Pulmonary arterial hypertension: Rationale for using multiple vs. single drug therapy

Area of Science:

• Cardiology
• Pulmonology
• Pharmacology

Background:

• Pulmonary arterial hypertension (PAH) exhibits heterogeneous pathobiology, leading to varied clinical presentations, treatment responses, and prognoses.
• The therapeutic landscape for PAH has shifted from managing end-stage disease to early intervention aimed at symptom improvement, functional capacity enhancement, and prolonged survival.

Purpose of the Study:

• To review the evolution of pharmacotherapeutics in Pulmonary arterial hypertension (PAH).
• To summarize current evidence supporting multidrug therapy over monotherapy for PAH.
• To discuss future directions in PAH treatment, including precision medicine.

Main Methods:

• Review of clinical trial data spanning over twenty years.
• Analysis of treatment strategies for patients at various disease stages.
• Evaluation of evidence for multidrug therapy, including upfront combination therapy.

Main Results:

• Evidence supports multidrug therapy as the preferred approach for most PAH patients.
• Up-front combination therapy with agents like ambrisentan and tadalafil is recommended for incident PAH patients.
• Future strategies may involve upfront triple therapy and precision medicine based on pathobiology.

Conclusions:

• Current PAH treatment emphasizes early, evidence-based multidrug regimens.
• Combination therapy, particularly upfront ambrisentan and tadalafil, is a cornerstone of modern PAH management.
• Precision medicine and novel therapies hold promise for future PAH treatment advancements.