The thrombin hypothesis in ACS: a disappointing disconnect between bench data and bedside clinical trials.
Studies have demonstrated the efficacy and safety of unfractionated heparin and low-molecular-weight heparin in the management of patients with acute coronary syndrome. However, a common limitation of unfractionated heparin and low-molecular-weight heparin is that neither can neutralize clot-bound thrombin. To overcome this limitation of the broad heparin-based anticoagulants, novel anticoagulants targeted for both the free and clot-bound forms of thrombin (direct thrombin inhibitors), or other individual components of the coagulation cascade (eg, direct and indirect factor Xa inhibitors), were developed. These targeted anticoagulation agents showed promising results in preclinical testing and have been evaluated in large-scale clinical acute coronary syndrome trials. This review discusses the disconnect between the excellent preclinical findings obtained with these novel, targeted agents and the efficacy and safety data observed in patients with acute coronary syndrome, compared with the broader-range heparin-based anticoagulants.
Cohen
Marc
M
Division of Cardiology, Newark Beth Israel Medical Center, Newark, NJ; Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA. marcohen@sbhcs.com
D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000925:Anticoagulants / Q000627:therapeutic use*; D065427:Factor Xa Inhibitors; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000627:therapeutic use; D013917:Thrombin / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D010975:Platelet Aggregation Inhibitors; D011480:Protease Inhibitors; D006493:Heparin; D013917:Thrombin