Update and Unmet Needs on the Use of Nonvitamin K Oral Anticoagulants for Stroke Prevention in Patients With Atrial Fibrillation

Menichelli, Danilo; Ettorre, Evaristo; Pani, Arianna; Violi, Francesco; Pignatelli, Pasquale; Pastori, Daniele

doi:10.1016/j.cpcardiol.2019.02.002

Cited by 8 publications

(4 citation statements)

References 36 publications

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“…However, despite the widespread use of these drugs in these clinical conditions, there is no evidence supporting their use in particular categories of patient such as patients with advanced liver disease (ALD) or cirrhosis and DOACs are not recommended in class C of Child‐Pugh‐Turcotte score (rivaroxaban also in class B) 3 . Indeed, patients with cirrhosis or with a significant increase in transaminases and/or bilirubin were excluded from phase 3 clinical trials and the limited data available on this category of patients derive mostly from observational studies or small randomized trials.…”

Section: Introductionmentioning

confidence: 99%

Direct oral anticoagulants and advanced liver disease: A systematic review and meta‐analysis

Menichelli

Ronca

Rocco

et al. 2020

Eur J Clin Investigation

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Background Direct oral anticoagulants (DOACs) are recommended for stroke prevention in patients with atrial fibrillation (AF) or for treatment of deep vein thrombosis, although some concerns about safety and efficacy were raised on the use of these drugs in patients with advanced liver disease (ALD). We want to investigate the association of DOACs use with the bleeding and ischaemic risk. Material and Methods We performed a systematic review and metanalysis of clinical studies retrieved from PubMed (via MEDLINE) and Cochrane (CENTRAL) databases addressing the impact of DOACs therapy on bleeding events including intracranial haemorrhage (ICH), gastrointestinal and major bleeding. Secondary end points were all‐cause death, ischaemic stroke/systemic embolism (IS/SE) and recurrence/progression of vein thrombosis (rDVT). Results 12 studies were included in the meta‐analysis: a total of 43 532 patients with ALD or cirrhosis, of whom 27 574 (63.3%) were on treatment with DOACs and 15 958 were in warfarin/low molecular weight heparin. DOACs reduced the incidence of major bleeding by 61% (pooled Hazard Ratio [HR] 0.39, 95% Confidence Interval [CI] 0.21‐0.70), ICH by 52% (HR 0.48, 95% CI 0.40‐0.59), while no difference in the reduction of any and gastrointestinal bleeding were observed. DOACs reduced also rDVT by 82% (HR 0.18, 95%CI 0.06‐0.57), but did not reduce death and IS/SE. No difference was shown according to oesophageal varices and Child Pugh score in the meta‐regression analysis between warfarin/heparin and DOACs performed on each outcome. Conclusions DOACs are associated with a lower incidence of bleeding and may be an attractive therapeutic option in patients with cirrhosis.

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Section: Introductionmentioning

confidence: 99%

Direct oral anticoagulants and advanced liver disease: A systematic review and meta‐analysis

Menichelli

Ronca

Rocco

et al. 2020

Eur J Clin Investigation

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“…Another interesting result of our study is that the treatment with DOAC, compared to VKA, is associated with a reduction of the risk of cardiovascular events. Of note, the use of DOACs was lower in patients with MetS, which may depend on the fact that the use of DOAC in morbid obese patients is still uncertain [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Non-alcoholic fatty liver disease (NAFLD), metabolic syndrome and cardiovascular events in atrial fibrillation. A prospective multicenter cohort study

et al. 2021

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Whether non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular events (CVEs) independently from metabolic syndrome (MetS) is still matter of debate. Aim of the study was to investigate the risk of CVEs in a high-risk population of patients with non-valvular atrial fibrillation (AF) according to the presence of MetS and NAFLD. Prospective observational multicenter study including 1,735 patients with non-valvular AF treated with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). NAFLD was defined by a fatty liver index ≥ 60. We categorized patients in 4 groups: 0 = neither MetS or NAFLD (38.6%), 1 = NAFLD alone (12.4%), 2 = MetS alone (19.3%), 3 = both MetS and NAFLD (29.7%). Primary endpoint was a composite of CVEs. Mean age was 75.4 ± 9.4 years, and 41.4% of patients were women. During a mean follow-up of 34.1 ± 22.8 months (4,926.8 patient-years), 155 CVEs were recorded (incidence rate of 3.1%/year): 55 occurred in Group 0 (2.92%/year), 12 in Group 1 (2.17%/year), 45 in Group 2 (4.58%/year) and 43 in Group 3 (2.85%/year). Multivariable Cox regression analysis showed that use of DOACs, and female sex were inversely associated with CVEs, whilst age, heart failure, previous cardiac and cerebrovascular events, and group 2 (Group 2, Hazard Ratio 1.517, 95% Confidence Interval, 1.010–2.280) were directly associated with CVEs. In patients with AF, MetS increases the risk of CVEs. Patients with NAFLD alone have lower cardiovascular risk but may experience higher liver-related complications.

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“… 1 However, there are still some subgroups of patients in whom the use of DOACs is not well established or contraindicated, such as those with liver cirrhosis Child-Pugh C, patients with end-stage renal disease, and morbid obese patients. 2 Furthermore, drug-drug interactions (DDIs) with medications interfering with the membrane permeability glycoprotein (p-gp) should be considered in DOAC-treated patients. In particular, in 2018, the European Heart Rhythm Association (EHRA) Practical Guide on the use of DOACs in patients with AF, 1 the authors advise against the concomitant use of dabigatran and levetiracetam, based on the supposed modulation of p-gp protein by levetiracetam as substrate.…”

Section: Introductionmentioning

confidence: 99%

Minimizing drug-drug interactions between dabigatran and levetiracetam through clinical management: a case report

Menichelli

Pastori

Pignatelli

et al. 2022

European Heart Journal - Case Reports

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Background Direct oral anticoagulants (DOACs) are useful for stroke prevention in atrial fibrillation (AF) patients. However, the concomitant administration of Levetiracetam limited their use in clinical practice, although some authors raise doubts about clinical relevance of the interaction. Case summary We report a case of a 54-year-old male with AF, cirrhosis and seizures, in which the assessment of Dabigatran plasma concentration was needed due to the concomitant use of Levetiracetam. In this case no relevant reduction of trough Dabigatran plasma concentration was found. An increased peak serum level of dabigatran may be obtained delaying levetiracetam administration. The patient was then followed in our clinic and during 32 months of follow up no ischemic or haemorrhagic events occurred. Discussion The evaluation of DOACs concentration could be helpful to start a tailored therapy in frailty patients.

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Update and Unmet Needs on the Use of Nonvitamin K Oral Anticoagulants for Stroke Prevention in Patients With Atrial Fibrillation

Cited by 8 publications

References 36 publications

Direct oral anticoagulants and advanced liver disease: A systematic review and meta‐analysis

Direct oral anticoagulants and advanced liver disease: A systematic review and meta‐analysis

Non-alcoholic fatty liver disease (NAFLD), metabolic syndrome and cardiovascular events in atrial fibrillation. A prospective multicenter cohort study

Minimizing drug-drug interactions between dabigatran and levetiracetam through clinical management: a case report

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