European journal of clinical investigation
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Eur. J. Clin. Invest. · Sep 2006
Bosentan therapy of pulmonary arterial hypertension in connective tissue diseases.
Pulmonary arterial hypertension (PAH) is a life-threatening and debilitating complication of several connective tissue diseases. We aimed to evaluate the effects of long-term treatment with bosentan, an oral dual endothelin ET(A)/ET(B) receptor antagonist, in a cohort of patients with PAH related to connective tissue diseases. ⋯ Long-term treatment with bosentan was effective in improving exercise capacity and pulmonary haemodynamics in patients with PAH related to connective tissue diseases.
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Eur. J. Clin. Invest. · Sep 2006
Randomized Controlled TrialSurvival in patients with pulmonary arterial hypertension treated with first-line bosentan.
Pulmonary arterial hypertension (PAH) is a devastating disease of the small pulmonary arteries and arterioles, characterized by intimal fibrosis, medial hypertrophy and plexiform lesions. When untreated both the idiopathic form (IPAH, formerly termed primary pulmonary hypertension, PPH) and PAH related to various other conditions such as scleroderma (SSc) often take a progressive course with high mortality. There is ongoing search for disease-specific treatments that are able to improve survival in these patients. The oral dual endothelin (ET(A)/ET(B)) antagonist bosentan has been shown to improve exercise capacity, time to clinical worsening, haemodynamics and quality of life in short-term studies. ⋯ The present analyses suggest that first-line bosentan therapy, followed by the addition of other disease-specific therapies as required, improves survival in patients with advanced PAH.
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Eur. J. Clin. Invest. · Sep 2006
Autoantibody against beta1-adrenergic receptor and left ventricular remodeling changes in response to metoprolol treatment.
Autoantibodies specific for the beta(1)-adrenoceptor (beta(1)-AR) have been implicated in the pathology of congestive heart failure (CHF). We hypothesized that the presence of autoantibodies against beta(1)-AR (anti-beta(1)-AR) is associated with left ventricular (LV) remodelling in response to metoprolol. Synthetic beta(1)-AR peptides served as the target antigen in an ELISA (enzyme-linked immunosorbent assay) were used to screen the sera of 106 CHF patients. ⋯ Response to target metoprolol dose occurred more rapidly in (+) anti-beta(1)-AR than (-) anti-beta(1)-AR of CHF patients (67.5 +/- 2.4 vs. 100.8 +/- 3.0 days, P < 0.01). These results demonstrated that CHF patients with (+) anti-beta(1)-AR had greater improvements in LV remodelling and heart function by metoprolol as compared to (-) anti-beta(1)-AR patients. Moreover, patients with (+) anti-beta(1)-AR have better tolerance to metoprolol therapy than patients without anti-beta(1)-AR.
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Eur. J. Clin. Invest. · Sep 2006
First experience with an oral combination therapy using bosentan and sildenafil for pulmonary arterial hypertension.
New oral substances such as beraprost, bosentan and sildenafil have proven effective in different forms of pulmonary arterial hypertension (PAH), both alone and in combination with standard treatment such as intravenous and inhaled prostacyclins. However, there are few reports so far on the effect of a combination of exclusively oral substances. In this paper, we present our initial findings of treatment using a combination of these oral substances in a heterogeneous group of patients with different forms of PAH. ⋯ In our patient group, a combination of oral bosentan and sildenafil proved to be safe and effective. Clearly, randomized, double-blind, placebo-controlled studies are warranted to define the role and type of combination therapies in PAH.