FRI0380 An indirect comparisons analysis of prostacyclins, endothelin receptor antagonists and phosphodiesterase inhibitors to evaluate for differences between the treatment for primary and secondary pulmonary hypertension

Background Differences in the pathogenesis between primary pulmonary hypertension (PpHTN) and secondary pulmonary hypertension (SpHTN) suggest autoimmunity plays a pivotal role in the latter. Connective tissue diseases (CTD) are the most common type of autoimmune disorders to present with SpHTN and it is considered the leading cause of death in these patients. There are primarily three classes of drugs for treatment of pulmonary arterial hypertension: prostacyclins (PC), endothelin receptor antagonists (ERA’s) and phosphodiesterase (PDE-5) inhibitors. In general, cost and patient/physician preference is what mandates the choice of drug which is due to the lack of evidence comparing these drugs to one another. Objectives To perform a network meta-analysis among these classes of drugs, using placebo group as common comparator, to determine whether differences exist among them and whether one class is more suitable for PpHTN versus SpHTN. Methods Studies were extracted from a computerized literature search of MEDLINE and EMBASE of all relevant RCT’s. 28 RCT’s, including 4,542 patients, were identified. 2766 patients were diagnosed with PpHTN while 1766 had SpHTN - the cause was almost always related to some form of CTD. Four outcomes were of interest: mortality, clinical worsening (CW), 6 minute walking distance (6-MWD) and adverse events leading to premature study discontinuation(AE). For each outcome, a fixed-effects meta-analysis was employed to compare each class of drugs to placebo. A mixed-treatment comparisons analysis was then used to compare each of these classes to one another indirectly. Calculation of the probability that each treatment is best was implemented using the Bayesian Markov chain Monte Carlo method. Results In an indirect comparison of PC to PDE-5 inhibitors in patients with PpHTN, those taking PC had a statistically significant decreased risk of mortality (RR 0.10, 95% CI 0.01 – 0.74) – this is in marked contrast to the overall mortality analysis which shows no mortality difference between these two. A similar degree of benefit from PC among patients with PpHTN does not extend to additional clinical outcomes like CW or 6-MWD. Conversely, PC are far more likely than the other two classes to cause an AE (and a similar degree of difference exists between PpHTN and SpHTN). By ranking probability, in patients with PpHTN, PC have the highest probability of being the optimal regimen to reduce mortality (83%). By ranking probability, in patients with SpHTN, ERA´s have a 56% and 80% probability of being the most likely treatment regimen to reduce mortality and CW, respectively. The degree of incoherence (measuring how closely the network fits together) was low for all outcomes. Conclusions PC seem to be associated with mortality benefits in PpHTN compared to SpHTN, these benefits do not extend to additional outcomes likely because the drug is difficult to tolerate (and so it may extend life without increasing quality of life). Conversely, ERA´s seem to be the ideal class for patients with SpHTN. More studies are needed among specifically patients with either PpHTN or SpHTN to better determine whether differences in the etiology of pulmonary hypertension require different treatment strategies. Disclosure of Interest : None Declared