Association of oral endothelin receptor antagonists with risks of cardiovascular events and mortality: meta-analysis of randomized controlled trials

Abstract

ERAs therapy is not significantly associated with increased all-cause death, but there are more cardiovascular events and edema or fluid retention, anemia, and liver enzymes disorder. Large clinical randomized controlled studies are needed to further confirm the safety of the clinical application of ERAs.

Evidence synthesis in pulmonary arterial hypertension: a systematic review and critical appraisal

“…PH due to left sided heart disease) were investigated in four studies [ 20 , 34 , 43 , 44 ] while patients with PAH were examined alongside other diseases (e.g. heart failure, prostate cancer) in two studies [ 45 , 58 ].…”

“…With a number of exceptions [ 17 , 20 , 24 , 25 , 34 , 35 , 39 – 41 , 45 , 47 , 54 , 58 , 59 , 61 , 62 , 64 ], most studies investigated treatments targeting all three pathways. All the approved treatments (ERA, PDE-5Is, PRAs, prostacyclin and sGCS) were investigated in nine recent studies [ 27 , 30 , 38 , 42 , 46 , 48 , 57 , 63 , 67 ].…”

“…Some studies included treatments approved in limited markets such as beraprost [ 38 , 40 , 48 , 50 , 51 , 57 , 61 , 65 , 67 ]. In nine studies, drugs targeting one pathway only were investigated: prostacyclins in five studies [ 40 , 47 , 59 , 61 , 64 ] and ERAs in four studies [ 25 , 45 , 58 , 62 ]. Fifteen studies [ 17 , 20 , 21 , 24 , 25 , 32 , 34 , 35 , 39 , 45 , 58 , 60 , 62 , 63 , 65 ] focused on oral treatments only.…”

“…In nine studies, drugs targeting one pathway only were investigated: prostacyclins in five studies [ 40 , 47 , 59 , 61 , 64 ] and ERAs in four studies [ 25 , 45 , 58 , 62 ]. Fifteen studies [ 17 , 20 , 21 , 24 , 25 , 32 , 34 , 35 , 39 , 45 , 58 , 60 , 62 , 63 , 65 ] focused on oral treatments only. Besides the approved treatments, non-approved PAH treatments were included in seven studies: imatinib [ 50 , 51 , 54 , 60 ], terbogrel [ 29 , 60 ] and aspirin [ 50 ].…”

“…MEDLINE, Embase, CENTRAL [ 18 , 29 , 32 , 34 , 35 , 43 , 44 , 50 , 51 , 66 ]. Several studies did not provide details of the search strategy [ 18 – 21 , 24 – 26 , 29 , 31 , 32 , 35 , 36 , 39 , 40 , 43 – 45 , 48 , 50 – 53 , 57 – 59 , 61 , 65 – 67 ] and one study did not provide any details on the search strategy and searched databases [ 56 ].…”