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Incidence and Outcomes Associated With Early Heart Failure Pharmacotherapy in Patients With Ongoing Cardiogenic Shock

van Diepen, Sean MD, MSc1; Reynolds, Harmony R. MD2; Stebbins, Amanda MSc3; Lopes, Renato D. MD, PhD3; Džavík, Vladimír MD4; Ruzyllo, Witold MD, PhD5; Geppert, Alexander MD6; Widimsky, Petr MD7; Ohman, E. Magnus MD3; Parrillo, Joseph E. MD8; Dauerman, Harold L. MD9; Baran, David A. MD10; Hochman, Judith S. MD2; Alexander, John H. MD, MHS3

doi: 10.1097/CCM.0b013e31829f6242
Clinical Investigations

Objectives: Guidelines recommend β-blockers and renin-angiotensin-aldosterone system blockers to improve long-term survival in hemodynamically stable myocardial infarction patients with a reduced left ventricular ejection fraction. The prevalence and outcomes associated with β and renin-angiotensin-aldosterone system blocker therapy in patients with ongoing cardiogenic shock is unknown.

Design: Secondary analysis of a randomized controlled trial.

Setting: In patients with cardiogenic shock lasting more than 24 hours enrolled in Tilarginine Acetate Injection in a Randomized International Study in Unstable Myocardial Infarction Patients With Cardiogenic Shock, we compared 30-day mortality in patients who received β or renin-angiotensin-aldosterone system blockers (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or aldosterone antagonists) within 24 hours of randomization with those who did not.

Interventions: None.

Patients: The final study population included 240 patients. A total of 66 patients (27.5%) had either β blocker or renin-angiotensin-aldosterone system blocker administered within the first 24 hours after the diagnosis of cardiogenic shock. β-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and aldosterone antagonists were prescribed in 18.8%, 10.6%, and 5.0% of patients, respectively.

Measurements and Main Results: The observed 30-day mortality among patients was higher in patients who received β or renin-angiotensin-aldosterone system blockers prior to cardiogenic shock resolution (27.3% vs 16.9%; adjusted hazard ratio, 2.36; 95% CI, 1.06–5.23; p = 0.035). Compared with patients not given β or renin-angiotensin-aldosterone system blockers, the 30-day mortality was higher among patients treated only with β-blockers (33.3% vs 16.9%, p = 0.017) but not among those only treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (18.2% vs 16.9%, p = 1.000).

Conclusions: The administration of β or renin-angiotensin-aldosterone system blockers is common in North America and Europe in patients with myocardial infarction and cardiogenic shock prior to cardiogenic shock resolution. This therapeutic practice was independently associated with higher 30-day mortality, although a statistically significant difference was only observed in the subgroup of patients administered β-blockers.

1Divisions of Critical Care and Cardiology, University of Alberta, Edmonton, Alberta, Canada.

2Cardiovascular Clinical Research Center, New York University School of Medicine, New York, NY.

3Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.

4Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.

5Institute of Cardiology, Warsaw, Poland.

6Wilhelminen Hospital, Vienna, Austria.

7Third Faculty of Medicine, Charles University Prague, Czech Republic.

8Robert Wood Johnson Medical School and Cooper University Hospital, Camden, NJ.

9University of Vermont, Burlington, VT.

10Newark Beth Israel Medical Center, Newark, NJ.

This work was performed at the Duke Clinical Research Institute and at the University of Alberta.

Supported, in part, by the Duke Clinical Research Institute.

Dr. Reynolds’ institution received grant support and support for travel from Arginox Pharmaceuticals. Dr. Lopes consulted for Bristol-Meyers Squibb, Pfizer, Janssen, and Boehringer Ingelheim and lectured for Bristol-Meyers Squibb and Pfizer. His institution received grant support from Bristol-Meyers Squibb. Dr. Geppert received honorarium from Tilarginine Acetate Injection in a Randomized International Study in Unstable MI Patients With Cardiogenic Shock (TRIUMPH) study, received support for travel and participation in review activities from the TRIUMPH study, and lectured for Orion-Pharma and St. Jude. His institution received support for travel from Medtronic, BiotroniK, and Boston Scientific. Dr. Ohman and his institution received grant support from Daiichi Sankyo, Eli Lilly, and Gilead Sciences. He consulted for AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Janssen Pharmaceuticals, Lipscience, Merck, Pozen, Roche, Sanofi Aventis, The Medicines Company, and WedbMD. He lectured for Boehringer Ingelheim, Gilead Sciences, Janssen Pharmaceuticals, Liposcience, and The Medicines Company. Dr. Parrillo is a consultant for Artisan, Sangart, and Cytosorbents; he also serves on the Protocol Review Committee and Data Safety Monitoring Boards for the Heart Failure Network, National Heart, Lung and Blood Institute, and National Institute of Health. He has board membership with Artisan, Sangart, and Cytosorbents. His institution received grant support from the Salem Foundation. Dr. Dauerman is a consultant for The Medicines Company and Medtronic and has received research grants from Abbott Vascular and Medtronic. He provided expert testimony for Dartmouth Hitchcock. He received support for travel from Arginox, for participation in executive committee meetings from Arginox, and for development of educational presentations from The Medicines Company. He consulted for Arginox, Medtronic, and The Medicines Company. His institution received grant support from Medtronic, Abbott Vascular, and Arginox Pharmaceutical (sponsor of TRIUMPH trial). Dr. Baran lectured for Medtronic and Gilead and consulted for Maquet. His institution received grant support from Arginox Pharmaceutical (sponsor of TRIUMPH trial). Dr. Hochman received support for participation in review activities from Johnson & Johnson Pharmaceutical Research & Development and Bayer HealthCare AG (Independent Data Monitoring Committee for ATLAS 2 ACS-TIMI 51 Trial). She consulted for Glaxo Smith Kline (Steering Committee: SOLID-TIMI 52 and National Coordinator and Steering Committee: STABILITY Trial) and Eli Lily (TRILOGY Steering Committee). She received royalties from Wolters Kluwer Health (UpToDate Chapters). She serves as Senior Guest Editor for Circulation Journal for Partners Healthcare. Dr. Hochman and her institution received an honorarium from Arginox Pharmaceuticals and she served as Global Study Chair from 2005 to 2007. Arbor Pharmaceuticals donated Nitro-Spray to some ISCHEMIA Trial enrolling sites. Dr. Alexander received grant support from Bristol Myers Squibb, Pfizer, CSL Behring, Phyxius Pharmaceuticals, and Regado Biosciences and lectured for Bristol Myers Squibb. He consulted for Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Pfizer, Daiichi Sankyo, Janssen Pharmaceuticals, Moerae Matrix, Novartis, Orexigen, Regado Biosciences, Somahlution, and Xoma Pharmaceuticals. His institution received grant support and support for travel from Arginox Pharmaceuticals (Grant to Duke University to support past TRIUMPH trial coordinating center activities). Disclosures for Drs. Lopes and Alexander are publically listed at https://www.dcri.org/about-us/conflict-of-interest. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: sv9@ualberta.ca

© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins