Abnormal vaginal bleeding in women of reproductive age treated with edoxaban or warfarin for venous thromboembolism: a post hoc analysis of the Hokusai‐<scp>VTE</scp> study

Scheres, Luuk J. J.; Brekelmans, Marjolein P. A.; Ageno, Walter; Ay, Cihan; Büller, Harry R.; Eichinger, Sabine; Hutten, Barbara A.; Klok, Frederikus A.; Middeldorp, Saskia; Schreiber, Karen; Stach, Ksenija; Blondon, Marc; Delluc, Aurélien

doi:10.1111/1471-0528.15388

Cited by 55 publications

(21 citation statements)

References 32 publications

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“…Treatment with factor Xa inhibitors is indeed associated with an increased risk of abnormal uterine bleeding, particularly heavy menstrual bleeding in premenopausal women when compared with treatment with VKA. [20][21][22][23][24] The observation that these women were admitted because of heavy menstrual bleeding, although it was not specifically monitored in this cohort, underlines the relevance of monitoring and counseling the risk of heavy menstrual bleeding in premenopausal women after initiating DOAC therapy.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness and Safety of Apixaban for Treatment of Venous Thromboembolism in Daily Practice

Hendriks

Klok

Stenger

et al. 2020

TH Open

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Introduction Phase 3 trials have shown comparable efficacy of direct oral anticoagulants (DOACs) and vitamin K antagonists in patients with acute venous thromboembolism (VTE), with less major bleeding events in patients randomized to DOAC treatment. With DOACs being increasingly used in clinical practice, evaluation of the DOACs in daily practice-based conditions is needed to confirm their safety and effectiveness. The aim of this study is to evaluate the effectiveness and safety of apixaban in VTE patients in daily practice. Methods In this retrospective cohort study, consecutive patients diagnosed with VTE in two Dutch hospitals (Leiden University Medical Center, Leiden and Haga Teaching Hospital, The Hague) were identified based on administrative codes. We assessed recurrent VTE, major bleeding and mortality during a 3-month follow-up period in those treated with apixaban. Results Of 671 consecutive VTE patients treated with apixaban, 371 presented with acute pulmonary embolism (PE) and 300 patients with deep-vein thrombosis. During 3 months treatment, 2 patients had a recurrent VTE (0.3%; 95% confidence interval [CI]: 0.08–1.1), 12 patients had major bleeding (1.8%; 95% CI: 1.0–3.2), and 11 patients died (1.6%; 95% CI: 0.9–2.9), of which one patient with recurrent PE and one because of a intracerebral bleeding. Conclusion In this daily practice-based cohort, apixaban yielded a low incidence of recurrent VTE, comparable to the phase 3 AMPLIFY study patients. The incidence of major bleeding was higher than in the AMPLIFY-study patients, reflecting the importance of daily practice evaluation and the fact that results from phase III clinical studies cannot be directly extrapolated toward daily practice.

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Section: Discussionmentioning

confidence: 99%

Effectiveness and Safety of Apixaban for Treatment of Venous Thromboembolism in Daily Practice

Hendriks

Klok

Stenger

et al. 2020

TH Open

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“…Women represent a special population concerning DOACs safety. Post-hoc analysis of phase 3 studies pointed to increased risk of uterine bleeding with rivaroxaban and edoxaban, and the relative occurrence of vaginal bleeds was higher in apixabantreated than in warfarin-treated women (36,37,38). It remains debatable whether these findings should discourage physicians from prescribing some of the DOACs in women.…”

Section: Doacs In the Treatment Of Acute Vte And Secondary Preventionmentioning

confidence: 99%

The current place of direct oral anticoagulants in the prevention/treatment of venous thromboembolism

Tomić¹

2020

Arhiv za farmaciju

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Venous thromboembolism (VTE; includes deep venous thrombosis, DVT, and pulmonary embolism, PE) represents the third most common acute cardiovascular syndrome. Contemporary VTE management comprises primary prevention in high-risk patients, treatment of established VTE, and prevention of its recurrence (secondary prevention). Anticoagulants are the basis of VTE pharmacological prophylaxis and treatment. For several decades, parenteral (heparin and low-molecular-weight heparins, LMWHs) and oral anticoagulants (vitamin K antagonists, VKAs) have been the cornerstone of VTE prevention/treatment. The introduction of direct oral anticoagulants (DOACs: thrombin inhibitor dabigatran and Xa inhibitors rivaroxaban, apixaban, edoxaban, and betrixaban) markedly improved the management of VTE by overcoming many disadvantages of conventional anticoagulants. For primary VTE prevention in patients after total hip/knee arthroplasty, rivaroxaban, apixaban, and dabigatran are preferred over LMWHs, due to comparable efficacy and safety, but favourable acceptability (avoided everyday injections). In other high-risk populations (other surgical patients, acutely ill medical patients), LMWHs are still the recommended option. Betrixaban is currently the only DOAC approved for VTE prophylaxis in medically ill patients during and after hospitalization. For acute VTE treatment and secondary prevention, DOACs (rivaroxaban, apixaban, edoxaban, and dabigatran) are recommended as the first-line therapy in the general population. DOACs proved to be similarly effective but safer than VKAs. In some specific populations, DOACs also seem to be advantageous over conventional treatment (patients with renal impairment, elderly, long-term secondary prevention in cancer patients). Currently, there is no data from randomized head-to-head comparative studies between the DOAC classes or representatives so the choice is made mainly according to patient characteristics and pharmacokinetic properties of the drug.

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“…Rates of AUB did not differ between apixaban and VKA (odds ratio [OR] 1.2; 95% CI 0.7‐2.0) in the AMPLIFY trial (n = 2228), but clinically relevant non‐major bleeding was more likely to be of vaginal origin with apixaban (45%) than with warfarin (20%) . The HOKUSAI‐VTE study (n = 1293) found an increased risk of AUB in the edoxaban group compared with the VKA group (hazard ratio 1.9; 95% CI 1.1‐2.5) . An individual patient data meta‐analysis of the phase 3 trials showed that major bleeding of vaginal origin, although rare, occurred more often with use of factor Xa‐inhibitor than with VKA (17/10595 vs. 3/10957) .…”

Section: Periodmentioning

confidence: 99%

Sex matters: Practice 5P's when treating young women with venous thromboembolism

Bistervels

Scheres

Middeldorp

2019

Journal of Thrombosis and Haemostasis

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Sex matters when it comes to venous thromboembolism (VTE). We defined 5P'speriod, pill, prognosis, pregnancy, and postthrombotic syndrome -that should be discussed with young women with VTE. Menstrual blood loss (Period) can be aggravated by anticoagulant therapy. This seems particularly true for direct oral anticoagulants.Abnormal uterine bleeding can be managed by hormonal therapy, tranexamic acid, or modification of treatment. The use of combined oral contraceptives (Pill) is a risk factor for VTE. The magnitude of the risk depends on progestagen types and estrogen doses used. In women using therapeutic anticoagulation, concomitant hormonal therapy does not increase the risk of recurrent VTE. Levonorgestrel-releasing intrauterine devices and low-dose progestin-only pills do not increase the risk of VTE. In young women VTE is often provoked by transient hormonal risk factors that affects prognosis. Sex is incorporated as predictor in recurrent VTE risk assessment models.However, current guidelines do not propose using these to guide treatment duration.Pregnancy increases the risk of VTE by 4-fold to 5-fold. Thrombophilia and obstetric risk factors further increase the risk of pregnancy-related VTE. In women with a history of VTE, the risk of recurrence during pregnancy or post partum appears to be influenced by risk factors present during the first VTE. In most women with a history of VTE, antepartum and postpartum thromboprophylaxis with low-molecular-weight heparin is indicated. Women generally are affected by VTE at a younger age then men, and they have to deal with long-term complications (Post-thrombotic syndrome) of deep vein thrombosis early in life. K E Y W O R D Santicoagulants, contraceptives, female, pregnancy, venous thromboembolism

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Abnormal vaginal bleeding in women of reproductive age treated with edoxaban or warfarin for venous thromboembolism: a post hoc analysis of the Hokusai‐VTE study

Cited by 55 publications

References 32 publications

Effectiveness and Safety of Apixaban for Treatment of Venous Thromboembolism in Daily Practice

Effectiveness and Safety of Apixaban for Treatment of Venous Thromboembolism in Daily Practice

The current place of direct oral anticoagulants in the prevention/treatment of venous thromboembolism

Sex matters: Practice 5P's when treating young women with venous thromboembolism

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