RITZ 1–5

Intravenous tezosentan (25–100 mg/h)

Acute heart failure

No difference in all endpoints

VERITAS 1 and 2

Intravenous tezosentan

Acute heart failure

No difference in dyspnoea at 24 h or survival at 7days

Mild haemodynamic benefit

No survival difference at 6 months

REACH 1

High dose bosentan (250 mg twice a day)

Chronic heart failure (WHO class IIIb–IV)

Early hepatotoxicity (10% versus 2% receiving placebo)

Trial terminated early

Trend towards clinical improvement in those receiving 6 months bosentan

ENABLE 1 and 2

Bosentan (125 mg twice a day)

Chronic heart failure (WHO class IIIb– IV)

No improvement in endpoints

Early toxicity with clinical worsening of heart failure with bosentan

ENCOR

Enrasentan

Chronic heart failure (WHO class II–III)

Increased adverse events, heart failure hospitalizations and trend towards increased mortality with enrasentan

EARTH

Darusentan

Chronic heart failure (WHO class II–IV)

Increased adverse events, and worsening of cardiac failure in darusentan groups

No benefit with darusentan