dialysis or transplantation available or initiated; or doubling of the baseline serum creatinine level. RESULTS: The trial was stopped prematurely after the second interim efficacy analysis. After a median follow-up of 32.9 months, the primary end point had occurred in 783 patients (18.3%) assigned to aliskiren as compared with 732 (17.1%) assigned to placebo (hazard ratio, 1.08; 95% confidence interval [CI], 0.98 to 1.20; P=0.12). Effects on secondary renal end points were similar. Systolic and diastolic blood pressures were lower with aliskiren (between-group differences, 1.3 and 0.6 mm Hg, respectively) and the mean reduction in the urinary albumin-to-creatinine ratio was greater (between-group difference, 14 percentage points; 95% CI, 11 to 17). The proportion of patients with hyperkalemia (serum potassium level, ≥6 mmol per liter) was significantly higher in the aliskiren group than in the placebo group (11.2% vs. 7.2%), as was the proportion with reported hypotension (12.1% vs. 8.3%) (P<0.001 for both comparisons). CONCLUSIONS: The addition of aliskiren to standard therapy with renin-angiotensin system blockade in patients with type 2 diabetes who are at high risk for cardiovascular and renal events is not supported by these data and may even be harmful. (Funded by Novartis; ALTITUDE ClinicalTrials.gov number, NCT00549757.)

Cardiorenal End Points in a Trial of Aliskiren for Type 2 Diabetes

BACKGROUND This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both. METHODS In a double-blind fashion, we randomly assigned 8561 patients to aliskiren (300 mg daily) or placebo as an adjunct to an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker. The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation; nonfatal myocardial infarction; nonfatal stroke; unplanned hospitalization for heart failure; end-stage renal disease, death attributable to kidney failure, or the need for renal-replacement therapy with no dialysis or transplantation available or initiated; or doubling of the baseline serum creatinine level. RESULTS The trial was stopped prematurely after the second interim efficacy analysis. After a median follow-up of 32.9 months, the primary end point had occurred in 783 patients (18.3%) assigned to aliskiren as compared with 732 (17.1%) assigned to placebo (hazard ratio, 1.08; 95% confidence interval [CI], 0.98 to 1.20; P = 0.12). Effects on secondary renal end points were similar. Systolic and diastolic blood pressures were lower with aliskiren (between-group differences, 1.3 and 0.6 mm Hg, respectively) and the mean reduction in the urinary albumin-to-creatinine ratio was greater (between-group difference, 14 percentage points; 95% CI, 11 to 17). The proportion of patients with hyperkalemia (serum potassium level, = 6 mmol per liter) was significantly higher in the aliskiren group than in the placebo group (11.2% vs. 7.2%), as was the proportion with reported hypotension (12.1% vs. 8.3%) (P <0.001 for both comparisons). CONCLUSIONS The addition of aliskiren to standard therapy with renin-angiotensin system blockade in patients with type 2 diabetes who are at high risk for cardiovascular and renal events is not supported by these data and may even be harmful. (Funded by Novartis; ALTITUDE ClinicalTrials.gov number, NCT00549757.

A Survey of Empirical Results on Program Slicing

International audienceBACKGROUND:Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications.METHODS:This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS:Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043).INTERPRETATION:Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding

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.)