Three- Versus Two-Drug Therapy for Patients With Newly Diagnosed Pulmonary Arterial Hypertension

Chin, Kelly; Sitbon, Olivier; Doelberg, Martin; Feldman, Jeremy; Gibbs, J. Simon R.; Grünig, Ekkehard; Hoeper, Marius M.; Martin, Nicolas; Mathai, Stephen C.; McLaughlin, Vallerie V.; Perchenet, Loı̈c; Poch, David; Saggar, Rajan; Simonneau, Gérald; Galiè, Nazzareno

doi:10.1016/j.jacc.2021.07.057

Cited by 117 publications

(114 citation statements)

References 16 publications

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“…Preliminary findings from the TRITON study revealed similar reductions in PVR with upfront triple combination (macitentan, tadalafil, selexipag) as with dual combination (macitentan, tadalafil) therapy after 26 weeks of treatment (−54% vs −52%, respectively). 30 The effect on 6-minute walking distance and N-terminal pro brain natriuretic peptide was similar. 30…”

Section: Initial Triple Oral Combination Therapymentioning

confidence: 84%

“…30 The effect on 6-minute walking distance and N-terminal pro brain natriuretic peptide was similar. 30…”

Section: Initial Triple Oral Combination Therapymentioning

confidence: 84%

“…There have been smaller, mostly open-label studies that address the hemodynamic effect of this approach (Table ). [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] The summary of these observations suggests that initial oral combination therapy can significantly improve hemodynamic status, with PVR reduction of 27% to 59% and mPAP reduction of 10% to 23% (from baseline). It appears clear that initial oral combination therapy produces a more pronounced hemodynamic improvement than monotherapy with a larger impact on RV morphology/function.…”

Section: Initial Oral Combination Therapy In Pahmentioning

confidence: 94%

“…Historically, treatment with parenteral prostanoids improved hemodynamic status, with mPAP reduction of 8% to 16% and PVR reduction of 14% to 39%, both from baseline (Table ). [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] Contemporary treatment with parenteral treprostinil (sometimes as sequential combination) uses considerably higher doses, with additional gains in all relevant hemodynamic measures. 34,40,44…”

Section: Initial or Early Parenteral Prostanoidsmentioning

confidence: 99%

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Aggressive Afterload Lowering to Improve the Right Ventricle: A New Target for Medical Therapy in Pulmonary Arterial Hypertension?

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Lang

Badagliacca

et al. 2022

Am J Respir Crit Care Med

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Despite numerous therapeutic advances in pulmonary arterial hypertension, patients continue to suffer high morbidity and mortality, particularly considering a median age of 50 years. This article explores whether early, robust reduction of right ventricular afterload would facilitate substantial improvement in right ventricular function and thus whether afterload reduction should be a treatment goal for pulmonary arterial hypertension. The earliest clinical studies of prostanoid treatment in pulmonary arterial hypertension demonstrated an important link between lowering mean pulmonary arterial pressure (or pulmonary vascular resistance) and improved survival. Subsequent studies of oral monotherapy or sequential combination therapy demonstrated smaller reductions in mean pulmonary arterial pressure and pulmonary vascular resistance. More recently, retrospective reports of initial aggressive prostanoid treatment or initial combination oral and parenteral therapy have shown marked afterload reduction along with significant improvements in right ventricular function. Some data suggest that reaching threshold levels for pressure or resistance (components of right ventricular afterload) may be key to interrupting the self-perpetuating injury of pulmonary vascular disease in pulmonary arterial hypertension and could translate into improved long-term clinical outcomes.Based on these clues, the authors postulate that improved clinical outcomes might be achieved by targeting significant afterload reduction with initial oral combination therapy and early parenteral prostanoids.

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Section: Initial Triple Oral Combination Therapymentioning

confidence: 84%

“…30 The effect on 6-minute walking distance and N-terminal pro brain natriuretic peptide was similar. 30…”

Section: Initial Triple Oral Combination Therapymentioning

confidence: 84%

Section: Initial Oral Combination Therapy In Pahmentioning

confidence: 94%

Section: Initial or Early Parenteral Prostanoidsmentioning

confidence: 99%

See 2 more Smart Citations

Aggressive Afterload Lowering to Improve the Right Ventricle: A New Target for Medical Therapy in Pulmonary Arterial Hypertension?

Vizza

Lang

Badagliacca

et al. 2022

Am J Respir Crit Care Med

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“…Registry-based observational studies further supported the concept of initial oral dual combination therapy in PAH ( 8 ), which was studied in the AMBITION (Ambrisentan and Tadalafil in Patients with Pulmonary Arterial Hypertension) trial ( 5 ). Initial data supporting the potential of initial triple combination therapy targeting the three pathways ( 7 ) ultimately supported the need for a trial of initial triple therapy versus dual oral therapy, the TRITON (Efficacy and Safety of Initial Triple versus Dual Oral Combination Therapy in Patients with Newly Diagnosed Pulmonary Arterial Hypertension) trial ( 9 ). Although TRITON was a negative study with respect to the effect of initial triple oral therapy with macitentan, tadalafil, and selexipag on pulmonary vascular resistance, we contend that further long-term studies are needed to evaluate the effect of an initial triple therapy regimen on clinical outcomes.…”

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confidence: 99%

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Savale

et al. 2021

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Diagnosis and Treatment of Pulmonary Arterial Hypertension

Ruopp

Cockrill

2022

JAMA

292

144

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ulmonary arterial hypertension (PAH) is a life-threatening disorder characterized by elevated pressure in the pulmonary arteries due to increased pulmonary vascular resistance. 1 Symptoms of PAH are nonspecific but commonly include dyspnea on exertion and fatigue. 2 The estimated prevalence of PAH is 10.6 per 1 million adults in the US. Untreated, PAH typically progresses to right ventricular failure and death. 3 Treatment has significantly improved outcomes in the last decade. 4 The diagnosis should be considered in any patient presenting with unexplained exertional dyspnea. This Review summarizes current evidence regarding diagnosis and treatment of PAH. MethodsPubMed was searched for English-language articles from 1985 through December 30, 2021, using search terms for pulmonary arterial hypertension. Articles were selected for inclusion based on relevance to current clinical practice. Randomized clinical trials, large longitudinal observational studies, and more recent articles were prioritized. Bibliographies of retrieved articles were searched for other relevant articles. Of the articles identified, 99 were included, consisting of 23 randomized clinical trials, 3 meta-analyses and systematic reviews, 36 observational studies, 16 registry-based studies, and 21 clinical practice guidelines or other reports. Definition and Classification of Pulmonary HypertensionThe clinical classification of pulmonary hypertension (PH), of which PAH is a subtype, is important for understanding the approach to both diagnosis and treatment of PAH. Pulmonary hypertension is currently defined by a mean pulmonary artery pressure greater than IMPORTANCE Pulmonary arterial hypertension (PAH) is a subtype of pulmonary hypertension (PH), characterized by pulmonary arterial remodeling. The prevalence of PAH is approximately 10.6 cases per 1 million adults in the US. Untreated, PAH progresses to right heart failure and death.OBSERVATIONS Pulmonary hypertension is defined by a mean pulmonary artery pressure greater than 20 mm Hg and is classified into 5 clinical groups based on etiology, pathophysiology, and treatment. Pulmonary arterial hypertension is 1 of the 5 groups of PH and is hemodynamically defined by right heart catheterization demonstrating a mean pulmonary artery pressure greater than 20 mm Hg, a pulmonary artery wedge pressure of 15 mm Hg or lower, and a pulmonary vascular resistance of 3 Wood units or greater. Pulmonary arterial hypertension is further divided into subgroups based on underlying etiology, consisting of idiopathic PAH, heritable PAH, drug-and toxin-associated PAH, pulmonary veno-occlusive disease, PAH in long-term responders to calcium channel blockers, and persistent PH of the newborn, as well as PAH associated with other medical conditions including connective tissue disease, HIV, and congenital heart disease. Early presenting symptoms are nonspecific and typically consist of dyspnea on exertion and fatigue. Currently approved therapy for PAH consists of drugs that enhance the nitric oxide-cyclic guanosine m...

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Three- Versus Two-Drug Therapy for Patients With Newly Diagnosed Pulmonary Arterial Hypertension

Cited by 117 publications

References 16 publications

Aggressive Afterload Lowering to Improve the Right Ventricle: A New Target for Medical Therapy in Pulmonary Arterial Hypertension?

Aggressive Afterload Lowering to Improve the Right Ventricle: A New Target for Medical Therapy in Pulmonary Arterial Hypertension?

Reply to Jin et al. and to Sun et al.

Diagnosis and Treatment of Pulmonary Arterial Hypertension

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