Survival and quality of life in incident systemic sclerosis-related pulmonary arterial hypertension

Abstract

BackgroundPulmonary arterial hypertension (PAH) is a leading cause of mortality in systemic sclerosis (SSc). We sought to determine survival, predictors of mortality, and health-related quality of life (HRQoL) related to PAH in a large SSc cohort with PAH.MethodsWe studied consecutive SSc patients with newly diagnosed (incident) World Health Organization (WHO) Group 1 PAH enrolled in a prospective cohort between 2009 and 2015. Survival methods were used to determine age and sex-adjusted standardised mortality ratio (SMR) and years of life lost (YLL), and to identify predictors of mortality. HRQoL was measured using the Short form 36 (SF-36) instrument.ResultsAmong 132 SSc-PAH patients (112 female (85%); mean age 62 ± 11 years), 60 (45.5%) died, with a median (±IQR) survival time from PAH diagnosis of 4.0 (2.2–6.2) years. Median (±IQR) follow up from study enrolment was 3.8 (1.6–5.8) years. The SMR for patients with SSc-PAH was 5.8 (95% CI 4.3–7.8), with YLL of 15.2 years (95% CI 12.3–18.1). Combination PAH therapy had a survival advantage (p < 0.001) compared with monotherapy, as did anticoagulation compared with no anticoagulation (p < 0.003). Furthermore, combination PAH therapy together with anticoagulation had a survival benefit compared with monotherapy with or without anticoagulation and combination therapy without anticoagulation (hazard ratio 0.28, 95% CI 0.1–0.7). Older age at PAH diagnosis (p = 0.03), mild co-existent interstitial lung disease (ILD) (p = 0.01), worse WHO functional class (p = 0.03) and higher mean pulmonary arterial pressure at PAH diagnosis (p = 0.001), and digital ulcers (p = 0.01) were independent predictors of mortality.ConclusionsDespite the significant benefits conferred by advanced PAH therapies suggested in this study, the median survival in SSc PAH remains short at only 4 years.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1341-x) contains supplementary material, which is available to authorized users.

Cost savings with a novel algorithm for early detection of systemic sclerosis‐related pulmonary arterial hypertension: alternative scenario analyses

“…Pulmonary arterial hypertension (PAH) is a leading cause of death in SSc, affecting approximately 12% of patients . Recent advances in therapy for PAH delay disease progression, reduce hospitalisations and improve survival, and there is evidence that earlier detection of PAH and initiation of treatment has beneficial effects on functional capacity and survival . However, early detection of PAH can be challenging as the disease is often clinically silent early in its course, eventually presenting with non‐specific symptoms of dyspnoea, fatigue and decreased exercise tolerance, at which time there has already been substantial loss of pulmonary vascular reserve.…”

“…1 Recent advances in therapy for PAH delay disease progression, reduce hospitalisations and improve survival, 2,3 and there is evidence that earlier detection of PAH and initiation of treatment has beneficial effects on functional capacity and survival. 4,5 However, early detection of PAH can be challenging as the disease is often clinically silent early in its course, eventually presenting with non-specific symptoms of dyspnoea, fatigue and decreased exercise tolerance, at which time there has already been substantial loss of pulmonary vascular reserve. Regular screening has been shown to detect PAH in patients earlier than in the course of routine clinical practice; 6 this has led to the recommendation for annual screening for all patients with SSc.…”

Pulmonary arterial hypertension associated with connective tissue diseases: A review focusing on distinctive clinical aspects

“…Calcium channel blockers may not be recommended as a vasodilator therapy for CTD‐PAH since acute vasoreactivity during haemodynamic testing is <1% in SSc‐PAH patients . Anticoagulation in CTD‐PAH remains controversial because there have been conflicting results on a survival benefit …”

“…A recent study by Michelfelder et al compared 27 SSc‐PAH patients with 24 SSc‐PAH patients coexisting ILD with mean FVC of 60 (±14) % and found a lower survival rate in SSc‐PAH‐ILD patients but did not find a difference in haemodynamic measurements, NT‐proBNP levels, FVC/DL CO ratio, 6MWD, WHO FC, presence of pericardial effusion and scleroderma‐specific autoantibody levels. The impact of ILD, even with FVC of >60%, on the mortality of SSc‐PAH patients was shown in another cohort study . Given the high‐mortality rate and the possible unwanted effect of aggressive vasodilation through an increase of ventilation‐perfusion mismatch, the treatment regimen for SSc‐PAH coexisting ILD, particularly moderate‐to‐severe ILD, may differ from that for other PAH but needs further studies to be established.…”

“…The impact of ILD, even with FVC of >60%, on the mortality of SSc-PAH patients was shown in another cohort study. 51 Given the high-mortality rate and the possible unwanted effect of aggressive vasodilation through an increase of ventilation-perfusion mismatch, the treatment regimen for SSc-PAH coexisting ILD, particularly moderate-to-severe ILD, may differ from that for other PAH but needs further studies to be established.…”