Efficacy of Pharmacologic and Cardiac Implantable Electronic Device Therapies in Patients With Heart Failure and Reduced Ejection Fraction

Andrew S. Tseng, Katie L. Kunze, Justin Z. Lee, Mustapha Amin, Matthew R. Neville, Diana Almader-Douglas, Ammar M. Killu, Malini Madhavan, Yong-Mei Cha, Samuel J Asirvatham, Paul Andrew Friedman, Bernard J. Gersh, Siva Mulpuru

Research output: Contribution to journalArticle

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Abstract

Background The treatment of heart failure with reduced ejection fraction has been the subject of numerous randomized controlled trials involving medications and cardiac implantable electronic device therapies. As newer effective pharmacological therapies suggest significant reductions in all-cause mortality, the role of additional device therapy in heart failure with reduced ejection fraction deserves further scrutiny. Methods A systematic review and network meta-analysis on the effect of medication and device therapies in heart failure with reduced ejection fraction on all-cause mortality was performed. Randomized controlled trials published between January 1980 and July 2017 were identified using Medline, EMBASE, and Cochrane Controlled Register of Trials databases. Pcnetmeta package in R was used to calculate treatment arm-based estimated rates, rate ratios, and probability ranks with 95% credible intervals. Results Combination therapy of ACE (angiotensin-converting enzyme) inhibitors or ARBs (angiotensin receptor blockers) with β-blockers (BBs) alone or in addition to implantable cardiac defibrillators or cardiac resynchronization therapy with defibrillators demonstrated a significant reduction of all-cause mortality when compared with placebo. By probability rank, implantable cardiac defibrillator+ACE inhibitor or ARB+BB+mineralocorticoid receptor antagonist, implantable cardiac defibrillator+ACE inhibitor or ARB+BB, and angiotensin receptor-neprilysin inhibitor+BB+mineralocorticoid receptor antagonist combination therapies have the highest probability of being ranked the best treatment. There was no significant difference in the rate of mortality when comparing angiotensin receptor-neprilysin inhibitor+BB+mineralocorticoid receptor antagonist to implantable cardiac defibrillator+optimal pharmacological combination therapy. Conclusions BB and renin-angiotensin system blockers alone or in combination with defibrillator device therapy have robust evidence for a reduction in mortality compared with placebo. The comparative efficacy of pharmacological therapy with angiotensin receptor-neprilysin inhibitors and device therapy deserves further investigation.

Original languageEnglish (US)
Pages (from-to)e006951
JournalCirculation. Arrhythmia and electrophysiology
Volume12
Issue number6
DOIs
StatePublished - Jun 1 2019

Fingerprint

Heart Failure
Equipment and Supplies
Implantable Defibrillators
Mineralocorticoid Receptor Antagonists
Neprilysin
Angiotensin Receptors
Angiotensin Receptor Antagonists
Therapeutics
Angiotensin-Converting Enzyme Inhibitors
Mortality
Defibrillators
Pharmacology
Randomized Controlled Trials
Placebos
Cardiac Resynchronization Therapy
Renin-Angiotensin System
Treatment Failure
Databases

Keywords

  • cardiac resynchronization therapy
  • defibrillators, implantable
  • heart failure
  • meta-analysis
  • neprilysin
  • renin-angiotensin system

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Efficacy of Pharmacologic and Cardiac Implantable Electronic Device Therapies in Patients With Heart Failure and Reduced Ejection Fraction. / Tseng, Andrew S.; Kunze, Katie L.; Lee, Justin Z.; Amin, Mustapha; Neville, Matthew R.; Almader-Douglas, Diana; Killu, Ammar M.; Madhavan, Malini; Cha, Yong-Mei; Asirvatham, Samuel J; Friedman, Paul Andrew; Gersh, Bernard J.; Mulpuru, Siva.

In: Circulation. Arrhythmia and electrophysiology, Vol. 12, No. 6, 01.06.2019, p. e006951.

Research output: Contribution to journalArticle

Tseng, Andrew S. ; Kunze, Katie L. ; Lee, Justin Z. ; Amin, Mustapha ; Neville, Matthew R. ; Almader-Douglas, Diana ; Killu, Ammar M. ; Madhavan, Malini ; Cha, Yong-Mei ; Asirvatham, Samuel J ; Friedman, Paul Andrew ; Gersh, Bernard J. ; Mulpuru, Siva. / Efficacy of Pharmacologic and Cardiac Implantable Electronic Device Therapies in Patients With Heart Failure and Reduced Ejection Fraction. In: Circulation. Arrhythmia and electrophysiology. 2019 ; Vol. 12, No. 6. pp. e006951.
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abstract = "Background The treatment of heart failure with reduced ejection fraction has been the subject of numerous randomized controlled trials involving medications and cardiac implantable electronic device therapies. As newer effective pharmacological therapies suggest significant reductions in all-cause mortality, the role of additional device therapy in heart failure with reduced ejection fraction deserves further scrutiny. Methods A systematic review and network meta-analysis on the effect of medication and device therapies in heart failure with reduced ejection fraction on all-cause mortality was performed. Randomized controlled trials published between January 1980 and July 2017 were identified using Medline, EMBASE, and Cochrane Controlled Register of Trials databases. Pcnetmeta package in R was used to calculate treatment arm-based estimated rates, rate ratios, and probability ranks with 95{\%} credible intervals. Results Combination therapy of ACE (angiotensin-converting enzyme) inhibitors or ARBs (angiotensin receptor blockers) with β-blockers (BBs) alone or in addition to implantable cardiac defibrillators or cardiac resynchronization therapy with defibrillators demonstrated a significant reduction of all-cause mortality when compared with placebo. By probability rank, implantable cardiac defibrillator+ACE inhibitor or ARB+BB+mineralocorticoid receptor antagonist, implantable cardiac defibrillator+ACE inhibitor or ARB+BB, and angiotensin receptor-neprilysin inhibitor+BB+mineralocorticoid receptor antagonist combination therapies have the highest probability of being ranked the best treatment. There was no significant difference in the rate of mortality when comparing angiotensin receptor-neprilysin inhibitor+BB+mineralocorticoid receptor antagonist to implantable cardiac defibrillator+optimal pharmacological combination therapy. Conclusions BB and renin-angiotensin system blockers alone or in combination with defibrillator device therapy have robust evidence for a reduction in mortality compared with placebo. The comparative efficacy of pharmacological therapy with angiotensin receptor-neprilysin inhibitors and device therapy deserves further investigation.",
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AU - Kunze, Katie L.

AU - Lee, Justin Z.

AU - Amin, Mustapha

AU - Neville, Matthew R.

AU - Almader-Douglas, Diana

AU - Killu, Ammar M.

AU - Madhavan, Malini

AU - Cha, Yong-Mei

AU - Asirvatham, Samuel J

AU - Friedman, Paul Andrew

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N2 - Background The treatment of heart failure with reduced ejection fraction has been the subject of numerous randomized controlled trials involving medications and cardiac implantable electronic device therapies. As newer effective pharmacological therapies suggest significant reductions in all-cause mortality, the role of additional device therapy in heart failure with reduced ejection fraction deserves further scrutiny. Methods A systematic review and network meta-analysis on the effect of medication and device therapies in heart failure with reduced ejection fraction on all-cause mortality was performed. Randomized controlled trials published between January 1980 and July 2017 were identified using Medline, EMBASE, and Cochrane Controlled Register of Trials databases. Pcnetmeta package in R was used to calculate treatment arm-based estimated rates, rate ratios, and probability ranks with 95% credible intervals. Results Combination therapy of ACE (angiotensin-converting enzyme) inhibitors or ARBs (angiotensin receptor blockers) with β-blockers (BBs) alone or in addition to implantable cardiac defibrillators or cardiac resynchronization therapy with defibrillators demonstrated a significant reduction of all-cause mortality when compared with placebo. By probability rank, implantable cardiac defibrillator+ACE inhibitor or ARB+BB+mineralocorticoid receptor antagonist, implantable cardiac defibrillator+ACE inhibitor or ARB+BB, and angiotensin receptor-neprilysin inhibitor+BB+mineralocorticoid receptor antagonist combination therapies have the highest probability of being ranked the best treatment. There was no significant difference in the rate of mortality when comparing angiotensin receptor-neprilysin inhibitor+BB+mineralocorticoid receptor antagonist to implantable cardiac defibrillator+optimal pharmacological combination therapy. Conclusions BB and renin-angiotensin system blockers alone or in combination with defibrillator device therapy have robust evidence for a reduction in mortality compared with placebo. The comparative efficacy of pharmacological therapy with angiotensin receptor-neprilysin inhibitors and device therapy deserves further investigation.

AB - Background The treatment of heart failure with reduced ejection fraction has been the subject of numerous randomized controlled trials involving medications and cardiac implantable electronic device therapies. As newer effective pharmacological therapies suggest significant reductions in all-cause mortality, the role of additional device therapy in heart failure with reduced ejection fraction deserves further scrutiny. Methods A systematic review and network meta-analysis on the effect of medication and device therapies in heart failure with reduced ejection fraction on all-cause mortality was performed. Randomized controlled trials published between January 1980 and July 2017 were identified using Medline, EMBASE, and Cochrane Controlled Register of Trials databases. Pcnetmeta package in R was used to calculate treatment arm-based estimated rates, rate ratios, and probability ranks with 95% credible intervals. Results Combination therapy of ACE (angiotensin-converting enzyme) inhibitors or ARBs (angiotensin receptor blockers) with β-blockers (BBs) alone or in addition to implantable cardiac defibrillators or cardiac resynchronization therapy with defibrillators demonstrated a significant reduction of all-cause mortality when compared with placebo. By probability rank, implantable cardiac defibrillator+ACE inhibitor or ARB+BB+mineralocorticoid receptor antagonist, implantable cardiac defibrillator+ACE inhibitor or ARB+BB, and angiotensin receptor-neprilysin inhibitor+BB+mineralocorticoid receptor antagonist combination therapies have the highest probability of being ranked the best treatment. There was no significant difference in the rate of mortality when comparing angiotensin receptor-neprilysin inhibitor+BB+mineralocorticoid receptor antagonist to implantable cardiac defibrillator+optimal pharmacological combination therapy. Conclusions BB and renin-angiotensin system blockers alone or in combination with defibrillator device therapy have robust evidence for a reduction in mortality compared with placebo. The comparative efficacy of pharmacological therapy with angiotensin receptor-neprilysin inhibitors and device therapy deserves further investigation.

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KW - renin-angiotensin system

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