Safety and efficacy of direct oral anticoagulants in patients with chronic thromboembolic pulmonary hypertension.

INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) remains an underdiagnosed disease. Anticoagulation is essential in its therapy to prevent recurrent venous thromboembolism (VTE). According to some international guidelines, vitamin K antagonists (VKA) remain the gold standard. Nevertheless, direct oral anticoagulants (DOAC) are widely used, partly because of numerous advantages. The objective of this study was to determine if DOAC is an effective and safe alternative to VKA in CTEPH patients. MATERIALS AND METHODS: A retrospective observational study was conducted between 2001 and 2021 in a CTEPH Clinic of a tertiary care hospital. We recorded demographic characteristics, anticoagulant therapies and pulmonary hypertension treatments received. Safety outcomes were bleeding events and deaths while efficacy outcomes were recurrent VTE events. RESULTS: Among the study population (N = 205), the distribution of anticoagulant used transitioned from majority on VKA to majority on DOAC. In 2020, 23 (19 %) were on VKA and 97 (78 %) on DOAC. Among 11 VTE events occurring during follow-up, 7 were in the VKA group (1.10 %/person-year) and 1 in the DOAC group (0.32 %/person-year). Rates of VTE recurrence were not significantly different in those treated with DOAC compared to VKA (P = 0.21). Total bleeding rate on VKA (2.52 %/person-year) and DOAC (2.52 %/person-year) were the same (P = 1.00). Among 27 patients who died, no deaths occurred as a consequence of bleeding or VTE events. CONCLUSION: Bleeding and VTE events were not higher in CTEPH patients receiving DOAC compared to VKA which adds confidence to considering DOAC as an effective and safe alternative for long term anticoagulation in CTEPH patients.

Right ventricular ST-elevation myocardial infarction as a cause of death in idiopathic pulmonary arterial hypertension.

A 32-year-old woman with advanced idiopathic pulmonary arterial hypertension (PAH), treated with oral tadalafil and intravenous epoprostenol, presented with typical angina pectoris of one day's duration. Her electrocardiogram, previously typical of pulmonary hypertension, revealed an acute ST-elevation myocardial infarction in the anterior precordial leads. She had a prior coronary angiogram, in preparation for lung transplantation, that revealed normal coronary arteries. Urgent coronary angiography showed acute occlusion of several acute marginal coronary branches that feed the right ventricle (RV). Coronary angioplasty and stenting was unable to adequately restore coronary perfusion. Despite support, she developed progressive cardiogenic shock and died three days later. This is an unusual complication of PAH.

Pregnancy as a possible trigger for heritable pulmonary arterial hypertension.

It is unclear whether pregnancy is a trigger or accelerant for idiopathic pulmonary arterial hypertension (PAH). Alternatively, its frequency close to the onset of symptoms and diagnosis in the idiopathic PAH population may represent a coincidence in a disease that predominates in young women. We describe a carrier of a BMPR2 gene mutation who had an uneventful first pregnancy but had aggressive PAH during her second pregnancy and now has ongoing heritable PAH. The possible role of pregnancy as a trigger in this vulnerable patient is discussed. Databases of patients with heritable PAH should be explored to see whether pregnancy is related to overt manifestation of the disease.

Hemodynamic stability after transitioning between endothelin receptor antagonists in patients with pulmonary arterial hypertension.

BACKGROUND: Maintenance of a favourable hemodynamic profile is central to therapeutic success in pulmonary arterial hypertension (PAH). There is little information about the safety of transitioning patients between oral therapies for PAH. Endothelin receptor antagonists (ERAs) have been a therapeutic mainstay in PAH, providing benefit to many patients. Three ERAs, bosentan, sitaxsentan, and ambrisentan have been approved for clinical use. Sitaxsentan was voluntarily withdrawn from the market in late 2010 resulting in the need to quickly transition a large number of stable patients. METHODS: We transitioned 30 clinically stable patients to either ambrisentan or bosentan. Patients underwent a right heart catheterization, measurement of serum N-terminal pro-brain natriuretic peptide (NT-proBNP), and assessment of functional class before changing ERA and again 4 months later. We present a retrospective analysis of those data. RESULTS: Of the 30 patients transitioned (15 to ambrisentan, 15 to bosentan), 23 had complete hemodynamic data. No significant change was observed in the groups in right atrial, mean pulmonary artery, and pulmonary artery wedge pressures, or in cardiac output, pulmonary vascular resistance, or NT-proBNP levels. There was no change in World Health Organization functional class. Four ambrisentan and 2 bosentan-treated patients reported fluid retention, and 3 bosentan-treated patients had elevation of hepatic transaminases. Two of the patients had a right atrial pressure increase of ≥5 mm Hg, and 4 had pulmonary artery wedge pressure increase of ≥5 mm Hg. CONCLUSIONS: Transitioning between ERAs in stable PAH patients does not result in hemodynamic or clinical deterioration during the first 4 months posttransition. A minority of patients have developed increased cardiac filling pressures.

Sustained symptomatic, functional, and hemodynamic benefit with the selective endothelin-A receptor antagonist, sitaxsentan, in patients with pulmonary arterial hypertension: a 1-year follow-up study.

STUDY OBJECTIVES: To examine the long-term efficacy and safety of the selective endothelin-A receptor (ET-A) antagonist, sitaxsentan sodium, after 1 year of therapy in patients with pulmonary arterial hypertension (PAH). DESIGN: The study was a Canadian, open-label extension of at least 1-year total of active therapy (sitaxsentan, 100 mg/d), following a preceding, blinded, 12-week placebo controlled trial of sitaxsentan (placebo, or sitaxsentan, 100 mg/d or 300 mg/d), which had then been followed by a blinded active-therapy continuation study (sitaxsentan, 100 mg/d or 300 mg/d). PATIENTS: Eleven patients with PAH were enrolled. The condition of one patient worsened at 7 months of therapy, and the patient transferred to epoprostenol therapy. The remaining 10 patients (idiopathic [n = 3], connective tissue disease [n = 3], congenital heart disease [n = 4]) completed the evaluation after 1 year of active therapy. INTERVENTIONS: The end points of the study included the 6-min walk test, World Health Organization (WHO) functional class, and cardiopulmonary hemodynamic parameters. RESULTS: After 1 year of sitaxsentan therapy, there were significant improvements in 6-min walk distance (50-m treatment effect), WHO functional class, and hemodynamics, as compared to baseline. There were no serious adverse events, and no instances of hepatotoxicity or bleeding. CONCLUSION: Long-term selective ET-A blockade with sitaxsentan sodium is safe and may improve exercise capacity, functional class, and hemodynamics in patients with PAH.