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

Abstract:

BACKGROUND:Circulating mediators, including thromboxane A2, the vasoconstrictor, platelet aggregant, and smooth muscle mitogen, may contribute to the progression of vascular narrowing in primary pulmonary hypertension (PPH). METHODS:To further understand the contribution of thromboxane and to provide novel therapy for PPH, we administered the potent orally active thromboxane synthetase inhibitor and thromboxane receptor antagonist terbogrel for 12 weeks to patients with New York Heart Association functional classification II and III PPH. The study had a multicenter randomized placebo-controlled design. The primary endpoint was a change in the distance walked during 6 minutes. The pharmacologic effects of terbogrel on thromboxane and prostacyclin metabolism also were studied. RESULTS:Although the planned enrollment was 135 patients, the study was halted after only 71 patients had been randomized because of the unforeseen side effect of leg pain, which occurred almost exclusively in patients with terbogrel treatment. Only 52 patients completed the 12-week study, and only 22 patients (31%) were fully compliant with the study medication. The leg pain confounded the primary endpoint of walking distance. On an intention-to-treat analysis, no improvements in 6-minute walk distance or in hemodynamics in patients with terbogrel treatment were seen. However, terbogrel was effective from a pharmacologic standpoint, reducing thromboxane metabolites by as much as 98% (P <.0001), with a modest but statistically insignificant (39%) rise in prostacyclin metabolites. CONCLUSION:Inhibition of thromboxane with an orally active agent is feasible in PPH, but the incidence of severe leg pain with terbogrel precludes its use in this disorder. Similar therapeutic efforts, with other thromboxane inhibitors, should be considered.

journal_name

Am Heart J

journal_title

American heart journal

authors

Langleben D,Christman BW,Barst RJ,Dias VC,Galiè N,Higenbottam TW,Kneussl M,Korducki L,Naeije R,Riedel A,Simonneau G,Hirsch AM,Rich S,Robbins IM,Oudiz R,McGoon MD,Badesch DB,Levy RD,Mehta S,Seeger W,Solèr M

doi

10.1067/mhj.2002.121806

subject

Has Abstract

pub_date

2002-05-01 00:00:00

pages

E4

issue

5

eissn

0002-8703

issn

1097-6744

pii

S0002870302839151

journal_volume

143

pub_type

临床试验,杂志文章,多中心研究,随机对照试验
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    更新日期:2005-05-01 00:00:00

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    更新日期:2019-08-01 00:00:00

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    journal_title:American heart journal

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

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    更新日期:2003-02-01 00:00:00

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    更新日期:1982-08-01 00:00:00

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    pub_type: 杂志文章

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    更新日期:1999-08-01 00:00:00

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    pub_type: 杂志文章

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    更新日期:1984-04-01 00:00:00

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    pub_type: 杂志文章

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    更新日期:1993-11-01 00:00:00

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    journal_title:American heart journal

    pub_type: 临床试验,杂志文章

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    更新日期:1976-10-01 00:00:00

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    pub_type: 杂志文章

    doi:10.1016/j.ahj.2012.06.021

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    更新日期:2012-09-01 00:00:00

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    pub_type: 杂志文章,评审

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    更新日期:1998-06-01 00:00:00

  • Sinus node recovery times following the spontaneous termination of supraventricular tachycardia and following atrial overdrive pacing: a comparison.

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    更新日期:1983-02-01 00:00:00

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    pub_type: 杂志文章,多中心研究,随机对照试验

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    更新日期:2009-05-01 00:00:00

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    更新日期:1993-07-01 00:00:00

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    pub_type: 杂志文章,评审

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