title: Combining bosentan and sildenafil in pulmonary arterial hypertension patients failing monotherapy: real-world insights.
abstract: Pulmonary arterial hypertension is a severe disease with a complex pathogenesis, for which combination therapy is an attractive option.This study aimed to assess the impact of sequential combination therapy on both short-term responses and long-term outcomes in a real-world setting.Patients with idiopathic/heritable pulmonary arterial hypertension, or pulmonary arterial hypertension associated with congenital heart disease or connective tissue disease and who were not meeting treatment goals on either first-line bosentan or sildenafil monotherapy, were given additional sildenafil or bosentan and assessed after 3-4 months. Double combination therapy significantly improved clinical and haemodynamic parameters, independent of aetiology or the order of drug administration. Significant improvements in functional class were observed in patients with idiopathic/heritable pulmonary arterial hypertension. The 1-, 3- and 5-year overall survival estimates were 91%, 69% and 59%, respectively. Patients with pulmonary arterial hypertension associated with connective tissue disease had significantly poorer survival rates compared to other aetiologies (p<0.003).The favourable short-term haemodynamic results and good survival rates, observed in patients receiving both bosentan and sildenafil, supports the use of sequential combination therapy in patients failing on monotherapy in a real-world setting.
authors.affiliation: Dept of Experimental, Diagnostic and Specialty Medicine-DIMES, Bologna University Hospital, Bologna, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Dardi
authors.affiliation: Dept of Experimental, Diagnostic and Specialty Medicine-DIMES, Bologna University Hospital, Bologna, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Manes
authors.affiliation: Dept of Experimental, Diagnostic and Specialty Medicine-DIMES, Bologna University Hospital, Bologna, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Palazzini
authors.affiliation: Dept of Experimental, Diagnostic and Specialty Medicine-DIMES, Bologna University Hospital, Bologna, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bachetti
authors.affiliation: Dept of Experimental, Diagnostic and Specialty Medicine-DIMES, Bologna University Hospital, Bologna, Italy.
authors.forename: Gaia
authors.initials: G
authors.lastname: Mazzanti
authors.affiliation: Dept of Experimental, Diagnostic and Specialty Medicine-DIMES, Bologna University Hospital, Bologna, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rinaldi
authors.affiliation: Dept of Experimental, Diagnostic and Specialty Medicine-DIMES, Bologna University Hospital, Bologna, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Albini
authors.affiliation: Dept of Experimental, Diagnostic and Specialty Medicine-DIMES, Bologna University Hospital, Bologna, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Gotti
authors.affiliation: Dept of Experimental, Diagnostic and Specialty Medicine-DIMES, Bologna University Hospital, Bologna, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Monti
authors.affiliation: Dept of Experimental, Diagnostic and Specialty Medicine-DIMES, Bologna University Hospital, Bologna, Italy.
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Bacchi Reggiani
authors.affiliation: Dept of Experimental, Diagnostic and Specialty Medicine-DIMES, Bologna University Hospital, Bologna, Italy nazzareno.galie@unibo.it.
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Galiè
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000077300:Bosentan; D002423:Cause of Death; D002648:Child; D003240:Connective Tissue Diseases / Q000150:complications; D004359:Drug Therapy, Combination; D005080:Exercise Test; D065627:Familial Primary Pulmonary Hypertension / Q000150:complications*; D005260:Female; D006330:Heart Defects, Congenital / Q000150:complications; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D007558:Italy; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D000068677:Sildenafil Citrate / Q000008:administration & dosage* / Q000627:therapeutic use; D013449:Sulfonamides / Q000008:administration & dosage* / Q000627:therapeutic use; D015996:Survival Rate; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D013449:Sulfonamides; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D000077300:Bosentan