Fig. 2
Analysis of survival by adverse event. a Analysis of the time to exacerbation of subjective dyspnea. Among the untreated patients with borderline or less severe PH, the time to exacerbation of dyspnea was 152.00 ± 89.94 days (mean ± SD) in 7 of 12 patients confirmed to have experienced exacerbation of subjective symptoms of dyspnea by the data obtained on the cut-off date. Among the drug-treated patients with borderline or less severe PH, the time to exacerbation of dyspnea was 259.00 ± 49.87 days (mean ± SD) in 3 of 12 patients confirmed to have experienced exacerbation of dyspnea by the data obtained on the cut-off date. Proportional hazard analysis showed that the risk ratio of the drug-treated to untreated groups was 0.58, but with no significant difference noted. The time to exacerbation of dyspnea at the time of analysis was 218.17 ± 35.62 days (mean ± SE) in the untreated group and 290.71 ± 12.036 days in the drug-treated group, but with no significant difference noted. b Analysis of the time to an increase in the dose of O2 (event). Increase of the O2 dose: In the untreated patients with borderline or less severe PH, the time to the dose increase was 199.00 ± 132.90 days (mean ± SD) in 5 of 12 patients confirmed to have required an increase of the dose of O2 by the data obtained on the cutoff date. In the drug-treated patients with borderline or less severe PH, the time to the dose increase was 335.00 ± 182.43 days (mean ± SD) in 3 of 12 patients confirmed to have required an increase of the O2 dose based on the data obtained on the cut-off date. The risk ratio analysis showed that the hazard ratio of the drug-treated to untreated groups was 0.58. The time to O2 dose increase at the time of analysis was 357.71 ± 50.83 days in the untreated group and 438.20 ± 34.61 days in the drug-treated group with no significant difference between the groups, despite the results favoring the drug-treated group. In addition, only 1 drug-treated patient with borderline or less severe PH achieved a decrease of the O2 dose on day 243 due to an improvement of respiratory function. c Hospital-free survival. Of the 12 untreated patients with borderline or less severe PH, 8 were confirmed to have been hospitalized (event) by the data obtained on the cut-off date with the time to hospitalization being 241.50 ± 192.24 days (mean ± SD). Of the 12 drug-treated patients with borderline or less severe PH, 2 was confirmed to have been hospitalized by the data obtained on the cut-off date with the time to hospitalization being 239.002 ± 169.00 days. At the time of survival time analysis, hospital-free survival in the untreated group was 358.87 ± 68.65 days (mean ± SE) (median, 331 days), which was shown to be significantly different from that in the drug-treated group (603.44 ± 50.074) by proportional hazard analysis (hazard ratio [HR] of the drug-treated to untreated groups, 0.10; P = 0.017). d Overall survival. Of the 12 untreated patients with borderline or less severe PH, 7 were confirmed dead (event) by the data obtained on the cut-off date with the time to event being 309.29 ± 195.13 days (mean ± SD); of the drug-treated patients with borderline or less severe PH, 1 was confirmed dead by the data on the cut-off date with the time to event being 671 days. At the time of survival analysis, the time to event in the untreated group was 433.78 ± 66.98 days (mean ± SE), which was significantly different from that in the drug-treated group by proportional hazard analysis (HR of the drug-treated to untreated groups, 0.10; P = 0.0082)