pulmonary disorders
Pulmonary Hypertension
Treatment of Pulmonary Hypertension
Avoidance of activities that may exacerbate the condition (eg, cigarette smoking, high altitude, pregnancy, use of sympathomimetics) Idiopathic and familial pulmonary arterial hypertension: IVepoprostenol; inhaled, oral, subcutaneous, or IV prostacyclin analogs; oral endothelin-receptor antagonists; oral phosphodiesterase 5 inhibitors, oral soluble guanylate cyclase stimulators; oral prostacyclin (IP2) receptor agonists Secondary pulmonary arterial hypertension: Treatment of the underlying disorder Lung transplantation Adjunctive therapy: Supplemental oxygen, diuretics, and/or anticoagulants Treatment of pulmonary arterial hypertension (PAH) is rapidly evolving. Drugs target 4 aberrant pathways implicated in the development of PAH: Endothelin pathway Nitric oxide pathway Prostacyclin pathway BMPR2 pathway Theendothelin pathwayis targeted bybosentan,ambrisentan, andmacitentan, which are oral endothelin-receptor antagonists (ERAs). Thenitric oxide pathwayis targeted bysildenafil,tadalafil, andvardenafil, which are oral phosphodiesterase 5 (PDE5) inhibitors.Riociguat, a soluble guanylate cyclase stimulator, also acts via the nitric oxide pathway. , a prostacyclin analog, which improves function and lengthens survival even in patients who are unresponsive to a vasodilator during catheterization ( Treatment references ). Disadvantages are the need for continuous central catheter infusion and frequent, troubling adverse effects, including flushing, diarrhea, and bacteremia due to the indwelling central catheter. Prostacyclin analogs that are inhaled, taken orally, or given subcutaneously or IV ( is the most common gene mutation in patients with inheritable PAH and in idiopathic PAH. Sotatercept helps restore the balance between anti-proliferation and pro-proliferation signaling pathways that is dysregulated in patients with PAH related to BMP signaling. When added to background therapy for pulmonary hypertension, sotatercept reduced pulmonary vascular resistance in a dose-dependent manner. This change was driven by a reduction in mean pulmonary artery pressures rather than pulmonary artery wedge pressure or cardiac output. This finding was consistent among all background therapy (including prostacyclin infusion therapy) subgroups ( Treatment references ). 40 mg to combination therapy of these same 2 drugs all taken once daily ( Treatment references ). Adverse clinical outcomes (death, hospitalization, disease progression, or poor long-term outcome) were fewer with combination therapy than with monotherapy. Combination therapy also significantly reduced NT-proBNP levels and increased 6-minute walk distances and the percentage of satisfactory clinical responses. This example supports targeting multiple pathways by beginning treatment of PAH with combination therapy. However, phosphodiesterase 5 inhibitors cannot be combined with increased 6-minute walk distance, decreased pulmonary vascular resistance, and improved functional class as sequential combination therapy in patients receiving an endothelin-receptor antagonist or prostacyclin analog (as well as when used as monotherapy) ( Treatment references ). The FREEDOM-EV study found that adding oral is combined with a PDE 5 inhibitor, an ERA, or both ( Treatment references ). However, studies suggest that initial triple-therapy combining may be evolving. The current recommendation is to do vasoactive testing in the catheterization laboratory. If patients are vasoreactive, they should be treated with a calcium channel blocker. Patients who are not vasoreactive should be treated based on their New York Heart Association (NYHA) Classification of Heart Failure (NYHA). Patients who are NYHA class II to III should be started on an ERA plus a PDE5 inhibitor. Clinicians can consider adding are sometimes treated differently. Prostacyclin analogs, endothelin-receptor antagonists, and guanylate cyclase stimulators have been studied primarily in idiopathic PAH; however, these drugs can be used cautiously (attending to drug metabolism and drug-drug interactions) in patients with PAH due to connective tissue disease, HIV, or Portopulmonary Hypertension . Vasodilators should be avoided in patients with PAH due to pulmonary veno-occlusive disease due to the risk of catastrophic pulmonary edema ( Lung and Heart-Lung Transplantation None Adjunctive therapiesto treat heart failure, including diuretics, are necessary for many patients. Most patients should receivewarfarinunless contraindicated. Primary treatment involves management of the underlying disorder. Patients withleft-sided heart diseasemay need surgery for valvular disease. No multi-center trials have demonstrated benefit from using PAH-specific therapies for pulmonary hypertension secondary to left-heart disease. Therefore, the use of these drugs is not recommended for group 2 patients. The inhaled prostacyclin analogtreprostinilhas been shown to improve exercise capacity. has been shown to improve exercise capacity in patients with pulmonary hypertension secondary to interstitial lung disease ( Treatment references ). The use of has improved exercise capacity and pulmonary vascular resistance in patients who are not surgical candidates or for whom the risk to benefit ratio is too high ( Treatment references ). Patients withsickle cell diseasewho have pulmonary hypertension are aggressively treated usinghydroxyurea, iron chelation, and supplemental oxygen as indicated. In symptomatic patients with elevated pulmonary vascular resistance with normal pulmonary artery wedge pressure confirmed by right heart catheterization (similar to PAH pathophysiology), selective pulmonary vasodilator therapy (withepoprostenolor an endothelin-receptor antagonist) can be considered.Sildenafilincreases incidence of painful crises in patients with sickle cell disease and so should be used only if patients have limited vaso-occlusive crises and are being treated withhydroxyureaor transfusion therapy. 1.Barst RJ, Rubin LJ, Long WA, et al: A comparison of continuous intravenousepoprostenol(prostacyclin) with conventional therapy for primary pulmonary hypertension.N Engl J Med334(5):296–301, 1996. doi: 10.1056/NEJM199602013340504 2.Sitbon O, Channick R, Chin KM, et al:Selexipagfor the treatment of pulmonary arterial hypertension.N Engl J Med373: 2522-33, 2015. doi: 10.1056/NEJMoa1503184 3.Humbert M, McLaughlin V, Gibbs JSR, et al:Sotaterceptfor the treatment of pulmonary arterial hypertension.N Engl J Med384(13):1204–1215, 2021. doi: 10.1056/NEJMoa2024277 4.Galie N, Barbera JA, Frost AE, et al: Initial use ofambrisentanplustadalafilin pulmonary arterial hypertension.N Engl J Med373: 834-44, 2015. doi: 10.1056/NEJMoa1413687 5.Ghofrani HA, Galiè N, Grimminger F, et al:Riociguatfor the treatment of pulmonary arterial hypertension.N Engl J Med369(4): 330-40, 2013. doi: 10.1056/NEJMoa1209655 6.White RJ, Jerjes-Sanchez C, Bohns Meyer GM, et al: Combination therapy with oraltreprostinilfor pulmonary arterial hypertension. 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