The new clinical trials on pharmacological treatment in pulmonary arterial hypertension.
Past medical therapy for pulmonary arterial hypertension included the use of calcium-channel antagonists in acute vasoreactive subjects and oral anticoagulants and continuous intravenous administration of epoprostenol in the more severe cases. Recently, the thromboxane inhibitor terbogrel, the prostacyclin analogues treprostinil, beraprost and iloprost, and the endothelin receptor antagonist bosentan have been tested in clinical trials in >1,100 patients. Except for terbogrel, all compounds improved the mean exercise capacity by different degrees, as assessed by the 6-min walk test. In the evaluation of the clinical relevance of exercise capacity improvements, additional elements need to be considered, such as baseline functional class and concomitant favourable effects on combined clinical events (including hospitalisations, mortality and rescue therapies), quality of life and haemodynamics. No trials have shown effects on mortality, as the study protocols were not designed for assessing this end-point. Each new compound presents side-effects that are unpredictable in the individual patient and require appropriate attention upon treatment initiation and maintenance. These new therapeutic options will be available in the near future and will allow tailoring of the most appropriate treatment to the single patient, according to an individualised benefit-to-risk ratio.
Galiè
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n.galie@bo.nettuno.it
Manes
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Branzi
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D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D011464:Epoprostenol / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D016285:Iloprost / Q000008:administration & dosage*; D008297:Male; D011379:Prognosis; D011725:Pyridines / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D015996:Survival Rate; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage*
D011725:Pyridines; D014665:Vasodilator Agents; C048081:beraprost; C112331:terbogrel; D011464:Epoprostenol; D016285:Iloprost; C427248:treprostinil