Should I start anticoagulation in my patient newly diagnosed with pulmonary hypertension?

Tark Abou-Elmagd; Shraddha Narechania

doi:10.3949/ccjm.92a.24083

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TABLE 1

World Health Organization (WHO) classification of pulmonary hypertension

WHO classification	Etiology
Group I: pulmonary arterial hypertension	Idiopathic; drug- or toxin-related; associated with connective tissue disease, human immunodeficiency virus infection, portal hypertension, congenital heart disease, schistosomiasis; persistent pulmonary hypertension of the newborn; pulmonary arterial hypertension with venous or capillary involvement
Group II: pulmonary hypertension associated with left heart disease	Heart failure, valvular heart disease, congenital or acquired heart conditions leading to postcapillary pulmonary hypertension
Group III: pulmonary hypertension associated with lung disease, hypoxia, or both	Obstructive lung disease or emphysema, restrictive lung disease, lung disease with mixed pattern, hypoventilation syndromes, hypoxia without lung disease, developmental lung disease
Group IV: pulmonary hypertension associated with pulmonary artery obstruction	Chronic thromboembolic pulmonary hypertension, other pulmonary artery obstructions (malignant tumors, sarcomas)
Group V: pulmonary hypertension with unclear or multifactorial mechanisms	Hematologic disorders, systemic disorders, metabolic disorders, chronic renal failure with or without dialysis, fibrosing mediastinitis, pulmonary tumor thrombotic microangiopathy

Based on information from reference 1.

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TABLE 2

Meta-analyses and original studies evaluating anticoagulation therapy in PAH

Study, design, population	Outcomes	Results	Comments and limitations
Rich et al (1992)⁹ Prospective post hoc cohort analysis of 64 patients with PAH	5-year survival	Improved survival in the 35 patients who received VKA	VKA started if lung perfusion scan was abnormal
Ngian et al (2012)¹⁰ Prospective multicenter cohort of 117 patients with incident CTD-PAH	3-year survival	Improved survival in patients with CTD-PAH who received VKA	Lack of information on length of therapy and presence of concomitant venous thromboembolism or atrial fibrillation
Johnson et al (2012)¹¹ Retrospective cohort study of 66 patients with idiopathic PAH and 98 patients with SSc-PAH	3-year survival Time from PAH diagnosis until death from all causes Probability that VKA improved median survival by ≥ 6 months	VKA showed low probability for improving survivability in idiopathic PAH and SSc-PAH	Small study size Included all patients exposed to VKA regardless of minimum duration or dosing Didn’t include all prognostic factors for survival of patients with PAH
COMPERA (2014)² Prospective post hoc cohort analysis of 1,283 patients with PAH (800 idiopathic, 208 SSc-PAH)	3-year survival	Improved survival in patients with idiopathic PAH who mainly received VKA, but not in other forms of PAH	Lack of information on length of therapy and presence of concomitant venous thromboembolism or atrial fibrillation
REVEAL (2015)⁴ Prospective post hoc cohort analysis of 144 patients with idiopathic PAH and 43 with SSc-PAH who received VKA anytime during study, matched with 187 who did not	3-year survival	Similar survival between 2 groups Lower survival in patients with SSc-PAH who had taken VKA	Lack of information on length of therapy and presence of concomitant venous thromboembolism or atrial fibrillation Mix of prevalent and incident cases
HEMA-HTP (ongoing)¹² Prospective multicenter cohort of 203 patients (88 PAH, 115 chronic thromboembolic pulmonary hypertension); 152 on VKA, 51 on direct oral anticoagulants, 4 on combined antiplatelet therapy	Major bleeding (International Society on Thrombosis and Haemostasis definition)	Preliminary results showed significant bleeding risk, with 22 patients experiencing major bleeding (12 with PAH, 10 with chronic thromboembolic pulmonary hypertension) Two patients died from major bleeding
Khan et al (2018)⁶ Systematic review and meta-analysis of 12 studies (8 retrospective, 4 prospective); 2,512 patients (1,342 on anticoagulation; 1,170 controls)	Impact of adjunctive oral anticoagulants in PAH and whether response differed by PAH subtype	Anticoagulation significantly reduced mortality in overall PAH group—reduction most significant in idiopathic PAH, with no difference in CTD-PAH Increased mortality seen in patients with SSc-PAH on anticoagulation therapy	Absence of randomized clinical trials Heterogeneity of results, possibly secondary to various concomitant therapies Possibility of publication bias
Wang et al (2020)⁸ Systematic review and meta-analysis of 8 observational studies (1,812 patients with idiopathic PAH)	Efficacy of anticoagulation therapy in idiopathic PAH	No significant difference in survivability in treated vs untreated patients with idiopathic PAH	Absence of randomized clinical trials Definitions and patient inclusion criteria differed between the 8 studies, leading to bias Unbalanced patient characteristics

COMPERA = Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension; CTD = connective tissue disease; HEMA-HTP = Bleeding Frequency Under Anticoagulant Treatment in Pulmonary Hypertension; PAH = pulmonary arterial hypertension; REVEAL = Registry to Evaluate Early and Long-Term PAH Disease Management; SSc = systemic sclerosis; VKA = vitamin K antagonist