Multinational, multicentre, single-arm, phase 4 trial

N= 402

To ascertain whether treatment of acute intermediate-risk pulmonary embolism with parenteral anticoagulation for a short period of 72 h followed by treatment with the direct oral anticoagulant (DOAC), dabigatran, for 6 months is effective and safe

All patients (n= 402)

Adult patients (aged ≥18 years) with symptomatic intermediate-risk pulmonary embolism, with or without deep-vein thrombosis, confirmed by CT pulmonary angiography, a ventilation or perfusion lung scan, or selective invasive pulmonary angiography

Indication for long-term anticoagulation treatment other than the index pulmonary embolism episode; contraindications to dabigatran; active bleeding or risk of clinically significant bleeding; creatinine clearance <30 mL/min; severe chronic liver disease; pregnancy or lactation; use of fibrinolytic agent, surgical thrombectomy, or cava filter; treatment with anticoagulant for more than 48 h before enrolment; artificial heart valves; strong inhibitors of p-glycoprotein; medical or psychological condition preventing trial completion; participation in another clinical trial within the last 3 months; life expectancy <6 months

Patients received parenteral low-molecular-weight or unfractionated heparin for 72 h after diagnosis of pulmonary embolism before switching to oral dabigatran 150 mg twice per day following a standard clinical assessment. The primary and safety outcomes were assessed in the intention-to-treat population.

January 1, 2016, to July 31, 2019

Primary: Recurrent symptomatic venous thromboembolism or pulmonary embolism-related death within 6 months

Secondary: Pulmonary embolism-related and all-cause death, hemodynamic collapse or decompensation within 30 days, death from any cause within 6 months, duration of unscheduled hospital stay due to complications or bleeding within 6 months

Age, years, median (IQR)

>80 years

Female

Major trauma in the past 30 days

Major surgery in the past 30 days

Immobilisation (for at least 3 days)

Previous pulmonary embolism or deep vein thrombosis

Active cancer

History of cancer

Ongoing chemotherapy

History of chronic cardiopulmonary disease

BMI, kg/m², median (IQR)

Heart rate, BPM, median (IQR)

Heart rate >100 beats per minute

Systolic/diastolic blood pressure, mm Hg, median (IQR)

Systolic blood pressure <100 mm Hg

Oxygen saturation <90%

Simplified Pulmonary Embolism Severity Index ≥1

Signs of right ventricular dysfunction on at least one imaging method

Signs of right ventricular dysfunction on echocardiography

Signs of right ventricular dysfunction on CT pulmonary angiography

Elevated cardiac troponin concentrations

Abbreviations: IQR, interquartile range; BMI, body mass index; BPM, beats per minute

Recurrent symptomatic venous thromboembolism or death related to pulmonary embolism within the first 6 months

Recurrent pulmonary embolism

Recurrent deep-vein thrombosis

Death related to pulmonary embolism

Pulmonary embolism-related death, hemodynamic collapse, or hemodynamic decompensation within the first 30 days

Death from any cause, hemodynamic collapse, or decompensation within the first 30 days

Death from any cause within the first 6 months

At least one major bleeding event within 6 months

At least one clinically relevant non-major bleeding within 6 months

At least one major or clinically relevant non-major bleeding event within 6 months

At least one serious adverse event within 30 days

At least one serious adverse event within 6 months

Data are n (%; upper bound of right-sided 95% confidence interval [CI]), n (%), or n (%; 95% CI)

At least one major bleeding event within 6 months (3%); at least one clinically relevant non-major bleeding within 6 months (4%); at least one major or clinically relevant non-major bleeding event within 6 months (7%); at least one serious adverse event within 30 days (9%); at least one serious adverse event within 6 months (18%)

In conclusion, this prospective multinational trial focusing on patients with intermediate-risk pulmonary embolism found that a management strategy of early switch from heparin to dabigatran after rigorous clinical assessment of stabilisation at 72 h was both effective and safe. Our results help to close existing gaps in the evidence base concerning the initial treatment of patients who have an elevated risk of early complications with anticoagulants. They also support the clinical relevance of identifying patients with intermediate-high-risk pulmonary embolism, presenting with signs of both right ventricular dysfunction and with elevated cardiac troponin concentrations, because this patient group might need closer early monitoring and long-term follow-up to prevent a complex disease course than those with intermediate-low-risk and low-risk pulmonary embolism. The knowledge obtained from the PEITHO-2 study aids in refining future recommendations on the risk-adjusted management of acute pulmonary embolism.

The study provided valuable insights into the management of intermediate-risk pulmonary embolism with a novel anticoagulation strategy. However, the lack of a control group receiving standard care limits the ability to directly compare outcomes. The study's single-arm design and the absence of randomisation may introduce bias. Additionally, the study's focus on dabigatran limits the generalisability of the findings to other DOACs. Despite these limitations, the study's rigorous selection criteria and multicentre design enhance the applicability of the findings to clinical practice.

Evaluation of Dabigatran for Appropriateness of Use and Bleeding Events in a Community Hospital Setting

Retrospective chart review

N= 458

To describe and to evaluate the use of dabigatran at a community hospital to identify areas for improvement in its prescribing

All patients (n= 458)

Patients who received at least 1 dose of dabigatran between December 2010 and June 2012

Patients without available data on serum creatinine, height, or weight

Eligible patients were identified through the hospital pharmacy information system. Baseline demographic and clinical data were collected, including age, sex, race, length of stay, height, weight, serum creatinine, creatinine clearance at dabigatran initiation, indication for dabigatran, outpatient anticoagulant use, concomitant antithrombotic therapy, and potentially interacting medications. Appropriateness of the initial dabigatran regimen was evaluated according to FDA-approved recommendations for stroke prophylaxis in nonvalvular atrial fibrillation based on valvular disease, dose, and dosing frequency; patients receiving dabigatran for off-label indications, including venous thromboembolism (VTE) and pulmonary embolism (PE), were not evaluated for regimen appropriateness. For the inquiry-specific analysis, the investigators identified 6 patients treated for PE and determined whether they had received the recommended 5 to 10 days of parenteral anticoagulation before dabigatran initiation. Bleeding was assessed using hospital readmission within 1 year for bleeding, a hemoglobin decrease of ≥2 g/dL, transfusion of ≥2 units of blood, or documentation of bleeding in the medical record. Descriptive statistics characterized prescribing patterns; bleeding and nonbleeding groups were compared using the Student t test, chi-square test, or Fisher exact test, as applicable.

December 2010 to June 2012

Primary: Appropriateness of dabigatran use

Secondary: Composite endpoint of bleeding including hospital readmission, hemoglobin decrease, blood transfusion, or bleeding notation

All patients (n= 458)

Mean age, years

Male 

Race

Caucasian

Black

419 (91.5%)

18 (3.9%)

Mean length of hospital stay, days

Mean body mass index, kg/m2 (median)

Mean weight, kg (median)

Weight <50 kg

Weight >100 kg

Indication for dabigatran

Atrial fibrillation

VTE 

426 (93%)

18 (3.9%)

Inappropriate regimen

Home medication inappropriately continued

Medication inappropriately initiated in hospital

Contraindicated due to renal function

Inappropriate dose

Inappropriate frequency

Bioprosthetic valve

Moderate or severe mitral stenosis

The composite endpoint for bleeding was reported in 66 (14.4%) patients, including 23 (5%) with confirmed gastrointestinal bleeding.

High-risk medications such as dabigatran require monitoring of prescribing habits to improve patient safety and outcomes. Various initiatives, such as pharmacist interventions, therapeutic interchanges, and obtaining appropriate patient parameters, can be implemented in the practice setting to ensure the appropriate use of oral anticoagulants and improved patient outcomes.

This study documents real-world dabigatran initiation without the recommended 5- to 10-day parenteral anticoagulation course in 5 of 6 patients treated for PE. However, it does not distinguish between no lead-in and a lead-in lasting fewer than 5 days or report thromboembolic and bleeding outcomes for these patients separately; therefore, it demonstrates that this prescribing practice occurred but does not provide evidence supporting its efficacy or safety.