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Optimal medical therapy decreases mortality and heart failure (HF) hospitalizations in HF patients with reduced left ventricular ejection fraction. Women have been underrepresented in clinical trials and not specifically evaluated. This study aimed to compare the safety and effectiveness of drug titration in women vs men.This post hoc gender study of the ETIFIC multicenter randomized trial included hospitalized patients with new-onset HF with reduced ejection fraction and New York Heart Association II-III and no contraindications to beta-blockers. A structured 4-month titration process was implemented in HF clinics. The primary endpoint was the mean relative dose (% of target dose) of beta-blockers achieved by women vs men. Secondary endpoints included the mean relative doses of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists, adverse events, and other clinical outcomes at 6 months.A total of 320 patients were included, 83 (25.93%) women and 237 (74.06%) men (76 vs 213 analyzed). The mean±standard deviation of the relative doses achieved by women vs men were as follows: beta-blockers 62.08%±30.72% vs 64.4%±32.77%, with a difference of-2.32% (95%CI,-10.58-5.94), P = .580; and mineralocorticoid receptor antagonists 79.85%±27.72% vs 67.29%±31.43%, P =.003. No other differences in drug dosage were found. Multivariate analysis showed nonsignificant differences. CV mortality was 1 (1.20%) vs 3 (1.26%), P=1, and HF hospitalizations 0 (0.00%) vs 10 (4.22%), P=.125.In a post hoc analysis from the HF-titration ETIFIC trial, we found nonsignificant gender differences in drug dosage, cardiovascular mortality, and HF hospitalizations. Trial registry number: NCT02546856.

Beta-blockers, angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin-II-receptor-blockers (ARB), and mineralocorticoid-receptor antagonists decrease mortality and heart failure (HF) hospitalizations in HF patients with reduced left ventricular ejection fraction. The effect is dose-dependent. Careful titration is recommended. However, suboptimal doses are common in clinical practice. This study aimed to compare the safety and efficacy of dose titration of the aforementioned drugs by HF nurses vs HF cardiologists.ETIFIC was a multicenter (n=20) noninferiority randomized controlled open label trial. A total of 320 hospitalized patients with new-onset HF, reduced ejection fraction and New York Heart Association II-III, without beta-blocker contraindications were randomized 1:1 in blocks of 4 patients each stratified by hospital: 164 to HF nurse titration vs 156 to HF cardiologist titration (144 vs 145 analyzed). The primary endpoint was the beta-blocker mean relative dose (% of target dose) achieved at 4 months. Secondary endpoints included ACE inhibitors, ARB, and mineralocorticoid-receptor antagonists mean relative doses, associated variables, adverse events, and clinical outcomes at 6 months.The mean±standard deviation relative doses achieved by HF nurses vs HF cardiologists were as follows: beta-blockers 71.09%±31.49% vs 56.29%±31.32%, with a difference of 14.8% (95%CI, 7.5-22.1), P.001; ACE inhibitors 72.61%±29.80% vs 56.13%±30.37%, P.001; ARB 44.48%±33.47% vs 43.51%±33.69%, P=.93; and mineralocorticoid-receptor antagonists 71%±32.12% vs 70.47%±29.78%, P=.86; mean±standard deviation visits were 6.41±2.82 vs 2.81±1.58, P.001, while the number (%) of adverse events were 34 (23.6) vs 30 (20.7), P=.55; and at 6 months HF hospitalizations were 1 (0.69) vs 9 (5.51), P=.01.ETIFIC is the first multicenter randomized trial to demonstrate the noninferiority of HF specialist-nurse titration vs HF cardiologist titration. Moreover, HF nurses achieved higher beta-blocker/ACE inhibitors doses, with more outpatient visits and fewer HF hospitalizations. Trial registry number: NCT02546856.

Resumen Introduccion y objetivos Los bloqueadores beta, inhibidores de la enzima de conversion de la angiotensina (IECA), antagonistas de los receptores de la angiotensina II (ARA-II) y antagonistas de receptores mineralocorticoides, disminuyen mortalidad y hospitalizaciones por insuficiencia cardiaca (IC) en pacientes con IC y fraccion de eyeccion del ventriculo izquierdo reducida. Efecto dosis-dependiente. Se recomienda titulacion cuidadosa. Sin embargo, las dosis suboptimas son habituales. Se comparo eficacia y seguridad de la titulacion de farmacos enfermeras de IC frente a cardiologos de IC. Metodos ETIFIC fue un ensayo de no inferioridad, multicentrico (20), abierto, controlado y aleatorizado. 320 pacientes hospitalizados con IC de debut, fraccion de eyeccion reducida y New York Heart Association II-III. Sin contraindicacion para bloqueadores beta, fueron aleatorizados 1:1, estratificados en bloques de 4 pacientes/hospital, 164 a titulacion de enfermeras de IC frente a 156 cardiologos de IC (analizados 144 frente a 145). El objetivo principal fue la dosis relativa media (% de dosis objetivo) de bloqueadores beta alcanzada a 4 meses. Los objetivos secundarios fueron: la dosis relativa media de IECA, ARA-II y antagonistas de receptores mineralocorticoides, variables asociadas, eventos adversos y resultados clinicos a 6 meses. Resultados La dosis relativa media ± desviacion estandar alcanzada por enfermeras de IC frente a cardiologos de IC: bloqueadores beta 71,09 ± 31,49% frente a 56,29 ± 31,32%, diferencia 14,8% (IC95%, 7,5-22,1); p Conclusiones ETIFIC es el primer ensayo aleatorizado multicentrico que prueba la no inferioridad de titulacion de farmacos por enfermeras de IC frente a cardiologos de IC. Las enfermeras especialistas consiguieron mayores dosis de bloqueadores beta/IECA con mas visitas y menos hospitalizaciones por IC. Registro del ensayo: NCT02546856.

Aims Heart failure (HF) is associated with many hospital admissions and relatively high mortality, rates decreasing with administration of beta-blockers (BBs), angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists. The effect is dose dependent, suboptimal doses being common in clinical practice. The 2012 European guidelines recommend close monitoring and dose titration by HF nurses. Our main aim is to compare BB doses achieved by patients after 4 months in intervention (HF nurse-managed) and control (cardiologist-managed) groups. Secondary aims include comparing doses of the other aforementioned drugs achieved after 4 months, adverse events, and outcomes at 6 months in the two groups. Methods We have designed a multicentre (20 hospitals) non-inferiority randomized controlled trial, including patients with new-onset HF, left ventricular ejection fraction ≤40%, and New York Heart Association class II–III, with no contraindications to BBs. We will also conduct qualitative analysis to explore potential barriers to and facilitators of dose titration by HF nurses. In the intervention group, HF nurses will implement titration as prescribed by cardiologists, following a protocol. In controls, cardiologists will both prescribe and titrate doses. The study variables are doses of each of the drugs after 4 months relative to the target dose (%), New York Heart Association class, left ventricular ejection fraction, N-terminal pro B-type natriuretic peptide levels, 6 min walk distance, comorbidities, renal function, readmissions, mortality, quality of life, and psychosocial characteristics. Conclusions The trial seeks to assess whether titration by HF nurses of drugs recommended in practice guidelines is safe and not inferior to direct management by cardiologists. The results could have an impact on clinical practice.

Introduction and objectives Heart failure management programs reduce hospitalizations. Some studies also show reduced mortality. The determinants of program success are unknown. The aim of the present study was to update our understanding of the reductions in mortality and readmissions produced by these programs, elucidate their components, and identify the factors determining program success. Methods Systematic literature review (1990-2014; PubMed, EMBASE, CINAHL, Cochrane Library) and manual search of relevant journals. The studies were selected by 3 independent reviewers. Methodological quality was evaluated in a blinded manner by an external researcher (Jadad scale). These results were pooled using random effects models. Heterogeneity was evaluated with the I 2 statistic, and its explanatory factors were determined using metaregression analysis. Results Of the 3914 studies identified, 66 randomized controlled clinical trials were selected (18 countries, 13 535 patients). We determined the relative risks to be 0.88 for death (95% confidence interval [95%CI], 0.81-0.96; P 2 , 6.1%), 0.92 for all-cause readmissions (95%CI, 0.86-0.98; P 2 , 58.7%), and 0.80 for heart failure readmissions (95%CI, 0.71-0.90; P 2 , 52.7%). Factors associated with program success were implementation after 2001, program location outside the United States, greater baseline use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, a higher number of intervention team members and components, specialized heart failure cardiologists and nurses, protocol-driven education and its assessment, self-monitoring of signs and symptoms, detection of deterioration, flexible diuretic regimen, early care-seeking among patients and prompt health care response, psychosocial intervention, professional coordination, and program duration. Conclusions We confirm the reductions in mortality and readmissions with heart failure management programs. Their success is associated with various structural and intervention variables.

Resumen Introduccion y objetivos Los programas de atencion a pacientes de insuficiencia cardiaca reducen ingresos hospitalarios. Algunos estudios reducen mortalidad. Se desconocen los determinantes del exito. El objetivo es actualizar el conocimiento sobre la reduccion de mortalidad y reingresos de estos programas, describir sus componentes e identificar factores condicionantes de resultados. Metodos Revision sistematica de la bibliografia (1990-2014) (PubMed, EMBASE, CINAHL, Cochrane Library) y busqueda manual en revistas relevantes. Tres revisores independientes seleccionaron los estudios. La calidad metodologica fue evaluada a ciegas por una investigadora externa (escala Jadad). Los resultados se combinaron mediante modelos de efectos aleatorios. La heterogeneidad se evaluo con el estadistico I2, y se determinaron sus factores explicativos mediante analisis de metarregresion. Resultados Se identificaron 3.914 estudios. Se seleccionaron 66 ensayos clinicos controlados y aleatorizados (18 paises, 13.535 pacientes), y se observaron riesgos relativos de muerte de 0,88 (intervalo de confianza del 95% [IC95%], 0,81-0,96; p II , mayor numero de profesionales y componentes de la intervencion, especializacion del cardiologo y la enfermera, educacion protocolizada y evaluada, automonitorizacion de signos y sintomas, reconocimiento de descompensacion, pauta flexible de diureticos, aviso y atencion precoz, intervencion psicosocial, coordinacion de profesionales y duracion del programa. Conclusiones Se confirma la reduccion de mortalidad y reingresos con los programas de insuficiencia cardiaca, cuyo exito se asocio con diferentes variables de estructura e intervencion.

Aims Heart failure (HF) is associated with many hospital admissions and relatively high mortality, rates decreasing with administration of beta‐blockers (BBs), angiotensin‐converting‐enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists. The effect is dose dependent, suboptimal doses being common in clinical practice. The 2012 European guidelines recommend close monitoring and dose titration by HF nurses. Our main aim is to compare BB doses achieved by patients after 4 months in intervention (HF nurse‐managed) and control (cardiologist‐managed) groups. Secondary aims include comparing doses of the other aforementioned drugs achieved after 4 months, adverse events, and outcomes at 6 months in the two groups. Methods We have designed a multicentre (20 hospitals) non‐inferiority randomized controlled trial, including patients with new‐onset HF, left ventricular ejection fraction ≤40%, and New York Heart Association class II–III, with no contraindications to BBs. We will also conduct qualitative analysis to explore potential barriers to and facilitators of dose titration by HF nurses. In the intervention group, HF nurses will implement titration as prescribed by cardiologists, following a protocol. In controls, cardiologists will both prescribe and titrate doses. The study variables are doses of each of the drugs after 4 months relative to the target dose (%), New York Heart Association class, left ventricular ejection fraction, N‐terminal pro B‐type natriuretic peptide levels, 6 min walk distance, comorbidities, renal function, readmissions, mortality, quality of life, and psychosocial characteristics. Conclusions The trial seeks to assess whether titration by HF nurses of drugs recommended in practice guidelines is safe and not inferior to direct management by cardiologists. The results could have an impact on clinical practice.