CHEST Guidelines-Ambitions-for-Pulmonary-Arterial-Hypertension-Comp

Ambitions-for-Pulmonary-Arterial-Hypertension-Comp

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This article discusses the complexities and implications of treatment strategies for Pulmonary Arterial Hypertension (PAH), particularly focusing on the use of combination therapies in low-risk patients. The recent guidelines from the European Cardiology Society/European Respiratory Society encourage initial combination therapy for most symptomatic PAH patients, even those at low risk. This approach predominantly builds on findings from the AMBITION trial, which demonstrated a 50% reduction in clinical failure events with upfront dual therapy of ambrisentan plus tadalafil, compared to monotherapy. However, inconsistencies arise when contrasting these findings with real-world data, such as from the French PAH Registry, which only showed a mortality benefit for intermediate-risk, not low-risk, patients.<br /><br />The article highlights a reanalysis of the AMBITION trial by Fauvel et al., which argues that the benefits of combination therapy in low-risk patients may be overstated, primarily influenced by the inclusion of the "unsatisfactory clinical response" in the composite endpoint. When this proxy is removed, there’s no significant difference between combination therapy and monotherapy outcomes for low-risk patients. This reevaluation suggests a need to emphasize genuinely clinically relevant endpoints, as composite endpoints may be skewed by less critical components, which may not reflect real-world efficacy.<br /><br />Moreover, despite notable advances in PAH treatments, no trial has conclusively shown a mortality benefit of combination therapy, with registries like COMPERA suggesting minimal mortality improvements despite a shift toward combination therapy. The article emphasizes the importance of incorporating patient-reported outcomes and patient preferences in clinical trials and therapeutic decisions, suggesting future trials must address low-risk patients more thoughtfully to delineate true benefits amidst potential side effects.

Keywords

Pulmonary Arterial Hypertension

combination therapy

low-risk patients

European Cardiology Society

AMBITION trial

ambrisentan

tadalafil

clinical endpoints

real-world data

patient-reported outcomes