Effect of Age on Phenotype and Outcomes in Pulmonary Arterial Hypertension Trials

Rose, Jonathan A.; Cleveland, Jody M.; Rao, Youlan; Minai, Omar A.; Tonelli, Adriano R.

doi:10.1016/j.chest.2015.11.008

Cited by 16 publications

(13 citation statements)

References 29 publications

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“…Few studies have assessed the characteristics of patients with IPAH based on their age [10,26] or the effect of age on treatment response [10,27]. The COMPERA study used a cut-off age of 65 years [10].…”

Section: Discussionmentioning

confidence: 99%

“…In 2016, data from six large randomised controlled trials including patients with IPAH and associated PAH were presented in a meta-analysis [27]. The results indicated that older patients were more often classified into New York Heart Association FC III-IV and had shorter 6MWD, but had better hemodynamic status at baseline than younger patients.…”

Section: Discussionmentioning

confidence: 99%

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Impact of age and comorbidity on risk stratification in idiopathic pulmonary arterial hypertension

et al. 2018

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Recent reports from worldwide pulmonary hypertension registries show a new demographic picture for patients with idiopathic pulmonary arterial hypertension (IPAH), with an increasing prevalence among the elderly.We aimed to investigate the effects of age and comorbidity on risk stratification and outcome of patients with incident IPAH.The study population (n=264) was categorised into four age groups: 18-45, 46-64, 65-74 and ≥75 years. Individual risk profiles were determined according to a risk assessment instrument, based on the European Society of Cardiology and the European Respiratory Society guidelines. The change in risk group from baseline to follow-up (median 5 months) and survival were compared across age groups. In the two youngest age groups, a significant number of patients improved (18-45 years, Z= -4.613, p<0.001; 46-64 years, Z= -2.125, p=0.034), but no significant improvement was found in the older patient groups. 5-year survival was highest in patients aged 18-45 years (88%), while the survival rates were 63%, 56% and 36% for patients in the groups 46-64, 65-74 and ≥75 years, respectively (p<0.001). Ischaemic heart disease and kidney dysfunction independently predicted survival.These findings highlight the importance of age and specific comorbidities as prognostic markers of outcome in addition to established risk assessment algorithms.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Impact of age and comorbidity on risk stratification in idiopathic pulmonary arterial hypertension

et al. 2018

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“…1−7 At least in Western countries, the proportion of patients being diagnosed at a more advanced age and/or with more risk factors for left ventricular diastolic dysfunction is increasing. 8,9 Clinical outcomes are worse in such patients relative to their younger counterparts who have fewer risk factors for left ventricular diastolic dysfunction. 8,9 These observations have led to some uncertainty in how best to categorize and treat these patients based on the current clinical classification of pulmonary hypertension.…”

Section: Introductionmentioning

confidence: 99%

“…8,9 Clinical outcomes are worse in such patients relative to their younger counterparts who have fewer risk factors for left ventricular diastolic dysfunction. 8,9 These observations have led to some uncertainty in how best to categorize and treat these patients based on the current clinical classification of pulmonary hypertension. 10−13 Traditionally, patients with advanced age and/or risk factors for left ventricular diastolic dysfunction have largely been excluded from clinical trials with PAH medications.…”

Section: Introductionmentioning

confidence: 99%

Patients with pulmonary arterial hypertension with and without cardiovascular risk factors: Results from the AMBITION trial

McLaughlin

Vachiéry

Oudiz

et al. 2019

The Journal of Heart and Lung Transplantation

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“…In addition, gender, cardiovascular risk factors and age have recently been identified as potential predictors of therapeutic response. 2 – 5 …”

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confidence: 99%

Novel approach to classifying patients with pulmonary arterial hypertension using cluster analysis

et al. 2017

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Pulmonary arterial hypertension (PAH) patients have distinct disease courses and responses to treatment, but current diagnostic and treatment schemes provide limited insight. We aimed to see if cluster analysis could distinguish clinical phenotypes in PAH. An unbiased cluster analysis was performed on 17 baseline clinical variables of PAH patients from the FREEDOM-M, FREEDOM-C, and FREEDOM-C2 randomized trials of oral treprostinil versus placebo. Participants were either treatment-naïve (FREEDOM-M) or on background therapy (FREEDOM-C, FREEDOM-C2). We tested for association of clusters with outcomes and interaction with respect to treatment. Primary outcome was 6-minute walking distance (6MWD) change. We included 966 participants with 12-week (FREEDOM-M) or 16-week (FREEDOM-C and FREEDOM-C2) follow-up. Four patient clusters were identified. Compared with Clusters 1 (n = 131) and 2 (n = 496), Clusters 3 (n = 246) and 4 (n = 93) patients were older, heavier, had worse baseline functional class, 6MWD, Borg Dyspnea Index, and fewer years since PAH diagnosis. Clusters also differed by PAH etiology and background therapies, but not gender or race. Mean treatment effect of oral treprostinil differed across Clusters 1–4 increased in a monotonic fashion (Cluster 1: 10.9 m; Cluster 2: 13.0 m; Cluster 3: 25.0 m; Cluster 4: 50.9 m; interaction P value = 0.048). We identified four distinct clusters of PAH patients based on common patient characteristics. Patients who were older, diagnosed with PAH for a shorter period, and had worse baseline symptoms and exercise capacity had the greatest response to oral treprostinil treatment.

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Effect of Age on Phenotype and Outcomes in Pulmonary Arterial Hypertension Trials

Cited by 16 publications

References 29 publications

Impact of age and comorbidity on risk stratification in idiopathic pulmonary arterial hypertension

Impact of age and comorbidity on risk stratification in idiopathic pulmonary arterial hypertension

Patients with pulmonary arterial hypertension with and without cardiovascular risk factors: Results from the AMBITION trial

Novel approach to classifying patients with pulmonary arterial hypertension using cluster analysis

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