EINSTEIN-DVT Trial and Acute Pulmonary Embolism
No, the EINSTEIN-DVT trial did not include patients with acute pulmonary embolism (PE). The EINSTEIN-DVT trial specifically enrolled patients with acute symptomatic deep vein thrombosis (DVT) without pulmonary embolism, while a separate trial called EINSTEIN-PE was conducted for patients with acute symptomatic PE with or without DVT 1, 2.
Trial Design and Patient Populations
The EINSTEIN program consisted of two separate trials with distinct patient populations:
Both trials compared rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) to standard therapy of enoxaparin followed by vitamin K antagonist (VKA) 2, 1
The separation of these two clinical presentations into different trials allowed for specific evaluation of rivaroxaban in these distinct manifestations of venous thromboembolism (VTE) 3
Evidence Supporting the Separation of Trials
The FDA label for rivaroxaban clearly states that EINSTEIN-DVT and EINSTEIN-PE were separate studies with different inclusion criteria 2
The NCCN guidelines specifically note that "EINSTEIN-DVT: acute symptomatic DVT without PE; EINSTEIN-PE: acute symptomatic PE ± DVT" 1
The British Thoracic Society guideline references both trials separately, noting that 90% (4328/4821) of EINSTEIN-PE patients were admitted to hospital 1
Clinical Implications
While PE and DVT are different clinical manifestations of the same disease entity (venous thromboembolism), they were studied in separate trials 4
Autopsy studies have established that PE arises from a lower limb DVT in 90% of patients, and when venography is performed in patients with confirmed PE, a residual DVT is found in 70% of cases 4
Despite this pathophysiological connection, the EINSTEIN program maintained separate trials for these two clinical presentations 2, 5
Pooled Analyses
Several subsequent analyses have pooled data from both EINSTEIN-DVT and EINSTEIN-PE trials to evaluate specific subgroups:
These pooled analyses combined data from both trials but do not change the fact that the original EINSTEIN-DVT trial did not include patients with acute PE 5, 7
Common Misunderstanding
The confusion may arise because both trials are often discussed together as part of the EINSTEIN program 5
Some publications refer to "EINSTEIN DVT and PE studies" collectively, which might lead to misunderstanding about the individual trial populations 6, 8
When reviewing bleeding risk data, both trials are often presented in the same table, but they represent different patient populations 1
In conclusion, the EINSTEIN-DVT trial specifically enrolled patients with acute symptomatic DVT without PE, while the EINSTEIN-PE trial was conducted separately for patients with acute symptomatic PE (with or without DVT).