Abstract:
BACKGROUND: Several cellular pathways are implicated in the pathogenesis of pulmonary arterial hypertension (PAH) and attempts to arrest disease progression with a single drug would not be expected to succeed in the medium term. In clinical practice, combination therapy is often used in patients deteriorating on monotherapy, despite the absence of firm evidence from randomized controlled controls. METHODS: From January 2005 to August 2009, 112 patients with World Health Organisation Functional Class (FC) II-IV PAH deteriorating on monotherapy received non-parenteral combination therapy at six Australian PAH expert hospitals. Combination therapy included bosentan, sitaxentan, ambrisentan, iloprost and sildenafil. Data were prospectively collected for survival status, 6-min walk distance, FC and echocardiographic parameters at the start of monotherapy through to commencement of combination therapy and at 6-monthly intervals thereafter. RESULTS: After varying periods of monotherapy (18.7±13.4onths), survival estimates on combination therapy were 88%, 71% and 61% for the additional 1, 2 and 3years respectively. Survival on dual therapy in patients with idiopathic PAH/familial PAH was 93% at 1year and 79% at 2years, and for scleroderma-related PAH, 72% at 1 year and 48% at year 2 after initiation of combination therapy. In survivors, dual therapy reversed the deterioration in FC, from 3.1±0.6 on monotherapy to 2.2±0.6 at 12months. Similarly, dual therapy improved 6-min walk distance from 316±119m to 406±129m at 12months, and sequential echocardiography demonstrated a fall in pulmonary artery systolic pressure and improved right ventricular function. CONCLUSIONS: Dual non-parenteral therapy appears safe and effective and should be considered for PAH patients who are deteriorating on monotherapy to improve long-term outcomes.
journal_name
Intern Med Jjournal_title
Internal medicine journalauthors
Keogh A,Strange G,Kotlyar E,Williams T,Kilpatrick D,Macdonald P,Brown K,Pidoux A,Kermeen F,Steele P,Dalton B,Gabbay Edoi
10.1111/j.1445-5994.2010.02403.xsubject
Has Abstractpub_date
2011-03-01 00:00:00pages
235-44issue
3eissn
1444-0903issn
1445-5994journal_volume
41pub_type
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