Abstract
The optimal management of systolic heart failure includes combination therapy to influence
myocardial remodelling favourably by affecting neurohormonal activation and underlying
maladaptive pathophysiological pathways. These medications include modulators of the renin-angiotensin-aldosterone
system (eg, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers,
mineralocorticoid receptor antagonists) and β-adrenergic receptor blockers. In addition,
an agent with a distinct and complementary mechanism of bradycardic action, the selective
pacemaker-current (If) inhibitor ivabradine, provides further reduction of heart rate. Also, a new drug
that incorporates neprilysin inhibition combined with angiotensin receptor blockade
shows incremental effectiveness. The primary goal of this review is to provide a mechanistic
explanation of the complementary role of therapeutic interventions in modulating pathways
leading to progressive systolic heart failure. A secondary goal is to summarize the
key findings of the pivotal clinical trials that have demonstrated the efficacy of
these agents in this population.
Résumé
La prise en charge optimale de l’insuffisance cardiaque systolique comprend le traitement
combiné pour influencer favorablement le remodelage myocardique en affectant l’activation
neurohormonale et les voies physiopathologiques maladaptatives sous-jacentes. Ces
médicaments comprennent les modulateurs du système rénine-angiotensine-aldostérone
(p. ex. les inhibiteurs de l’enzyme de conversion de l’angiotensine, les antagonistes
des récepteurs de l’angiotensine, les antagonistes du récepteur minéralocorticoïde)
et les inhibiteurs des récepteurs β-adrénergiques. De plus, un agent ayant un mécanisme
d’action bradycardique distinct et complémentaire, l’ivabradine, un inhibiteur sélectif
du courant If, réduit davantage la fréquence cardiaque. Également, un nouveau médicament qui combine
l’inhibition de la néprilysine au blocage des récepteurs de l’angiotensine montre
une efficacité supplémentaire. Le principal objectif de la présente revue est de fournir
une explication mécaniste du rôle complémentaire des interventions thérapeutiques
dans la modulation des voies menant à l’insuffisance cardiaque systolique. Un objectif
secondaire est de résumer les principaux résultats des essais cliniques charnières
qui ont démontré l’efficacité de ces agents dans cette population.
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Article info
Publication history
Published online: February 19, 2015
Accepted:
February 16,
2015
Received:
February 5,
2015
Footnotes
See page 1290 for disclosure information.
Identification
Copyright
© 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
