Dabigatran after Short Heparin Anticoagulation for Acute Intermediate-Risk Pulmonary Embolism: Rationale and Design of the Single-Arm PEITHO-2 Study

Abstract

Patients with intermediate-risk pulmonary embolism (PE) may, depending on the method and cut-off values used for definition, account for up to 60% of all patients with PE and have an 8% or higher risk of short-term adverse outcome. Although four non-vitamin K-dependent direct oral anticoagulants (NOACs) have been approved for the treatment of venous thromboembolism, their safety and efficacy as well as the optimal anticoagulation regimen using these drugs have not been systematically investigated in intermediate-risk PE. Moreover, it remains unknown how many patients with intermediate-high-risk and intermediate-low-risk PE were included in most of the phase III NOAC trials. The ongoing Pulmonary Embolism International Thrombolysis 2 (PEITHO-2) study is a prospective, multicentre, multinational, single-arm trial investigating whether treatment of acute intermediate-risk PE with parenteral heparin anticoagulation over the first 72 hours, followed by the direct oral thrombin inhibitor dabigatran over 6 months, is effective and safe. The primary efficacy outcome is recurrent symptomatic venous thromboembolism or death related to PE within the first 6 months. The primary safety outcome is major bleeding as defined by the International Society on Thrombosis and Haemostasis. Secondary outcomes include all-cause mortality, the overall duration of hospital stay (index event and repeated hospitalizations) and the temporal pattern of recovery of right ventricular function over the 6-month follow-up period. By applying and evaluating a contemporary risk-tailored treatment strategy for acute PE, PEITHO-2 will implement the recommendations of current guidelines and contribute to their further evolution.

Keywords

dabigatran - pulmonary embolism - intermediate risk - venous thromboembolism recurrence - right ventricular function - major bleeding

Authors' Disclosures

Frederikus Klok reports research grants from Bayer, research grants from Bristol-Myers Squibb, research grants from Boehringer Ingelheim and non-financial research support from Daiichi Sankyo. Stefano Barco has received congress and travel payments from Daiichi Sankyo and Bayer HealthCare and financial support for the printing costs of his PhD thesis from Pfizer bv, CSL Behring bv, Sanquin Plasma Products, Boehringer Ingelheim bv, Aspen Netherlands and Bayer bv. Benjamin Brenner declares receiving honoraria for lectures and advisory board contributions from Pfizer, LEO Pharma, Sanofi and ROVI Laboratories. Matthias Held reports grants from Actelion, honoraria for lectures from Actelion, Bayer HealthCare, Berlin-Chemie, Boehringer Ingelheim, GSK, Novartis, Pfizer, honoraria for advisory board activities from Actelion, Bayer HealthCare, GSK, MSD and participation in clinical trials of Actelion, Bayer HealthCare, GSK, Pfizer, United Therapeutics, outside the submitted work. Daniel Duerschmied has received lecture honoraria from Bayer HealthCare and Pfizer and payment for travel accommodation/meeting expenses from Bayer HealthCare and Orion Pharma. Menno V. Huisman received research grants as well as fees for speaking and consulting from Boehringer Ingelheim, Bayer HealthCare, BMS-Pfizer, Daiichi Sankyo, MSD and Aspen. Guy Meyer reports travel support from Leo Pharma, BMS-Pfizer, Stago and Bayer HaelthCare and institutional grants from Leo Pharma, Bayer HaelthCare and BMS-Pfizer. Antoniu Petriş reports having received consultancy and lecture honoraria from Bayer HealthCare, Boehringer Ingelheim, Servier Pharma, AstraZeneca Pharma and BMS-Pfizer and payment for travel accommodation/meeting expenses from Bayer HealthCare and Boehringer Ingelheim. Franck Verschuren reports research support from Boehringer Ingelheim, Portola Pharmaceuticals, Daiichi Sankyo. Stavros Konstantinides reports having received consultancy and lecture honoraria from Bayer HealthCare, Boehringer Ingelheim, Actelion, Servier and BMS-Pfizer, payment for travel accommodation/meeting expenses from Bayer HealthCare and institutional grants from Boehringer Ingelheim, Bayer HealthCare, Daiichi Sankyo and Actelion.

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