| Patients with event | Time to event days | HR (95% CI) | Two-sided p-value | |||
| Roflumilast | Placebo | Roflumilast | Placebo | |||
| All patients | ||||||
| First | 717 (46.6) | 821 (52.8) | 80.0 (18.0–245.0) | 71.0 (19.0–200.0) | 0.886 (0.802–0.980) | 0.0185 |
| Second | 329 (21.4) | 430 (27.7) | 177.0 (72.0–307.0) | 148.0 (71.0–267.0) | 0.791 (0.685–0.914) | 0.0014 |
| Third# | 152 (9.9) | 218 (14.0) | 224.5 (123.0–328.0) | 197.0 (114.0–308.0) | 0.730 (0.593–0.899) | 0.0031 |
| With LABA# | ||||||
| First | 376 (50.2) | 463 (58.4) | 74.5 (17.0–220.0) | 67.0 (17.0–198.0) | 0.863 (0.753–0.990) | 0.0349 |
| Second | 180 (24.0) | 250 (31.5) | 160.5 (71.0–301.0) | 148.0 (71.0–252.0) | 0.792 (0.653–0.961) | 0.0179 |
| Third | 82 (10.9) | 133 (16.8) | 222.5 (129.0–312.0) | 201.0 (112.0–304.0) | 0.684 (0.518–0.903) | 0.0075 |
| Without LABA# | ||||||
| First | 341 (43.3) | 358 (47.0) | 85.0 (20.0–266.0) | 74.0 (21.0–212.0) | 0.924 (0.796–1.073) | 0.3002 |
| Second | 149 (18.9) | 180 (23.7) | 194.0 (75.0–316.0) | 151.0 (75.0–289.0) | 0.803 (0.646–0.999) | 0.0493 |
| Third | 70 (8.9) | 85 (11.2) | 226.5 (119.0–332.0) | 189.0 (114.0–309.0) | 0.792 (0.576–1.090) | 0.1530 |
| Infrequent exacerbators#,¶ | ||||||
| First | 470 (41.8) | 545 (47.9) | 85.0 (21.0–255.0) | 76.0 (20.0–216.0) | 0.885 (0.781–1.001) | 0.0523 |
| Second | 197 (17.5) | 260 (22.9) | 188.0 (79.0–312.0) | 155.0 (75.0–277.0) | 0.808 (0.671–0.973) | 0.0245 |
| Third | 85 (7.6) | 118 (10.4) | 224.0 (129.0–312.0) | 198.5 (114.0–312.0) | 0.776 (0.586–1.027) | 0.0765 |
| Frequent exacerbators#,¶ | ||||||
| First | 247 (59.8) | 276 (66.2) | 69.0 (14.0–215.0) | 59.0 (17.0–182.0) | 0.895 (0.752–1.065) | 0.2101 |
| Second | 132 (32.0) | 170 (40.8) | 155.0 (60.0–289.0) | 141.0 (71.0–246.0) | 0.740 (0.588–0.932) | 0.0107 |
| Third | 67 (16.2) | 100 (24.0) | 227.0 (122.0–332.0) | 194.0 (113.5–289.0) | 0.653 (0.478–0.892) | 0.0074 |
Data are presented as n (%) or median (68% range), unless otherwise stated. Hazard ratio (HR), 95% CI and p-values are based on Cox proportional hazards model with the following factors and covariates: treatment, age, sex, smoking status and strata (study and country pool). For all groups apart from LABA usage, concomitant treatment with a LABA was also included as a factor. Moderate exacerbations are defined as those requiring corticosteroid treatment. Severe exacerbations are defined as those resulting in hospitalisation or death. #: post hoc analyses; ¶: exacerbations in the previous year (based on patient recall), defined as infrequent if fewer than two and frequent if two or more exacerbations.