Whither Anticoagulation in Pulmonary Arterial Hypertension?

Despite availability of a burgeoning array of therapies for pulmonary arterial hypertension (PAH), including agents targeting the prostaglandin, endothelin, and nitric oxide pathways, long- term outcome remains of concern. Providers therefore seek to leverage every possible advantage in the battle to prolong the lives of these compelling patients. Historically that effort has included the use of warfarin, based upon the pathophysiologic concepts of the potential role of in situ thrombosis and/or superimposed thromboemboli in disease progression, and buttressed by early nonrandomized analyses of factors impacting patient outcome. Warfarin anticoagulation has been such a dogmatic component of the approach to PAH that the precarious evidence base upon which it rests may be underappreciated. In this issue of Circulation, an analysis from the Registry to Evaluate Early and Long-Term Disease Management in PAH (REVEAL) appears to have further eroded the rather wobbly legs of that base(1). The REVEAL registry is the largest PAH registry ever developed, and has been mined for an astonishing array of useful analyses including changing demographics of PAH, temporal trends of treatment and outcome, and development of prognostic tools. This registry owes its success to a highly motivated, collaborative team, dedicated and sophisticated statistical support, and proper funding. However, registry based forays into analysis of the impact of specific treatment on outcome is of course fraught with well-known hazards. Statistical methods can to some extent correct for known confounders such as disease severity, but other confounders may be unknown or difficult to take into account (e.g., disease trajectory; patient compliance). Yet in the persisting absence of randomized trials of anticoagulation in PAH, registry based analyses remain the best available source of information in this regard.