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Theoretically, selective ET A R antagonists should be more effective than dual ERAs in that they only target the vasoconstrictive and mitogenic activities of ET-1ET A R, while preserving the vasodilatory and antimitogenic effect of ET-1ET B R.59 Despite its selectivity for ET A R, ambrisentan has not shown greater efficacy in non-comparative monotherapy clinical trials, compared with bosentan.60 This may be because the distribution or function of ET B R is altered in disease states, and thus dual receptor blockers appear to perform as well as those ERAs with a specific target.61 Unlike bosentan, ambrisentan was not associated with elevated liver toxicity,62 ,32 but peripheral oedema was reported more frequently compared with placebo.27 Details of the ARIES-1 and ARIES-2 trials are given in table 3, and the ARIES-E extension study is detailed in table 4

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The study was powered for a clinically meaningful effect size

10.1056/NEJM200007203430304 N Engl J Med