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Argirios Argiriou:
August 11, 2014

David Green, MD, PhD reviewing Sanford D et al. J Thromb Haemost 2014 Jul. van der Hulle T et al. J Thromb Haemost 2014 Jul.

Low-molecular-weight heparin did not improve survival; new oral anticoagulants were safe but not more effective than vitamin K antagonists.

Cancer patients are at increased risk for thrombosis and have shortened survival. Whether anticoagulants improve survival in these patients is controversial. Investigators have now conducted two meta-analyses to evaluate the effect of prophylactic low-molecular-weight heparin (LMWH) on cancer-patient survival and the efficacy of the new oral anticoagulants (NOACs) in patients with cancer-associated acute venous thromboembolism (VTE).

Sanford and colleagues analyzed nine studies encompassing 5987 patients with stage III or IV solid cancers and without VTE who received LMWH or placebo. LMWH had no effect on mortality. However, LMWH recipients had fewer thrombotic events (odds ratio, 0.56; 95% confidence interval, 0.40–0.81), without a significant increase in bleeding events.

Van der Hulle and colleagues conducted a meta-analysis of five studies encompassing 19,060 patients with VTE who received NOACs or vitamin K antagonists (VKAs); of these patients, 5.1% had active cancer. No significant differences between cancer patients treated with NOACs or VKAs were observed in the incidence rates of recurrent VTE (4.1% and 6.1%, respectively) or bleeding (15% and 16%).
Comment

Previous studies had suggested that the prophylactic use of LMWH might improve the survival of cancer patients, but these reports are not confirmed by the Sanford meta-analysis. Also, the NOACs seem to be safe for cancer patients, as shown in the van der Hulle analysis, but whether they are as effective as LMWH has not yet been determined.


Citation(s):

    Sanford D et al. The effect of low molecular weight heparin on survival in cancer patients: An updated systematic review and meta-analysis of randomized trials. J Thromb Haemost 2014 Jul; 12:1076. (Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος)

    PubMed abstract (Free)
    van der Hulle T et al. Meta-analysis of the efficacy and safety of new oral anticoagulants in patients with cancer-associated acute venous thromboembolism. J Thromb Haemost 2014 Jul; 12:1116. (Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος)

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Δ. Κουναλάκης:
Dabigatran Linked to More Bleeding Events Than Warfarin in Atrial Fibrillation

By Amy Orciari Herman

Edited by David G. Fairchild, MD, MPH, and Jaye Elizabeth Hefner, MD

Dabigatran is associated with greater bleeding risks than warfarin among older adults with atrial fibrillation, according to a retrospective analysis in JAMA Internal Medicine.

Using Medicare data on adults who were newly diagnosed with atrial fibrillation in 2010-2011, researchers compared outcomes in some 1300 who filled prescriptions for dabigatran and 8100 who filled prescriptions for warfarin. During roughly 6 to 7.5 months' follow-up, dabigatran users had significantly higher bleeding risks than warfarin users in terms of any bleeding (33% vs. 27%), major bleeding (9% vs. 6%), and gastrointestinal bleeding (17% vs. 10%). Intracranial hemorrhage occurred more often with warfarin (0.6% vs. 1.8%).

The risk for major bleeding with dabigatran was particularly high for blacks and patients with chronic kidney disease, while the increased risk for intracranial bleeding with warfarin was limited to those aged 75 and older.

The authors conclude: "Before more evidence is available, dabigatran should be prescribed with caution in high-risk patients."

Πηγη: Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος

Argirios Argiriou:
Καρδιολόγος από γειτονικό μου Νοσοκομείο έχει ξεσκιστεί να γράφει νεότερα αντιπηκτικά (κόστος θεραπείας για το κράτος γύρω στα 60 €/μήνα ή 720 €/έτος) αντί του δοκιμασμένου Sintrom (κόστος θεραπείας για το κράτος γύρω στα 3 €/μήνα ή 36 €/έτος).

Τον ρωτώ δημοσίως:

Ρε φίλε, σου έχουν κόψει τον μισθό,

σου χρωστούν εφημερίες μηνών,

και τα Νοσοκομεία δεν έχουν καλά καλά γάζες.

ΤΙ ΔΕΝ ΚΑΤΑΛΑΒΑΙΝΕΙΣ;

Argirios Argiriou:
June 16, 2015

Gastrointestinal Bleeding Associated with Dabigatran or Rivaroxaban Is Similar to That Associated with Warfarin.

Paul S. Mueller, MD, MPH, FACP Reviewing Vaughan Sarrazin MS and Rose A., BMJ 2015 Apr 24; 350:h1679

Nonetheless, clinicians should be cautious when prescribing novel anticoagulants to elders and patients with renal impairment.

In randomized trial of treatment for atrial fibrillation, the novel oral anticoagulants, dabigatran (Pradaxa) and rivaroxaban (Xarelto), were associated with slightly higher risk for gastrointestinal (GI) bleeding than did warfarin (NEJM JW Gen Med Feb 1 2014 and Lancet 2014; 383:955); in trials of treatment for thromboembolism, GI bleeding risks with novel anticoagulants and warfarin were similar (NEJM JW Gen Med Jan 1 2015 and Blood 2014; 124:1968). But how is this playing out in real-world use?

In a retrospective study, researchers used a large administrative database of commercially insured patients and compared risk for GI bleeding among 46,000 new adult users of dabigatran, rivaroxaban, and warfarin. After adjusting for multiple potential confounders, the investigators found no statistically significant differences in risks for GI bleeding between either dabigatran or rivaroxaban use and warfarin use.

In a similar study that included propensity matching, researchers compared risk for GI bleeding among 93,000 new adult users of these anticoagulants. Risks for GI bleeding associated with dabigatran and rivaroxaban were similar to that associated with warfarin in both patients with atrial fibrillation (AF) and those without AF. Notably, risk for GI bleeding increased at a faster rate with increasing age among novel anticoagulant users than among warfarin users, especially among the oldest patients (age, >75).

Comment

These two “real-world” retrospective studies suggest that, in general, risk for GI bleeding associated with dabigatran or rivaroxaban is similar to that associated with warfarin. Nonetheless, clinicians should be cautious when prescribing novel anticoagulants to elders and patients with renal impairment and should use the lowest available effective dose. For example, an editorialist notes that, in most U.S. studies, researchers have evaluated 150-mg dabigatran. Yet, evidence suggests that the 110-mg dose (not available in the U.S.) is not only effective, but also is associated with lower GI bleeding risk for patients with AF. Similar evidence exists for rivaroxaban dosing.

Editor Disclosures at Time of Publication

Disclosures for Paul S. Mueller, MD, MPH, FACP at time of publication

Consultant / advisory board

Boston Scientific (Patient Safety Advisory Board)

Editorial boards

Medical Knowledge Self-Assessment Program (MKSAP 17 General Internal Medicine Committee); MKSAP 17 General Internal Medicine (author/contributor)

Leadership positions in professional societies

American Osler Society (Vice President)

Citation(s):

Chang H-Y et al. Risk of gastrointestinal bleeding associated with oral anticoagulants: Population based retrospective cohort study. BMJ 2015 Apr 24; 350:h1585. (Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος)

Abraham NS et al. Comparative risk of gastrointestinal bleeding with dabigatran, rivaroxaban, and warfarin: Population based cohort study. BMJ 2015 Apr 24; 350:h1857. (Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος)

Vaughan Sarrazin MS and Rose A.Safety of new oral anticoagulants. BMJ 2015 Apr 24; 350:h1679. (Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος)


Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος

Argirios Argiriou:
Ενδιαφέρον. Πόσο όμως κοστίζει αυτό το αντίδοτο και πότε θα έρθει στην χρεοκοπημένη Ελλάδα;

June 24, 2015
Reversing Dabigatran-Induced Anticoagulation

David Green, MD, PhD reviewing Glund S et al. Lancet 2015 Jun 15. Treschan TA and Beiderlinden M. Lancet 2015 Jun 15. Pollack CV Jr et al. N Engl J Med 2015 Jun 22.
Idarucizumab immediately reversed dabigatran-induced increases in clotting variables without causing serious adverse events.

Dabigatran is a direct thrombin inhibitor that is approved for the prevention of stroke in atrial fibrillation and for the treatment of venous thromboembolism. Bleeding is usually managed by discontinuing the drug or, if severe, by giving a prothrombin complex concentrate. However, a specific antidote would be required if more urgent reversal of the drug were needed.

Now, researchers have developed a monoclonal antibody fragment, idarucizumab, which tightly binds to dabigatran and nullifies its anticoagulant activity. The agent has now been evaluated in two studies: a randomized, placebo-controlled, double-blind, proof-of-concept phase 1 study in healthy male volunteers, and a prospective cohort trial in patients requiring urgent reversal because of bleeding or need for a surgical procedure.

In the first study, conducted by the drug manufacturer, participants were given dabigatran for 4 days and then intravenous doses of idarucizumab, ranging from 1 to 5 g. Coagulation variables (thrombin times, ecarin clotting time, activated clotting time, and partial thromboplastin time) were all prolonged on day 3 of dabigatran dosing, and mild bleeding was observed in four participants (3 with hematuria and 1 with epistaxis). Infusion of idarucizumab resulted in an immediate and complete reversal of the dabigatran-induced increases in clotting tests, which was maintained for at least 72 hours with all but the 1 g dose of idarucizumab. The antidote was well-tolerated; no serious or severe adverse events were observed.

The second study included 90 patients who were being treated with dabigatran, 51 with bleeding (intracranial, 18; gastrointestinal, 20), and 39 requiring urgent interventions. The median time since the last dose of dabigatran was 15.4 hours, and the dose of idarucizumab used for reversal was 5 g. After infusion of the antidote, the dilute thrombin time was normalized in more than 90% of patients, and the concentration of unbound dabigatran was <20 ng/mL at 24 hours in 79%. In the patients with hemorrhage, the median time for bleeding cessation was 11.4 hours, and in those undergoing surgery, normal intraoperative hemostasis was reported in 92%. In the 72 hours following administration of idarucizumab, only one patient had a thrombotic event.

COMMENT

The safety and specificity of idarucizumab in reversing the anticoagulant effects of dabigatran are well documented in these studies of healthy volunteers, bleeding patients, and those undergoing surgery. The introduction of this and other antidotes to the new oral anticoagulants is an important step in the development of these agents, and it raises the question of whether every patient starting on one of these drugs should receive a vial containing the specific antidote in case bleeding occurs and the reversal agent might not be immediately available.

EDITOR DISCLOSURES AT TIME OF PUBLICATION

Disclosures for David Green, MD, PhD at time of publication
Grant / Research supportNIH

CITATION(S):

Glund S et al. Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: A randomised, placebo-controlled, double-blind phase 1 trial. Lancet 2015 Jun 15; [e-pub]. (Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος)
Treschan TA and Beiderlinden M.Antidotes for anticoagulants: A long way to go. Lancet 2015 Jun 15; [e-pub]. (Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος)

Pollack CV Jr et al. Idarucizumab for dabigatran reversal. N Engl J Med 2015 Jun 22; [e-pub]. (Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος)

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