Effects on Outcomes of Heart Rate Reduction by Ivabradine in Patients With Congestive Heart Failure: Is There an Influence of Beta-Blocker Dose?

Swedberg, Karl; Komajda, Michel; Böhm, Michael; Borer, Jeffrey S.; Robertson, Michele; Tavazzi, Luigi; Ford, Ian; Investigators, Shift

doi:10.1016/j.jacc.2012.01.020

Cited by 242 publications

(189 citation statements)

References 22 publications

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“…27 The magnitude of heart rate reduction caused by beta-blocker and ivabradine, rather than background beta-blocker dose, primarily determines subsequent effect on outcomes. 28 The beneficial effects of ivabradine in SHIFT population was confirmed in all subgroups including patients with diabetes, arterial hypertension, concomitant treatment with MRAs or beta-blocker treatment and chronic obstructive pulmonary disease. [29][30][31][32][33] Furthermore, the effect of heart rate reduction with ivabradine is maintained regardless of presence and number of co-morbidities.…”

Section: Effects On Rehospitalisation and Mortalitymentioning

confidence: 83%

The Role of Ivabradine and Trimetazidine in the New ESC HF Guidelins

Milinković

Rosano

Lopatin

et al. 2016

Cardiac Failure Review

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TherapeuticsAccess at: www.CFRjournal.com Chronic heart failure (HF), a complex and heterogeneous clinical syndrome, is a major cause of morbidity and mortality worldwide, and represents a major challenge to health care systems. The prevalence of HF and the number of hospitalisations is rising, even more in the ageing population.1 The direct costs of HF management reached 1-2 % of total health care expenditure and approximately two-thirds are attributable to hospitalisations. In 2012, in 197 countries, covering 99 % of the world's population, the overall cost of HF management was estimated at US$108 billion per annum, and is predicted to rise. 4 Around 60 % of total HF patients has HFrEF, which is associated with high reninangiotensin-aldosterone and sympathetic nervous systems activation.Most recent therapeutic improvements in these patients are due to the use of pharmacological agents that modulate these neuro-hormonal axes, angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), beta-blockers and mineralocorticoid receptor antagonists (MRAs). The beneficial effects of these treatments include the reduction of HF mortality by approximately one-third in a period of two decades. Despite this success, HF mortality rates remain high:the 5-year survival is worse than in many cancers. 5,6The 2016 European Society of Cardiology (ESC) HF guidelines recommend ACEI and beta-blockers as first-line therapy in symptomatic patients with HFrEF. 4 However, both registries and clinical reports underline that the treatment of HF patients is suboptimal much more than expected, and that the heart rate is increased despite beta-blocker therapy.7-12 The registry of 12,440 patients demonstrated heterogeneity in treatment strategies, due to the drug side effects and contraindications.7 A European registry 13 reported that only 17 % of patients were receiving the optimal combination and recommended dose of diuretic, ACEI and beta-blockers. Results from a French registry on 50,000 HF patients 14 also confirmed suboptimal treatment of HF, demonstrating that after the first month following hospitalisation for worsening HF, only 47 % received an ACEI, 54 % a beta-blocker, and 17 % MRAs. The I Brazilian Registry of Heart Failure (BREATHE) 15 , conducted in 57 hospitals in Brazil, revealed that 69 % of HF patients were receiving an ACEI or ARB, 60 % a beta-blocker, and 49 % MRAs. However, only 17 % were receiving all three drugs together. Therefore, a need to identify a novel pathways and strategies for HF treatment is obvious and clinically justified. This article reviews the clinical evidence and guidelines recommendations for the use of two novel therapies in HF: ivabradine and trimetazidine. AbstractThe prevalence of heart failure (HF) is increasing, representing a major cause of death and disability, and a growing financial burden on healthcare systems. Despite the use of effective treatments with both drugs and devices, mortality remains high. There is therefore a need for new and effective therapeutic a...

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Section: Effects On Rehospitalisation and Mortalitymentioning

confidence: 83%

The Role of Ivabradine and Trimetazidine in the New ESC HF Guidelins

Milinković

Rosano

Lopatin

et al. 2016

Cardiac Failure Review

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“…This effect persisted after adjustment for baseline beta blocker dose 8. A meta‐analysis of the effects of beta blockers on outcome showed that achieved heart rate, not beta blocker dose, predicted outcome 16.…”

Section: Discussionmentioning

confidence: 96%

“…Heart rate is a simple and prognostic surrogate of sympathetic activity,8, 9 but its value depends on numerous factors besides sympathetic activation. Exercise heart rate and heart rate variability are other indirect markers that reflect the balance between sympathetic and parasympathetic activities,10 but they are not routinely measured.…”

Section: Introductionmentioning

confidence: 99%

“…While there may be a dose‐response relationship between beta blocker dose and hard outcomes,15 a recent meta‐analysis showed that outcome in HF was more related to heart rate achieved with beta blockers than with the achieved dose 16. Clinical registries17 and recent studies of non‐beta blocker drugs (ivabradine) have shown that heart rate is associated with outcome, even after adjustment for other risk factors 8…”

Section: Introductionmentioning

confidence: 99%

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Beta blocker dose and markers of sympathetic activation in heart failure patients: interrelationships and prognostic significance

2017

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AimsExtent of cardiac sympathetic activation can be estimated from physiological parameters, blood biomarkers, and imaging findings. This study examined the prognostic value of three markers of sympathetic activity and their relationship to beta blocker dose in heart failure patients.Methods and resultsA post hoc analysis of 858 heart failure subjects in the ADMIRE‐HF trial was performed. Variables related to sympathetic activity were plasma norepinephrine, baseline heart rate, the heart to mediastinum (H/M) ratio of 123I‐mIBG uptake, and beta blocker dose. Univariate and multivariate analyses for occurrence of mortality (all‐cause and cardiac) and arrhythmic events were performed. Beta blocker dose was significantly related to age, heart rate, b‐type natriuretic peptide (negatively), body mass index, body weight and plasma norepinephrine. Univariate predictors of all‐cause and cardiac mortality were baseline heart rate (χ 2 = 4.5, P = 0.029 and χ 2 = 5 .2, P = 0.022, respectively), plasma norepinephrine level (χ 2 = 8.9, P = 0.0006 and χ 2 = 8.6, P = 0.003, respectively), and H/M (χ = 22.4, P < 0.0001 and χ 2 = 17.8, P < 0.0001, respectively). In multivariate analyses, carvedilol‐equivalent dose (P = 0.017), plasma norepinephrine (P = 0.002), and H/M (P = 0.0001) were significant predictors of all‐cause mortality. In separate analyses using multiple measurements of heart rate, mean heart rate >67 b.p.m. was associated with significantly higher cardiac mortality.ConclusionsHigher beta blocker dose was associated with lower mortality, but of the variables associated with sympathetic activity examined, cardiac 123I‐mIBG uptake was the most powerful prognostic marker in heart failure patients. Elevated heart rate was associated with greater risk for cardiac death.

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“…En los últimos tiempos a estas medidas (uso de inhibidores del Enzima conversor de angiotensina/bloqueadores del receptor de angiotensina, implantación de dispositivos cardioversoresdesfibriladores, anticoagulación para la fibrilación auricular y medidas educadoras en IC 5 y seguramente también el uso de agonistas de aldosterona 6 , se ha unido la ibavradina que ha mostrado aumentar la supervivencia y disminución de hospitalizaciones en IC 7 . La presente publicación de actualización sobre la IC, surge como consecuencia de la colaboración de las secciones gallegas de la Sociedad Española de Cardiología y de Medicina interna (SOGACAR y SOGAMI), que son las especialidades mayoritariamente encargadas de su manejo.…”

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Insuficiencia cardiaca: la epidemia creciente de una enfermedad multisistémica y de abordaje multidisciplinario

Román¹,

Santiago²

2012

Gal. Clin.

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La insuficiencia cardiaca (IC) constituye una epidemia de proporciones colosales, distribución universal y que supone gravosas cargas económicas para los sistemas sanitarios. En efecto, se calcula que en Europa hay de más de 15 millones de personas con dicha enfermedad, 2,4 millones en Japón, 0,3 millones en Australia y constituye el 3-7% de las hospitalizaciones en África. En EEUU existen 6,6 millones de afectados mayores de 19 años pero se calcula que habrá cerca de 10 millones en 2030En 2010 en España se produjeron más de 113000 altas hospitalarias y se calculan cercanas a 150000 las hospitalizaciones para el año 2020. El coste hospitalario calculado actual (2010) es de 473 millones (2,6% del gasto hospitalario) pero puede superar largamente los 510 millones si se incluyen trasplantes y dispositivos resincronizadores/desfibriladores. El coste real incluyendo seguimiento extrahospitalario y de cuidadores puede llegar a superar los 2200 millones anuales ( 4% del gasto sanitario global). Por otra parte, 2 de cada 3 pacientes ingresados son >75 años. La mortalidad hospitalaria en >35 años se sitúa en el 10,4% y la mortalidad tras la 1ª hospitalización puede rondar en torno al 26% 2 . Estas cifras son muy superiores a las de los cánceres más habituales, por lo que aun puede seguir afirmándose, con razón, que "la insuficiencia cardiaca es más maligna que el cáncer" 3 .En cuanto a los pacientes >35 años ingresados, cuya media de edad es de 78 años, y en su mayor parte mujeres (56%), se ha demostrado que el 61% presentan IC con fracción de eyección preservada (>50%). Explicando en parte la alta mortalidad y complejidad de su manejo, se registra la frecuente presencia de entidades comórbidas, lo que hacen de la IC una entidad fundamentalmente sistémica: EPOC (35%), enfermedad cardiovascular y demencia (9%), insuficiencia renal (13%), diabetes mellitus (38%) y fibrilación auricular (48%) 1 .Por fortuna, en los últimos años se ha demostrado que el uso gradual of terapias ajustadas a las Guías se asocia con una apreciable mejoría en la supervivencia 4,5 . Ello resalta la necesidad de implicarse fuertemente en la implementación lo más completa posible de las terapias sugerida en las Guías.En los últimos tiempos a estas medidas (uso de inhibidores del Enzima conversor de angiotensina/bloqueadores del receptor de angiotensina, implantación de dispositivos cardioversoresdesfibriladores, anticoagulación para la fibrilación auricular y medidas educadoras en IC 5 y seguramente también el uso de agonistas de aldosterona 6 , se ha unido la ibavradina que ha mostrado aumentar la supervivencia y disminución de hospitalizaciones en IC 7 . La presente publicación de actualización sobre la IC, surge como consecuencia de la colaboración de las secciones gallegas de la Sociedad Española de Cardiología y de Medicina interna (SOGACAR y SOGAMI), que son las especialidades mayoritariamente encargadas de su manejo. En España en 2010 el 81% de pacientes con IC ingresaron a cargo de Servicios de Cardiología o Medicina Interna) (Ministerio de S...

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Effects on Outcomes of Heart Rate Reduction by Ivabradine in Patients With Congestive Heart Failure: Is There an Influence of Beta-Blocker Dose?

Cited by 242 publications

References 22 publications

The Role of Ivabradine and Trimetazidine in the New ESC HF Guidelins

The Role of Ivabradine and Trimetazidine in the New ESC HF Guidelins

Beta blocker dose and markers of sympathetic activation in heart failure patients: interrelationships and prognostic significance

Insuficiencia cardiaca: la epidemia creciente de una enfermedad multisistémica y de abordaje multidisciplinario

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