Speaker's Highlight

• Don Sin University of British Columbia, St. Paul Hospital (Canada)
  Kenneth R. Chapman Toronto General Hospital Research Institute (Canada)
• Parameswaran Nair McMaster University (Canada)
  Carolyn Calfee UCSF (U.S.A.)
• Gregory P. Downey University of Colorado School of Medicine (U.S.A.)
  David A. Schwartz University of Colorado School of Medicine (U.S.A.)
• Neil Schluger Tuberculosis Control Branch, California Department of Public Health (U.S.A.)
  Nick Kim Critical Care & Sleep Medicine, University of California San Diego (U.S.A.)
• Nicola Hananiah Baylor College of Medicine (U.S.A.)
  Jae-Joon Yim Seoul National University College of Medicine (Republic of Korea)
• Koichiro Asano Tokai University School of Medicine (Japan)
  Diahn-Warng Perng Taipei Veterans General Hospital (Taiwan)
• Konstantinos Kostikas University of Ioannina (Greece)
  Karin Klooster University Medical Center Groningen (Kingdom of the Netherlands)

• Dual versus triple therapy for initial pulmonary arterial hypertension

  Selecting the opening regimen in pulmonary arterial hypertension (PAH) requires a confirmed diagnosis, an estimate of prognosis and a realistic plan for follow-up. The central choice is between oral dual therapy and triple therapy that adds a prostacyclin pathway agent.

  Contemporary guidance supports early combination therapy for many low- and intermediate-risk patients. High-risk disease, associated PAH and individual phenotype can shift the balance, so the regimen must also account for comorbidity, treatment burden and follow-up capacity.

  Why the initial regimen depends on risk

  PAH is a progressive vasculopathy in which inadequate pulmonary vascular adaptation places strain on the right ventricle. Treatment goals include improving symptoms and exercise capacity, reducing right-heart strain, preventing hospitalisation and extending survival. A stronger initial regimen may help, but it also introduces more adverse effects and logistical demands.

  Three-strata risk assessment guides treatment intensity. WHO functional class, six-minute walk distance, natriuretic peptides, right-ventricular function, renal function and other clinical findings are considered together. Patients classified as high risk generally warrant more intensive therapy, while lower-risk patients may begin with oral combination treatment and close reassessment.

  Defining dual and triple regimens

  Dual therapy combines a phosphodiesterase-5 inhibitor, such as sildenafil or tadalafil, with an endothelin receptor antagonist, such as bosentan or macitentan. These drugs act through complementary pathways, and tablets can usually be managed through an outpatient specialist service with routine blood pressure, renal and liver monitoring.

  Triple therapy adds a prostacyclin pathway agonist—such as parenteral epoprostenol or treprostinil, or inhaled iloprost—to the dual regimen. When selected initially, it is planned from diagnosis rather than introduced after treatment failure. Monotherapy remains an option for selected patients based on disease severity, comorbidities, frailty and the likelihood of a sustained response to less intensive treatment.

  What comparative evidence can show

  Observational cohorts and meta-analyses generally favour combination therapy over monotherapy for newly diagnosed low- and intermediate-risk PAH. Triple therapy can produce greater haemodynamic and functional improvement, although direct randomised comparisons with dual therapy remain limited. Studies can also be confounded because clinicians tend to reserve intensive therapy for patients with poorer prognosis.

  For background reading, clinicians and patients may find general medical references useful, provided the source, publication date and applicability are checked. Current international guidelines, product information and specialist assessment should take precedence over general educational material.

  Access and prescribing across Australia

  Specialist PAH services are concentrated in Sydney, Melbourne, Brisbane, Perth and Adelaide. For people living in rural NSW, Queensland or Western Australia, telehealth, nurse-led calls and local general practitioner support can reduce travel, although prescriptions may still be controlled by a public hospital team.

  Medicare covers general practitioner visits, and public outpatient care is generally free at the point of use after referral. PAH medicines generally receive no routine Pharmaceutical Benefits Scheme subsidy, so access depends on specialist public-hospital funding, local formularies and sometimes hospital-pharmacy dispensing rather than standard retail dispensing.

  The Australian market includes bosentan, macitentan, sildenafil, tadalafil, epoprostenol, treprostinil and iloprost, but availability and selection remain constrained by supply and service capacity. Starting epoprostenol commonly requires inpatient training, reliable cold-chain delivery and access to 24-hour clinical support, which can be challenging for patients distant from a major PAH centre.

  Weighing efficacy against treatment burden

  Dual therapy offers oral administration, simpler titration and less intensive home support. Triple therapy may provide stronger vasodilator effects and more favourable early outcomes, but it adds infusion or inhalation routines, central-line or inhaler complications, hypotension and greater monitoring requirements. The additional clinical benefit must therefore be weighed against adherence and safety in the home setting.

  Success should be judged using several measures rather than symptom improvement alone. Functional class, exercise capacity, natriuretic peptides, right-ventricular function, renal function and hospitalisation history should be reassessed after treatment starts. Deterioration in any of these domains may require earlier escalation than the original risk category would suggest.

  Using congress resources in context

  APSR 2022 is relevant to this question because PAH care sits at the intersection of respiratory medicine, cardiology, imaging and multidisciplinary nursing. Scientific sessions can help clinicians interpret risk stratification and contemporary treatment pathways, particularly where local PAH service expertise is limited.

  The congress website also exposes a Wild Robin event page, which belongs to the wider event listing rather than the clinical evidence base. It may assist users tracing historical online material, but it should not be used to guide diagnosis, prescribing or follow-up.

  A practical pathway for newly diagnosed patients

  The practical sequence begins with diagnostic confirmation, risk stratification, medication review and a shared decision about treatment intensity and monitoring. The main differences between the two regimens can be summarised by their clinical context, practical requirements and likely trade-offs.

  Feature	Dual therapy	Triple therapy
  Common starting context	Low or intermediate risk when rapid oral treatment is preferred	Intermediate risk requiring greater intensity, or high risk needing early prostacyclin therapy
  Core regimen	PDE-5 inhibitor plus endothelin receptor antagonist	PDE-5 inhibitor, endothelin receptor antagonist and prostacyclin pathway agonist
  Practical strengths	Oral administration, simpler titration and generally less complex home care	Greater haemodynamic effect and potential for earlier functional improvement
  Main risks and burden	Hypotension, dizziness, liver toxicity, fluid retention or an inadequate response	Additional infusion or inhalation burden, bleeding or infection risk and more intensive monitoring
  Australian delivery	Specialist outpatient prescribing and telehealth review are usually feasible	Often requires a hospital pharmacy, infusion expertise, cold-chain supply and rapid access to PAH nurses

  Before the first prescription:

  • Confirm PAH and haemodynamics with appropriate right-heart catheterisation after excluding left-heart and lung disease.
  • Record WHO functional class, six-minute walk distance, BNP or NT-proBNP, right-ventricular function, renal function and comorbidities.
  • Match the regimen to a funded pharmacy, monitoring plan and reliable follow-up, particularly when triple therapy is considered.
  • Discuss pregnancy intentions, drug interactions, adverse effects and adherence before issuing prescriptions.

  At the first structured review:

  • Reassess symptoms, functional class, exercise capacity, oxygen saturation, weight and adherence within one to three months.
  • Check blood pressure, renal and liver function, haemoglobin and drug interactions according to the prescribed combination.
  • Repeat echocardiography or cardiac MRI when needed, then escalate promptly for syncope, worsening right-heart failure or rising biomarkers.

  The practical takeaway is to confirm PAH, stratify risk and begin combination therapy promptly when appropriate, while reserving triple therapy for patients whose disease intensity, phenotype or early trajectory justifies its greater complexity.

  Richard Russell Nuffield Department of Clinical Medicine, University of Oxford (United Kingdom)
• Mona Bafadhel King’s College London (United Kingdom)
  David Jackson Guy’s and St Thomas’ Hospital, King’s College London (United Kingdom)
• James Chalmers University of Dundee (United Kingdom)
  David Price University of Aberdeen (United Kingdom)