The diagnosis and treatment of pulmonary embolism: A metaphor for medicine in the evidence-based medicine era

Background: The history of pulmonary embolism (PE) provides a fascinating portrait of a well-established diagnosis and standard of care treatment moving into the age of evidence-based medicine. Methods: We examined the history of PE and the practice of treating PE with anticoagulation. Results: Pulmonary embolism is a diagnostic category whose definition and treatment have both changed in the past century. Initially, PE was recognizable only when massive, with the signs and symptoms of right heart failure. Anticoagulants were established as the cornerstone of PE management with a single randomized controlled trial of 35 patients in 1960 and based on commonsense pathophysiologic reasoning. Since then, the diagnostic category of PE has been broadened, and the advent of computed tomography pulmonary angiography has yielded nearly a doubling of the incidence of the disease, without a concordant decrease in mortality. Although anti-coagulation remains the cornerstone of management, open questions remain: what end points are altered by anti-coagulation? What is the number needed to treat? Conclusions: Trials of newer anticoagulants and longer durations of anticoagulation have not yielded real improvements over heparin, inviting doubts regarding its efficacy. Thus, PE is the quintessential diagnosis of medicine not because it represents our greatest success, but because it captures all the complexity of medicine in the evidence-based era. It may serve as a metaphor for many other conditions in medicine, including coronary artery disease. New trials in the field continue to test trivialities, whereas fundamental questions are unanswered.