Therapeutic Role of Innovative Anti-Inflammatory Medications in the Prevention of Acute Coronary Syndrome.
An improved understanding of the pathogenesis of acute coronary syndromes and its relationship to atherosclerotic plaque rupture and thrombosis has contributed to the investigation of novel therapies for prevention and treatment. New data ascribe an increasingly important role of active inflammation in contributing to thinning of the atherosclerotic fibrous cap and plaque instability. Despite this understanding, there are currently no therapeutic approaches to specifically target the unstable plaque. Multiple randomized trials investigating treatment strategies have recently been completed or are currently being conducted, using anti-inflammatory medications, such as methotrexate, colchicine, darapladib, varespladib, losmapimod, and canakinumab, to reduce the incidence of cardiovascular events including acute coronary syndromes. These anti-inflammatory medications differ in their mechanism of action from having widespread targets (as is the case for methotrexate and colchicine) to having specific targets (as is the case for darapladib, varespladib, losmapimod, and canakinumab). The trials investigating the efficacy of darapladib in reducing cardiovascular events revealed no significant benefit when compared with the current standard of care. The varespladib studies were terminated early because of adverse outcomes. However, the outcomes of the remaining drug studies may still contribute to novel therapeutic approaches in the treatment of patients with unstable coronary artery disease.
From the *Department of Medicine, New York Presbyterian Hospital, Cornell Medical Center, New York, NY; and †Department of Medicine, New York Medical College, Westchester Medical Center, Valhalla, NY.
Raymond Anthony
RA
Pashun
William H
WH
Frishman
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000037:antagonists & inhibitors; D000085:Acetates / Q000627:therapeutic use; D054058:Acute Coronary Syndrome / Q000517:prevention & control*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001547:Benzaldehydes / Q000627:therapeutic use; D003078:Colchicine / Q000627:therapeutic use; D003521:Cyclopropanes / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007211:Indoles / Q000627:therapeutic use; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use; D007651:Keto Acids; D008727:Methotrexate / Q000627:therapeutic use; D010091:Oximes / Q000627:therapeutic use; D064801:Phospholipase A2 Inhibitors / Q000627:therapeutic use*; D054497:Phospholipases A2, Secretory / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D001713:Biphenyl Compounds; D004048:Diethylamines; D011744:Pyrimidinones; D013440:Sulfides
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000085:Acetates; D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; D001547:Benzaldehydes; D003078:Colchicine; D003521:Cyclopropanes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D053590:Interleukin 1 Receptor Antagonist Protein; D007651:Keto Acids; D008727:Methotrexate; D010091:Oximes; D064801:Phospholipase A2 Inhibitors; D054497:Phospholipases A2, Secretory; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D048051:p38 Mitogen-Activated Protein Kinases; C543534:6-(5-((cyclopropylamino)carbonyl)-3-fluoro-2-methylphenyl)-N-(2,2-dimethylprpyl)-3-pyridinecarboxamide; C117948:varespladib; C529040:darapladib; D001713:Biphenyl Compounds; D004048:Diethylamines; D011744:Pyrimidinones; D013440:Sulfides