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Editorial Pulmonary Arterial Hypertension
Pulmonary Arterial Hypertension
Management – A New Approach For a
Pulmonary Vascular Diseases Clinic, Department of Cardiology, Cliniques Universitaires de Bruxelles, Hôpital Erasme, Brussels, Belgium
P ulmonary Arterial Hypertension is a rare, deadly and incurable condition for which management guidelines have recently been
revised. Important and remarkable changes include a new strategy-oriented treatment algorithm, based on a risk-stratification
approach. Combination therapy is recommended as soon as diagnosis is established for all patients, with a parenteral prostacyclin
for the most severe cases. The uncommon nature of the disease and the management complexity require that care is delivered by expert
Keywords Pulmonary arterial hypertension, guidelines,
combination therapy, expert, risk stratification,
Disclosure: Jean-Luc Vachiery has nothing to disclose in
relation to this paper. This article is a short opinion piece
and has not been submitted to external peer reviewers.
No funding was received for the publication of this article.
Open Access: This article is published under the
Creative Commons Attribution Noncommercial License,
which permits any non-commercial use, distribution,
adaptation and reproduction provided the original
author(s) and source are given appropriate credit.
Pulmonary arterial hypertension (PAH) is a rare, deadly and incurable condition. 1 With a five-year
survival rate below 60%, the outcome of this disease is not any better than that of many cancers. 1,2
However, numerous treatment options are currently available: more than 20 randomised
controlled trials (RCTs) have been conducted over the past 10 years, allowing for the approval of
10 PAH-specific drugs by regulatory agencies worldwide. 1,2 In addition, the recent completion
of four event-driven RCTs geared the management of PAH towards a new era. 3–6 PAH is therefore
one of the very few rare conditions for which international practice guidelines were established
more than 10 years ago. In 2015, the European Society of Cardiology and the European Respiratory
Society (together with the International Society for Heart and Lung Transplantation) joined forces
to revise previous guidelines and present the most recent standards for the management of PAH. 1
Three major changes warrant special attention.
Received: 8 July 2016
Published Online: 12 August 2016
Citation: European Respiratory & Pulmonary Diseases,
2016;2(2):50–1 Corresponding Author: Jean-Luc Vachiery,
Department of Cardiology, CUB – Hopital Erasme,
808 Route de Lennik 1070 – Brussels, Belgium.
The first change is risk stratification, which has been proposed as the gatekeeper to the treatment
algorithm. Such an essential exercise requires careful assessment and allows clinicians to stratify
individual patients based on three factors:
1. Clinical, which includes New York Heart Association (NYHA) functional class and signs of right
2. Exercise capacity, using either the six-minute walking distance (6MWD) test or the more
sophisticated cardiopulmonary exercise test; and
3. Right ventricular function, with special attention to invasive haemodynamics.
Up to 14 meaningful, easily retrievable variables are considered in this analysis to establish whether
the one-year mortality risk is low (<5%), intermediate (5–10%) or high (>10%). This evaluation is
recommended both at baseline (in treatment-naïve patients) and during follow up (to demonstrate
inadequate clinical response).
The second change is a new strategy-oriented treatment algorithm, moving away from a more
traditional drug-driven standard. This algorithm reflects an important paradigm shift in the
management of PAH. There is indeed little question that combination therapy is effective in PAH.
Recently published RCTs demonstrate that adding a second agent improves exercise capacity
(by 6MWD) in patients receiving riociguat 7 (a soluble guanalyte cyclase stimulator, GCs) or
macitentan 3 (an endothelin receptor antagonist [ERA]), and delays clinical worsening in patients
receiving macitentan 3 or selexipag 5 (a prostacyclin receptor agonist). In newly diagnosed patients,
combination therapy with ambrisentan (an ERA) and tadalafil (a phosphodiesterase type 5 inhibitor,
PDE5i) delays time to clinical worsening compared with monotherapy with either compound. 4
Finally, patients presenting severe, high-risk PAH appear to benefit from a combination of parenteral
prostacyclin and oral agents. 1 Therefore, a sound strategy would favour initial combination therapy
in patients with intermediate or high risk, the latter including a parenteral prostacyclin.
50 TOU C H ME D ICA L ME D IA