Identifying "super responders" in pulmonary arterial hypertension

Abstract

Pharmacotherapeutic options for pulmonary arterial hypertension (PAH) have increased dramatically in the last two decades and along with this have been substantial improvements in survival. Despite these advances, however, PAH remains a progressive and ultimately fatal disease for most patients and only epoprostenol has been shown to improve survival in a randomized control trial. Clinical observations of the heterogeneity of treatment response to different classes of medications across the phenotypically diverse PAH population has led to the identification of patients who derive significantly more benefit from certain medications than the population mean, the so-called "super responders." This was first recognized among PAH patients with acute vasodilator response during invasive hemodynamic testing, a subset of whom have dramatically improved survival when treated with calcium channel blocker (CCB) therapy. Retrospective studies have now suggested a sex discrepancy in response to endothelin receptor antagonists (ERA) and phosphodiesterase inhibitors, and more recently a few studies have found genomic associations with response to CCBs and ERAs. With increasing availability of "omics" technologies, recognition of these "super responders," combined with careful clinical and molecular phenotyping, will lead to advances in pharmacogenomics, precision medicine, and continued improvements in survival among PAH patients.

Keywords: Precision medicine; pharmacogenomics; pulmonary arterial hypertension; super responder.

Fig. 1.

Change in PVR after initiation of i.v. Prostanoid. PVR in 27 patients with PAH with a RHC 17 ± 10 months after initiation of parenteral prostanoid therapy. Detailed data for two of the highlighted patients are provided in Table 2.