017). Furthermore, multivariable regression analysis confirmed the beneficial effect of anticoagulation on survival of idiopathic PAH patients (hazard ratio, 0.79; Carfilzomib price 95% confidence interval, 0.66–0.94) In patients with other forms of PAH, during the 3-year follow-up period, mortality rate in anticoagulation group was 21.9% versus 15% in the no anticoagulation group without statistically significant survival difference (p = 0.156). Among the 208 patients with scleroderma-spectrum of disease associated with PAH, 26.9% of patients in the coagulation group

died, compared to 17.3% in the no anticoagulation group without statistically significant survival difference (p = 0.28). However, the use of anticoagulants in these patients was associated with a non-significant trend toward a worse survival in the single predictor analysis (HR, 1.82; 95% CI, 0.94 to 3.54; P = 0.08) As regards bleeding risk, the COMPERA database was not designed to systematically capture all bleeding events. Available data denote that, among the 219 deaths, bleeding was attributed as a cause of death in 4 patients (2%). In addition, there were 3 nonfatal but serious bleeding events resulting in hospital admission. Of note, among these 7 bleeding events, 6 occurred in the anticoagulation group. What have we learned? Data of the COPMERA registry lend support

to current recommendations for the use of anticoagulant therapy in patients with idiopathic PAH, but not in other forms of PAH. Also, the data substantiated the previously reported concern that anticoagulant therapy may be harmful in patients

with scleroderma-associated PAH. The importance of the COMPERA lies in: (1) being the largest study so far assessing the effects of anticoagulation therapy in patients with PAH; (2) the prospective design; (3) the 3-year observation period; (4) the low number of patients lost to follow-up ( < 3%); and (4) the use of modern PAH-targeted therapy including combination therapy in 45% of all patients, reflecting the current real-world practice. Results of the COMPERA registry open the gate for several GSK-3 unanswered questions related to criteria that should be used to select patients for anticoagulant therapy; risk stratification for bleeding; the optimum target international normalized ratio (INR); the potential role of new oral anticoagulants; and the need for further randomized controlled trials. Patient selection The decision of anticoagulant therapy in a patient with PAH should consider the balance between the risk of PAH-related mortality versus the risk of bleeding related to anticoagulant therapy in this particular patient. Risk of PAH-related mortality Mortality risk in PAH patients can be assessed by focusing on parameters with established prognostic importance.