Thrombolytics Reduce Pulmonary Embolism Deaths by 47%
Adding thrombolytic drugs to conventional therapy may offer significant benefits for patients with intermediate-risk sudden-onset pulmonary embolism (PE), according to a new meta-analysis in the Journal of the American Medical Association.
Adding these clot-busting medications to standard treatment was associated with 47% fewer deaths than using standard anticoagulant therapy.
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“Most importantly, we discovered that thrombolytic therapy was associated with mortality benefit in intermediate-risk pulmonary embolism,” says senior study author Jay Giri, MD, MPH, an assistant professor of clinical medicine at the University of Pennsylvania, in Philadelphia.
“This is a hotly debated topic and no prior study has had the statistical power to demonstrate this finding,” he says. “Of course, this potential benefit must be balanced against potential bleeding risks in the individual patient, which we also attempted to clarify.”
Giri and his colleagues conducted a meta-analysis of 16 published, randomized, controlled trials from the past 40 years comparing thrombolytic therapy vs. anticoagulant therapy in PE patients. In total, they analyzed data from 2,115 PE patients—about half received both thrombolytics and conventional anticoagulation treatment and the other half only received conventional treatment.
While thrombolytic therapy is a standard approach for patients at a high risk of dying from PE, its use in intermediate-risk patients has been extensively debated, particularly because it could increase the risk of intracranial bleeding in these patients.
In fact, the study did show associated increases in intracranial hemorrhage—1.46% with thrombolytics vs. 0.19% with blood-thinners alone. But it also suggested that patients 65 and younger might be at less bleeding risk from thrombolytic therapy than those above age 65.
In intermediate-risk PE patients with advanced age or any increased bleeding risks (recent surgery/trauma, thrombocytopenia, history of stroke), Giri tends to take a more conservative approach, with anticoagulation alone as an initial strategy.
However, for intermediate-risk patients who are younger without key relative bleeding contraindications, he considers thrombolysis to be a therapy that leads to faster symptom resolution, more rapid normalization of pulmonary pressures and right ventricular dysfunction, reduced chances of acute hemodynamic decompensation, and a potential mortality benefit.
“Our research indicates that thrombolytic therapy may be a viable initial strategy for a subset of intermediate-risk pulmonary embolism patients who are hemodynamically stable with high-risk features,” Giri says. “The finding of a small but quantifiable associated mortality benefit may give reassurance to clinicians who favor this more aggressive strategy in selected patients that are judged to potentially benefit from thrombolysis.”
He says more research is needed to clarify quantitative risk-stratification strategies in these intermediate-risk patients for both mortality and bleeding risks.
“Additionally, research should focus on standardization of dosages of thrombolytics and method of administration to accrue maximal clinical benefits with minimization of bleeding risk,” Giri says. “Future trials should also mandate longer-term follow-up of pulmonary embolism patients treated with thrombolytics to determine whether late benefits/harms emerge from their use.”
—Colleen Mullarkey
Reference
Chatterjee S, Chakraborty A, Weinberg I, Kadakia M, Wilensky RL, Sardar P, et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA. 2014 Jun 18;311(23):2414-21.