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