title: Pharmacologic Options for the Management of Systolic Heart Failure: Examining Underlying Mechanisms.
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.
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: mancini@mail.ubc.ca.
authors.forename: G B John
authors.initials: GB
authors.lastname: Mancini
authors.affiliation: Libin Cardiovascular Institute of Alberta and University of Calgary, Calgary, Alberta, Canada.
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Howlett
authors.affiliation: State University of New York Downstate Medical Center, New York, New York, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Borer
authors.affiliation: University of Ottawa Heart Institute, Ottawa, and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Liu
authors.affiliation: Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Mandeep R
authors.initials: MR
authors.lastname: Mehra
authors.affiliation: Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Pfeffer
authors.affiliation: Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, and Institute of Heart and Lung, Imperial College, London, United Kingdom.
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tardif
mesh_terms: D002317:Cardiovascular Agents / Q000145:classification / Q000494:pharmacology; D019468:Disease Management; D054143:Heart Failure, Systolic / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D012084:Renin-Angiotensin System / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D002317:Cardiovascular Agents