Table 3

Summary of adverse events among patients with CTD-PAH and SSc-PAH

CTD-PAH SSc-PAH
n (%)COMB (n=103)AMB mono (n=44)TAD mono (n=40)COMB (n=71)AMB mono (n=23)TAD mono (n=24)
Any AE*102 (99)42 (95)39 (98)70 (99)22 (96)23 (96)
Oedema peripheral48 (47)15 (34)13 (33)32 (45)6 (26)8 (33)
Headache34 (33)14 (32)15 (38)20 (28)6 (26)8 (33)
Diarrhoea30 (29)14 (32)10 (25)20 (28)4 (17)7 (29)
Dyspnoea23 (22)9 (20)10 (25)18 (25)2 (9)6 (25)
Serious AEs†45 (44)15 (34)20 (50)31 (44)9 (39)14 (58)
Pulmonary hypertension‡7 (7)3 (7)6 (15)4 (6)05 (21)
Pneumonia6 (6)3 (7)2 (5)3 (4)3 (13)1 (4)
Dyspnoea4 (4)2 (5)2 (5)4 (6)1 (4)2 (8)
Anaemia3 (3)03 (8)3 (4)01 (4)
Syncope2 (2)1 (2)1 (3)000
AEs leading to permanent study drug discontinuation§14 (14)8 (18)6 (15)10 (14)3 (13)3 (13)
Oedema peripheral2 (2)3 (7)1 (3)2 (3)2 (9)0
Diarrhoea2 (2)001 (1)00
Nausea2 (2)002 (3)00
Headache2 (2)001 (1)00
Dyspnoea1 (<1)001 (1)00
Pulmonary oedema01 (2)001 (4)0
  • Post hoc summary.

  • *AEs occurring in ≥25% of patients on combination therapy in either the CTD-PAH or SSc-PAH populations.

  • †SAEs occurring in ≥4% of patients on combination therapy in either the CTD-PAH or SSc-PAH populations; only the iPAH/hPAH population met this criterion for syncope (after rounding) (see online supplementary table S4), but rates are shown in this table to allow for comparison.

  • ‡In each case, the investigator reported the events using additional text not captured in the preferred term, describing this as worsening of pulmonary hypertension. However, an AE report of worsening pulmonary hypertension does not necessarily become a primary endpoint event, which has specific criteria.

  • §AEs leading to permanent study drug discontinuation in ≥2 patients on combination therapy in either the CTD-PAH or SSc-PAH populations; only the iPAH/hPAH population met this criterion for dyspnoea and pulmonary oedema (see online supplementary table S4), but rates are shown in this table to allow for comparison.

  • AE, adverse event; AMB, ambrisentan; COMB, combination therapy; CTD, connective tissue disease; hPAH, heritable pulmonary arterial hypertension; iPAH, idiopathic pulmonary arterial hypertension; Mono, monotherapy; PAH, pulmonary arterial hypertension; SAE, serious adverse event; SSc, systemic sclerosis; TAD, tadalafil.