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Intravenous nPA for Treatment of Infarcting Myocardium Early - InTime-2
Description:
Lanoteplase vs. alteplase for 30-day mortality in acute myocardial infarction
Study Design
Study Design:
Patients Screened: Not given
Patients Enrolled: 15078
Patient Populations:
Age > 18
Chest pain of less than 6 hours' duration
ST segment elevation or new left bundle branch block
Men or nonpregnant women
Exclusions:
Increased risk for bleeding
Risk of aortic dissection
Cardiogenic shock
Primary Endpoints:
All-cause mortality at 30 days
Secondary Endpoints:
New or worsened heart failure, intracranial hemorrhage, death, or stroke
Drug/Procedures Used:
nPA (120kU/kg) or tPA
Principal Findings:
The 30-day mortality between the two groups was statistically similar: 6.6% in the tPA group versus 6.77% in the nPA group. Interestingly, the 24-hour mortality was slightly better in the nPA-treated subjects: 2.39% versus 2.49% in the tPA group. Among patients expiring, intracranial hemorrhage was a more frequent event in those treated with nPA: 0.66% versus 0.4% (P value - 0.051). Overall, the incidence of stroke was similar in the two treatment groups: 1.52% in tPA-treated versus 1.89% in nPA-treated (P-value - 0.103). Once again, intracranial hemorrhage occurred more frequently in nPA-treated individuals: 1.13% versus 0.62% (P-value - 0.003). The incidence of disabling strokes was similar however.
Overall bleeding complications were equal in the two treatment groups. However, mild complications occurred more frequently in nPA-treated individuals: 19.6% versus 14.7% (P< 0.001). Secondary endpoints of urgent revascularization, severe heart failure, recurrent myocardial infarction, death+MI were similar in the groups, with a trend toward more favorable outcomes among those treated with nPA. Data on 180-day mortality reveal nearly identical results between the two treatment strategies.
Interpretation:
Lanoteplase or nPA is a new genetically-engineered plasminogen activator with full fibrinolytic potency and a long plasma half-life, allowing for single intravenous bolusing. The InTime-I trial tested the safety and efficacy of nPA in a dose-dependent manner. A dose-response in efficacy was seen up to a maximum dosage of 120kU/kg, with better results than patients treated with standard, accelerated-dose tPA. The investigators conclude that lanoteplase (nPA) is equally effective in reducing 30-day mortality when compared with tPA. The overall survival of nPA-treated patients is similar despite a higher incidence of intracranial bleeding complications, with little difference in the incidence of disabling stroke. The clinical benefits of single-bolus nPA over traditionally-dosed tPA include accelerated treatment times, less chance of a dosing error, and simpler mode of administration, which may facilitate emergency room or pre-hospital treatment.
References:
1. Presented at the ACC 48th Scientific Sessions, New Orleans, LA, 1999
Keywords: Thrombolytic Therapy, Myocardial Infarction, Stroke, Intracranial Hemorrhages, Chest Pain, Plasminogen, Heart Failure, Bundle-Branch Block, Fibrinolytic Agents, Tissue Plasminogen Activator
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