Influence of Patient Characteristics on the Effectiveness of Inhaled Nitric Oxide Therapy for Pulmonary Hypertension Following Cardiac Surgery: A Post-marketing Surveillance in Japan

Background A post-marketing surveillance (PMS) of INOflo^® for Inhalation 800 ppm in Japan (N = 2,817) established its real-world safety and effectiveness in improving hemodynamic parameters during the perioperative period in patients undergoing cardiac surgery. However, the patient population was heterogeneous with respect to characteristics such as age and baseline hemodynamic parameters. Objective The objective of this study is to evaluate patient characteristics associated with the effectiveness of inhaled nitric oxide (iNO) for pulmonary hypertension following cardiac surgery in Japan. Methods This study was a retrospective analysis of the PMS data of INOflo. Adults aged ≥15 years with a mean pulmonary artery pressure (mPAP) ≥20 mmHg at baseline (i.e., prior to iNO initiation) who commenced iNO following cardiac surgery were included. The PMS prospectively monitored the safety and effectiveness of INOflo in Japan. The primary endpoint was the change in mPAP from baseline to 24 hours after iNO initiation. Multivariable regression analysis explored patient characteristics (age, BMI, sex, and prior pulmonary vasodilator medication) associated with the primary endpoint. Results A total of 427 Japanese patients were included (median (IQR) age: 71.0 (60.0-77.0) years). Significant improvements in hemodynamic parameters were observed, including mPAP at 24 and 48 hours from baseline. No patient characteristics were significantly associated with the change in mPAP from baseline to 24 hours after iNO initiation. However, patients aged 30 years or with a BMI of 35 did not show significant changes in mPAP, whereas other age and BMI categories demonstrated statistically significant improvements. Conclusions iNO treatment was associated with improvements in hemodynamics in patients with pulmonary hypertension following cardiac surgery, irrespective of patient characteristics such as age, BMI, sex, or prior pulmonary vasodilator therapy in this analysis. Conversely, the models suggest that differences in age and BMI may influence the magnitude of iNO effectiveness on the change in mPAP.