Early Switch to Oral Anticoagulation in Intermediate-Risk Pulmonary Embolism

Quick Takes

  • Patients with intermediate (submassive) pulmonary embolism (PE) can be safely transitioned from parenteral heparin to oral anticoagulation after just 72 hours.
  • A strategy using only 72 hours of parenteral heparin is safe and effective prior to initiating oral dabigatran for acute PE management.

Study Questions:

What are the outcomes of patients who switched from parenteral to oral anticoagulation after just 72 hours following an acute intermediate-risk pulmonary embolism (PE)?

Methods:

The authors conducted a multinational, multicenter, single-arm, phase 4 trial at 42 hospitals in Europe. Adult patients with symptomatic intermediate-risk (submassive) PE received parenteral low molecular weight heparin or unfractionated heparin for 72 hours before switching to oral dabigatran 150 mg twice a day. The primary outcome was recurrent symptomatic venous thromboembolism or PE-related death within 6 months. The primary safety outcome was major bleeding. The study was terminated early at the recommendation of the data safety and monitoring board.

Results:

Between January 2016–July 2019, 1,418 patients with PE were screened and 402 were enrolled (median age 69.5 years, 48% women). Over a median follow-up of 217 days, 370 (92%) patients adhered to the protocol. The primary outcome occurred in seven (2%) patients, all of whom were intermediate–high risk at presentation. At 6 months, 11 (3%, 95% confidence interval [CI], 1-5%) patients had at least one major bleeding event and 16 (4%, 95% CI, 2-6%) had at least one clinically relevant nonmajor bleeding event. The one fatal hemorrhage occurred in a patient prior to switch to dabigatran.

Conclusions:

A strategy of early switch from heparin to dabigatran was effective and safe in patients with intermediate-risk PE.

Perspective:

This phase 4 multicenter study helps address two important issues in acute management of intermediate/submassive PE. First, patients who do not have hemodynamic decompensation can safely transition from parenteral heparin to an oral anticoagulant after just 72 hours. Second, transition from parenteral heparin to oral dabigatran anticoagulation can safely occur without a full 5- to 10-day lead-in period. While this study is unlikely to officially change the Food and Drug Administration package label instruction for dabigatran, this management strategy may become more popular when dabigatran becomes generic in the coming year(s). While this study did not explore an oral-only strategy with apixaban or rivaroxaban, these medications are commonly used after a short parenteral heparin period as well.

Clinical Topics: Anticoagulation Management, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Anticoagulation Management and Venothromboembolism

Keywords: Anticoagulants, Dabigatran, Hemodynamics, Hemorrhage, Heparin, Heparin, Low-Molecular-Weight, Pulmonary Embolism, Rivaroxaban, Secondary Prevention, Vascular Diseases, Venous Thromboembolism


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