The report by Stein and colleagues [1] is biostatistically elegant but is compromised by multiple assumptions and data selection. However, even if the statistical manipulations, assumptions, and data sources are accepted, the authors skirt the central issues: Are thrombolytic agents of value in acute pulmonary embolism and, if so, in what patients?

The authors state that "thrombolytic therapy for patients with massive acute pulmonary embolism is indicated for patients who are hypotensive, hypoxic when receiving high levels of oxygen, or clinically stable with echocardiographic evidence of right ventricular failure." This statement is not referenced. In my view, there is good reason for the absence of a reference; I find this bland statement of "indications" unwarranted. It simply has not yet been shown that thrombolytic therapy—with any of the available agents—alters patient outcome, even in proven massive embolism. What has been shown is that patients treated with such agents show earlier hemodynamic, lung perfusion scan, and angiographic improvement. However, any effect on true outcome variables—death, duration of hospital stay, recurrence rates, long-term hemodynamic performance—remains to be adequately shown. Until convincing evidence of efficacy is provided, the criteria for administering and taking the risk of such therapy—including the diagnostic justification—remain controversial.

In my view, it is certainly not time to consider "... a broadening of the indications for thrombolytic therapy in acute pulmonary embolism," as these distinguished investigators suggest. Scans, angiograms, clinical impressions, and bleeding risk are not the real issues in this arena. We need more definitive data about outcomes. Until such data exist, selection of patients for thrombolytic therapy remains uncertain.