Data from PHAROS Trial Reveals Danger of Poorer Outcomes for Scleroderma Patients At-Risk of PH

Alice Melão, MSc avatar

by Alice Melão, MSc |

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PHAROS trial outcome

Patients with systemic sclerosis (SSc) at risk of having pulmonary hypertension (PH) also have similar risk factors for a poorer outcome as patients with SSc-PH and SSc-pulmonary arterial hypertension (PAH), a study shows.

Being male, having accumulation of fluids around the heart, low oxygen desaturation during exercise, and reduced capacity to clear carbon monoxide (CO) in the lungs, contribute to an increased likelihood of mortality in these patients at-risk for PH.

Those findings were reported in the study “Risk Factors for Mortality and Cardiopulmonary Hospitalization in Systemic Sclerosis Patients At Risk for Pulmonary Hypertension, in the PHAROS Registry,” published in The Journal of Rheumatology.

SSc, also known as scleroderma, is an autoimmune disease characterized by chronic inflammation and increased deposits of collagen within the skin and internal organs, leading to scarring and harder tissues. Pulmonary involvement in SSc is associated with severe complications including PAH, which affects about 8-12% of SSc patients. PAH and interstitial lung disease (ILD) are the leading causes of death among SSc patients.

To better understand disease progression in SSc patients at risk of PH, researchers reviewed the clinical records of 236 at-risk patients who were included in the PHAROS registry trial (NCT00377949). Among this group, 35 patients developed PH as determined by right heart catheterization (RHC) after entering the study.

Patients were defined as being at risk of having PH if they had a systolic pulmonary arterial pressure (sPAP) higher than 40 mmHg, or reduced capacity to clear carbon monoxide levels — as determined by the diffusing capacity of the lungs for carbon monoxide (DLCO) bellow 55% — or reduced respiratory capacity.

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Those who developed PH initially were found to have significantly higher mean values of sPAP, and reduced exercise capacity (determined by the 6-minute walk test). While oxygen saturation at rest was similar in both groups of patients, those who develop PH experienced oxygen desaturation (a drop in blood’s oxygen level) more frequently during exercise.

During four years of follow-up, 32 deaths were reported, of which 25 were patients who did not develop PH. Among those deaths, 36% were due to cardiopulmonary-related reasons, and 64% were unrelated to SSc, including infection and cancer. The remaining seven cases, which occurred in the group that developed PH, 75% were due to cardiopulmonary complications, and 25% were due to other causes, including infection.

In general, patients identified as being at risk of PH had 2.99 times increased risk of death, compared to those who did not undergo RHC treatment at the beginning of the study. Further analysis revealed that, in the at-risk population, males had a 4.72-times increased risk of overall mortality. Also, low pulmonary function test readings, anemia, fluid accumulation around the heart (pericardial effusion), and low oxygen desaturation during exercise were associated (respectively, by category), with a 2.07-, 3.76-, 5.32-, and 5.39-fold increased risk of death.

Overall, the team concluded: “Risk factors for worse outcome in those patients with SSc at risk for PH were similar to others with confirmed SSc-PH and SSc-PAH. Male sex, %DLCO [less than] 50%, exercise oxygen desaturation, and the presence of pericardial effusions in those at risk for PH were independently associated with higher mortality.”

“Patients with these risk factors should undergo RHC and receive appropriate intervention if PH is confirmed,” the researchers advised.