Prognosis and response to first-line single and combination therapy in pulmonary arterial hypertension

Abstract

Objectives. To investigate survival, treatment escalation, effects of first-line single- and first-line combination therapy and prognostic markers in idiopathic- (IPAH), hereditary- (HPAH) and connective tissue disease-associated (CTD-PAH) pulmonary arterial hypertension (PAH). Design. Retrospective analysis of medical journals from PAH patients at Skåne University Hospital 2000–2011. Results. 1-, 2- and 3-year survival was 87%, 67%, and 54%, respectively, for the entire population, but worse (p = 0.003) in CTD-PAH than IPAH/HPAH. After 1, 2 and 3 years, 58%, 41% and 24% of patients starting on single therapy were alive on single therapy. 37.5% of patients on first-line single therapy received escalated treatment at first follow-up. First-line combination therapy more greatly decreased pulmonary vascular resistance index (PVRI, p = 0.017) than first-line single therapy. Only first-line combination therapy improved (p = 0.042) cardiac index (CI). Higher mean right atrial pressure (MRAP, p = 0.018), MRAP/CI (p = 0.021) and WHO functional class (p < 0.001) and lower 6-min walking distance (6MWD, p = 0.001) at baseline, and higher PVRI (p = 0.008) and lower 6MWD (p = 0.004) at follow-up were associated with worse outcome. Conclusions. We confirm improved survival with PAH-targeted therapies. Survival is still poor and early treatment escalation frequently needed. First-line combination therapy may more potently improve haemodynamics. MRAP/CI may represent a new prognostic marker in PAH.

Key words::

• combination therapy
• human
• prognosis
• pulmonary arterial hypertension
• survival

Acknowledgements

We acknowledge the support of the staff at the Clinic for Heart Failure and Valvular Disease and the Rheumatology Clinic, Skåne University Hospital, Lund, Sweden.

We acknowledge the financial support of the “ALF”- and Skåne University Hospital Foundations. The foundations have no role in the data collection, analysis or interpretation and have no right in disapproving of the manuscript.

Declaration of interest: Dr. Kylhammar reports unrestricted research grants from The Swedish Society of Pulmonary Hypertension, Actelion Pharmaceuticals Sweden and Pfizer outside the submitted work. Dr. Kylhammar reports personal lecture fees from Actelion Pharmaceuticals Sweden outside the submitted work.

Mrs. Persson reports no relevant conflict of interest.

Dr. Hesselstrand reports no relevant conflict of interest.

Dr. Rådegran reports unrestricted research grants from the “ALF”- and Skåne University Hospital Foundations to complete the work with the present study. Dr. Rådegran reports unrestricted research grants from the Anna-Lisa and Sven-Erik Lundgren- and Maggie Stephens Foundations, as well as Actelion Pharmaceuticals Sweden outside the submitted work. Dr. Rådegran reports personal lecture fees from Actelion Pharmaceuticals Sweden and Sandoz/Novartis outside the submitted work. Dr. Rådegran is and has been primary- or co-investigator in clinical PAH trials for GlaxoSmithKline, Actelion Pharmaceuticals Sweden, Pfizer, Bayer and United Therapeutics, and in clinical post-heart transplantation immunosuppression trials for Novartis. The authors alone are responsible for the content and writing of the paper.