AUTHOR PROOF A Critical Review of the Use of Carvedilol in Ischemic Heart Disease Carol Chen-Scarabelli, 1,2 Louis Saravolatz II, 2 Yahya Murad, 2 Wen-Shi Shieh, 2 Waqas Qureshi, 2 Justin Di Rezze, 2 Rodeo Abrencillo, 2 Tova Gardin, 2 Umesh K. Gidwani, 3 Louis Saravolatz, 2 Giuseppe Faggian 4 and Tiziano M. Scarabelli 1 1 Center for Heart and Vessel Preclinical Studies, St John Hospital and Medical Center, Wayne State University School of Medicine, Detroit, MI, USA 2 Division of Cardiology, VA Ann Arbor, University of Michigan, Ann Arbor, MI, USA 3 Cardiovascular Institute, Mount Sinai Hospital, New York, NY, USA 4 Department of Cardiac Surgery, University of Verona Medical School, Verona, Italy Contents Abstract ............................................................................................................. 1 1. Background ...................................................................................................... 2 2. Carvedilol and Ischemia ............................................................................................ 2 2.1 Antioxidant Effect of Carvedilol.................................................................................. 3 2.2 Effect of Carvedilol on Neutrophil Activation ...................................................................... 3 2.3 Effect of Carvedilol through Free Radical-Scavenging Properties ..................................................... 3 2.4 Effect of Carvedilol on Preserving the Nitric Oxide System ........................................................... 3 2.5 Effect of Carvedilol through a 1 -Adrenoreceptor Blocking Vasodilation................................................. 4 3. Pre-Treatment with Carvedilol in Acute Myocardial Infarction (AMI) ....................................................... 4 4. Carvedilol Treatment in AMI ......................................................................................... 5 4.1 Immediately Following AMI ..................................................................................... 5 4.2 Following Thrombolysis ......................................................................................... 5 4.3 Following Percutaneous Transluminal Coronary Angioplasty and Coronary Artery Bypass Grafting......................... 6 5. Ventricular Remodeling Post-AMI ..................................................................................... 7 6. Carvedilol Treatment in Chronic Stable Angina ........................................................................ 8 6.1 Carvedilol and Exercise Tolerance ............................................................................... 8 6.2 Ambulatory Monitoring of Silent Ischemia ......................................................................... 8 7. Anti-Arrhythmic Properties of Carvedilol ............................................................................... 8 8. Conclusion ....................................................................................................... 9 Abstract b-Adrenoreceptor antagonists (b-blockers) have been recognized for their cardioprotective properties, prompting use of these pharmacologic agents to become more mainstream in acute myocardial infarction (AMI) and congestive heart failure (CHF). Despite their popularity as a class, the ability to protect the myocardium varies significantly between different agents. Carvedilol is a non-selective b-blocker with a 1 -adrenoreceptor antagonism properties. It is unique among b-blockers because in addition to improving exercise tolerance and its anti-ischemic properties secondary to a reduction in heart rate and myocardial contractility, carvedilol exerts other beneficial effects including: antioxidant effects; reduction in neutrophil infiltration; apoptosis inhibition; reduction of vascular smooth muscle migration; and improvement of myocardial remodeling post-AMI. These properties, documented in animal models and subsequent clinical trials, are consistent with established evidence demonstrating decreased morbidity and mortality in patients with CHF and post-AMI. This article reviews the role of carvedilol compared with other b-blockers in the treatment of CHF and post-AMI management. Approval for publication Signed Date Number of amended pages returned REVIEW ARTICLE Am J Cardiovasc Drugs 2012; 12 (6): 1-11 1175-3277/12/0006-0001/$49.95/0 Adis ª 2012 Springer International Publishing AG. All rights reserved.