Impact of Initial Therapeutic Strategy on Long-Term Outcomes in Pulmonary Arterial Hypertension: An Analysis of the PHSANZ Registry

Abstract

<h3>Purpose</h3> The relationship between initial treatment strategy and survival in pulmonary arterial hypertension (PAH) is uncertain, although early combination therapy is proposed by current guidelines for majority of patients. <h3>Methods</h3> Data were extracted from the Pulmonary Hypertension Society of Australia and New Zealand registry for all patients with a diagnosis with idiopathic/heritable/toxin-induced (I/H/D-PAH) with survival, treatment response and medication data. Patients were divided into prevalent (diagnosed < 2011), early incident (diagnosed 2011-2015) and recent incident (diagnosed 2016-2019) cohort. Early combination therapy was defined as the use of 2 or more drugs within 3 months of treatment initiation. <h3>Results</h3> A total of 489 patients diagnosed between 2006 and 2019 were included with 318 (65%) started on monotherapy, 156 (32%) on early double combination therapy and 13 (3%) on early triple therapy. All patients on triple therapy were on parenteral prostacyclin, as well as 20 (13%) patients of double therapy and 2 (0.6%) receiving monotherapy. Rates of early combination therapy (double or triple) were 20%, 28% and 59% across the 3 treatment eras. In the entire population, there was no significant differences in transplant-free survival according to upfront treatment strategy (log rank test p=0.66). After adjustment for baseline risk according to REVEAL 2.0 score, HR for monotherapy compared to early combination therapy (2 or 3 agents) was 1.11 [0.79-1.62]. With analysis restricted to incident cases only, the adjusted HRs for monotherapy compared to early combination were 1.57 [0.86-2.84] for the period 2011-2015, and 0.78 [0.25-2.40] for period 2016-2019. Change in 6MWD was higher in the early combination group versus monotherapy group (51±86m vs 74±113m, p=0.017). <h3>Conclusion</h3> In a real-world registry where early combination therapy consisted mainly of dual oral agents, a survival benefit over monotherapy was not observed. Further studies are needed to determine impact of specific drug combinations (such as inclusion of parenteral prostacyclin) on long term outcomes.