Effect of bosentan in pulmonary hypertension development in systemic sclerosis patients with digital ulcers

Abstract

Systemic sclerosis is a disease where microcirculation damage is critical in their beginning and vascular complications have similar pathogenic findings. Digital ulcers are a frequent complication in systemic sclerosis patients and pulmonary hypertension is one of the leading causes of death. The use of bosentan has been shown to be useful for the treatment of pulmonary arterial hypertension and to prevent new digital ulcers. However, is unknown if bosentan can prevent pulmonary hypertension. Our objective was to determine if bosentan is useful to prevent pulmonary hypertension in SSc patients. A retrospective study in 237 systemic sclerosis patients with digital ulcers history treated or not with bosentan to prevent it was made. We analyzed the occurrence of pulmonary hypertension defined by an echocardiogram pulmonary arterial pressure > 40 mmHg in the entire cohort. Demographic, clinical, and treatment variables were recorded for all patients. Statistical significance was denoted by p values < 0.05. Fifty-nine patients were treated with bosentan a median of 34 months. 13.8% of treated patients had pulmonary hypertension vs 23.7% of untreated patients (p 0.13) during the follow up. In multivariate analysis patients not treated with bosentan had 3.9fold-increased risk of pulmonary hypertension compared with patients under bosentan treatment (p < 0.02). Moreover the percentage carbon monoxide diffusing capacity (DLCO) in bosentan treated patients did not decrease from baseline to the end of follow-up (61.8±14% vs 57±20.1%, p = 0.89). We concluded that Systemic sclerosis patients with digital ulcers treated with bosentan seems to have less risk to develop pulmonary hypertension and to stabilize DLCO

May Combination Therapy with Endothelin Receptor Antagonist and PDE5 Inhibitors Prevent Echocardiographic Findings Suspicious for PAH? Description of a Real-Life Case Series

“…However, to our knowledge few studies evaluated the incidence of new PAH cases in SSc patients treated with vasoactive drugs because of the presence of DUs. Castellvì et al [21] conducted a retrospective case-control study in 237 SSc patients with previous history of DUs and compared the occurrence of new PH echocardiographic diagnosis in patients treated (n=59) and not-treated (n=163) with bosentan for at least one month. The median treatment duration was of 34 (95% CI 5-59) months.…”

Systemic Sclerosis-Associated Pulmonary Arterial Hypertension: From Bedside to Bench and Back Again

“…In another study, Bosetan did not improve the frequency, duration, pain, or severity of Raynaud's phenomenon, but did significantly improved the functional scores compared to placebo [168]. While no prospective studies have demonstrated efficacy in SSc-PAH, a retrospective study of patients on bosentan for ulcers revealed a significant decrease in PAH incidence [169].…”

Kidney Involvement in Systemic Sclerosis

“…Significant change was observed on skin fibrosis, but not on lung involvement [ 84 ]. Bosentan, a dual endothelin-receptor antagonist, has been shown to be useful for the treatment of pulmonary arterial hypertension and to prevent new digital ulcers [ 85 , 86 ]. Sildenafil may reduce proinflammatory activation induced by oxidative stress and can improve the microvascular blood flow in patients with SSc [ 87 ].…”

“…The same effect has not been observed with ARBs [ 103 ]. Dihydropyridine calcium-channel blockers, such as nifedipine, can also reverse SRC [ 86 , 104 ]. Other therapeutic strategies have been tested; plasma-exchange seems to give some benefits, particularly in patients with SRC and microangiopathy or in subjects intolerant to ACE-inhibitors [ 105 , 106 ].…”