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🫀 Новое в терапии ФП/ВТЭ с ХБП: метаанализ сравнил ПОАК и варфарин

🔥 Главное в 3 пунктах:
- Пероральные антикоагулянты прямого действия (ПОАК) снижают риск геморрагического инсульта у пациентов с фибрилляцией предсердий (ФП) и ХБП по сравнению с варфарином (RR = 0,455; 95% ДИ: 0,275-0,752; p = 0,002).
- ПОАК связаны с меньшей частотой серьёзных кровотечений у пациентов с ФП и ХБП (RR = 0,604; 95% ДИ: 0,442-0,825; p = 0,002), а также значительно уменьшают риск внутричерепных кровоизлияний (RR = 0,424; 95% ДИ: 0,287-0,626; p < 0,001).
- При ВТЭ на фоне ХБП различий по эффективности (рецидив ВТЭ/летальность) и безопасности между группами ПОАК и варфарина не выявлено.

Контекст:
Систематический обзор и метаанализ 15 РКИ (16 361 пациента) с ХБП и ФП/ВТЭ. Сравнивались ПОАК и варфарин по риску тромбозов, инсульта и крупного кровотечения.

Практическая польза:
ПОАК предпочтительны для больных ФП и ХБП: выше профиль безопасности и меньший риск геморрагических осложнений. Для ВТЭ у пациентов с ХБП — выбор препарата можно индивидуализировать.

Источник:
PubMed
DOI

ФП #ХБП #ПОАК #ВТЭ


❓Вопрос практики:
Как безопасно использовать антикоагулянты для продлённого лечения ВТЭ, особенно при повышенном риске кровотечений и/или онкологии?

Ответ исследования:
Метаанализ 5 РКИ (n = 8781) показал, что сниженные дозы ПОАК (в т.ч. апиксабан, ривароксабан) так же эффективны, как и полные дозы для профилактики рецидива ВТЭ (HR = 0,89; 95% ДИ: 0,78-1,02; p = 0,10), но значительно безопаснее по риску мажорных и клинически значимых кровотечений (HR = 0,61; 95% ДИ: 0,57-0,66; p < 0,001).

Как применить:
- Снижение дозы ПОАК оправдано для продлённой терапии ВТЭ, включая пациентов с онкологическими заболеваниями.
- Расширяет возможности индивидуализации антикоагуляции — важный выбор для пациентов с высоким риском кровотечения.
- Нет различий в общей смертности и эффективности — приоритет безопасности без ущерба пользе.

Источник:
PubMed
DOI

ВТЭ #ПОАК #онкология

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

Intervention

Postoperative ADVOS albumin hemodialysis for shock, multi-organ failure, acidosis, and apixaban removal

title

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

journal

The Thoracic and Cardiovascular Surgeon Reports

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.

keywords

['ADVOS', 'albumin hemodialysis', 'apixaban', 'direct oral anticoagulants', 'emergency surgery', 'bleeding complications']

main_findings

The ADVOS albumin hemodialysis system accelerated apixaban removal in a postoperative patient with multi-organ failure, suggesting its promise in preventing bleeding complications in patients on DOACs after emergency surgery.

study_type

case report

population

{'age': 72, 'sex': 'male', 'indications': ['cardiogenic shock', 'acute prosthetic valve endocarditis', 'severe aortic regurgitation', 'atrial fibrillation']}

outcomes

{'apixaban_clearance': 'accelerated', 'bleeding': 'only moderate drainage losses observed'}

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

2. 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

abstract

While current guidelines recommend extended therapeutic anticoagulation for venous thromboembolism (VTE), the optimal dosing strategy for direct oral anticoagulants (DOACs) remains uncertain, particularly in cancer-associated VTE. This meta-analysis evaluates the efficacy and safety of reduced-dose versus full-dose DOACs for extended VTE treatment. We conducted a comprehensive search of major electronic databases through April 2025 for randomized controlled trials (RCTs) comparing reduced-dose versus full-dose DOACs for VTE treatment. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using random-effects models. Time-to-event data were reconstructed from Kaplan-Meier curves. Trial sequential analysis (TSA) was employed to assess the conclusiveness of the evidence. Our analysis included five RCTs involving 8781 patients. Reduced-dose DOACs were associated with comparable efficacy to full-dose therapy in preventing recurrent VTE (RR, 0.94; 95% CI, 0.68-1.29; P = 0.70), supported by time-to-event analysis (HR, 0.89; 95% CI 0.78-1.02; p = 0.10). However, reduced-dose regimens significantly reduced major or clinically relevant non-major bleeding (RR, 0.71; 95% CI 0.61-0.82; P < 0.0001), with consistent findings on Kaplan-Meier analysis (HR, 0.61; 95% CI 0.57-0.66; P < 0.001). Subgroup analyses showed consistent results in patients with and without active cancer, and also across different DOAC types (apixaban and rivaroxaban). No differences were observed in all-cause mortality. TSA confirmed sufficient evidence for both efficacy and safety outcomes. Reduced-dose DOACs were as effective as full-dose regimens in preventing recurrent VTE, with a better safety profile, suggesting they may be preferred for patients requiring extended anticoagulation, especially those at high risk of recurrence.

registration

CRD420251048675

study_type

Meta-analysis; Randomized Controlled Trials

sample_size

8781

RCTs_included

5

key_results

{'recurrent_VTE_RR': {'value': 0.94, '95%_CI': [0.68, 1.29], 'p_value': 0.7}, 'recurrent_VTE_HR': {'value': 0.89, '95%_CI': [0.78, 1.02], 'p_value': 0.1}, 'bleeding_RR': {'value': 0.71, '95%_CI': [0.61, 0.82], 'p_value': '<0.0001'}, 'bleeding_HR': {'value': 0.61, '95%_CI': [0.57, 0.66], 'p_value': '<0.001'}, 'mortality': 'No significant difference'}

subgroup_results

['Results consistent in patients with and without active cancer', 'Consistent across apixaban and rivaroxaban']

tsa_results

Sufficient evidence for both efficacy and safety outcomes

conclusion

Reduced-dose DOACs are as effective as full-dose for preventing recurrent VTE and offer improved safety, supporting their use for extended anticoagulation, particularly in high recurrence risk patients.

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

3. 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

date

2025-09-16

impact_factor

4.57

quartile

Q1

doi

10.1212/WNL.0000000000214140

pmid

40953341

design

Meta-analysis of retrospective cohort studies

objective

To evaluate the safety of direct oral anticoagulants (DOACs) versus low-molecular-weight heparin (LMWH) with respect to intracranial hemorrhage (ICH) risk in patients with brain tumors on therapeutic anticoagulation.

databases_searched

['MEDLINE', 'Embase', 'Web of Science', 'Cochrane Central Register of Controlled Trials']

search_period

January 2010 - June 2025

inclusion_criteria

['Adults (≥18 years) with primary or metastatic brain tumors', 'Therapeutic use of DOACs (apixaban, rivaroxaban, edoxaban, betrixaban, dabigatran) or LMWH (enoxaparin, dalteparin, nadroparin, tinzaparin)']

exclusion_criteria

['Prophylactic dosing', 'Non-brain tumor patients']

registration

PROSPERO (CRD42025635334)

studies_included

10

patients_total

1572

doac_patients

645

lmwh_patients

895

age_range_doac

60.4-67 years (mean/median)

age_range_lmwh

53-64 years (mean/median)

followup_duration

3-12 months

main_outcome

Risk ratio (RR) of any intracranial hemorrhage (ICH)

main_results

{'overall': {'RR': 0.5, 'CI_95': '0.29–0.87', 'p_value': 0.01, 'I2': '49.50%'}, 'three_month_followup': {'RR': 0.23, 'CI_95': '0.09–0.57', 'p_value': '<0.01', 'I2': '<0.01%'}, 'primary_brain_tumors': {'studies': 5, 'RR': 0.2, 'CI_95': '0.08–0.54', 'p_value': '<0.01', 'I2': '<0.01%'}, 'metastatic_brain_tumors': {'studies': 5, 'RR': 0.86, 'CI_95': '0.44–1.68', 'p_value': 0.66, 'I2': '36.04%'}}

robustness_checks

{'leave_one_out': 'Confirmed robustness', 'cumulative_meta_analysis': 'Stable estimates with narrowing CIs'}

publication_bias

{'Egger_test_p': 0.19, 'Begg_test_p': 0.59, 'evidence': 'No statistical evidence of publication bias'}

conclusion

DOACs are associated with significantly lower ICH risk than LMWH in anticoagulated brain tumor patients, particularly those with primary brain tumors. Findings support DOACs as a safe option for arterial and venous thromboembolism; however, observational design warrants cautious interpretation.

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

4. 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

publication_date

2025-04-21

impact_factor

5.35

quartile

Q1

doi

10.3389/fphar.2025.1615284

pmid

40949128

trial_registry

{'url': 'http://www.clinicaltrials.gov', 'identifier': 'CRD42024510727'}

background

The choice of oral anticoagulants for patients with chronic kidney disease (CKD) combined with atrial fibrillation (AF) or venous thromboembolism (VTE) remains controversial.

objective

To compare the efficacy and safety of warfarin and direct oral anticoagulants (DOACs) in the treatment of CKD with AF or VTE.

methods

{'data_sources': ['PubMed', 'Embase', 'Web of Science', 'Cochrane Library', 'ClinicalTrials.gov'], 'search_end_date': '2024-06-30', 'study_selection': 'Randomized controlled trials (RCTs) assessing the efficacy and safety of warfarin and DOACs for treating CKD with AF or VTE.', 'outcomes': [{'population': 'CKD with VTE', 'efficacy': 'thrombosis recurrence or VTE-related deaths', 'safety': 'major bleeding'}, {'population': 'CKD with AF', 'efficacy': 'stroke or systemic embolism', 'safety': 'major bleeding'}], 'risk_of_bias_tool': "Cochrane Collaboration's tool"}

results

{'studies_screened': 540, 'studies_included': 15, 'participants': 16361, 'AF_with_CKD': {'hemorrhagic_stroke': {'intervention': 'DOACs', 'comparator': 'warfarin', 'risk_ratio': 0.455, 'confidence_interval': '0.275-0.752', 'p_value': 0.002, 'direction': 'DOACs reduced risk'}, 'ischemic_stroke': {'difference': 'not significant'}, 'major_bleeding': {'intervention': 'DOACs', 'comparator': 'warfarin', 'risk_ratio': 0.604, 'confidence_interval': '0.442-0.825', 'p_value': 0.002, 'direction': 'DOACs reduced risk'}, 'intracranial_bleeding': {'intervention': 'DOACs', 'comparator': 'warfarin', 'risk_ratio': 0.424, 'confidence_interval': '0.287-0.626', 'p_value': '<0.001', 'direction': 'DOACs reduced risk'}}, 'VTE_with_CKD': {'recurrent_vte_or_vte_death': {'risk_ratio': 0.663, 'confidence_interval': '0.409-1.073', 'p_value': 0.094, 'difference': 'not significant'}, 'major_bleeding': {'risk_ratio': 0.543, 'confidence_interval': '0.209-1.407', 'p_value': 0.208, 'difference': 'not significant'}}}

conclusion

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

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