Abstract: Poster Presentations |


Tomas Pulido, MD*; Ivonne Roquet, MD; Rocio Gutiérrez, RN; Tania Rueda, MD; Gabriel Pérez, MD; Ma. Teresa Miranda, RN; Efrén Santos, MD; Héctor Peña, MD; Julio Sandoval, MD
Author and Funding Information

Instituto Nacional de Cardiologia, Ignacio Chávez, Mexico City, Mexico


Chest. 2008;134(4_MeetingAbstracts):p161003. doi:10.1378/chest.134.4_MeetingAbstracts.p161003
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PURPOSE: Sitaxsentan is a selective endothelin-A receptor antagonist approved for the treatment of pulmonary arterial hypertension (PAH). As an inhibitor of the cytochrome 2C9 enzyme, sitaxsentan inhibits the metabolism of warfarin, resulting in a need for routine measurement and adjustment of warfarin doses when both drugs are co-administered. In Mexico and other countries including Spain and Portugal, the vitamin K antagonist acenocoumarol is used in preference to warfarin. Here we report on the long-term effects on bleeding of acenocoumarol co-administered with sitaxsentan in a subset of patients enrolled in STRIDE-3.

METHODS: STRIDE-3 is an ongoing, long-term, open-label trial, evaluating the safety and efficacy of sitaxsentan 100mg qd in PAH. Information on bleeding events was collected prospectively, including type of event, severity, anticoagulant use and investigator attribution of causality. Coagulation tests were performed monthly. A clinically significant interaction was defined as an international normalized ratio (INR) ≥4.0, or any minor bleeding event.

RESULTS: Of 55 patients enrolled in STRIDE-3 in our department, two received no anticoagulant therapy, two warfarin and 51 acenocoumarol. Average follow-up was 148±54weeks. The average dose of anticoagulant therapy was 3.9±1.3mg (range 1.5–7mg/week). At baseline, the average INR was 1.8±0.8. Following treatment, an INR≥4 in at least one INR determination, was observed in 26 patients (n=18,idiopathic PAH [IPAH]; n=8,PAH associated with connective tissue disease [CTD]), of which none had a clinically significant bleeding event. Dose reductions in acenocoumarol were performed to adjust a target INR between 1.6–2.0 (average dose reduction=80% of regular dose in patients on acenocoumarol). Few, minor bleeding events of nose bleeds or gingivitis were observed (n=2,IPAH; n=5,CTD-PAH). Two patients with IPAH died, which in both cases were not considered by the investigator to be drug related.

CONCLUSION: While it is recognized that sitaxsentan affects the metabolism of vitamin K antagonists, no clinically significant bleeding events were recorded with co-administration of sitaxsentan and acenocoumarol in these patients.

CLINICAL IMPLICATIONS: These results suggest that co-administration of sitaxsentan and acenocoumarol is clinically manageable and well tolerated.

DISCLOSURE: Tomas Pulido, Grant monies (from industry related sources) The author has been a principal investigator for some of the STRIDE studies and his institution has received research grants from Encysive.; No Product/Research Disclosure Information

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