Dabigatran treatment simulation in patients undergoing maintenance haemodialysis

SummaryPatients with atrial fibrillation requiring maintenance haemodialysis are at increased risk of ischaemic stroke and bleeds. Currently, vitamin K antagonists such as warfarin are predominantly used in these patients as limited data are available on the use of non-vitamin K oral anticoagulants, including dabigatran etexilate (dabigatran). Dabigatran is approximately 85 % renally eliminated, thus, its half-life is prolonged in renal impairment. This study simulated the dose-exposure relationship of dabigatran in patients undergoing haemodialysis. Dabigatran exposure was modelled at once- and twice-daily doses of 75 mg, 110 mg and 150 mg and at variations in non-renal clearance and dialysis settings. Resultant dose exposure (area under the curve [AUC]) was compared with values simulated from typical patients in the RE-LY® trial (based on a previously characterised pharmacometric model). In this simulation, all twice-daily dosages resulted in exposures above those simulated from typical RE-LY patients (1.5- to 3.3-fold increase in AUC) and thus may not be optimal for use in haemodialysis patients. However, dabigatran doses of 75 mg or 110 mg once daily produced exposures comparable to those simulated in typical RE-LY patients (-13.3 and +4.4 %, respectively). Of patient and dialysis variables, non-renal clearance had the highest impact on exposure (≤30.8 % change). These data could potentially inform dose selection in patients undergoing maintenance haemodialysis and the findings warrant investigation in future clinical trials.

Download Full-text

Abstract 11473: Dabigatran Treatment Simulation in Patients Undergoing Maintenance Hemodialysis

Circulation ◽

10.1161/circ.132.suppl_3.11473 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Karl-Heinz Liesenfeld ◽

Andreas Clemens ◽

Joerg Kreuzer ◽

Martina Brueckmann ◽

Azhar Ahmad ◽

...

Keyword(s):

Renal Clearance ◽

Vitamin K ◽

Vitamin K Antagonists ◽

Dabigatran Etexilate ◽

Oral Anticoagulants ◽

Blood Flow Rate ◽

Fold Increase ◽

Maintenance Hemodialysis ◽

Once Daily ◽

Increased Risk

Background: Patients undergoing maintenance hemodialysis (HD) with atrial fibrillation (AF) are at increased risk of ischemic stroke and bleeds. At present, vitamin K antagonists, e.g. warfarin, are predominantly used for anticoagulation in this patient population. In such patients, limited data are available on the use of non-vitamin K oral anticoagulants. Dabigatran etexilate (DE) is mainly (85%) renally eliminated, thus its half-life is prolonged in renal impairment. It has been established that 4-hour HD can remove up to 60% of dabigatran from the plasma. The aim of the presented study is to evaluate the dose-exposure relationship for DE in HD patients considering different dosages and HD modalities by pharmacokinetic modeling. The resulting data could inform DE dose selection in future clinical trials. Method: We compared modeled DE exposure at once- and twice-daily doses of 75 mg, 110 mg, 150 mg in HD patients from pre- and post-dialysis dosing, with values simulated from AF patients in the RE-LY ® trial, based on a previously characterized pharmacometric model. Furthermore, variations in non-renal clearance, and several dialysis settings were simulated. Exposure (area under the curve, AUC) was compared to those from typical clinical HD settings. Results: Twice-daily DE doses showed a 1.5- to 3.3-fold increase in AUC of dabigatran compared with a typical RE-LY ® patient. A once-daily dose of 75 mg given after dialysis or 110 mg given before dialysis achieved an AUC comparable (-13.3 and +4.4%, respectively) to typical RE-LY ® patients. Of the patient and dialysis variables, non-renal clearance had the highest impact on exposure (≤ 31% change). Duration of dialysis, dialysate and blood flow rate changed exposure by ≤14%. Conclusion: Twice-daily dosing of all DE doses tested in this simulation resulted in exposures clearly above what can be seen in typical RE-LY ® patients and thus might not be recommendable, although this is based on modeling only and the clinical impact is unknown. In patients undergoing maintenance HD, DE 75 mg once daily (given after dialysis) or 110 mg once daily (given before dialysis), resulted in exposure comparable to that simulated in typical RE-LY ® patients.

Download Full-text

New Oral Anticoagulants vs. Vitamin K Antagonists Among Patients With Cardiac Amyloidosis: Prognostic Impact

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.742428 ◽

2021 ◽

Vol 8 ◽

Author(s):

Eve Cariou ◽

Kevin Sanchis ◽

Khailène Rguez ◽

Virginie Blanchard ◽

Stephanie Cazalbou ◽

...

Keyword(s):

Vitamin K ◽

Cardiac Amyloidosis ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Bleeding Complications ◽

Prognostic Impact ◽

Transthyretin Amyloidosis ◽

Increased Risk ◽

All Cause Mortality ◽

History Of

Background: Atrial arrhythmia (AA) is common among patients with cardiac amyloidosis (CA), who have an increased risk of intracardiac thrombus. The aim of this study was to explore the prognostic impact of vitamin K-antagonists (VKA) and direct oral anticoagulants (DOAC) in patients with CA.Methods and Results: 273 patients with CA and history of AA with long term anticoagulation−69 (25%) light chain amyloidosis (AL), 179 (66%) wild-type transthyretin amyloidosis (ATTRwt) and 25 (9%) variant transthyretin amyloidosis (ATTRv)–were retrospectively included between January 2012 and July 2020. 147 (54%) and 126 (46%) patients received VKA and DOAC, respectively. Patient receiving VKA were more likely to have AL with renal dysfunction, higher NT-proBNP and troponin levels. Patients with ATTRwt were more likely to receive DOAC therapy. There were more bleeding complications among patients with VKA (20 versus 10%; P = 0.013) but no difference for stroke events (4 vs. 2%; P = 0.223), as compared to patients with DOAC. A total of 124 (45%) patients met the primary endpoint of all-cause mortality: 96 (65%) and 28 (22%) among patients with VKAs and DOACs, respectively (P < 0.001). After multivariate analysis including age and renal function, VKA was no longer associated with all-cause mortality.Conclusion: Among patients with CA and history of AA receiving oral anticoagulant, DOACs appear to be at least as effective and safe as VKAs.

Download Full-text

HEMATURIA AND OTHER KINDS OF BLEEDINGS ON NON-VITAMIN K ANTAGONIST ORAL ANTICOAGULANTS IN PATIENTS WITH ATRIAL FIBRILLATION: AN UPDATED OVERVIEW ON OCCURRENCE, PATHOMECHANISMS AND MANAGEMENT

Wiadomości Lekarskie ◽

10.36740/wlek202011135 ◽

2020 ◽

Vol 73 (11) ◽

pp. 2528-2534

Author(s):

Dagmara Wojtowicz ◽

Anna Tomaszuk-Kazberuk ◽

Jolanta Małyszko ◽

Marek Koziński

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Anticoagulant Activity ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

Bleeding Complications ◽

Reversal Agents ◽

Limited Availability ◽

Increased Risk

Non-vitamin K antagonist oral anticoagulants (NOACs) are currently recommended for oral anticoagulation in patients with non-valvular atrial fibrillation. In the setting, NOACs effectively prevent from stroke and systemic embolic events. In spite of the favorable safety profile of NOACs when compared with vitamin K antagonists, the use of any kind of anticoagulation is associated with an increased risk of bleeding. However, there is still a lack of direct comparisons of effectiveness and safety among NOACs. The results of indirect comparisons and meta-analyses suggest that the risk of various types of hemorrhagic complications differ among the particular NOACs. Management of bleeding in patients under NOAC therapy can be challenging because of limited availability of antidotes and the lack of routine laboratory test monitoring the NOAC anticoagulant effect. In case of life-threatening or critical site bleeding, reversal of NOAC anticoagulant activity is essential together with immediate implementation of causative treatment. Moreover, some patients on chronic NOAC therapy may require urgent surgery or invasive procedures. Specific reversal agents for NOACs have been developed, i.e. more widely available idarucizumab for the factor IIa inhibitor (dabigatran) and andexanet alfa for the factor Xa inhibitors (rivaroxaban, apixaban, edoxaban) with limited availability. This review summarizes the occurrence and management of NOAC-related bleeding complications with a particular emphasis on hematuria.

Download Full-text

RE-COVERY DVT/PE: Rationale and design of a prospective observational study of acute venous thromboembolism with a focus on dabigatran etexilate

Thrombosis and Haemostasis ◽

10.1160/th16-07-0566 ◽

2017 ◽

Vol 117 (02) ◽

pp. 415-421 ◽

Cited By ~ 6

Author(s):

Walter Ageno ◽

Ivan B. Casella ◽

Chee Kok Han ◽

Gary E. Raskob ◽

Sebastian Schellong ◽

...

Keyword(s):

Venous Thromboembolism ◽

Vitamin K ◽

Large Scale ◽

Vitamin K Antagonists ◽

Phase 1 ◽

Dabigatran Etexilate ◽

Oral Anticoagulants ◽

Phase Iii ◽

Real World Data ◽

Phase Iii Studies

SummaryThe therapeutic management of venous thromboembolism (VTE) is rapidly evolving. Following the positive results of pivotal large-scale randomised trials, the non-vitamin K antagonist oral anticoagulants (NOACs) represent an important alternative to standard anticoagulation. In phase III studies, dabigatran was as effective as, and significantly safer than warfarin. Additional information on real-world data of dabigatran is now warranted. RE-COVERY DVT/PE is a multi-centre, international, observational (i. e. non-interventional) study enrolling patients with acute DVT and/or PE within 30 days after objective diagnosis. The study is designed with two phases. Phase 1 has a cross-sectional design, enrolling approximately 6000 patients independently of treatment choice, with the aim of providing a contemporary picture of the management of VTE worldwide. Phase 2 has a prospective cohort design, with follow-up of one year, enrolling 8000 patients treated with dabigatran or vitamin K antagonists (VKAs) with the aim of comparing their safety, defined by the occurrence of major bleeding, and effectiveness, defined by the occurrence of symptomatic recurrent VTE. RE-COVERY DVT/PE will complement both the results of other observational studies in this field and the results of phase III studies with dabigatran, in particular by assessing its clinical benefit in various patient subgroups treated in routine clinical practice.

Download Full-text

Patients Taking Direct Oral Anticoagulants (DOAC) Undergoing Oral Surgery: A Review of the Literature and a Proposal of a Peri-Operative Management Protocol

Healthcare ◽

10.3390/healthcare8030281 ◽

2020 ◽

Vol 8 (3) ◽

pp. 281

Author(s):

Saturnino Marco Lupi ◽

Arianna Rodriguez y Baena

Keyword(s):

Vitamin K ◽

Oral Surgery ◽

Dabigatran Etexilate ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

Thrombin Inhibitor ◽

Review Of The Literature ◽

Risk Of Bleeding ◽

Management Protocol ◽

Increased Risk

Patients on anticoagulant therapy for the prevention of cardiovascular accidents present an increased risk of bleeding following dental and oral surgery. Four recently introduced non-vitamin K antagonist oral anticoagulants, namely dabigatran etexilate (direct thrombin inhibitor), rivaroxaban, apixaban, and edoxaban (Xa factor direct inhibitor), are widely spreading for convenience of use compared to the older drug class. Dental management of patients taking these drugs has substantial differences compared to patients on vitamin K antagonist therapy. Anticoagulation is not assessed directly through a hematological test, but indirectly by renal function. The interventions must be scheduled at the time of minimum blood concentration of the drug. Bleeding can occur even after several days following the surgery. The interaction with drugs administered for dental care must be carefully evaluated. The peri-operative diet can influence the risk of bleeding. Local measures favoring coagulation must be adopted. The interventions with higher risk must be divided into multiple less invasive interventions. Although antidotes exist for these drugs, their use does not seem necessary for dental interventions that have been planned optimally. Furthermore, in this review of the literature a decision protocol is proposed for the evaluation of the suspension of the anticoagulant drug before oral surgery. Cessation of any anticoagulant should only be made in consultation with the patient’s general practitioner/cardiologist, who will weigh up the risk of bleeding from the proposed procedure with the risk of thrombosis/stroke in each individual patient.

Download Full-text

Men who live alone have high risk of NOAC discontinuation

European Heart Journal ◽

10.1093/ehjci/ehaa946.2425 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

C Binding ◽

J.B Olesen ◽

C Lee ◽

C Sindet-Petersen ◽

C.T Pedersen ◽

...

Keyword(s):

Vitamin K ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

Male Gender ◽

Living Alone ◽

Funding Source ◽

Hazard Ratios ◽

Increased Risk ◽

And Gender

Abstract Background/Introduction Patients with atrial fibrillation (AF), who are considered at risk of stroke, are treated with oral anticoagulants (OACs), and non-vitamin K antagonist oral anticoagulants (NOACs) are preferred over vitamin K antagonists in recent guidelines. Poor NOAC compliance among patients with AF could result in an increased risk of thromboembolism and major bleeding, however, it has yet to be evaluated how cohabitant status and gender affects compliance with NOAC treatment among patients with AF. Purpose The aim of this study was to evaluate the risk of NOAC discontinuation among patients with AF according to cohabitant status and gender. Methods Using the Danish national registries we identified and included patients with AF aged 40–90 years in treatment with NOAC. The study period was from 2013 to 2017, and patients were followed for two years, or until death, outcome or emigration. The main outcome was discontinuation of NOAC-treatment for at least 30 days. Absolute risks were calculated as cumulative incidences using the Aalen Johansen estimator, and multiple covariate adjusted Cox regressions were used to calculate hazard ratios (HR). Results We included 32,380 patients with AF in NOAC treatment, where 16.8% were men living alone (median age 72 years), 25.8% were women living alone (median age 79 years), 37.2% were men living with a partner (median age 70 years), and 20.2% were women living with a partner (median age 79 years). Absolute two-year risk of NOAC discontinuation was highest among men living alone (Cumulative Incidence (CI) 0.19; 95% CI: 0.17 to 0.20), followed by men living with a partner (CI 0.18; 0.17 to 0.19), women living with a partner (CI 0.16; 0.15 to 0.17), and women living alone (CI 0.13; 0.12 to 0.14). After adjustment, living alone was associated with an increased risk of NOAC discontinuation among men (HR 1.15, 95% CI: 1.05 to 1.26), but not among women (HR 1.04, 95% CI: 0.93 to 1.15, interaction p=0.32). In an analysis evaluating gender, we found that being male was associated with a significantly higher risk of NOAC-discontinuation (HR 1.18, CI: 1.10 to 1.25) compared to women. Results were similar when we used 60 days discontinuation instead of 30 days discontinuation as outcome. Conclusion Gender and cohabitant status was significantly associated with risk of NOAC discontinuation. Male gender and living alone was associated with a higher risk of NOAC discontinuation among patients with AF in a nationwide population. Adjusted relative two-year risks Funding Acknowledgement Type of funding source: None

Download Full-text

P4757Vitamin k antagonists are associated with higher risk of osteoporotic fractures compared to non-vitamin k antagonist oral anticoagulants among atrial fibrillation patients: a nationwide cohort study

European Heart Journal ◽

10.1093/eurheartj/ehz745.1133 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

C Binding ◽

J B Olesen ◽

B Abrahamsen ◽

L Staerk ◽

G Gislason ◽

...

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Lower Risk ◽

Absolute Risk ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Osteoporotic Fractures ◽

University Hospital ◽

Osteoporosis Medication ◽

Increased Risk

Abstract Background/Introduction Osteoporotic fractures are associated with high mortality and reduced life quality in an elderly population. Several studies report an increased risk of fractures among patients treated with oral anticoagulants (OAC), however, only sparse research has been made to clarify the difference between treatment with vitamin K antagonists (VKA) and non-VKA oral anticoagulants (NOACs) regarding the risk of osteoporotic fractures. Purpose The purpose of this study was to evaluate the risk of osteoporotic fractures among patients with atrial fibrillation (AF) in long-term VKA or NOAC treatment. Methods Patients with AF were identified using Danish national registries and were included when they had undergone 180 days OAC treatment, and only if they had no prior use of osteoporosis medication. The study period was from 1 January 2013 until 30 June 2017, and patients were followed for 2 years, or until death, outcome or emigration. Outcomes were hip fracture, major osteoporotic fracture, any fracture, initiation of osteoporosis medication, and a combined endpoint. G-formula was used to determine standardized absolute risk, and multiple covariate adjusted Cox regressions were used to calculate hazard ratios (HR). Results Overall, 37,350 patients with AF were included; 32.6% received VKA treatment (median age 72 years, 61.8% men) and 67.4% received NOAC treatment (median age 73 years, 55.9% men). The standardized absolute 2-year risk of any fracture was low among NOAC treated patients (3.1%; 95% CI: 2.9% to 3.3%), and among VKA treated patients (3.8%; 95% CI: 3.4% to 4.2%). NOAC was associated with a significantly lower relative risk of any fracture (HR: 0.85; 95% CI: 0.74 to 0.97), of major osteoporotic fractures (HR: 0.85; 95% CI: 0.72 to 0.99), and of initiating osteoporotic medication (HR: 0.82; 95% CI: 0.71 to 0.95). A combined endpoint showed that patients treated with NOAC had a significantly lower risk of suffering from any fracture or initiating osteoporosis medication (HR: 0.84; 95% CI: 0.76 to 0.93). Adjusted relative two-year risks Conclusion In a nationwide population, the absolute risk of osteoporotic fractures was low among AF patients on OAC, but NOAC was associated with a significantly lower risk of osteoporotic fractures compared to VKA. Acknowledgement/Funding Scholarship from The Copenhagen University Hospital Herlev and Gentofte

Download Full-text

Atrial Fibrillation and Malignancy: The Clinical Performance of Non–Vitamin K Oral Anticoagulants—A Systematic Review

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0038-1661386 ◽

2018 ◽

Vol 45 (02) ◽

pp. 205-214 ◽

Cited By ~ 11

Author(s):

Roberta Bottino ◽

Anna Rago ◽

Pierpaolo Micco ◽

Antonio D' Onofrio ◽

Biagio Liccardo ◽

...

Keyword(s):

Atrial Fibrillation ◽

Systematic Review ◽

Vitamin K ◽

Clinical Performance ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Anticoagulation Therapy ◽

Therapeutic Anticoagulation ◽

Increased Risk ◽

Active Cancer

AbstractAtrial fibrillation (AF) is commonly diagnosed in the setting of active cancer. Because of an increased risk of either thromboembolic events or bleeding, the decision to initiate therapeutic anticoagulation in patients with active cancer can be challenging. Moreover, little is still known about the optimal anticoagulation therapy in the setting of AF and cancer, and no guidelines are as yet available. Considering that nonvitamin K antagonist oral anticoagulants (NOACs) are recommended as alternatives to vitamin K antagonists for stroke prevention in AF patients with CHA2DS2-VASc score ≥2, the authors performed a systematic review of the current literature to describe the efficacy and safety of NOACs in AF patients with malignancy.

Download Full-text

Idarucizumab, a Specific Antidote for Dabigatran: Immediate, Complete and Sustained Reversal of Dabigatran Induced Anticoagulation in Elderly and Renally Impaired Subjects

Blood ◽

10.1182/blood.v124.21.344.344 ◽

2014 ◽

Vol 124 (21) ◽

pp. 344-344 ◽

Cited By ~ 38

Author(s):

Stephan Glund ◽

Joachim Stangier ◽

Michael Schmohl ◽

Viktoria Moschetti ◽

Wouter Haazen ◽

...

Keyword(s):

Vitamin K Antagonists ◽

Dabigatran Etexilate ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Anticoagulant Effect ◽

Thrombin Time ◽

Double Blind ◽

Male And Female ◽

Increased Risk ◽

Pharmacologically Active

Abstract Introduction Oral anticoagulation is an effective therapy to prevent and treat thromboembolic events. So far, Vitamin K antagonists have been the main drug of choice. Recently, the advent of the direct oral anticoagulants (DOAC) has changed medical practice significantly; nevertheless all anticoagulants are associated with an increased risk of bleeding. Bleeding management can be achieved through established therapies; however specific antidotes are not yet available for these agents to further facilitate patient management in cases needed. Previously the dabigatran antidote (idarucizumab) has demonstrated immediate, complete and sustained reversal of dabigatran induced anti-coagulation in healthy male volunteers. In the present study it was determined whether and to what extent doses of up to 5 g idarucizumab would reverse the anticoagulant effects of dabigatran in male and female healthy mid-aged, elderly and renally impaired volunteers. In addition, it was tested whether oral intake of dabigatran etexilate 24 hrs after idarucizumab treatment could restore dabigatran related anticoagulation. It was further tested if a second administration of idarucizumab 2 months later was safe and well tolerated. Methods Safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of idarucizumab were investigated in a randomized, double-blind, placebo controlled two-way cross-over study in 46 male and female volunteers. Dabigatran etexilate (DE), 220 mg bid in healthy subjects and 150 mg bid in subjects with mild or moderate renal impairment (CLCR60 to <90 or 30 to <60 [mL/min], respectively) was given over 4 days to achieve the steady state conditions. Idarucizumab doses of 1 g, 2.5 g, 5 g or 5 g given as 2x2.5 g one hour apart were administered as 5 min i.v. infusion 2 hrs after the last dose of DE. Concentrations of unbound dabigatran were determined as a measure of pharmacologically active dabigatran. The anticoagulant effect of dabigatran and its reversal were assessed by coagulation time measurements, including diluted Thrombin Time (dTT, Hemoclot® DTI assay), Ecarin Clotting Time (ECT) and activated Partial Thromboplastin Time (aPTT). Results All administered doses of idarucizumab were safe and well tolerated. PK measurements of unbound dabigatran indicated that idarucizumab binding and thus reversal of the anticoagulant effect of dabigatran occurred immediately after end of infusion. Prolongation of clotting times induced by dabigatran was reversed to baseline at the end of the 5 minute infusion of the antidote. This was consistently demonstrated by all clotting assays. Sustained reversal over the entire observation period was observed for idarucizumab doses of 2.5 g, 5 g and 2x2.5 g. For the 1g dose, there was partial return of dabigatran induced anticoagulation around 2-4 hours after i.v. infusion. Also a second administration of idarucizumab (two months after the first) was safe and resulted in complete reversal. In addition, PD and PK measurements at selected time points and in comparison to placebo treatment confirmed that effective dabigatran anticoagulation could be re-established 24 hours after administration of idarucizumab. Conclusions The dabigatran antidote, idarucizumab, was well tolerated under all conditions tested. The administration of 5 g or 2x2.5 g led to sustained reversal of dabigatran induced anticoagulation in male and female subjects of different age and renal function. In addition, idarucizumab administered 2 months apart achieved the same degree of reversal. Dabigatran anticoagulation could be re-established 24 hrs after idarucizumab dosing. These results support the use of a total dose of 5 g idarucizumab as an effective dose in further clinical testing. Disclosures Glund: Boehringer Ingelheim: Employment. Off Label Use: Idarucizumab, a specific antidote for dabigatran, is in clinical development.. Stangier:Boehringer Ingelheim: Employment. Schmohl:Boehringer Ingelheim: Employment. Moschetti:Boehringer Ingelheim: Employment. Haazen:SGS Life Science Services (contracted by Boehringer Ingelheim to conduct the study): Employment. De Smet:SCS Boehringer Ingelheim Comm. V.: Employment. Gansser:Boehringer Ingelheim: Employment. Norris:Boehringer Ingelheim: Employment. Lang:Boehringer Ingelheim: Employment. Reilly:Boehringer Ingelheim: Employment.

Download Full-text

DOACs vs Vitamin K Antagonists: a Comparison of Phase III Clinical Trials and a Prescriber Support Tool

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2019.289 ◽

2019 ◽

Vol 7 (7) ◽

pp. 1226-1232 ◽

Cited By ~ 1

Author(s):

Alina-Maria Pirlog ◽

Cristian Daniel Pirlog ◽

Marius Adrian Maghiar

Keyword(s):

Clinical Trials ◽

Vitamin K ◽

Primary Outcome ◽

Vitamin K Antagonists ◽

Dabigatran Etexilate ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Phase Iii ◽

Support Tool ◽

Phase Iii Clinical Trials

AIM: The purpose of this article was to systematically review the literature assessing the efficacy and safety of phase III clinical trials for each direct oral anticoagulant versus vitamin K antagonists and to design a ’’go-to’’ table for the prescriber. MATERIAL AND METHODS: A systematic review of specialist literature was conducted to identify RCTs which compared direct oral anticoagulants (DOACs) with standard warfarin treatment. Medline, Em-base, and the Cochrane databases were searched from January 2005- January 2019. The inclusion criteria were randomised controlled trials of oral anticoagulants in patients with non-valvular atrial fibrillation (NVAF). Four publications were phase III randomised control trials (RCTs) included in the final analysis. RESULTS: Regarding the primary outcome in RELY the results were 1.69% per 100-year patients (p/y) for Warfarin compared to 1.11% p/y dabigatran etexilate 150mg BD (twice daily). In ROCKET AF the rates of the primary outcome were 2.2% p/y for warfarin compared to 1.7% p/y for rivaroxaban 20 mg OD (once daily). In ARISTOTLE trial the rates of the primary outcome were 1.60% p/y for warfarin compared to 1.27% p/y for apixaban 5 mg BD. In ENGAGE AF TIMI, the rates of the primary outcome were 1.50% p/y for warfarin compared to 1.18% p/y for edoxaban 60mg BD. CONCLUSION: DOACs showed to be either noninferior or superior to warfarin with regards to the primary outcome with better safety patterns. Our ’’go-to’’ table provides a supportive tool for physicians in preventing medical errors when managing patients on oral anticoagulants.

Download Full-text