A multi-institution meta-analysis has found that adding clot-busting medications known as thrombolytics to conventional approaches when treating sudden-onset pulmonary embolism patients is associated with 47 percent fewer deaths than using standard intravenous or under-the-skin anticoagulant medications alone.

The meta-analysis of 16 published, randomized, controlled trials over the past 40 years assessed 2,115 pulmonary embolism patients, approximately half of whom received both thrombolysis and conventional anticoagulation treatment, namely IV-administered and injectable blood-thinners such as heparin; and half of whom only received the conventional treatment.

The authors found a 2.17 percent mortality rate among patients undergoing thrombolysis in addition to the other drugs. This compares to a 3.89 percent mortality rate for patients receiving the conventional blood-thinning regimen alone. Thus, the addition of thrombolysis was associated with 47 percent less mortality than standard anticoagulant therapy.

There has been extensive debate about whether patients classified as having an intermediate risk of forming pulmonary embolisms could benefit from thrombolysis as well as high-risk patients, especially in light of the fact that the procedure could put them at greater risk for bleeding in their brains. Indeed, the reduction in death rate observed in the study was partially balanced by significant, associated increases in intracranial hemorrhage: 1.46 percent with thrombolysis vs. 0.19 percent with blood-thinners alone. But the study also revealed patterns in where those side effects may be more common: According to the meta-analysis, patients 65 and younger might be at less bleeding risk from thrombolysis than those above age 65.

“We discovered that thrombolysis was associated with a clear reduction in deaths in gray-area, intermediate-risk, pulmonary embolism patients,” said the study’s senior author, Jay Giri, M.D., of the Perelman School of Medicine at the University of Pennsylvania. “Of course, this potential benefit must be balanced against potential bleeding risks, which we also attempted to clarify. With this knowledge, future research can help identify subgroups of patients who are most likely to obtain this mortality benefit and least likely to be harmed by bleeding, particularly intracranial hemorrhage.

“Additionally, research should focus on standardization of dosages of medication in thrombolysis as well as explore the optimal method of administration, namely intravenous versus catheter-directed therapy into the pulmonary arteries, to determine maximal clinical benefits with minimization of bleeding risk.”

The study findings are published online in the Journal of the American Medical Association here.

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