Changes in REVEAL risk score in patients with pulmonary arterial hypertension treated with macitentan in clinical practice: results from the PRACMA study

Changes in REVEAL risk score in patients with pulmonary arterial hypertension treated with macitentan in clinical practice: results from the PRACMA study

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Escribano-Subias P, López R, Almenar L, Lázaro M, Forn I, Torrent A, Blanco I, Barberà JA; PRACMA investigators.
BMC Pulm Med. 2020 Jun 2;20(1):154. doi: 10.1186/s12890-020-01197-5.
PMID: 32487059

Take Home Points:

  • REVEAL = Registry to Evaluate Early and Long-Term PAH Disease Management.
  • The PRACMA study is a Spanish retrospective, observational analysis of patients with pulmonary hypertension or pulmonary arterial hypertension associated with connective tissue disease or CHD.
  • All patients were treated with macitentan for > 6 months as monotherapy or as part of combined therapy.
  • The REVEAL risk score and risk strata were calculated at the start of macitentan treatment and > 6 months in patients with > 7 out of 12 valid REVEAL components
  • In the final analysis, 57 patients had enough data to calculate a REVEAL score
  • Median time of macitentan treatment was 10.5 months. The mean REVEAL score was 8.7 points at baseline and 7.2 points after > 6 month follow up.
  • REVEAL components which significantly improved with macitentan treatment were WHO class (64% class III at initiation and 24% after > 6 months, p=0.00001); 6 minute walk test (mean change 42m, p<0.01); BNP or NTproBNP (mean change of -157pg/ml and -530 pg./ml, respectively, p<005) and pulmonary vascular resistance (mean change -3.4 WU, p<0.01).
  • Only 12% of patients (n=10) had ACHD.

Dr Damien Cullington

Commentary from Dr. Damien Cullington (Liverpool, UK), section editor of ACHD Journal Watch:  The PRACMA study is a Spanish observational dataset of patients with inherited and acquired pulmonary hypertension (PH) – only 12% of patients in this study had congenital heart disease. 28 PH centres in Spain contributed data between Sept 2016-Sept 2017. This primary aim was to measure change in REVEAL risk score in patients with PH who were started on macitentan treatment.

The REVEAL score (originally published in 2012) is calculated from 12 variables (Figure 1). It is generically used  as a composite measure of disease stability/improvement/deterioration in patients with PH.

In the analysis, ‘incident’ patients were defined as those diagnosed < 6 months prior to starting macitentan. ‘Prevalent’ patients were those diagnosed with PH > 6 months before starting macitentan. The REVEAL risk score was calculated at baseline and at > 6 month time points. Patients were selected with at least 7/12 valid components. Although 88 patients were originally assessed for eligibility for this analysis, only 57 patients of the original group had enough data points to calculate a REVEAL score. The demographics of the baseline dataset are shown in Table 1.

PAH risk score

Patiend Demographics and Disease Characteristics at Baseline


At baseline, the mean REVEAL score was 8.7 points, and at > 6 month time point, had decreased to 7.2 points – the mean change in score was -1.4 (-2.0, -0.9 ) points (p<00001). In the ‘incident’ patient group, the REVEAL score improved in 61% versus, in the ‘prevalent’ group, 56% of patients’ REVEAL scores improved. A more detailed analysis of the change in REVEAL risk score within incident/prevalent groups and according to their mono or combination therapy with macitentan is shown in Table 2. The REVEAL score improved in 57% of patients – 26% had no change and it increased in 16% (Figure 2).

Changes in REVEAL risk score

Evolution of REVEAL risk strata

The mean effect of Macitentan in a aetiologically heterogenous cohort of patients with PH is an improvement functional capacity and objective measures such as 6MWT, natriuretic peptide levels and PVR in patients with PH who are new to treatment (‘incident’) or who are known to have PH and macitentan is introduced either as an add on agent or new treatment (Table 3).

Table 3. Changes in individual REVEAL components at > 6-month time point

changes in individual reveal component


This observational study had very low numbers of ACHD patients and we should not be tempted to draw generic conclusions to then generically treat ACHD-PH patients with macitentan. The MAESTRO study in 2019, which enrolled patients with Eisenmenger syndrome, showed that macitentan had no statistically significant benefit compared to placebo in terms of improving exercise capacity over a 4 month follow up. Further research and longer term follow up will be helpful to guide longer term treatment decisions.


Macitentan is no doubt useful agent in the therapeutic armamentarium to selectively treat patients with PH. The PRACMA study shows that therapeutic improvements are possible in patients either as a mono-agent treatment or as part of a combined regimen – improvements are seen in REVEAL score across all severities of PH. This was a relatively small study group with mixed aetiology of PH and a very small number of patients with ACHD. Extrapolating these results to specifically guide treatment choice in our patient group requires caution and comparative review of other larger studies.