New anticoagulants in ischemic heart disease.
Fibrinolysis is the reference treatment for most myocardial infarctions with ST-segment elevation; alternatives are angioplasty, with or without stent. The earlier fibrinolysis is performed (preferably before hospitalization), the more effective it is. It can be optimized by adjuvant antiplatelet therapy, such as aspirin, and probably by anticoagulant treatment as well. Because fibrinolytic therapy is accompanied by intensive thrombin generation and activation, immediate and continuous adjunctive simultaneous heparin therapy is recommended. The efficacy of subcutaneous low-molecular-weight heparin (LMWH) HBPM) is at least equivalent to that of intravenous unfractionated heparin (UFH), but its risk of severe (but not cerebral) hemorrhage is greater. Bolus LMWH on the other hand is associated with an increased risk of cerebral hemorrhage. Antithrombotic treatment thus appears optimal with bolus UFH at fibrinolysis and for at least 48 hours afterwards. An alternative after this bolus might be subcutaneous enoxaparin until discharge. Because the major drawback of both types of heparin is their rebound activation of thrombosis, oral anticoagulants are recommended thereafter. The combination of anticoagulant treatment + (low-dose) aspirin is not superior to aspirin alone when the target INR is below 2. Adequate anticoagulation with INRs greater than 2.0 consistently improves angiographic and clinical outcome. Bleeding (except intracerebral) is significantly increased whether the INR is greater than or less than 2.0. Other treatments are being investigated. Pentasaccharide (anti-Xa) combined with fibrinolysis seems to reduce reocclusion more effectively than UFH. Oral postinfarction treatment with ximelagatran (a thrombin inhibitor), combined with aspirin, is associated with fewer cardiovascular events than aspirin alone. More studies are needed.
Verheugt
F W A
FW
Department of Cardiology, University Medical Center St Radboud, Nijmegen, The Netherlands. f.verheugt@cardio.umcn.nl
D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use; D001384:Azetidines / Q000008:administration & dosage / Q000627:therapeutic use; D001596:Benzylamines; D002543:Cerebral Hemorrhage / Q000139:chemically induced; D003328:Coronary Thrombosis / Q000188:drug therapy; D004359:Drug Therapy, Combination; D015951:Factor Xa / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D005544:Forecasting; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D009203:Myocardial Infarction / Q000188:drug therapy; D017202:Myocardial Ischemia / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D000925:Anticoagulants; D001384:Azetidines; D001596:Benzylamines; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D010975:Platelet Aggregation Inhibitors; C426686:ximelagatran; D006493:Heparin; D015951:Factor Xa; D001241:Aspirin