title: Patency trials with reteplase (r-PA): what do they tell us?
abstract: Thrombolytic therapy has been shown to reduce mortality and morbidity after acute myocardial infarction. Therapeutic benefit seems to be directly correlated with completeness of reperfusion (Thrombolysis in Myocardial Infarction [TIMI] grade 3 flow) of the infarct-related coronary artery, as well as the timeliness of reperfusion. To determine which regimen of reteplase (r-PA), a deletion mutant of wild-type tissue plasminogen activator (t-PA), is most effective for clinical thrombolysis, several reteplase regimens were compared with the most successful standard regimens of recombinant t-PA (alteplase) in 2 large-scale, randomized studies. All patients received aspirin and intravenous heparin. In the Reteplase Angiographic Phase II International Dose Finding Trial (RAPID-1), results in 606 randomized patients showed that a 10 + 10 U double bolus of reteplase was more effective than a 15 U single bolus, a 10 + 5 double bolus, or conventional alteplase (100 mg over 3 hours). In the Reteplase versus Alteplase Patency Investigation During Acute Myocardial Infarction (RAPID-2) trial, results in 324 patients showed that significantly more patients achieved patency of the infarct-related artery (TIMI grade 2 or 3 flow) at 90 minutes with reteplase (10 + 10 U double bolus) than with accelerated alteplase (100 mg over 90 minutes): 83.4% versus 73.3%, respectively (p = 0.03). The incidence of complete patency (TIMI grade 3 flow) at 90 minutes was likewise greater with reteplase than with accelerated alteplase (59.9% vs 45.2%, respectively; p = 0.01). At 60 minutes, the incidence of TIMI grade 2 or 3 flow was also significantly higher with reteplase than with alteplase (81.8% vs 66.1%, respectively; p = 0.01), as was the incidence of TIMI grade 3 flow (51.2% vs 37.4%, respectively; p < 0.031). The 35-day mortality rate was 4.1% for reteplase and 8.4% for alteplase (p = not significant). Reteplase and alteplase did not differ significantly with regard to the occurrence of severe bleeding (12.4% vs 9.7%, respectively) or hemorrhagic stroke (1.2% vs 1.9%, respectively). The results of these trials show that reteplase, given as a 10 + 10 U double bolus, achieves significantly higher rates of early reperfusion of the infarct-related coronary artery and is associated with significantly fewer acute coronary interventions when compared with front-loaded alteplase. The benefits of reteplase are achieved without any apparent increased risk of complications.
authors.affiliation: Medizinische Klinik III (Kardiologie, Angiologie und Pulmonologie, Heidelberg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Bode
authors.forename: T K
authors.initials: TK
authors.lastname: Nordt
authors.forename: K
authors.initials: K
authors.lastname: Peter
authors.forename: R W
authors.initials: RW
authors.lastname: Smalling
authors.forename: M S
authors.initials: MS
authors.lastname: Runge
authors.forename: W
authors.initials: W
authors.lastname: Kübler
mesh_terms: D002543:Cerebral Hemorrhage / Q000139:chemically induced; D017322:Clinical Trials, Phase II as Topic; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D004334:Drug Administration Schedule; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D015994:Incidence; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology; D010960:Plasminogen Activators / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D015996:Survival Rate; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D014654:Vascular Patency / Q000187:drug effects
chemical_list: D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; C087896:reteplase; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator