What question did this study set out to answer?

To review preclinical and clinical evidence supporting combination therapy targeting both the nitric oxide and prostacyclin pathways in pulmonary arterial hypertension.

April 9, 2021Journal of Cardiovascular Pharmacology and TherapeuticsOpen Access

Combination Therapy in Pulmonary Arterial Hypertension—Targeting the Nitric Oxide and Prostacyclin Pathways

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Why the study?

Despite a paucity of prospective data, combination therapy targeting the nitric oxide and prostacyclin pathways has been adopted as an alternative therapeutic strategy in PAH, warranting a review of preclinical and clinical evidence.

Does combination therapy targeting the nitric oxide and prostacyclin pathways provide clinical advantages in patients with pulmonary arterial hypertension?

Population

Patients with PAH

Comparison

Combination therapy targeting NO and PGI2 pathways vs other treatment strategies

Design

Review of preclinical and clinical data

Authors

SMStacy MandrasAdventHealth Orlando GKGábor KovácsVascular / Pulmonary Vascular HOHorst OlschewskiUniversité Paris-Sud

Discussion

Member takes

Implication

Targeted PAH therapies via NO/PGI2/endothelin pathways improve morbidity; leaves open optimal combinations and sequencing in trials.

Key Points

To review preclinical and clinical evidence supporting combination therapy targeting both the nitric oxide and prostacyclin pathways in pulmonary arterial hypertension.
Synthesized findings from preclinical models and secondary data analyses of clinical studies evaluating therapies targeting nitric oxide and prostacyclin signaling pathways.
Evaluated the biochemical interplay and therapeutic utility of combining phosphodiesterase-5 inhibitors or soluble guanylate cyclase stimulators with prostacyclin class agents.
Preclinical evidence demonstrates cooperative biochemical interactions between nitric oxide and prostacyclin signaling that enhance pulmonary vasodilation and attenuate vascular remodeling.
Secondary clinical data indicate dual targeting of nitric oxide and prostacyclin provides a clinically effective alternative to standard initial combinations of endothelin receptor antagonists and phosphodiesterase-5 inhibitors.

Structured PICO

Does combination therapy targeting the nitric oxide and prostacyclin pathways provide clinical advantages in patients with pulmonary arterial hypertension?

Population

Patients with pulmonary arterial hypertension (PAH)

Intervention

Combination therapy simultaneously targeting the nitric oxide (NO) and prostacyclin (PGI2) signaling pathways

Combination therapy targeting the NO and prostacyclin pathways represents a theoretically advantageous and clinically reasonable alternative approach for managing pulmonary arterial hypertension.

Limitations

Paucity of prospective data

Cite This Study

Mandras et al. (2021) studied this question.

synapsesocial.com/papers/6a72995035aa2c282ce3553b https://doi.org/10.1177/10742484211006531

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Combination Therapy in Pulmonary Arterial Hypertension—Targeting the Nitric Oxide and Prostacyclin Pathways

Discussion

Member takes

Implication

Key Points

Structured PICO

Limitations

Cite This Study

Combination Therapy in Pulmonary Arterial Hypertension—Targeting the Nitric Oxide and Prostacyclin Pathways

Discussion

Member takes

Implication

Key Points

Structured PICO

Limitations

Cite This Study

Also Consider

Also Consider