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Is Anticoagulation Beneficial in Pulmonary Arterial Hypertension?: A Systematic Review and Meta-Analysis

Background Data about anticoagulation in pulmonary arterial hypertension (PAH) patients are inconsistent. The objective of this study was to examine the impact of adjunctive oral anticoagulants in patients with PAH through meta-analysis, and to further assess whether response differs by PAH subtype. Methods and Results Cochrane CENTRAL, Medline, and Scopus databases were searched for randomized or nonrandomized studies that assessed the association between anticoagulation and outcomes in patients with PAH. Hazard ratios (HRs) for mortality were pooled using the random effects model. Subgroup analyses were performed for type of PAH and study design. Twelve nonrandomized studies, at moderate risk of bias, were included. These consisted of 2512 patients (1342 receiving anticoagulation and 1170 controls). Anticoagulation significantly reduced mortality in the overall PAH cohort (HR, 0.73 [0.57, 0.93]; P=0.001; I2=64%). On subgroup analysis, a significant mortality reduction was seen in idiopathic PAH patients (HR, 0.73 [0.56, 0.95]; P=0.02; I2=46%), whereas no significant difference was observed in connective tissue disease–related PAH (HR, 1.16 [0.58, 2.32]; P=0.67; I2=71%). Sensitivity analysis specific to scleroderma-associated PAH demonstrated a significant increase in mortality with anticoagulant use (HR, 1.58 [1.08, 2.31]; P=0.02; I2=9%). Conclusions This meta-analysis shows that use of anticoagulation may improve survival in idiopathic PAH patients, while increasing mortality when used in scleroderma-associated-PAH patients. Currently, no randomized clinical trials have been published, and until randomized data are available, anticoagulant use in PAH should be tailored to PAH subtype.