Dual therapy in IPAH and SSc-PAH. A qualitative systematic review.
2012
Summary Background Use of endothelin receptor antagonists (ERA), phosphodiesterase type-5 (PDE-5) inhibitors and prostaglandin analogues has resulted in improved outcomes in idiopathic pulmonary arterial hypertension (IPAH) and systemic sclerosis-associated PAH (SSc-PAH) patients. However, patients often deteriorate on monotherapy. The objective of this study is to evaluate the effect of dual therapy on outcomes in IPAH and SSc-PAH. Methods A systematic review of MEDLINE (1950–2011), EMBASE (1980–2011) and CINAHL (inception-2011) was conducted to identify studies that evaluated the effect of any dual combination of ERA, PDE-5 inhibitors or prostaglandin analogues on 6-min walk distance (6MWD), functional class (FC), haemodynamics, quality-of-life (QoL) or time-to-clinical-worsening in IPAH or SSc-PAH. A standardized form was used to abstract design, sample size, aetiology, outcome and treatment effect. Results Twenty-six observational studies and 6 randomized trials were identified. Using combination PDE-5 inhibitor and prostaglandin analogues, 6/7 studies reported improvement in 6MWD, 6/8 studies reported improvement in FC, 6/6 studies reported improvement in haemodynamics and 1 trial demonstrated improvement in QoL and time-to-clinical-worsening. Using combination ERA and prostaglandin analogues, 4/6 studies and 1 trial reported improvement in 6MWD, 3/3 studies and 1 trial reported improvement in FC, 4/5 studies and 1 trial reported improvement in PAP. Using combination ERA and PDE-5 inhibitor, 4/7 studies reported an improvement in 6MWD, and 2/6 report improvement in FC. Conclusion The evidence suggests a beneficial effect of dual therapy in IPAH and SSc-PAH, particularly those who are deteriorating on monotherapy. Research should focus on subsets of patients to identify the optimal timing and combination of dual therapy.
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