Elderly patients diagnosed with idiopathic pulmonary arterial hypertension: Results from the COMPERA registry,☆☆

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Abstract

Background

Originally reported to occur predominantly in younger women, idiopathic pulmonary arterial hypertension (IPAH) is increasingly diagnosed in elderly patients. We aimed to describe the characteristics of such patients and their survival under clinical practice conditions.

Methods

Prospective registry in 28 centers in 6 European countries. Demographics, clinical characteristics, hemodynamics, treatment patterns and outcomes of younger (18–65 years) and elderly (> 65 years) patients with newly diagnosed IPAH (incident cases only) were compared.

Results

A total of 587 patients were eligible for analysis. The median (interquartile, [IQR]) age at diagnosis was 71 (16) years. Younger patients (n = 209; median age, 54 [16] years) showed a female-to-male ratio of 2.3:1 whereas the gender ratio in elderly patients (n = 378; median age, 75 [8] years) was almost even (1.2:1). Combinations of PAH drugs were widely used in both populations, albeit less frequently in older patients. Elderly patients were less likely to reach current treatment targets (6 min walking distance > 400 m, functional class I or II). The survival rates 1, 2, and 3 years after the diagnosis of IPAH were lower in elderly patients, even when adjusted for age- and gender-matched survival tables of the general population (p = 0.006 by log-rank analysis).

Conclusions

In countries with an aging population, IPAH is now frequently diagnosed in elderly patients. Compared to younger patients, elderly patients present with a balanced gender ratio and different clinical features, respond less well to medical therapy and have a higher age-adjusted mortality. Further characterization of these patients is required.

Clinical trials registration: NCT01347216.

Introduction

The term pulmonary arterial hypertension (PAH) describes a group of diseases characterized by pre-capillary pulmonary hypertension in the absence of known causes such as lung disease or chronic thromboembolic disease [1], [2]. PAH may occur in association with various diseases including congenital heart disease, connective tissue disease, portal hypertension and infection with the human immunodeficiency virus. Some cases are related to the use of appetite-suppressants, some are heritable, but the majority are idiopathic in origin (IPAH) [3].

IPAH is a rare disease, which has classically been described as affecting young women. It has an incidence between 2.4 and 7.1 cases per million population [4], [5]. As often the case with rare conditions, registries have made important contributions to our current understanding of this disease. One of the first was the National Institutes of Health (NIH) registry of primary pulmonary hypertension. This registry assembled data between 1981 and 1985 when no targeted drug therapies for PAH were available [6], [7]. In this registry, the mean age at diagnosis was 36 years, 59% of the patients were female, and the survival rates at 1 and 3 years were 68% and 48%, respectively [6], [7].

With the emergence of effective therapies, [1], [8] the awareness of PAH has risen among patients and physicians. At the same time, the population of most western countries is aging. Recent data from Europe and the US suggest that the demographics of patients diagnosed with IPAH are changing [9], [10], [11]. Most importantly, there has been an increase in the age of patients diagnosed with IPAH and nowadays it is not uncommon to see patients being diagnosed with IPAH in their seventies, eighties, or even nineties [4], [10], [12]. In the more recent US-based Registry to evaluate early and long-term pulmonary arterial disease management (REVEAL), the mean age at diagnosis was 50 years, and 5% of the patients were diagnosed at ≥ 75 years of age [12]. Comparable data were reported from the French National PAH registry, where the average age at diagnosis of IPAH was 52 years [4]. It is unclear whether elderly patients diagnosed with IPAH have the same clinical features as younger patients.

In June 2007, we launched COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension), a European-based registry on medical therapies for pulmonary hypertension. COMPERA recruits patients from pulmonary hypertension centers in Austria, Belgium, Germany, Italy, Netherlands, Switzerland, and United Kingdom. The first interim analyses from this database showed that the mean age of the enrolled patients was 65 years [13]. These numbers proved robust when more patients were enrolled into the registry over the ensuing years.

We therefore decided to investigate the characteristics of elderly patients diagnosed with IPAH. The objective of the present analysis was to compare older and younger patients in terms of demographics, hemodynamics, clinical presentation, treatments and survival.

Section snippets

Setting and participants

COMPERA is an investigator-initiated, on-going, multinational, registry of patients receiving targeted medical therapy with prostacyclin analogs, endothelin receptor antagonists, or phosphodiesterase-5 (PDE-5) inhibitors for any type of pulmonary hypertension. The project is endorsed by the German Societies of Cardiology and Respiratory Medicine. It is planned to enroll 4000 patients and follow them for a minimum of 3 years. The primary outcome is survival. In order to avoid selection bias,

Patient characteristics at time of diagnosis

As of November 19th 2011, a total of 2654 patients with pulmonary hypertension had been enrolled into the COMPERA registry (87% by German centers). After exclusion of patients not fulfilling the inclusion criteria for the present analysis, 587 patients with IPAH were eligible for the present analysis; n = 209 in the younger (18–65 yr) and n = 378 in the older (> 65 yr) group (Fig. 1). The survival status of almost all patients could be ascertained except for 20 (3.4%) patients who were lost to

Discussion

Key findings from the present analysis include: (1) the changing characteristics of patients diagnosed with IPAH and the predominance of elderly patients; (2) the differences in the invasive hemodynamic profile between elderly and younger patients; (3) the widespread use of combination therapy with at least two PAH drugs in clinical practice; and (4) the apparently poorer age-adjusted outcome of elderly compared to younger patients.

The present study confirms previous observations that the

Conclusions

The demographic pattern of patients diagnosed with IPAH is changing, at least in some European countries. The disease is increasingly diagnosed in older age where men and women are almost equally affected. Physicians, especially general practitioners, cardiologists and pulmonologists should be aware of this trend since published data from previous clinical studies have been assimilated in patients with different characteristics. The hemodynamic profile of elderly patients with IPAH differs from

Disclosures

MM Hoeper has received speaker fees and honoraria for consultations from Actelion, Bayer, Gilead, GSK, Lilly, Novartis and Pfizer.

D Huscher has no conflicts of interest.

HA Ghofrani has received honorariums for consultations and/or speaking at conferences from Bayer HealthCare AG, Actelion, Encysive, Pfizer, Ergonex, Lilly, and Novartis. He is a member of the advisory boards for Bayer HealthCare AG, Pfizer, GSK, Actelion, Lilly, Merck, Encysive, and Ergonex. He has also received governmental

Acknowledgments

The authors wish to thank the following individuals for their contribution:

R Wipplinger, Medical University Heidelberg, Germany

Dr C Neurohr, University of Munich, Grosshadern, Germany

Dr M Claussen, Grosshansdorf, Germany

Prof C Kaehler, University of Innsbruck, Austria

Dr C Schumann, University of Ulm, Germany

Dr M D'Alto, Ospedale Monaldi, Napoli, Italy

Dr L Scelsi, Fondazione IRCCS San Matteo, Pavia, Italy

Dr. J Pepke-Zaba, Cambridge, United Kingdom

Prof F Grimminger MD, Dr Melanie Thamm MD, Dr

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    Authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

    ☆☆

    The registry is investigator-initiated and supported by unrestricted grants from Actelion, AOP Orphan, Bayer, GSK, Lilly, Novartis, Pfizer.

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