Age, risk and outcomes in idiopathic pulmonary arterial hypertension

Abstract

The current European pulmonary hypertension (PH) guidelines recommend a risk-based therapeutic approach to patients with idiopathic pulmonary arterial hypertension (IPAH) [1,2]. The goal is reaching and maintaining a low risk profile. Recent studies from the French PH registry and from the European PH registry COMPERA have confirmed that IPAH patients who meet 3-4 distinct low risk criteria with targeted therapies have 5-year survival rates of 95% or higher [3,4]. Unfortunately, this was accomplished only in 19% of the patients in the French series and 9% of the patients in COMPERA [4,5]. The reasons why the majority of patients fail to reach a low risk profile with targeted therapies have not been fully explored.In this issue of the European Respiratory Journal, HJALMARSSON et al.[6] present data from the Swedish PH registry showing that the likelihood that IPAH patients meet a low risk profile with targeted therapies diminishes with increasing age. Almost 80% of patients aged between 18 and 45 years reached the low risk category with PAH treatment, compared with approximately 20% of patients aged ⩾65 years and less than 10% of patients aged ⩾75 years. Improvements in risk category were rarely observed in patients aged ⩾65 years. Similar data have been recently reported from COMPERA [3]. In the present Swedish series, the 5-year transplantation-free survival decreased from 88% in patients aged 18-45 years to 36% in patients aged ⩾75 years.The high mortality risk of older IPAH patients is probably due to various reasons including comorbidities, unique disease phenotypes, different treatment patterns, and a diminished response to PAH targeted therapies. These factors are tightly interconnected but can be assessed separately. Increasing age and mortality in IPAHThe mean age of patients enrolled between 1981 and 1985 in the US National Institutes of Health (NIH) registry was 36 years at the time of diagnosis; only 9% of the patients were more than 60 years of age [7]. Since then, the age of IPAH patients has increased considerably, at least in Western countries [4,[8][9][10][11]. In Germany, the mean age of patients newly diagnosed with IPAH in 2014 was 65 years [12]. In a recent Swedish registry, the mean age at diagnosis was 69 years [13]. Naturally, older patients have a higher mortality risk in general, but it has already been shown that older patients (>65 years) diagnosed with IPAH have a significantly higher mortality risk than younger patients (18-65 years), even when adjusted for their respective statistical life expectancies [14].

Intravenous treprostinil as an add-on therapy in patients with pulmonary arterial hypertension

“…Age needs to be considered as well, as older patients are less likely to reach a low-risk status than younger patients. 25,26 The median age of the patients in this series was 48 years, which is comparable to other cohorts, 21 but the patients who reached a low-risk profile in this series were younger than the patients who did not (median age, 39 vs 51 years; p = 0.012). Given that almost all patients in the current series had been treated with double or triple combinations of PAH drugs prior to the initiation of intravenous treprostinil, we assume that the overall efficacy of intravenous prostacyclin analogues is limited when this treatment is administered in patients who have already exhausted other treatment options.…”

Characteristics of Japanese elderly patients with pulmonary arterial hypertension

“…Although there were no long-term survivors in the elderly group, there was no significant difference in survival between the elderly and younger groups, in contrast to poorer survival in elderly patients from western countries. 11,12,13 The COMPERA 19 and Swedish studies 15,20,21 (they used WHO-FC, 6MWD, BNP, echocardiography, and hemodynamics as risk criteria) suggested that patients with high risk were older and had a lower survival rate. In the French study, they selected WHO-FC I or II, 6MWD > 440 m, right atrial pressure <8 mmHg, and CI !…”

“…The COMPERA 19 and Swedish studies 15 , 20 , 21 (they used WHO‐FC, 6MWD, BNP, echocardiography, and hemodynamics as risk criteria) suggested that patients with high risk were older and had a lower survival rate. In the French study, they selected WHO‐FC I or II, 6MWD > 440 m, right atrial pressure <8 mmHg, and CI ≥ 2.5 L/min/m 2 as low‐risk criteria.…”

Influence of demographic characteristics on the clinical course and results of therapy in patients with precapillary pulmonary hypertension

“…В этом же регистре у более молодых пациентов с ХТЭЛГ на фоне специфической терапии чаще наблюдалось достижение низкого риска летального исхода [6,26]. Таким образом, высокая смертность у пожилых пациентов с ЛГ, вероятно, может быть связана как с особенностями коморбидного статуса и уникальным фенотипом заболевания, так и разными подходами к лечению и нестандартным ответом на специфическую терапию [27][28][29].…”