Abstract
Pulmonary arterial hypertension (PAH) is a progressive and life-threatening disease
leading to right ventricular failure and death if left untreated. Over the past two
decades, progress in the understanding of pathophysiological mechanisms of the disease
has led to the development of medications targeting the three major pathways of endothelial
dysfunction: prostanoids, endothelin-receptor antagonists, and phosphodiesterase type-5
inhibitors. Efficacy of PAH-targeted medications has been demonstrated in monotherapy
through randomized clinical trials leading to their regulatory approval. However,
despite the growing numbers of available PAH-targeted medications, many patients with
PAH continue to deteriorate and the disease ultimately remains fatal. The availability
of multiple classes of drugs targeting different pathophysiological pathways provides
strong biological rationale for the use of combination therapy in PAH. Evidence to
support this strategy is growing, and many studies have demonstrated that combination
therapy, administered as either a sequential or an initial regimen, can improve long-term
outcomes in PAH. Treatment strategy for PAH has thereby changed significantly over
the past decade, combination therapy becoming progressively the gold standard of care
in patients with PAH. This is underscored by the current European Society of Cardiology/European
Respiratory Society guidelines, in which combination therapy now plays a central part
in the treatment algorithm.
Keywords
hypertension, pulmonary - pulmonary arterial hypertension - therapy - prostacyclin
- endothelin - nitric oxide - phosphodiesterase type-5
