Up-front combination therapy in pulmonary arterial hypertension: from clinical trials to 'real world' observational studies.

Combination therapy in pulmonary arterial hypertension is widely used in daily clinical practice. There is a wide variation among reference centers, with respect to not only when and how combination therapy should be initiated, but also what constitutes the most effective multidrug regimen. Presently, no combination therapy has proven to be more effective than the other. However, add-on therapy, in case of unsatisfactory improvements after initiation of specific monotherapy, seems to have more evidence of effectiveness than up-front therapy at the diagnosis. Data from national pulmonary arterial hypertension registries provide valuable information on practice patterns on diagnosis and treatment in 'real world'. In the study of Bergot et al. the current use of epoprostenol in newly diagnosed patients with severe idiopathic, heritable or anorexigen-use associated pulmonary arterial hypertension enrolled in the French pulmonary hypertension registry was investigated. Up-front combination of epoprostenol and oral pulmonary arterial hypertension tended to be more beneficial compared with epoprostenol alone. New drug trials with well-defined morbidity and mortality end-points are likely to help not only identify novel agents that may help in the treatment of pulmonary arterial hypertension but also determine the most useful combination strategies to maximize efficacy of existing drugs.