Clinical question: Is recombinant tissue-type plasminogen activator (rt-PA) at 50 mg/2 hr as effective and safe as 100 mg/2 hr for acute pulmonary thromboembolism (PTE)?
Background: The U.S. Food and Drug Administration approved a 100 mg/2 hr dose of rt-PA, which has been recommended as the standard regimen for PTE. Lower doses potentially have less bleeding but their clinical efficacy in PTE has not yet been evaluated. If efficacious, rt-PA at 50 mg/2 hr used for treating acute MI might prove to be a better regimen for acute PTE.
Study design: Prospective, randomized, open-label, multicenter trial.
Setting: Multiple centers in China.
Synopsis: 118 patients with PTE, with either hemodynamic instability or anatomically massive obstruction, were assigned to receive rt-PA at 50 mg/2 hr (n=65) or 100 mg/2 hr (n=53) and followed for 14 days. Clinical efficacy as serially measured by improvement in pulmonary artery pressure and right ventricular function on echocardiogram, lung perfusion on V/Q scan, and pulmonary artery obstruction by CTPA was not significantly different between the two groups.
Though mortality was not significantly different between both groups (three in the high-dose group and one in the low-dose group), there was one fatal ICH in the high-dose group. As can be expected, total bleeding prevalence (major and minor) was lower in the 50-mg group (17% vs. 32%, p=0.084), especially in patients with body weight <65 kgs or BMI <24 kg/m2.
The fact that two-thirds of the patients had only anatomically massive PTE without any hemodynamic instability limits the extrapolation of the efficacy of low-dose rt-PA because heparin alone is generally used in these cases. Also, patients with body weight >100 kg may need the higher dose but were not evaluated adequately in this study.
Bottom line: A lower-dose regimen of 50 mg/2 hr of rt-PA is as efficacious as 100 mg/2 hr in treatment of PTE but offers a better safety profile in patients with weight <65kg.
Citation: Wang C, Zhai Z, Yang Y, et al. Efficacy and safety of low dose recombinant tissue-type plasminogen activator for the treatment of acute pulmonary thromboembolism: a randomized, multicenter, controlled trial. Chest. 2010;137(2):254-262.