Why the study?
Sequential triple combination therapy is recommended for PAH patients not at therapeutic goal on dual therapy, but long-term efficacy and safety data are scarce.
Does add-on sequential triple combination therapy improve functional, echocardiographic, and hemodynamic parameters in patients with pulmonary arterial hypertension who are not at goal on dual therapy?
Does add-on sequential triple combination therapy improve functional, echocardiographic, and hemodynamic parameters in patients with pulmonary arterial hypertension who are not at goal on dual therapy?
In a real-world cohort of PAH patients not at goal on dual therapy, sequential triple combination therapy significantly improved functional class, exercise capacity, hemodynamics, and risk scores.
Supports sequential triple therapy in real-world PAH not at goal on dual; leaves open need for randomized confirmation.
Background: Sequential triple combination therapy is recommended for pulmonary arterial hypertension (PAH) patients who are not at therapeutic goal on dual therapy, but long-term data on efficacy and safety is scarce. Objective: To assess the long-term impact of sequential triple combination therapy in patients with PAH who are not at goal on dual combination therapy. Study Design and Methods: We performed a retrospective observational study in a racially/ethnically diverse cohort of consecutive PAH patients on a stable dual therapy regimen who remained in intermediate- or high-risk category and were subsequently initiated on sequential triple combination therapy. We studied interval change in functional, echocardiographic, and hemodynamic parameters, REVEAL 2.0 risk category and ERS/ESC 2022 simplified four-strata risk category. Multivariate logistic regression analysis was performed to identify independent predictors of successful risk reduction (achievement or maintenance of REVEAL 2.0 low-risk category). Kaplan–Meier survival curves were created to assess the effect of risk reduction on survival. Results: Out of 414 PAH patients seen in our program, 55 patients received add-on sequential triple combination regimen and had follow-up hemodynamic data. The mean age was 57 years, with 85% women. The most common etiology of PAH was idiopathic/heritable (41.8%). Most patients were WHO functional class III (76.4%), and 34.5% of patients were in high-risk category (REVEAL 2.0). On a median follow-up of 68 weeks, there was a significant improvement in WHO Functional Class ( p < 0.001), six-minute walk distance (35 m) with 61.8% of patients achieving low-risk status by REVEAL 2.0, and a 28% of patients’ improvement in pulmonary vascular resistance. Female gender was identified as a strong predictor of successful risk reduction, whereas Hispanic ethnicity estimated right atrial pressure on echocardiogram and pericardial effusion predicted lower probability of risk reduction. Patients who achieved or maintained low-risk status had significantly improved survival. Conclusion: Add-on sequential triple combination therapy significantly increased functional, echocardiographic, and hemodynamic parameters with improvement in risk category and survival.
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Deshwal et al. (2023) studied this question.
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