The anticoagulant effects of warfarin and the bleeding risk associated with its use in patients with chronic thromboembolic pulmonary hypertension at a specialist center in Japan: a retrospective cohort study

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) require lifelong anticoagulation therapy. However, the bleeding risk and recurrence of venous thromboembolism (VTE) in CTEPH patients who are administered warfarin have not been adequately evaluated. The purpose of this study was to evaluate the risk of clinically relevant bleeding, recurrent VTE, and clinical worsening in patients with CTEPH who were administered warfarin. The clinical records of 72 patients with CTEPH who regularly visited our institution and were administered warfarin were retrospectively reviewed between 1 January 2011 and 31 December 2015. We investigated the incidence of clinically relevant bleeding events, recurrent VTE, and hospitalization for the deterioration of pulmonary hypertension or right heart failure (RHF) during the observation period. The mean observation period for the 72 patients was 3.60 ± 1.60 person-years. Clinically relevant bleeding, RHF, and recurrent VTE occurred in 21 (29.2%), eight (11.1%), and three (4.2%) of 72 patients, respectively, and the incidence rates for these events were 8.1%/person-year, 3.1%/person-year, and 1.2%/person-year, respectively. The incidence rates for the major and non-major bleeding events were 5.0%/person-year and 3.9%/person-year, respectively. The incidence of clinically relevant bleeding events was 20.8%/person-year during medical treatment with a soluble guanylate cyclase stimulator. One of 35 patients (2.9%) during the post-pulmonary endarterectomy period experienced hemoptysis during observation period (> 6 months after pulmonary endarterectomy). No bleeding events occurred during the post-balloon pulmonary angioplasty period. In conclusion, warfarin effectively prevents VTE recurrence in CTEPH patients, but its effects may be associated with a considerable bleeding risk.

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

Pulmonary Circulation ◽

10.1177/2045894019873545 ◽

2020 ◽

Vol 10 (1) ◽

pp. 204589401987354 ◽

Cited By ~ 3

Author(s):

Sert Sena ◽

Mutlu Bulent ◽

Kocakaya Derya ◽

Kaptan Deniz ◽

Ataş Halil ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Venous Thromboembolism ◽

Anticoagulant Therapy ◽

Major Bleeding ◽

Real Life ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Bleeding Events ◽

Warfarin Group ◽

Thromboembolic Pulmonary Hypertension ◽

Recurrent Vte

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.

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EXPRESS: Time Trends of Pulmonary Endarterectomy in Patients with Chronic Thromboembolic Pulmonary Hypertension

Pulmonary Circulation ◽

10.1177/20458940211008069 ◽

2021 ◽

pp. 204589402110080

Author(s):

Lukas Hobohm ◽

Karsten Keller ◽

Thomas MÃ¼nzel ◽

Stavros Konstantinides ◽

Mareike Lankeit

Keyword(s):

Pulmonary Hypertension ◽

Hospital Mortality ◽

Time Trends ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Annual Number ◽

Pulmonary Endarterectomy ◽

Bleeding Events ◽

Hospital Outcomes ◽

Thromboembolic Pulmonary Hypertension ◽

Over Time

Chronic thromboembolic pulmonary hypertension (CTEPH) is considered as a rare but severe complication after acute pulmonary embolism (PE) and is potentially curable by pulmonary endarterectomy (PEA). We aimed to evaluate, over an 11-year period, time trends of in-hospital outcomes of PEA in CTEPH patients and to investigate predictors of the in-hospital course. We analyzed data on the characteristics, comorbidities, treatments and in-hospital outcomes for all CTEPH patients treated with PEA in the German nationwide inpatient sample between 2006 and 2016. Overall, 1,398 inpatients were included. Annual number of PEA increased from 67 in 2006 to 194 in 2016 (P<0.001), in parallel with a significant decrease of in-hospital mortality (10.9% in 2008 to 1.5% in 2016; P<0.001). Patientsâ characteristics shifted slightly towards older age and higher prevalence of chronic renal insufficiency and obesity over time, whereas duration of hospital stay decreased over time. Independent predictors of in-hospital mortality were age (OR 1.03 [95%CI 1.01-1.05]; P=0.001), right heart failure (2.55 [1.37-4.76]; P=0.003), in-hospital complications such as ischemic stroke (6.87 [1.06-44.70]; P=0.044) and bleeding events like hemopneumothorax (24.93 [6.18-100.57]; P<0.001). Annual PEA volumes per center below 10 annual procedures were associated with higher rates of adverse in-hospital outcomes. Annual numbers of CTEPH patients treated with PEA increased markedly in Germany between 2006 and 2016, in parallel with a decrease of in-hospital mortality. Our findings suggest that perioperative management of PEA, institutional experience and patient-selection are crucial and have improved over time.

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Faculty Opinions recommendation of Bosentan as a bridge to pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1355970.827071 ◽

2010 ◽

Author(s):

John Augoustides ◽

Harish Ramakrishna

Keyword(s):

Pulmonary Hypertension ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Pulmonary Endarterectomy ◽

Thromboembolic Pulmonary Hypertension

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Pulmonary Endarterectomy: Assessment of Operability, Surgical Description, and Post-op Care

Advances in Pulmonary Hypertension ◽

10.21693/1933-088x-12.4.186 ◽

2014 ◽

Vol 12 (4) ◽

pp. 186-192 ◽

Cited By ~ 1

Author(s):

David Poch ◽

Victor Pretorius

Keyword(s):

Pulmonary Hypertension ◽

Pulmonary Artery ◽

Pulmonary Artery Pressure ◽

Pulmonary Arteries ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Pulmonary Artery Wedge Pressure ◽

Pulmonary Endarterectomy ◽

Pulmonary Thromboendarterectomy ◽

Thromboembolic Pulmonary Hypertension ◽

Wedge Pressure

Chronic thromboembolic pulmonary hypertension (CTEPH) is defined as a mean pulmonary artery pressure ≥25 mm Hg and pulmonary artery wedge pressure ≤15 mm Hg in the presence of occlusive thrombi within the pulmonary arteries. Surgical pulmonary thromboendarterectomy (PTE) is considered the best treatment option for CTEPH.

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EXPRESS: Chronic thromboembolic pulmonary hypertension following pulmonary embolism with a right ventricular thrombus: A report of two cases

Pulmonary Circulation ◽

10.1177/20458940211013668 ◽

2021 ◽

pp. 204589402110136

Author(s):

Tailong Zhang ◽

Weitao Liang ◽

Longrong Bian ◽

Zhong Wu

Keyword(s):

Pulmonary Hypertension ◽

Right Ventricular ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Imaging Features ◽

Pulmonary Endarterectomy ◽

Right Heart ◽

Thromboembolic Pulmonary Hypertension ◽

The Right ◽

Cardiac Masses

Right heart thrombus (RHT) accompanied by chronic thromboembolic pulmonary hypertension (CTEPH) is a rare entity. RHT may develop in the peripheral veins or in situ within the right heart chambers. The diagnosis of RHT is challenging, since its symptoms are typically non-specific and its imaging features resemble those of cardiac masses. Here, we report two cases of RHT with CTEPH that presented as right ventricular masses initially. Both patients underwent simultaneous pulmonary endarterectomy (PEA) and resection of the ventricular thrombi. Thus, when mass-like features are confirmed by imaging, RHT should be suspected in patients with CTEPH, and simultaneous RHT resection is required along with PEA.

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Atrial fibrillation and atrial tachycardia in patients with chronic thromboembolic pulmonary hypertension treated with pulmonary endarterectomy

European Heart Journal Supplements ◽

10.1093/eurheartj/suaa096 ◽

2020 ◽

Vol 22 (Supplement_F) ◽

pp. F30-F37

Author(s):

Stepan Havranek ◽

Zdenka Fingrova ◽

David Ambroz ◽

Pavel Jansa ◽

Jan Kuchar ◽

...

Keyword(s):

Atrial Fibrillation ◽

Pulmonary Hypertension ◽

Atrial Tachycardia ◽

Cox Regression ◽

Systolic Pressure ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Walking Distance ◽

Pulmonary Artery Systolic Pressure ◽

Pulmonary Endarterectomy ◽

Thromboembolic Pulmonary Hypertension

Abstract Atrial fibrillation (AF) and atrial tachycardia (AT) are frequently observed in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who were treated with pulmonary endarterectomy (PEA). Their prevalence and impact on prognosis of patients are not known. We analysed the prevalence of AF/AT and the clinical outcome in 197 patients with CTEPH treated with PEA (median age 62; interquartile range 53–68 years; 62% males). The prevalence of AF/AT was 29% (57 patients). Compared to patients without arrhythmia, the subjects with AF/AT were older [60 (50–67) vs. 62 (57–70) years], manifested an increased size of the left atrium [39 (35–44) vs. 45 (40–50) mm], had a reduced 6-min walking distance [411 (321–506) vs. 340 (254–460) m], and higher pulmonary artery systolic pressure after PEA [38 (30–47) vs. 45 (38–71) mmHg], all results with P-value <0.05. During the follow-up with a median 4.2 (1.6–6.3) years, 45 (23%) patients died. In a multivariate Cox regression model only the male gender [hazard ratio (HR) 2.27, 95% confidence interval (CI) 1.15–4.50], a reduced 6-min walking distance (HR 3.67, 95% CI 1.74–7.73), and an increased New York Heart Association class (HR 8.56, 95% CI 4.17–17.60) were associated with mortality (P < 0.05). The prevalence of AF/AT in patients with CTEPH treated with PEA is high. Arrhythmias are associated with reduced functional capacity but not with mortality.

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