• Jacob Y Cao, Kathryn M Wales, Rachael Cordina, Lau Edmund M T EMT Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia., and David S Celermajer.
• Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
• Int. J. Cardiol. 2018 Dec 15; 273: 213-220.

BackgroundPulmonary hypertension complicating left heart disease (PH-LHD) is the most common cause of PH. Off-label use of pulmonary arterial hypertension (PAH) medications for PH-LHD is prevalent, despite a lack of clinical data supporting their use.MethodsA systematic review and meta-analysis was performed. Comprehensive search of all available literature to date identified ten randomised, placebo controlled trials comprising 439 treated (Phosphodiesterase 5 inhibitors: n = 206; guanylate cyclase stimulators: n = 132; endothelin receptor antagonists: n = 101) and 338 placebo patients. Random effects model was employed to assess outcomes in the treatment compared to the placebo control arm.ResultsThe risks of all-cause mortality, cardiovascular mortality and worsening heart failure were numerically higher in the treated compared to the control group, although not statistically (all-cause mortality: RR = 1.97, 95% CI: 0.64-6.05, p = 0.24; cardiovascular mortality: RR = 2.01, 95% CI: 0.39-10.34, p = 0.4; worsening heart failure: RR = 1.23, 95% CI: 0.68-2.25, p = 0.49). Conversely, right heart hemodynamics improved numerically in the treated group, also without being significant (mean pulmonary artery pressure: MWD = -5.13 mm Hg, 95% CI: -13.2-2.9, p = 0.21; pulmonary vascular resistance: MWD = -0.87 WU, 95% CI: -1.75-0.1, p = 0.053).ConclusionsThe current meta-analysis demonstrated that there is no current evidence to support the widespread use of PAH therapy in PH-LHD. On the basis of a numerically increased risk of clinical harm, these agents should not be prescribed in this setting, unless further evidence of benefit arises in the future.Copyright © 2018 Elsevier B.V. All rights reserved.

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