Effects of the thromboxane synthetase inhibitor and receptor antagonist terbogrel in patients with primary pulmonary hypertension

Langleben, David; Christman, Brian W.; Barst, Robyn J.; Dias, Virgil C.; Galiè, Nazzareno; Higenbottam, T. W.; Kneußl, Meinhard; Korducki, L.; Naeije, Robert; Riedel, Axel; Simonneau, Gérald; Hirsch, Andrew; Rich, Stuart; Robbins, Ivan M.; Oudiz, Ronald J.; McGoon, Michael D.; Badesch, David B.; Levy, Robert D.; Mehta, Sanjay; Seeger, Werner; Solèr, Markus

doi:10.1067/mhj.2002.121806

Cited by 74 publications

(49 citation statements)

References 14 publications

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“…42 However, a larger trial involving a thromboxane inhibitor, terbogrel, had to be interrupted prematurely because of severe leg pain in the treatment group. 43 Nevertheless, significant inhibition of thromboxane in this study suggests a potential therapeutic role for a thromboxane inhibitor with a better safety profile.…”

Section: Thromboxanementioning

confidence: 99%

Endothelial Dysfunction in Pulmonary Hypertension

2004

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Section: Thromboxanementioning

confidence: 99%

Endothelial Dysfunction in Pulmonary Hypertension

2004

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“…The Human PSelectin immunoassay kit (R&D Systems Inc., Minneapolis, MN, USA) was used with protocols provided by the manufacturer. Serum TxB 2 and urinary levels of Tx-M and PGI-M were analysed using stable isotope dilution methodology with gas chromatography/mass spectrometry, as previously described [9].…”

Section: Methodsmentioning

confidence: 99%

“…Although platelets are the predominant source of TxA 2 in healthy volunteers [7,8], the source in IPAH is unknown. Due to the known adverse effects of TxA 2 on the pulmonary vasculature, investigators have previously attempted to treat IPAH with Tx synthase inhibitors, however, side effects and lack of efficacy limited these studies [9,10]. The failure of Tx synthase inhibitors in IPAH parallels their ineffectiveness in other cardiovascular diseases characterised by increased TxA 2 and platelet aggregation, which are, on the contrary, effectively treated with antiplatelet agents.…”

mentioning

confidence: 99%

A study of aspirin and clopidogrel in idiopathic pulmonary arterial hypertension

et al. 2006

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Idiopathic pulmonary arterial hypertension (IPAH) is characterised by in situ thrombosis and increased thromboxane (Tx) A 2 synthesis; however, there are no studies of antiplatelet therapy in IPAH. The aim of the current study was to determine the biochemical effects of aspirin (ASA) and clopidogrel on platelet function and eicosanoid metabolism in patients with IPAH.A randomised, double-blind, placebo-controlled crossover study of ASA 81 mg once daily and clopidogrel 75 mg once daily was performed. Plasma P-selectin levels and aggregometry were measured after exposure to adenosine diphosphate, arachidonic acid and collagen. Serum levels of TxB 2 and urinary metabolites of TxA 2 and prostaglandin I 2 (Tx-M and PGI-M, respectively) were assessed.A total of 19 IPAH patients were enrolled, of whom nine were being treated with continuous intravenous epoprostenol. ASA and clopidogrel significantly reduced platelet aggregation to arachidonic acid and adenosine diphosphate, respectively. ASA significantly decreased serum TxB 2 , urinary Tx-M levels and the Tx-M/PGI-M ratio, whereas clopidogrel had no effect on eicosanoid levels. Neither drug significantly lowered plasma P-selectin levels. Epoprostenol use did not affect the results.In conclusion, aspirin and clopidogrel inhibited platelet aggregation, and aspirin reduced thromboxane metabolite production without affecting prostaglandin I 2 metabolite synthesis. Further clinical trials of aspirin in patients with idiopathic pulmonary arterial hypertension should be performed.

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“…The effects of terbogrel were tested in a multicentre, randomised, placebo-controlled, 12-week study in NYHA class II and III PPH patients [27]. Although the planned enrolment was 135 patients, the study was halted after only 71 patients had been randomised, due to the unforeseen side-effect of leg pain, which occurred almost exclusively in terbogrel-treated patients.…”

Section: Terbogrel Studymentioning

confidence: 99%

“…The new compounds that were tested in these studies are the thromboxane inhibitor terbogrel [27], the prostacyclin analogues treprostinil (subcutaneous) [28], beraprost (oral) [29] and iloprost (inhaled) [30], and the endothelin receptor antagonist bosentan [31,32].…”

mentioning

confidence: 99%

The new clinical trials on pharmacological treatment in pulmonary arterial hypertension

Galiè¹,

Manes²,

Branzi³

2002

Eur Respir J

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The new clinical trials on pharmacological treatment in pulmonary arterial hypertension. N. Galiè, A. Manes, A. Branzi. #ERS Journals Ltd 2002. ABSTRACT: Past medical therapy for pulmonary arterial hypertension included the use of calcium-channel antagonists in acute vasoreactive subjects and oral anticoagulants and continuous intravenous administration of epoprostenol in the more severe cases. Recently, the thromboxane inhibitor terbogrel, the prostacyclin analogues treprostinil, beraprost and iloprost, and the endothelin receptor antagonist bosentan have been tested in clinical trials in w1,100 patients.Except for terbogrel, all compounds improved the mean exercise capacity by different degrees, as assessed by the 6-min walk test. In the evaluation of the clinical relevance of exercise capacity improvements, additional elements need to be considered, such as baseline functional class and concomitant favourable effects on combined clinical events (including hospitalisations, mortality and rescue therapies), quality of life and haemodynamics. No trials have shown effects on mortality, as the study protocols were not designed for assessing this end-point. Each new compound presents side-effects that are unpredictable in the individual patient and require appropriate attention upon treatment initiation and maintenance.These new therapeutic options will be available in the near future and will allow tailoring of the most appropriate treatment to the single patient, according to an individualised benefit-to-risk ratio.

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Effects of the thromboxane synthetase inhibitor and receptor antagonist terbogrel in patients with primary pulmonary hypertension

Cited by 74 publications

References 14 publications

Endothelial Dysfunction in Pulmonary Hypertension

Endothelial Dysfunction in Pulmonary Hypertension

A study of aspirin and clopidogrel in idiopathic pulmonary arterial hypertension

The new clinical trials on pharmacological treatment in pulmonary arterial hypertension

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