Glyceryl trinitrate may reduce thrombolytic efficacy of alteplase, but this is not thought to be clinically relevant.
Clinical evidence,mechanism, importance and management
In a randomised study,60 patients with acute anterior myocardial infarction were given intravenous alteplase 100mg over 3 hours, as well as heparin and aspirin. In addition, 27 of patients were also given intravenous glyceryl trinitrate 100 micrograms/minute for 8 hours. Patients receiving both alteplase and glyceryl trinitrate had signs of reperfusion less often (56%) than patients who received alteplase alone (76%). In combined treatment group time to reperfusion was also longer (37.8 versus 19.6 minutes) and incidence of coronary artery re-occlusion was higher (53% versus 24%). Giving alteplase with glyceryl trinitrate produced plasma levels of tissue plasminogen activator (tPA) antigen that were about two-thirds lower than when alteplase was given alone (See reference number 1). Impaired thrombolysis has been found in another study(See reference number 2) and also in an earlier study in dogs (See reference number 3).
It was postulated that glyceryl trinitrate increased hepatic blood flow and therefore increased metabolism of alteplase, which resulted in reduced plasma tPA levels (See reference number 1). However, an in vitro study found that glyceryl trinitrate enhanced degradation of alteplase, and therefore a mechanism other than increased hepatic blood flow seems likely to be involved (See reference number 4). It has been suggested that this interaction may not be clinically important,(See reference number 5) and current evidence is too sparse to warrant changing current practice.
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Boehringer Ingelheim. Personal communication,March 1999.