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🫀 DOAC при ФП и ВТЭ у пациентов с ХБП: свежий мета-анализ

🔥 Главное в 3 пунктах:
- У пациентов с ХБП и фибрилляцией предсердий (ФП) пероральные антикоагулянты прямого действия (ПОАК) достоверно снижают риск геморрагического инсульта и крупных кровотечений по сравнению с варфарином.
- При ВТЭ у больных с нарушением функции почек ПОАК не уступают варфарину по эффективности и безопасности.
- Важное преимущество ПОАК — меньше внутричерепных кровотечений.

🧪 Контекст: Мета-анализ 15 РКИ (n=16 361) сравнил ПОАК и варфарин у пациентов с ХБП при ФП или ВТЭ. Оценивались рецидив тромбоза/смерть от ВТЭ, инсульты (геморрагические, ишемические), крупные кровотечения.

📍 Практическое значение: ПОАК предпочтительнее варфарина для больных с ФП и ХБП (меньше кровотечений и геморрагических инсультов). Для пациентов с ВТЭ и сниженной функцией почек — ПОАК так же эффективны и безопасны, как антагонисты витамина К.

🔗 Источник: PubMed | DOI


❓ Пациент на ПОАК после ВТЭ: снижать ли дозу для длительной терапии?

✅ Ответ исследования: Мета-анализ 5 РКИ (n=8781) показал, что по сравнению с полной дозой, сниженные дозы ПОАК так же эффективны в профилактике рецидивов ВТЭ (RR 0,94; 95% ДИ 0,68–1,29; p=0,70), но значительно уменьшают большие и клинически значимые кровотечения (RR 0,71; 95% ДИ 0,61–0,82; p<0,0001).

📍 Как применить: Для пациентов с высоким риском кровотечений, которым требуется продолжительная антикоагуляция после ВТЭ (в том числе с онкологическими заболеваниями), снижение дозировки ПОАК (апиксабан, ривароксабан) не уменьшает защиту от тромбоза, но уменьшает кровотечения — рассмотрите этот вариант для долгосрочной стратегии.

🔗 Источник: PubMed | DOI


🧾 Пероральные антикоагулянты при опухолях мозга: как снизить риск ВЧК?

✅ Делать:
- У пациентов с первичными опухолями мозга, требующими антикоагуляции, предпочтительнее выбирать ПОАК (апиксабан и пр.).
- Контролировать пациента в первые 3 месяца после начала терапии (наибольший выигрыш по снижению внутримозговых кровоизлияний — RR 0,23 по сравнению с НМГ).
- Учитывать тип опухоли — преимущество ПОАК особенно выражено при первичных, но не метастатических новообразованиях.

⚠️ С осторожностью:
- У пациентов с метастатическими опухолями мозга эффект ПОАК по снижению риска ВЧК не доказан (RR 0,86; 95% ДИ 0,44–1,68).

🔗 Источник: PubMed | DOI

1. A Sole Case of Concurrent Arterial and Venous Thromboses with Massive Pulmonary Embolism and Carriage of Four Genetic Polymorphisms: Factor V Leiden, PAI-1 4G/5G, MTHFR C677T, and ACE I/D-A Case Report.

title

A Sole Case of Concurrent Arterial and Venous Thromboses with Massive Pulmonary Embolism and Carriage of Four Genetic Polymorphisms: Factor V Leiden, PAI-1 4G/5G, MTHFR C677T, and ACE I/D-A Case Report

journal

Reports (MDPI)

date

2025-09-22

doi

10.3390/reports8030167

pmid

40981125

background_and_significance

Arterial and venous thromboses are usually distinct, governed by separate mechanisms. The simultaneous occurrence, especially alongside massive pulmonary embolism, is extremely rare and clinically challenging.

case_presentation

{'age': 61, 'sex': 'male', 'comorbidities': ['well-controlled hypertension', 'type 2 diabetes'], 'thromboses': ['deep vein thrombosis (right popliteal vein)', 'arterial thrombosis (left iliac artery)', 'massive pulmonary embolism'], 'initial_management': ['unfractionated heparin (UFH)', 'low-molecular-weight heparin', 'direct oral anticoagulant (DOAC)', 'adjunctive therapy'], 'management_rationale': 'Conservative approach per ESC 2019 PE Guidelines due to absence of hemodynamic instability.', 'further_interventions': ['failed percutaneous revascularization', 'surgical thromboendarterectomy (TEA) for persistent arterial occlusion'], 'provoking_factors_absent': ['trauma', 'surgery', 'malignancy', 'antiphospholipid syndrome']}

genetic_findings

{'Factor_V_Leiden': 'heterozygous (R506Q genotype)', 'PAI-1': '4G/5G genotype', 'MTHFR': 'c.677C > T genotype', 'ACE_I_D': 'homozygous (DD genotype)'}

conclusion

Co-occurrence of these four thrombophilia-associated polymorphisms in a single patient with both arterial and venous thromboses is unprecedented. This suggests gene-gene interactions may amplify thrombotic risk beyond that conferred by each variant individually. The case highlights the need for multidisciplinary evaluation, consideration of pharmacogenetics in anticoagulation, and encourages research into the cumulative impact of multiple genetic variants in thrombotic disorders.

Journal: Reports (MDPI)
Impact Factor:
Date: 2025/9/22
PMID: 40981125
DOI: 10.3390/reports8030167

2. Accelerated Apixaban Removal by Using the ADVanced Organ Support (ADVOS) Albumin Hemodialysis System-A Case Report.

title

Accelerated Apixaban Removal by Using the ADVanced Organ Support (ADVOS) Albumin Hemodialysis System-A Case Report

journal

The Thoracic and Cardiovascular Surgeon Reports

publication_date

2024-07-01

doi

10.1055/a-2682-8640

pmid

40959463

abstract

In patients on direct oral anticoagulants (DOAC), emergency surgery is characterized by the occurrence of a massively increased tendency to bleed. Currently, there is no approved antidote for postoperative patients, making specific therapy challenging in these situations. Emergency surgery was required for a 72-year-old male patient who was in cardiogenic shock due to severe aortic regurgitation resulting from acute prosthetic valve endocarditis. Due to atrial fibrillation, the patient was on apixaban, a factor Xa (FXa) inhibitor anticoagulant, until surgery. We used the ADVanced Organ Support (ADVOS) albumin hemodialysis system postoperatively to treat persisting shock with multi-organ failure, acidosis, and DOAC removal. Serial drug-level measurements revealed strongly accelerated apixaban clearance. In line with this, we observed only moderate drainage losses. ADVOS accelerates the removal of apixaban and is a promising therapy for preventing bleeding complications in patients receiving DOAC therapy after emergency surgery.

authors

[]

keywords

['ADVOS', 'apixaban', 'direct oral anticoagulants', 'hemodialysis', 'emergency surgery', 'bleeding complications', 'cardiogenic shock', 'aortic regurgitation', 'prosthetic valve endocarditis']

case_details

{'patient_age': 72, 'patient_sex': 'male', 'condition': ['cardiogenic shock', 'severe aortic regurgitation', 'acute prosthetic valve endocarditis', 'atrial fibrillation'], 'medication': 'apixaban', 'reason_for_medication': 'atrial fibrillation', 'removal_method': 'ADVOS albumin hemodialysis system', 'postoperative_complications': ['persisting shock', 'multi-organ failure', 'acidosis']}

conclusions

['ADVOS accelerates removal of apixaban', 'ADVOS may prevent bleeding complications in DOAC-treated postoperative patients', 'No approved antidote exists for DOAC in postoperative setting, creating a need for alternative therapies']

study_type

case report

Journal: The Thoracic and cardiovascular surgeon reports
Impact Factor:
Date: 2024/7/1
PMID: 40959463
DOI: 10.1055/a-2682-8640

3. Efficacy and safety of reduced-dose versus full-dose direct oral anticoagulants for extended treatment of venous thromboembolism: A meta-analysis with trial sequential analysis and reconstructed time-to-event data.

title

Efficacy and safety of reduced-dose versus full-dose direct oral anticoagulants for extended treatment of venous thromboembolism: A meta-analysis with trial sequential analysis and reconstructed time-to-event data

journal

Thrombosis Research

publication_date

2025-06-25

impact_factor

5.05

quartile

Q1

doi

10.1016/j.thromres.2025.109476

pmid

40957133

registration_number

CRD420251048675

objective

To evaluate the efficacy and safety of reduced-dose versus full-dose direct oral anticoagulants (DOACs) for extended treatment of venous thromboembolism (VTE).

methods

{'design': 'Meta-analysis with trial sequential analysis', 'data_source': 'Major electronic databases (through April 2025)', 'inclusion_criteria': 'Randomized controlled trials (RCTs) comparing reduced-dose versus full-dose DOACs for VTE treatment', 'analysis': ['Pooled risk ratios (RR) using random-effects models', 'Reconstructed time-to-event data from Kaplan-Meier curves', 'Trial sequential analysis (TSA) to assess conclusiveness']}

studies_included

5

total_patients

8781

main_results

{'efficacy': {'description': 'Reduced-dose DOACs had comparable efficacy to full-dose for preventing recurrent VTE', 'risk_ratio': 0.94, 'confidence_interval': '0.68-1.29', 'p_value': 0.7, 'time_to_event_hr': 0.89, 'time_to_event_ci': '0.78-1.02', 'time_to_event_p_value': 0.1}, 'safety': {'description': 'Reduced-dose DOACs significantly reduced major or clinically relevant non-major bleeding', 'risk_ratio': 0.71, 'confidence_interval': '0.61-0.82', 'p_value': '<0.0001', 'time_to_event_hr': 0.61, 'time_to_event_ci': '0.57-0.66', 'time_to_event_p_value': '<0.001'}, 'subgroup': ['Efficacy and safety consistent in patients with and without active cancer', 'Consistent across different DOAC types (apixaban, rivaroxaban)'], 'all_cause_mortality': 'No difference observed'}

tsa_conclusion

Sufficient evidence for both efficacy and safety outcomes

conclusion

Reduced-dose DOACs are as effective as full-dose regimens for preventing recurrent VTE and have a better safety profile, suggesting they may be preferred for extended anticoagulation, especially in patients at high risk of recurrence.

Journal: Thrombosis research
Impact Factor: 5.05
Date: 2025/6/25
PMID: 40957133
DOI: 10.1016/j.thromres.2025.109476

4. Intracranial Hemorrhage With Direct Oral Anticoagulants vs Low-Molecular-Weight Heparin in Brain Tumors: A Review and Meta-Analysis.

title

Intracranial Hemorrhage With Direct Oral Anticoagulants vs Low-Molecular-Weight Heparin in Brain Tumors: A Review and Meta-Analysis

journal

Neurology

publication_date

2025-09-16

impact_factor

4.57

quartile

Q1

doi

10.1212/WNL.0000000000214140

pmid

40953341

prospero_registration

CRD42025635334

background

Patients with brain tumors are at increased risk of thromboembolic events. Anticoagulation is challenging due to concerns of intracranial hemorrhage (ICH). This meta-analysis compares the ICH risk of direct oral anticoagulants (DOACs) versus low-molecular-weight heparin (LMWH) in this patient population.

methods

{'databases': ['MEDLINE', 'Embase', 'Web of Science', 'Cochrane Central Register of Controlled Trials'], 'timeframe': 'January 2010 - June 2025', 'study_types': ['randomized-controlled trials', 'cohort studies'], 'population': 'Adults (age ≥18 years) with primary or metastatic brain tumors receiving therapeutic DOACs (apixaban, rivaroxaban, edoxaban, betrixaban, dabigatran) or LMWH (enoxaparin, dalteparin, nadroparin, tinzaparin)', 'exclusions': ['prophylactic dosing', 'non-brain tumor patients'], 'outcomes': ['intracranial hemorrhage (ICH)'], 'statistics': {'pooled_metric': 'risk ratio (RR)', 'confidence_interval': '95%', 'model': 'restricted random-effects', 'heterogeneity_metric': 'I2', 'publication_bias_tests': ['Egger (p=0.19)', 'Begg (p=0.59)']}, 'subgroup_analyses': ['tumor type', 'follow-up duration', 'study quality'], 'sensitivity_analysis': ['leave-one-out'], 'cumulative_meta_analysis': True}

results

{'studies_included': 10, 'designs': ['retrospective cohort'], 'total_patients': 1572, 'patients_DOAC': 645, 'patients_LMWH': 895, 'age_DOAC': 'mean/median 60.4-67 years', 'age_LMWH': 'mean/median 53-64 years', 'follow_up': '3-12 months', 'main_outcome': {'RR_any_ICH_DOAC_vs_LMWH': 0.5, '95%_CI': '0.29-0.87', 'p_value': 0.01, 'I2': 49.5}, 'followup_3months': {'studies': 3, 'RR': 0.23, '95%_CI': '0.09-0.57', 'p_value': '<0.01', 'I2': '<0.01'}, 'stratified': {'primary_brain_tumors': {'studies': 5, 'RR': 0.2, '95%_CI': '0.08-0.54', 'p_value': '<0.01', 'I2': '<0.01'}, 'metastatic_brain_tumors': {'studies': 5, 'RR': 0.86, '95%_CI': '0.44-1.68', 'p_value': 0.66, 'I2': 36.04}}, 'robustness': {'leave_one_out': True, 'cumulative_meta_analysis': 'stable estimates, narrowing CIs'}, 'publication_bias': False}

conclusions

In patients with brain tumors treated with anticoagulation, DOACs are associated with a significantly lower risk of intracranial hemorrhage compared to LMWH, particularly in primary brain tumors. Findings support DOACs as a safe anticoagulant option, but causal inference is limited by observational study designs.

Journal: Neurology
Impact Factor: 4.57
Date: 2025/9/16
PMID: 40953341
DOI: 10.1212/WNL.0000000000214140

5. Efficacy and safety of oral anticoagulants in the treatment of chronic kidney disease with atrial fibrillation or venous thromboembolism: a systematic review and meta-analysis.

title

Efficacy and safety of oral anticoagulants in the treatment of chronic kidney disease with atrial fibrillation or venous thromboembolism: a systematic review and meta-analysis

journal

Frontiers in Pharmacology

date

2025-04-21

impact_factor

5.35

quartile

Q1

doi

10.3389/fphar.2025.1615284

pmid

40949128

registration

CRD42024510727

registration_url

http://www.clinicaltrials.gov

objective

To compare the efficacy and safety of warfarin and direct oral anticoagulants (DOACs) in the treatment of CKD with atrial fibrillation or venous thromboembolism.

methods

{'databases': ['PubMed', 'Embase', 'Web of Science', 'Cochrane Library', 'ClinicalTrials.gov'], 'search_end_date': '2024-06-30', 'inclusion_criteria': ['RCTs assessing efficacy and safety of warfarin and DOACs', 'CKD patients with AF or VTE'], 'outcomes': {'VTE': ['thrombosis recurrence', 'VTE-related deaths', 'major bleeding'], 'AF': ['stroke or systemic embolism', 'major bleeding']}, 'risk_of_bias_tool': "Cochrane Collaboration's tool", 'n_studies_screened': 540, 'n_studies_included': 15, 'n_participants': 16361}

results

{'AF_and_CKD': {'hemorrhagic_stroke': {'RR': 0.455, '95%_CI': '0.275-0.752', 'P': 0.002, 'interpretation': 'DOACs reduced risk compared to warfarin'}, 'ischemic_stroke': {'difference': 'not significant'}, 'major_bleeding': {'RR': 0.604, '95%_CI': '0.442-0.825', 'P': 0.002, 'interpretation': 'DOACs reduced risk compared to warfarin'}, 'intracranial_bleeding': {'RR': 0.424, '95%_CI': '0.287-0.626', 'P': '<0.001', 'interpretation': 'DOACs significantly reduced risk'}}, 'VTE_and_CKD': {'recurrent_VTE_or_VTE_death': {'RR': 0.663, '95%_CI': '0.409-1.073', 'P': 0.094, 'interpretation': 'No significant difference'}, 'major_bleeding': {'RR': 0.543, '95%_CI': '0.209-1.407', 'P': 0.208, 'interpretation': 'No significant difference'}}}

conclusion

DOACs show superior efficacy and safety compared to warfarin in patients with AF and CKD, and comparable efficacy and safety to warfarin in patients with VTE and CKD.

Journal: Frontiers in pharmacology
Impact Factor: 5.35
Date: 2025/4/21
PMID: 40949128
DOI: 10.3389/fphar.2025.1615284