| First author [ref.] | Study acronym | Patients n | Study period weeks | Definition of time to clinical worsening | Events n | |
| Study drug | Comparator | |||||
| Galiè [12] | ALPHABET | 130 | 12 | All-cause mortality Hospitalisation for worsening of PH symptoms | Beraprost, n=4 | Placebo, n=3 |
| Olschewski [14] | AIR | 203 | 12 | Clinical deterioration Death Need for transplantation | Iloprost, n=6 | Placebo, n=13 |
| Hoeper [16] | COMBI | 40 | 12 | Death Hospitalisation for right heart failure Deterioration in FC Decrease in 6MWD by 20% from baseline or <150 m | Iloprost/bosentan, n=3 | Placebo/bosentan, n=4 |
| Channick [17] | 32 | 12 | Right ventricular heart failure Aggravated pulmonary hypertension | Bosentan, n=0 | Placebo, n=3 | |
| Rubin [18] | BREATHE-1 | 213 | 16 | Death Lung transplantation Atrial septostomy Hospitalisation for PH Lack of clinical improvement or worsening leading to discontinuation Need for epoprostenol therapy | Bosentan, n=25 | Placebo, n=34 |
| Galiè [19] | EARLY | 185 | 24 | Death Hospitalisation due to PAH Progression of PAH | Bosentan, n=3 | Placebo, n=13 |
| Galiè [23] | ARIES | 394 | 12 | Death Lung transplantation Atrial septostomy Hospitalisation for PAH Study withdrawal because of the addition of other PAH medications, or early escape criteria | Ambrisentan, n=12 | Placebo, n=20 |
| Barst [24] | STRIDE-1 | 178 | 12 | Death Transplantation Atrial septostomy Epoprostenol use | Sitaxentan, n=1 | Placebo, n=3 |
| Barst [25] | STRIDE-2 | 247 | 18 | Death Atrial septostomy Transplantation Hospitalisation for PAH Initiation of new chronic PAH treatment Combined WHO FC deterioration and 15% decrease in 6MWD from baseline | Sitaxentan, n=10 | Placebo, n=10 Bosentan, n=9 |
| Sandoval [26] | STRIDE-4 | 98 | 18 | Hospitalisation for worsening PAH Death Need for heart–lung or lung transplantation Atrial septostomy Addition of any new type of chronic treatment for PAH A combination of deterioration in WHO FC and 15% decrease in 6MWD from baseline | Sitaxentan, n=1 | Placebo, n=3 |
| Galiè [28] | SUPER-1 | 278 | 12 | Death Transplantation Hospitalisation for PAH Initiation of additional therapies for PAH | Sildenafil, n=10 | Placebo, n=7 |
| Simonneau [30] | PACES | 267 | 16 | Death Lung transplantation Hospitalisation due to PAH Initiation of bosentan therapy Change in epoprostenol dose of 10% due to clinical deterioration | Sildenafil, n=8 | Placebo, n=24 |
| Galiè [31] | PHIRST | 405 | 16 | Death Lung or heart–lung transplantation Atrial septostomy Hospitalisation due to worsening PAH Initiation of new PAH approved therapy Worsening WHO FC | Tadalafil, n=30 | Placebo, n=13 |
| Jing [32] | EVALUATION | 66 | 12 (+12 open label) | Death Hospitalisation for PAH progression | Vardenafil, n=1 | Placebo, n=4 |
| Hoeper [35] | IMPRES | 202 | 24 | Death Hospitalisation for worsening of PAH Worsening of WHO FC by at least one level or a 15% decrease from baseline in 6MWD | Imatinib, n=37 | Placebo, n=32 |
PH: pulmonary hypertension; FC: functional class; 6MWD: 6-min walk distance; PAH: pulmonary arterial hypertension; WHO: World Health Organization.