Real‐life data of direct anticoagulant use, bleeding risk and venous thromboembolism recurrence in chronic thromboembolic pulmonary hypertension patients: an observational retrospective study

Abstract

Introduction Lifelong anticoagulation is the cornerstone of the chronic thromboembolic pulmonary hypertension (CTEPH) treatment regardless of the additional pulmonary endarterectomy, balloon pulmonary angioplasty, or medical treatment alone. Aim of this study was to evaluate the rate of oral anticoagulant preferences and document direct oral anticoagulants’ (DOACs’) safety, efficacy in the CTEPH population. Methods Patients’ demographic data obtained from database between September 2011 and April 2018. In-hospital events, death, venous thromboembolism (VTE) recurrence, bleeding events and anticoagulant therapy transition were recorded. Results We reviewed 501 CTEPH patients who observed 9.0 ± 8.5 years. All-cause death, all bleeding, recurrent VTE was observed in 15.6%, 31% and 12%. Forty-one patients (8.2%) were diagnosed as inoperable. Of all, 15.2% of operable patients remained as residual. All-cause mortality rates were 13.8% (57 pts.) in the warfarin group as compared with 9.7% (13 pts.) in rivaroxaban group (HR: 1.61, 95% CI, 0.89–2.99; p: 0.11). Higher bleeding events occurred with warfarin group (27.1%) as compared with rivaroxaban (24.6%; HR: 1.28, 95% CI, 0.86–1.88; p: 0.22). Major bleeding was significantly higher with warfarin group (HR: 1.94, 95% CI, 1.05–3.62; p: 0.03). Subgroup analysis of all-cause death revealed that this significance dominated by the rate of death according to bleeding events; warfarin versus those seen with rivaroxaban (4.85% vs. 2.2%; HR: 4.75, 95% CI: 1.12–20.16; p = 0.03). The rate of recurrent VTE was found 8.9% in the rivaroxaban group, 10.9% in warfarin group (HR: 1.21, 95% CI, 0.64–2.23; p: 0.55). Conclusion DOACs could be a safe and effective alternative for lifelong anticoagulant therapy in CTEPH patients. Rivaroxaban produced similar rates of thromboembolism and non-relevant bleeding compared to those associated with warfarin. The main difference was found with major bleeding that it was mainly associated with the death rate according to major bleeding. Using DOACs might be a more reasonable way to prevent bleeding events without increasing thromboembolic risk.

Oral anticoagulants (NOAC and VKA) in chronic thromboembolic pulmonary hypertension

“…9 Other studies in CTEPH have reported similar or lower bleeding rates with NOACs than with VKAs, while results for venous thromboembolism recurrence have been inconsistent. 7,10,11 Our results show similar absolute and exposure-adjusted rates of hemorrhagic events with VKAs and NOACs, while exposure-adjusted rates of embolic/thrombotic events were higher with NOACs. However, the numbers of events were small and the excess of embolic/thrombotic events could be a chance observation or related to differences in baseline characteristics between the two groups.…”

Balloon Pulmonary Angioplasty in Patients With Inoperable or Recurrent/Residual Chronic Thromboembolic Pulmonary Hypertension: A Single-Centre Initial Experience

“…It demonstrates that BPA treatment improved the exercise capacity, oxygenation, NT pro-BNP levels, and haemodynamics of patients with inoperable or residual or recurrent CTEPH. Patients with inoperable or residual CTEPH are often treated with riociguat, which is approved for CTEPH therapy, or other PAH-specific drugs [14]. Riociguat improves haemodynamics, with a 10% decrease in mPAP, a 33% decrease in PVR, and a 10% increase in 6MWD [15].…”

“…This study used direct oral anticoagulants (DOACs) in most patients, although this is not recommended by the current guidelines. However, a recent report [14] indicated that DOACs could be a safe and effective alternative to warfarin treatment in CTEPH patients. This may be especially important for patients with limited access to health care facilities and noncompliance issues.…”

Association Between Anticoagulation Outcomes and Venous Thromboembolism History in Chronic Thromboembolic Pulmonary Hypertension

“…Although warfarin was recommended as the treatment of choice, direct oral anticoagulants (DOACs) have been alternatively used considering their proven therapeutic effects in VTE and administrative convenience over warfarin. Recently, several studies have reported the efficacy and safety of anticoagulants including warfarin and rivaroxaban in CTEPH patients (5)(6)(7)(8)(9). However, these studies failed to identify the differences in anticoagulation outcomes between CTEPH patients with and without prior VTE history.…”