Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial.
ABSTRACT Dabigatran 150 and 110 mg twice a day and warfarin are effective for stroke prevention in atrial fibrillation. The purpose of this study was to compare their risks of bleeding in the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) trial.
The RE-LY trial randomized 18 113 patients to receive dabigatran 110 or 150 mg twice a day or warfarin dose adjusted to an international normalized ratio of 2.0 to 3.0 for a median follow-up of 2.0 years. Compared with warfarin, dabigatran 110 mg twice a day was associated with a lower risk of major bleeding (2.87% versus 3.57%; P=0.002), whereas dabigatran 150 mg twice a day was associated with a similar risk of major bleeding (3.31% versus 3.57%; P=0.32). There was a significant treatment-by-age interaction, such that dabigatran 110 mg twice a day compared with warfarin was associated with a lower risk of major bleeding in patients aged <75 years (1.89% versus 3.04%; P<0.001) and a similar risk in those aged ≥75 years (4.43% versus 4.37%; P=0.89; P for interaction <0.001), whereas dabigatran 150 mg twice a day compared with warfarin was associated with a lower risk of major bleeding in those aged <75 years (2.12% versus 3.04%; P<0.001) and a trend toward higher risk of major bleeding in those aged ≥75 years (5.10% versus 4.37%; P=0.07; P for interaction <0.001). The interaction with age was evident for extracranial bleeding, but not for intracranial bleeding, with the risk of the latter being consistently reduced with dabigatran compared with warfarin irrespective of age.
In patients with atrial fibrillation at risk for stroke, both doses of dabigatran compared with warfarin have lower risks of both intracranial and extracranial bleeding in patients aged <75 years. In those aged ≥75 years, intracranial bleeding risk is lower but extracranial bleeding risk is similar or higher with both doses of dabigatran compared with warfarin.
http://www.clinicaltrials.gov. Unique identifier: NCT00262600.
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ABSTRACT: The factor Xa inhibitor apixaban is one of the novel anticoagulants to emerge as alternatives to long-standing standards of care that include low-molecular-weight heparin and warfarin. The development of apixaban reflects a strategy to optimize the clinical pharmacology profile, dosing posology, trial designs, and statistical analyses across multiple indications, and to seek alignment with global health authorities. The primary objective of dose selection was to maintain balance between efficacy and bleeding risk. Twice-daily dosing of apixaban, rather than once daily, was chosen to lower peak concentrations and reduce fluctuations between peak and trough levels. Our discussion here focuses on the use of apixaban for stroke prevention in nonvalvular atrial fibrillation (NVAF). Supporting this indication, a pair of registrational trials was conducted that enrolled the full spectrum of patients who, by guidelines, were eligible for anticoagulation. In the AVERROES study of patients who were unsuitable for warfarin therapy, apixaban was superior to aspirin in reducing the risk of stroke or systemic embolism (SSE), without a significant increase in major bleeding (MB). In the ARISTOTLE (Apixaban for Reduction In STroke and Other ThromboemboLic Events in Atrial Fibrillation) study, apixaban was superior to warfarin on the rates of SSE, MB, and all-cause mortality. Overall, these studies have demonstrated a substantially favorable benefit–risk profile for apixaban over warfarin and aspirin in NVAF.Annals of the New York Academy of Sciences 11/2014; · 4.38 Impact Factor
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ABSTRACT: In clinical trials new oral anticoagulants (NOAC) have proved to be as effective as warfarin for thromboprophylaxis in atrial fibrillation. The aim of this study was to evaluate the efficacy and safety of these drugs in clinical practise. All patients treated with new oral anticoagulants at Skåne University hospital and Halland County Hospital Halmstad between 2009 and September 2013 was identified in the Swedish national quality registry for atrial fibrillation and anticoagulation (AuriculA). Medical records were reviewed to identify thromboembolism and major bleeding and compared to a warfarin cohort with a time in therapeutic range (TTR) of 76%. There were 826 patients, mean age 70.6, follow up 591 years, with atrial fibrillation treated with NOAC. Dabigatran was the initial drug in 79% of the cohort. The incidences of ischemic stroke/ TIA and major bleeding were 1.9 (95% CI; 1.0-3.2) and 2.0 (95% CI; 1.1-3.5) per 100 patient-years respectively. The corresponding incidences for warfarin were 1.5 (95% CI; 1.0-2.2) and 2.5 (95% CI; 1.8-3.3), with no statistical significance between the groups. Two subdural hematomas occurred 0.4 (95% CI; 0.06-1.1) per 100 patient-years. Mean age of patients with complications was 77.9 (±5.9) and 69.3 (±11.3) for those without (p < 0.001). The discontinuation rate was 6.5% and 1.7% was due to dyspepsia for dabigatran, lower than the RE-LY trial. This study, largely based on dabigatran shows that treatment is efficient and safe in everyday clinical practice and not significantly different compared to a warfarin cohort with tight anticoagulation control.Thrombosis Journal 01/2014; 12(1):29. · 1.31 Impact Factor
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ABSTRACT: Background: Ultrasound guided fine needle aspiration biopsy (USGFNAB) is the most accurate form of evaluation for thyroid nodules. Many patients with thyroid nodules who present for USGFNAB are on anticoagulant agents, including the novel oral anticoagulants (NOACs), for stroke prevention in atrial fibrillation or venous thrombosis prophylaxis. Summary: There has been at least one retrospective study describing neck USGFNAB bleeding risks in patients on antithrombotic and/or anticoagulant agents. This study concluded that there was no major bleeding risk or increase in hematoma formation in patients on antithrombotic or anticoagulant agents while undergoing USGFNAB, and there was no need to discontinue these agents prior to the procedure. With the emergence of new anticoagulant agents referred to as the novel oral anticoagulants (NOACs), further recommendations should be made for patients on these agents who will be undergoing USGFNAB for thyroid nodules. Currently, there are no published studies regarding patients on NOACs who undergo USGFNAB. Conclusions: It has previously been established that patients on historical anticoagulant agents do not need to discontinue therapy prior to minor procedures such as needle aspirations or dental procedures. Therefore, in patients currently taking dabigatran, rivaroxaban, or apixaban, we conclude that is reasonable and safe to continue the novel oral anticoagulant agents prior to USGFNAB of thyroid nodules without major risk of bleeding. This conclusion is based not only on the fact that minor procedures are considered safe in patients on NOACs, but also because patients on historical anticoagulant agents do not need to discontinue therapy prior to minor procedures.Thyroid: official journal of the American Thyroid Association 01/2015; · 2.60 Impact Factor