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Heart, Lung and Circulation

Pharmacological Treatment of Pulmonary Arterial Hypertension in Australia: Current Trends and Challenges

Published:March 06, 2020DOI:https://doi.org/10.1016/j.hlc.2020.01.017

      Background

      Combination drug therapy for pulmonary arterial hypertension (PAH) is the international standard of care for most patients, however in Australia there are barriers to drug access. This study evaluates current treatment of PAH patients in Australia and the consistency of therapy with international guidelines.

      Methods

      Cross-sectional analysis of patients with Group 1 PAH enrolled in the Pulmonary Hypertension Society of Australia and New Zealand Registry (PHSANZ) at 31 December 2017. Drug treatment was classified as monotherapy or combination therapy and adequacy of treatment was determined by risk status assessment using the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) 2.0 risk calculator. Predictors of monotherapy were assessed using a generalised linear model with Poisson distribution and logarithmic link function.

      Results

      1,046 patients met the criteria for analysis. Treatment was classified as monotherapy in 536 (51%) and combination therapy in 510 (49%) cases. Based on REVEAL 2.0, 184 (34%) patients on monotherapy failed to meet low-risk criteria and should be considered inadequately treated. Independent predictors of monotherapy included age greater than 60 years (risk ratio [RR] 1.23, 95% confidence interval [CI] 1.09–1.38; p=0.001), prevalent enrolment in the registry (RR 1.21 [95%CI 1.08–1.36]; p=0.001) and comorbid systemic hypertension (RR 1.17 [95%CI 1.03–1.32]; p=0.014), while idiopathic/heritable/drug-induced PAH subtype (RR 0.85 [95%CI 0.76–0.96]; p=0.006), functional class IV (RR 0.50 [95%CI 0.29–0.86]; p=0.012), increased right ventricular systolic pressure (RR 0.99 [95%CI 0.99–1.00]; p<0.001) and increased pulmonary vascular resistance (RR 0.96 [95%CI 0.95–0.98]; p<0.001) were less likely to be associated with monotherapy.

      Conclusions

      Most Australian PAH patients are treated with monotherapy and a significant proportion remain at risk of poor outcomes. This is below the standard of care recommended by international guidelines and at risk patients should be escalated to combination therapy.

      Keywords

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      References

        • McGoon M.D.
        • Benza R.L.
        • Escribano-Subias P.
        • Jiang X.
        • Miller D.
        • Peacock A.
        • et al.
        Pulmonary arterial hypertension: epidemiology and registries.
        J Am Coll Cardiol. 2013; 62: D51-D59
        • Galiè N.
        • Humbert M.
        • Vachiery J.-L.
        • Gibbs S.
        • Lang I.
        • Torbicki A.
        • et al.
        2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS).
        Eur Respir J. 2015; 46: 903-975
        • Strange G.
        • Lau E.M.
        • Giannoulatou E.
        • Corrigan C.
        • Kotlyar E.
        • Kermeen F.
        • et al.
        Survival of idiopathic pulmonary arterial hypertension patients in the modern era in Australia and New Zealand.
        Heart Lung Circ. 2018; 27: 1368-1375
        • Strange G.
        • Playford D.
        • Stewart S.
        • Deague J.
        • Nelson H.
        • Kent A.
        • et al.
        Pulmonary hypertension: prevalence and mortality in the Armadale echocardiography cohort.
        Heart. 2012; 98: 1805-1811
        • Brown L.M.
        • Chen H.
        • Halpern S.
        • Taichman D.
        • McGoon M.D.
        • Farber H.W.
        • et al.
        Delay in recognition of pulmonary arterial hypertension: factors identified from the REVEAL Registry.
        Chest. 2011; 140: 19-26
        • Strange G.
        • Gabbay E.
        • Kermeen F.
        • Williams T.
        • Carrington M.
        • Stewart S.
        • et al.
        Time from symptoms to definitive diagnosis of idiopathic pulmonary arterial hypertension: the delay study.
        Pulm Circ. 2013; 3: 89-94
        • Jain S.
        • Khera R.
        • Girotra S.
        • Badesch D.
        • Wang Z.
        • Murad M.H.
        • et al.
        Comparative effectiveness of pharmacologic interventions for pulmonary arterial hypertension: a systematic review and network meta-analysis.
        Chest. 2017; 151: 90-105
        • Galie N.
        • Manes A.
        • Negro L.
        • Palazzini M.
        • Bacchi-Reggiani M.L.
        • Branzi A.
        • et al.
        A meta-analysis of randomized controlled trials in pulmonary arterial hypertension.
        Eur Heart J. 2009; 30: 394-403
      1. Post-market Review of Pulmonary Arterial Hypertension (PAH) Medicines; Appendix 2A.
        (Available from) ([accessed 28.8.19])
        • Simonneau G.
        • Hoeper M.M.
        • McLaughlin V.
        • Rubin L.
        • Galie N.
        Future perspectives in pulmonary arterial hypertension.
        Eur Respir Rev. 2016; 25: 381-389
        • Vachiery J.L.
        • Delcroix M.
        • Al-Hiti H.
        • Efficace M.
        • Hutyra M.
        • Lack G.
        • et al.
        Macitentan in pulmonary hypertension due to left ventricular dysfunction.
        Eur Respir J. 2018; 51 (pii: 1701886)
        • Redfield M.M.
        • Chen H.H.
        • Borlaug B.A.
        • Semigran M.J.
        • Lee K.L.
        • Lewis G.
        • et al.
        Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial.
        JAMA. 2013; 309: 1268-1277
        • Cao J.Y.
        • Wales K.M.
        • Cordina R.
        • Lau E.M.T.
        • Celermajer D.S.
        Pulmonary vasodilator therapies are of no benefit in pulmonary hypertension due to left heart disease: a meta-analysis.
        Int J Cardiol. 2018; 273: 213-220
        • Wright Jr., J.T.
        • Whelton P.K.
        • Reboussin D.M.
        A randomized trial of intensive versus standard blood-pressure control.
        N Engl J Med. 2016; 374: 2294
        • Galiè N.
        • Barberà J.A.
        • Frost A.E.
        • Ghofrani H.A.
        • Hoeper M.M.
        • McLaughlin V.V.
        • et al.
        Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension.
        N Engl J Med. 2015; 373: 834-844
        • Pulido T.
        • Adzerikho I.
        • Channick R.N.
        • Delcroix M.
        • Galie N.
        • Ghofrani H.A.
        • et al.
        Macitentan and morbidity and mortality in pulmonary arterial hypertension.
        N Engl J Med. 2013; 369: 809-818
        • Sitbon O.
        • Channick R.
        • Chin K.M.
        • Frey A.
        • Gaine S.
        • Galie N.
        • et al.
        Selexipag for the treatment of pulmonary arterial hypertension.
        N Engl J Med. 2015; 373: 2522-2533
        • Lajoie A.C.
        • Lauziere G.
        • Lega J.C.
        • Lacasse Y.
        • Martin S.
        • Simard S.
        • et al.
        Combination therapy versus monotherapy for pulmonary arterial hypertension: a meta-analysis.
        Lancet Respir Med. 2016; 4: 291-305
        • Gibbs J.S.R.
        • Sitbon O.
        Center-based care for pulmonary hypertension: a European perspective.
        Adv Pulm Hypertens. 2018; 16: 170-174
        • Benza R.L.
        • Gomberg-Maitland M.
        • Elliott C.G.
        • Farber H.W.
        • Foreman A.J.
        • Frost A.E.
        • et al.
        Predicting survival in patients with pulmonary arterial hypertension: The REVEAL Risk Score Calculator 2.0 and comparison with ESC/ERS-based risk assessment strategies.
        Chest. 2019; 156: 323-337
        • Galie N.
        • Channick R.N.
        • Frantz R.P.
        • Grunig E.
        • Jing Z.
        • Moiseeva O.
        • et al.
        Risk stratification and medical therapy of pulmonary arterial hypertension.
        Eur Respir J. 2019; 53 (pii: 1801889)
        • Benza R.L.
        • Miller D.P.
        • Gomberg-Maitland M.
        • Elliott C.G.
        • Farber H.W.
        • Foreman A.J.
        • et al.
        Predicting survival in pulmonary arterial hypertension: insights from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL).
        Circulation. 2010; 122: 164-172
        • Boucly A.
        • Weatherald J.
        • Savale L.
        • Jais X.
        • Cottin V.
        • Prevot G.
        • et al.
        Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension.
        Eur Respir J. 2017; 50 (pii:170889)
        • Humbert M.
        • Sitbon O.
        • Yaïci A.
        • Montani D.
        • O’Callaghan D.S.
        • Jais X.
        • et al.
        Survival in incident and prevalent cohorts of patients with pulmonary arterial hypertension.
        Eur Respir J. 2010; 36: 549-555
        • Rural and remote Australians
        Australian Institute of Health and Welfare (AIHW) Australian Institute of Health and Welfare (AIHW).
        (Available from) ([accessed 28.8.19])
      2. Pulmonary arterial hypertension designated centres. Department of Human Services, Australian Government, 2018 (Previously available from:) ([accessed 28.8.19])
        • Opitz C.F.
        • Hoeper M.M.
        • Gibbs J.S.R.
        • Kaemmerer H.
        • Pepke-Zaba J.
        • Coghlan J.G.
        • et al.
        Pre-capillary, combined, and post-capillary pulmonary hypertension: a pathophysiological continuum.
        J Am Coll Cardiol. 2016; 68: 368-378
        • Hoeper M.M.
        • Huscher D.
        • Ghofrani H.A.
        • Delcroix M.
        • Distler O.
        • Schweiger C.
        • et al.
        Elderly patients diagnosed with idiopathic pulmonary arterial hypertension: results from the COMPERA registry.
        Int J Cardiol. 2013; 168: 871-880
        • Stevenson M.D.
        • Macdonald F.C.
        • Langley J.
        • Hunsche E.
        • Akehurst R.
        The cost-effectiveness of bosentan in the United Kingdom for patients with pulmonary arterial hypertension of WHO functional class III.
        Value Health. 2009; 12: 1100-1105
        • Coyle K.
        • Coyle D.
        • Blouin J.
        • Lee K.
        • Jabr M.F.
        • Tran K.
        • et al.
        Cost effectiveness of first-line oral therapies for pulmonary arterial hypertension: a modelling study.
        Pharmacoeconomics. 2016; 34: 509-520