2010 April 02

Residual venous obstruction, alone and in combination with D-dimer, as a risk factor for recurrence after anticoagulation withdrawal following a first idiopathic deep vein thrombosis in the prolong study.

Eur J Vasc Endovasc Surg Start a Discussion »

Apr 022010

Residual venous obstruction, alone and in combination with D-dimer, as a risk factor for recurrence after anticoagulation withdrawal following a first idiopathic deep vein thrombosis in the prolong study.

Eur J Vasc Endovasc Surg. 2010 Mar;39(3):356-65

Authors: Cosmi B, Legnani C, Iorio A, Pengo V, Ghirarduzzi A, Testa S, Poli D, Tripodi A, Palareti G,

OBJECTIVE: This study aims to assess the predictive value of residual venous obstruction (RVO) for recurrent venous thrombo-embolism (VTE) in a study using D-dimer to predict outcome. DESIGN: This is a multicentre randomised open-label study. METHODS: Patients with a first episode of idiopathic VTE were enrolled on the day of anticoagulation discontinuation when RVO was determined by compression ultrasonography in those with proximal deep vein thrombosis (DVT) of the lower limbs. D-dimer was measured after 1 month. Patients with normal D-dimer did not resume anticoagulation while patients with abnormal D-dimer were randomised to resume anticoagulation or not. The primary outcome measure was recurrent VTE over an 18-month follow-up. RESULTS: A total of 490 DVT patients were analysed (after excluding 19 for different reasons and 118 for isolated pulmonary embolism (PE)). Recurrent DVT occurred in 19% (19/99) of patients with abnormal D-dimer who did not resume anticoagulation and 10% (31/310) in subjects with normal D-dimer (adjusted hazard ratio: 2.1; p = 0.02). Recurrences were similar in subjects either with (11%, 17/151) or without RVO (13%, 32/246). Recurrent DVT rates were also similar for normal D-dimer, with or without RVO, and for abnormal D-dimer, with or without RVO. CONCLUSIONS: Elevated D-dimer at 1 month after anticoagulation withdrawal is a risk factor for recurrence, while RVO at the time of anticoagulation withdrawal is not.

PMID: 20034816 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

Factors related to in-hospital heart failure are very different for unstable angina and non-ST elevation myocardial infarction.

Heart Vessels Start a Discussion »

Apr 022010

Factors related to in-hospital heart failure are very different for unstable angina and non-ST elevation myocardial infarction.

Heart Vessels. 2009 Nov;24(6):399-405

Authors: Saejueng B, Yipintsoi T, Chaisuksuwan R, Kehasukcharoen W, Boonsom W, Kanjanavanit R,

Non-ST-elevation myocardial infarction (NSTEMI) and unstable angina (UA) resulted in different degrees of damage to the heart muscle, and yet, when factors related to in-hospital outcomes were examined, these two subsets were often lumped together as non-STelevation acute coronary syndrome. Therefore, we investigated predictors of in-hospital heart failure (HF) in UA and NSTEMI separately. Factors related to HF (Killip > or = 2) were analyzed for NSTEMI and UA in a Thai Acute Coronary Syndrome (ACS) registry conducted in 17 institutions between 2002 and 2005. The registry comprised of 9373 single admissions age 65.1 +/- 12.3 years, 40.2% women, and 45.1% with HF. There were 3548 NSTEMI and 1989 UA with HF prevalence of 56.2% and 27.4%, respectively. Heart failure patients were older, more were women, sicker (as shown by more of those with shock, postcardiac arrest, and breathless on admission), more with diabetes mellitus (DM), received less intervention and medication, and showed higher total death (19.3% vs 5.3% for NSTEMI with and without HF; and correspondingly, 5.9% and 1.9% for UA). Independent predictors (at presentation) for the development of HF following NSTEMI or UA were age (not sex), breathlessness, and less prevalence of chest pain. However, shock and DM were risks only for NSTEMI but not UA. Heart failure was found to be a factor for in-hospital death for NSTEMI only, with odds ratio of 2.84 (confidence interval 2.11-3.82) and 3.23 (2.25-4.64) for total and cardiac deaths, respectively. Non-ST-elevation myocardial infarction and UA showed substantial differences in factors related to predictors for in-hospital outcome such that these should be examined separately.

PMID: 20108070 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

Coagulation factor IXa as a target for treatment and prophylaxis of venous thromboembolism.

Arterioscler Thromb Vasc Biol Start a Discussion »

Apr 022010

Coagulation factor IXa as a target for treatment and prophylaxis of venous thromboembolism.

Arterioscler Thromb Vasc Biol. 2010 Mar;30(3):382-7

Authors: Eikelboom JW, Zelenkofske SL, Rusconi CP

Venous thromboembolism remains a frequent cause of vascular death. Despite advances in anticoagulant drug development, unmet needs remain, including limited treatment options for patients with severe renal impairment and the inability to fully reverse the effects of anticoagulants approved or in late-stage development. Because coagulation factor IXa plays a pivotal role in tissue factor-mediated thrombin generation, it represents an attractive target for anticoagulant development. This article discusses the rationale for factor IXa as an anticoagulant target and the potential role in venous thromboembolism prevention or management of the 2 factor IXa inhibitors that have undergone testing in phase 1 or 2 trials: TTP889, an oral, small-molecule compound, and RB006, an aptamer-based compound, the intravenous and subcutaneous formulations of which are the anticoagulant components of the REG1 and REG2 anticoagulation systems, respectively.

PMID: 20139356 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

Rivaroxaban: a new oral factor Xa inhibitor.

Arterioscler Thromb Vasc Biol Start a Discussion »

Apr 022010

Rivaroxaban: a new oral factor Xa inhibitor.

Arterioscler Thromb Vasc Biol. 2010 Mar;30(3):376-81

Authors: Perzborn E, Roehrig S, Straub A, Kubitza D, Mueck W, Laux V

Rivaroxaban is a direct inhibitor of factor Xa, a coagulation factor at a critical juncture in the blood coagulation pathway leading to thrombin generation and clot formation. It is selective for human factor Xa, for which it has >10 000-fold greater selectivity than for other biologically relevant serine proteases (half-maximal inhibitory concentration [IC(50)], >20 micromol/L). Rivaroxaban inhibits factor Xa in a concentration-dependent manner (inhibitory constant [K(i)], 0.4 nmol/L) and binds rapidly (kinetic association rate constant [k(on)], 1.7x10(7) mol/L(-1) s(-1)) and reversibly (kinetic dissociation rate constant [k(off)], 5x10(-3) s(-1)). By inhibiting prothrombinase complex-bound (IC(50), 2.1 nmol/L) and clot-associated factor Xa (IC(50), 75 nmol/L), rivaroxaban reduces the thrombin burst during the propagation phase. In animal models of venous and arterial thrombosis, rivaroxaban showed dose-dependent antithrombotic activity. In healthy individuals, rivaroxaban was found to have predictable pharmacokinetics and pharmacodynamics across a 5- to 80-mg total daily dose range, inhibiting factor Xa activity and prolonging plasma clotting time. In phase III clinical trials, rivaroxaban regimens reduced rates of venous thromboembolism in patients after total hip or knee arthroplasty compared with enoxaparin regimens, without significant differences in rates of major bleeding, showing that rivaroxaban has a favorable benefit-to-risk profile.

PMID: 20139357 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

Inhibition of factor XIa as a new approach to anticoagulation.

Arterioscler Thromb Vasc Biol Start a Discussion »

Apr 022010

Inhibition of factor XIa as a new approach to anticoagulation.

Arterioscler Thromb Vasc Biol. 2010 Mar;30(3):388-92

Authors: Schumacher WA, Luettgen JM, Quan ML, Seiffert DA

The dose-limiting issue with available anticoagulant therapies is bleeding. Is there an approach that could provide antithrombotic protection with reduced bleeding? One hypothesis is that targeting proteases upstream from the common pathway provides a reduction in thrombin sufficient to impede occlusive thrombosis yet allows enough thrombin generation to support hemostasis. The impairment of intrinsic coagulation by selective inhibition of factor XI (FXI) leaves the extrinsic and common pathways of coagulation intact, making FXI a drug target. This concept is supported by the observation that human deficiency in FXI results in a mild bleeding disorder compared with other coagulation factor deficiencies, and that elevated levels of FXI are a risk factor for thromboembolic disease. Moreover, FXI knockout mice have reduced thrombosis with little effect on hemostasis. The results from genetic models have been supported by studies using neutralizing antibodies, peptide inhibitors, and small-molecule inhibitors. These agents impede thrombosis without affecting bleeding time in a variety of experimental animals, including primates. Together, these data strongly support FXIa inhibition as a viable method to increase the ratio of benefit to risk in an antithrombotic drug.

PMID: 20139363 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

Current treatment of venous thromboembolism.

Arterioscler Thromb Vasc Biol Start a Discussion »

Apr 022010

Current treatment of venous thromboembolism.

Arterioscler Thromb Vasc Biol. 2010 Mar;30(3):372-5

Authors: Key NS, Kasthuri RS

Venous thromboembolism, comprising deep vein thrombosis and pulmonary embolism, is a common disorder with at least 250 000 new events occurring each year in the United States alone. Treatment of venous thromboembolism includes anticoagulation, which is achieved initially with the use of a parenterally administered agent followed by a more prolonged course of treatment with an oral vitamin K antagonist. The duration of treatment depends on the clinical assessment of the benefit-to-risk ratio of prolonged anticoagulation versus the risk of recurrent events. In this review, we discuss some of the issues that we believe are among the most critical unanswered questions in the management of venous thromboembolism in the present era.

PMID: 20139364 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

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