Low-risk profile in pulmonary arterial hypertension patients predicts better survival
A comprehensive risk stratification at early follow-up determines prognosis in pulmonary arterial hypertension
Despite advances in drug therapy that target the endothelin, nitric oxide and prostacyclin pathways, pulmonary arterial hypertension (PAH) has still a poor prognosis [1-3]. Measures at baseline and during follow-up that reflect right ventricular performance, predict outcome [3-5]. Treatment protocols advocate a goal-oriented approach, meaning to achieve a low-risk profile preferably based on functional class (FC), exercise capacity and right ventricular function, which is included in a risk assessment instrument presented in the ESC/ERS guidelines as of 2009 [6,7].
It is possible that variables that are included in this risk assessment instrument predict prognosis during follow-up, however this is incompletely validated (level of evidence C) [4,5]. The goal of this study was to test the discriminatory ability of the risk assessment instrument, using the Swedish PAH register (SPAHR, started in 2008 ), and to explore the potential prognostic advantage of a low-risk profile at follow-up which was performed within one year from baseline. For this, 7 variables per patient were assessed at baseline and 5 during follow-up. The study included 261 patients with idiopathic PAH (IPAH), 7 with familiar PAH (FPAH), 162 with connective tissue disease-associated PAH (APAH-CTD), 67 with coronary heart disease-associated PAH (APAH-CHD), 16 with drugs- and toxins-induced PAH, 3 with HIV-associated PAH and 14 with portal hypertension-associated PAH. Median time to first follow-up was 4 months and total follow-up 27 months.
- At baseline, low-risk, intermediate-risk and high-risk corresponded to 23%, 67% and 10% of patients respectively. Age was on average lower in the low-risk group compared to intermediate (P<0.001) and high-risk (P=0.004) groups.
- At follow-up, intermediate-risk and high-risk corresponded to 29%, 60% and 11% of patients respectively. Also now, age was on average lower in the low-risk group compared to intermediate (P<0.001) and high-risk groups (P<0.001).
- Survival after 1, 3 and 5 years based on baseline risk groups were 99, 95 and 85% respectively for the low-risk group, 83, 67 and 52% respectively for the intermediate-risk group and 74, 51 and 35% for the high-risk group (P<0.001 for difference between risk groups).
- Survival after 1, 3 and 5 years based on follow-up risk groups were 99, 97 and 92% respectively for the low-risk group, 91, 73 and 56% respectively for the intermediate-risk group and 27, 25 and 6% for the high-risk group (P<0.001 for difference between risk groups).
- Survival for patients that remained in the low-risk group after 1, 3 and 5 years was 100, 98 and 89% respectively. This was 98, 96 and 96% for those who improved to low-risk. Accordingly, for those who remained in the intermediate-risk of high-risk groups survival was 90, 68 and 50% after 1, 3 and 5 years respectively and 81, 60 and 43% for those who worsened to intermediate or high-risk.
- After multivariable correction (age, sex and PAH subsets), mortality risk was reduced for patients in the low-risk group at follow-up (HR 0.2, 95% CI 0.1-0.4, P<0.001).
- Survival was also better for patients with a higher proportion of variables that were categorized as low-risk.
These results support the use of comprehensive risk assessments and goal-oriented treatment approach towards a low-risk profile, as proposed by the ESC/ERS guidelines 2015. Moreover, the fact that only 29% of patients were in the low-risk group at follow-up, urges for better treatments and treatment strategies in general. Furthermore, the risk assessment successfully discriminates patients with better or worse outcome both at baseline and at follow-up, in which determination at follow-up better predicts long-term outcome.