Relevance of comorbidities on initial combination therapy in pulmonary arterial hypertension

Abstract

RationaleDemographic characteristics of pulmonary arterial hypertension (PAH) patients have changed over time, but the effects of cardiovascular risk factors on risk status and pulmonary vascular resistance (PVR) reduction with initial oral combination therapy are not known. Therefore, we tested the relevance of cardiovascular comorbidities in this setting.MethodsThe study enrolled 181 treatment-naive PAH patients with a 6-months (IQR 144–363 days) right heart catheterization and risk assessment after initial oral combination therapy.ResultsGroup-A, 96 (53.0%) patients without cardiac comorbidities; Group-B, 54 (29.8%) patients with one cardiac comorbidity; Group-C, 31 (17.1%) patients with ≥2 cardiac comorbidities. Group-C patients were older with a balanced gender distribution. There was a significant difference in PVR reduction moving from the absence to one or ≥2 cardiac comorbidities, respectively, median −45.0%, −30.3%, −24.3%. A ERS/ESC low-risk status was present at first follow-up in 50 (52.0%) patients in Group-A, 19 (35.1%) in Group-B, and 9 (29.0%) in Group-C; a REVEAL 2.0 low-risk status was present at first follow-up in 41 (42.0%) patients in Group-A, 15 (27.7%) in Group-B, and 7 (22.6%) in Group-C. Group-A patients were 2.3 times more likely to achieve/maintain a low risk status compared with Group-B and -C (OR 2.27, 95% C.I. 1.15–4.54, p=0.02). No significant difference was observed between patients with non-cardiac comorbidities and those without comorbidities.ConclusionInitial oral combination therapy seems associated with a less effective response for patients with cardiovascular comorbidities compared with the others, related to the magnitude of treatment-induced decrease in PVR.

Phenotypes and treatment outcomes in idiopathic pulmonary arterial hypertension patients with comorbidities

“…It suggested that initial combination therapy with ERA + PDE5i is able to improve WHO functional class (WHO-FC), exercise capacity, and N-Terminal pro-B-type Natriuretic Peptide (NT-proBNP) at 6 months (weaker response in patients with cardiovascular risk factors). These data were consistent with those of the above mentioned AUMC analysis and those of the AMBITION study [36].…”

“…The authors concluded that there are no compelling reasons to withhold targeted PAH treatment from patients with pre-capillary PH diagnosed as IPAH and significant comorbidities or additional risk factors for LVDD. Another retrospective analysis [36] in 181 patients with IPAH, CTD-PAH and CHD-PAH from the Italian Pulmonary Hypertension Network (iPHNET) database assessed the impact of comorbidities on hemodynamic and clinical response to initial oral combination therapy. It suggested that initial combination therapy with ERA + PDE5i is able to improve WHO functional class (WHO-FC), exercise capacity, and N-Terminal pro-B-type Natriuretic Peptide (NT-proBNP) at 6 months (weaker response in patients with cardiovascular risk factors).…”

Clinical–imaging–pathological correlation in pulmonary hypertension associated with left heart disease

“…Despite the fact that some experts might call this case PH secondary to group 2 or group 3 disease, whereas others might classify this case as IPAH with cardiopulmonary comorbidities, the outcome is poor, irrespective of the name of the disease. This group of P(A)H patients experienced less effective responses from mono or combination therapies compared to “classic” PAH patients without (cardiopulmonary) comorbidities [ 113 , 114 ]. In addition, the first group of patients may experience higher rates of clinical failure [ 114 ].…”

Medikamentöse Therapie der pulmonalarteriellen Hypertonie mit Komorbiditäten – Welche Phänotypen gibt es, was gibt es zu beachten?

“…Die Analyse des COMPERA-Registers zeigte ein Therapieansprechen mit Verbesserung des Risikoprofils bei 34 % der Patient*innen mit 3-4 Komorbiditäten, 33 % bei 1-2 Komorbiditäten im Vergleich zu 52 % bei PAH-Patient*innen ohne kardiale Komorbiditäten [14]. Bei Einsatz einer initialen Kom- binationstherapie von ERA und PDE5-I scheinen PAH-Patient*innen mit kardialen Komorbiditäten gemäß Daten des italienischen Patient*innenregisters etwas geringer auf die Therapie anzusprechen als Patient*innen ohne kardiovaskuläre Risikofaktoren [15].…”

“…Daten zur Wirksamkeit spezifischer PAH-Medikamente bei Patient*innen mit Komorbiditäten stammen insbesondere aus Patient*innenregistern und Post-hoc-Analysen großer Therapiestudien. Aktuelle Analysen von Registerdaten deuten auf eine Wirksamkeit PAH-spezifischer Medikamente bei PAH-Patient*innen mit kardialen Komorbiditäten hin 14 15 16 . Die Analyse des COMPERA-Registers zeigte ein Therapieansprechen mit Verbesserung des Risikoprofils bei 34 % der Patient*innen mit 3–4 Komorbiditäten, 33 % bei 1–2 Komorbiditäten im Vergleich zu 52 % bei PAH-Patient*innen ohne kardiale Komorbiditäten 14 .…”