Title: “The 52 in 52 Review: Heparin plus TPA compared to Heparin alone for Submassive PE”
Article Citation: Konstantinides S, Geibel A, Heusel G, Heinrich F, Kasper W; Management Strategies and Prognosis of Pulmonary Embolism-3 Trial Investigators. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med. 2002 Oct 10;347(15):1143-50. PMID: 12374874
What we already know about the topic: Alteplase or thrombolysis is indicated therapy in hemodynamically unstable patients with massive pulmonary embolism (PE). Treatment for submassive hemodynamically stable PE remains controversial. Few studies have demonstrated a risk-benefit ratio for thrombolysis for submassive stable PE.
Why this study is important: In this study, the authors compare treatment of Heparin plus placebo to Heparin plus thrombolysis in patients with submassive PE to demonstrate risk vs benefit. This can potentially change practice management of stable submassive PE patients.
Brief overview of the study: This study is a prospective randomized double blinded placebo-controlled trial. 256 patients were randomized to receive either Heparin and Alteplase or Heparin and placebo. Randomized groups were similar in patient demographic and clinical parameters at baseline. Primary end-point was in hospital death or clinical deterioration which required an escalation in treatment. There was a statistically significant increased incidence of the primary endpoint in the Heparin/Placebo group vs the Heparin/Alteplase group. (24% vs 11%, p = 0.006). Escalation of treatment was also significantly higher in the placebo group as well (24% vs 10%, p = 0.004). Requirement for secondary thrombolysis was again increased in the placebo group (23% vs 9%, p = 0.001). All secondary endpoints; recurrent PE, major bleeding, fatal bleeding, hemorrhagic stroke, were similar in each group without statistical difference.
Limitations: My primary issues with this study are: (1) A very low (N), 286 patients were randomized to either group which is a small sample size. (2) In hospital mortality rates were uncharacteristically low in this study when compared to the national average for PE by the PE registry (8%), which may have been due to uncovered confounders.
Take home points: I believe further large scale multicentered studies are needed to determine the benefit of Alteplase and Heparin for hemodynamically stable sub massive PE patients.