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STATE-OF-THE-ART PAPER

Antithrombotics in Acute Coronary Syndromes

Marc P. Bonaca, MD^_*, Philippe Gabriel Steg, MD, Laurent J. Feldman, MD, John F. Canales, MD, James J. Ferguson, MD^,, Lars Wallentin, MD, PhD^||, Robert M. Califf, MD^¶, Robert A. Harrington, MD^¶ and Robert P. Giugliano, MD, SM^_*,_*

^_* TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts
Centre Hospitalier Bichat-Claude Bernard, Université Paris VII–Denis Diderot, Paris, France
Texas Heart Institute at St. Luke's Episcopal Hospital, Baylor College of Medicine, Houston, Texas
The University of Texas Health Science Center at Houston, Houston, Texas
^|| Uppsala Clinical Research Centre at Uppsala University, Uppsala, Sweden
^¶ Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina

Manuscript received June 26, 2007; revised manuscript received March 18, 2009, accepted March 25, 2009.

^_* Reprint requests and correspondence: Dr. Robert P. Giugliano, SM, TIMI Study Group, 350 Longwood Avenue, 1st Floor Offices, Boston, Massachusetts 02115 (Email: rgiugliano{at}partners.org).

Antithrombotic agents are an integral component of the medical regimens and interventional strategies currently recommended to reduce thrombotic complications in patients with acute coronary syndromes (ACS). Despite great advances with these therapies, associated high risks for thrombosis and hemorrhage remain as the result of complex interactions involving patient comorbidities, drug combinations, multifaceted dosing adjustments, and the intricacies of the care environment. As such, the optimal combinations of antithrombotic therapies, their timing, and appropriate targeted subgroups remain the focus of intense research. During the last several years a number of new antithrombotic treatments have been introduced, and new data regarding established therapies have come to light. Although treatment guidelines include the most current available data, subsequent findings can be challenging to integrate. This challenge is compounded by the complexity associated with different efficacy and safety measures and the variability in study populations, presenting syndromes, physician, and patient preferences. In this work we review recent data regarding clinically available antiplatelet and anticoagulation agents used in the treatment of patients with ACS. We address issues including relative efficacy, safety, and timing of therapies with respect to conservative and invasive treatment strategies. In specific cases we will highlight remaining questions and controversies and ongoing trials, which will hopefully shed light in these areas. In addition to reviewing existing agents, we take a look forward at the most promising new antithrombotics currently in late-stage clinical development and their potential role in the context of ACS management.

Key Words: antiplatelet • antithrombotic • anticoagulant • infarction • ischemia

Abbreviations and Acronyms   ACC = American College of Cardiology   ACS = acute coronary syndromes   ADP = adenosine diphosphate   AHA = American Heart Association   CABG = coronary artery bypass grafting   CrCl = creatine clearance   DTI = direct thrombin inhibitor   ESC = European Society of Cardiology   GPI = glycoprotein IIb/IIIa inhibitor   LMWH = low molecular weight heparin   MI = myocardial infarction   NSTE-ACS = non–ST-segment elevation acute coronary syndromes   PCI = percutaneous coronary intervention   STEMI = ST-segment elevation myocardial infarction   UFH = unfractionated heparin

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J. Am. Coll. Cardiol. 2009 54: A26. [Full Text] [PDF]