Herbal remedies and anticoagulant therapy

2005 ◽  
Vol 93 (01) ◽  
pp. 03-07 ◽  
Author(s):  
Noah Samuels
Keyword(s):  
Drug Interactions ◽  
Vitamin K ◽  
Anticoagulation Therapy ◽  
Vitamin K Antagonist ◽  
Herbal Remedies ◽  
Therapeutic Window ◽  
Sweet Clover ◽  
Increased Risk ◽  
Risk For Bleeding ◽  
Clover Plant

SummaryHerbal remedies, considered to be both safe and effective by most consumers, may interact with conventional drugs.Warfarin, a vitamin K antagonist originally derived from the sweet clover plant, has a narrow therapeutic window which can be monitored using prothrombin international normalized ratios (PT-INR). Many herbs can increase the risk for bleeding when combined with warfarin, either by augmenting the anticoagulant effects of the drug (with increased PT-INR levels) or through intrinsic anti-platelet properties (without altering PT-INR levels). The increased risk for bleeding among such patients may be difficult to predict, especially when formulas which contain many herbs are used. Further research into herb-drug interactions is warranted, as are guidelines for the use of herbal remedies by patients on chronic anticoagulation therapy.

scholarly journals Analysis of Influencing Factors of Compliance with Non-Vitamin K Antagonist Oral Anticoagulant in Patients with Nonvalvular Atrial Fibrillation and Correlation with the Severity of Ischemic Stroke

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Li Zhu ◽  
Xiaodan Zhang ◽  
Jing Yang
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Influencing Factors ◽  
Clinical Supervision ◽  
Vitamin K ◽  
Pearson Correlation ◽  
Anticoagulation Therapy ◽  
Vitamin K Antagonist ◽  
Nonvalvular Atrial Fibrillation ◽  
Increased Risk

Nonvalvular atrial fibrillation (NVAF) is associated with an increased risk of stroke and thrombus, and anticoagulant therapy is a key link in the prevention of stroke. At present, the anticoagulation rate of atrial fibrillation in China is low, and there are many factors affecting the adherence of patients with atrial fibrillation to anticoagulation. Non-vitamin K antagonist oral anticoagulants (NOACs) are anticoagulant with high application value due to their high safety and low risk of intracranial hemorrhage, stroke, and death. However, the compliance of NOACs is poor, and the current situation of anticoagulants in China is not optimistic. In this study, a total of 156 patients with NVAF who received NOAC anticoagulation therapy in our hospital from January 2018 to January 2019 were retrospectively analyzed. The results showed that education background, place of residence, number of complications, CHA2DS2-VASc score, and HAS-BLED score were independent influencing factors for NOACS compliance of NVAF patients. Also, the Pearson correlation analysis showed that there was a negative correlation (r = −0.465, P < 0.001 ) between NOAC compliance and severity of ischemic stroke in patients with NVAF. Therefore, clinical supervision and management of patients with NVAF after NOACs should be strengthened to improve the compliance of patients with NVAF after NOACs, reduce the damage of ischemic stroke, and improve their prognosis.

Prevalence of drug-drug interactions for oral anticoagulant drugs in patients with atrial fibrillation and relationship with outcomes: a population-based cohort study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Proietti ◽  
L Cortesi ◽  
F Spagnoli ◽  
A Nobili ◽  
A Marengoni
Keyword(s):  
Atrial Fibrillation ◽  
Drug Interactions ◽  
Vitamin K ◽  
Oral Anticoagulants ◽  
Population Based ◽  
Vitamin K Antagonist ◽  
Administrative Databases ◽  
Italian Region ◽  
Increased Risk ◽  
Anticoagulant Drugs

Abstract Introduction The introduction of non-vitamin K antagonist oral anticoagulants (NOACs) changed the treatment of atrial fibrillation (AF) patients, promising a better safety profile and a lower chance of interaction with drugs than vitamin K antagoniste (VKA). Aim To evaluate the prevalence of possible drug-drug interactions (DDIs) in a cohort of newly anticoagulated AF patients, their impact on outcomes and possible differences between VKA and NOACs users. Methods We performed an analysis derived from administrative databases in Lombardy Italian region. All patients ≥40 years admitted from 01/06/2013 to 30/06/2018 with an AF diagnosis that were VKA or NOACs new users were included in this analysis. Possible DDIs were evaluated according to the prescription of OAC therapy, on the basis of current available evidence. Stroke, intracerebral hemorrhage (ICH), any bleeding and all-cause death were the study outcomes. Results Among the 122816 patients included in the analysis, mean (SD) age 76.3 (9.6) with 47.3% females, a mean (SD) CHA2DS2-VASc of 3.5 (1.4) was found. A total of 70180 (57.1%) patients were prescribed with VKA and 52636 (42.9%) with NOACs. A possible DDI was recorded in 63273 (51.5%). Patients exposed to DDIs were older and less likely female (both p&lt;0.0001) and with a higher mean (SD) CHA2DS2-VASc (p&lt;0.0001). Rate of stroke, ICH, any bleeding and all-cause death were higher in those patients exposed to DDIs (all p&lt;0.001). After full adjustment, exposure to possible DDIs was associated with an increased risk for any bleeding (HR: 1.08, 95% CI: 1.05–1.12) and all-cause death (HR: 1.10, 95% CI: 1.07–1.13), with no differences for stroke and ICH. Comparing VKA and NOACs patients exposed to possible DDIs, we found that VKA users exposed to possible DDIs, after adjustments, were at higher risk for all the outcomes (Table). Conclusions In a large cohort of AF patients newly prescribed with OAC, possible DDIs were largely prevalent, in particular in VKA users. Presence of a possible DDI is associated with an increased risk of any bleeding and all-cause death. VKA users exposed to a possible DDI were at higher risk for any outcome than NOACs users exposed to a possible DDI. Funding Acknowledgement Type of funding source: None

453Use of Non-vitamin K antagonist Oral Anticoagulants in a real-world setting: a community pharmacy-based study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Capiau ◽  
E Mehuys ◽  
I Van Tongelen ◽  
T De Backer ◽  
T Christiaens ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Vitamin K ◽  
Real World ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Medication Possession Ratio ◽  
Heart Rhythm ◽  
Vitamin K Antagonist ◽  
Cross Sectional

Abstract Background The emergence of non-vitamin K antagonist oral anticoagulants (NOAC) has caused a paradigm shift in anticoagulation therapy, with NOAC being increasingly used compared to vitamin K antagonists. Despite the numerous RCTs with NOAC, further follow-up on how this high risk new drug class is used in real-world clinical practice is warranted. Purpose This study aimed to describe NOAC use in a primary care sample of long-term NOAC users, and investigated (i) adherence, (ii) patients' perceptions, (iii) drug interactions and (iv) appropriateness of dosing. Methods A cross-sectional observational study was conducted in 158 community pharmacies. Participants were home-dwelling adults treated with a NOAC for at least one year. They completed a questionnaire collecting data on socio-demographics, clinical characteristics, current medication use, self-reported adherence to NOAC (via Medication Adherence Report Scale, MARS), and beliefs and perceptions about NOAC (via Beliefs about Medicines Questionnaire, BMQ). Adherence to NOAC (self-reported (MARS) and calculated using pharmacy dispensing data (Medication Possession Ratio (MPR)); patients' beliefs and perceptions about NOAC (BMQ); and prevalence of drug interactions and inappropriate dosing (using the recommendations in the summary of product characteristics (SmPC) and the 2018 European Heart Rhythm Association (EHRA) Practical Guide) were assessed. Results Participants (n=766) had a mean age of 76.2±8.8 years, several co-morbidities (median of 5 (IQR 4–6)) and high thromboembolic risk (median CHA2DS2-VASc score of 4 (IQR 3–4)). The majority (93.5%) used NOAC for non-valvular atrial fibrillation, while the other 6.5% used it for the prevention of recurrent deep vein thrombosis or pulmonary embolism. Forty point five percent of the study sample used rivaroxaban, 36.2% apixaban, 21.1% dabigatran and 2.2% edoxaban. About 85% was adherent according to MPR (MPR ≥80%) and self-reported adherence was also high (mean MARS score 24.6±1.0). Two-thirds reported at least one adverse event of the NOAC, with easy bruising/bleeding being most prevalent (40.2% of patients). BMQ showed that 91.3% of patients favoured the “necessity” over the “concerns” of NOAC use. Thirty-one percent of patients had ≥1 drug interaction(s) with NOAC; amiodarone (10.4% of patients), antiplatelet agents (9.7%) and NSAIDs (9.0%) were the most common interacting drugs. NOAC dosing was inappropriate in 15.9% of patients according to SmPC and in 23.1% according to EHRA. Intriguingly, underdosing was more common using the SmPC as reference, while overdosing was more common using the EHRA guideline. Conclusions This real-world analysis of NOAC use revealed high adherence and necessity beliefs, drug interactions in 30% of patients, and suboptimal dosing in about one fifth of patients. These findings can inform the design of targeted community pharmacist interventions to improve quality of NOAC use.

scholarly journals Vitamin K antagonist anticoagulant usage is associated with increased incidence and progression of osteoarthritis

2021 ◽  
Vol 80 (5) ◽  
pp. 598-604
Author(s):  
Cindy G Boer ◽  
Ingrid Szilagyi ◽  
N Long Nguyen ◽  
Tuhina Neogi ◽  
Ingrid Meulenbelt ◽  
...  
Keyword(s):  
Vitamin K ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Matrix Gla Protein ◽  
Study Cohort ◽  
Single Nucleotide Variants ◽  
Increased Risk ◽  
Coagulation Proteins ◽  
Clinical Prevention

ObjectivesVitamin K is hypothesised to play a role in osteoarthritis (OA) pathogenesis through effects on vitamin K-dependent bone and cartilage proteins, and therefore may represent a modifiable risk factor. A genetic variant in a vitamin K-dependent protein that is an essential inhibitor for cartilage calcification, matrix Gla protein (MGP), was associated with an increased risk for OA. Vitamin K antagonist anticoagulants (VKAs), such as warfarin and acenocoumarol, act as anticoagulants through inhibition of vitamin K-dependent blood coagulation proteins. VKAs likely also affect the functioning of other vitamin K-dependent proteins such as MGP.MethodsWe investigated the effect of acenocoumarol usage on progression and incidence of radiographic OA in 3494 participants of the Rotterdam Study cohort. We also examined the effect of MGP and VKORC1 single nucleotide variants on this association.ResultsAcenocoumarol usage was associated with an increased risk of OA incidence and progression (OR=2.50, 95% CI=1.94–3.20), both for knee (OR=2.34, 95% CI=1.67–3.22) and hip OA (OR=2.74, 95% CI=1.82–4.11). Among acenocoumarol users, carriers of the high VKORC1(BB) expression haplotype together with the MGP OA risk allele (rs1800801-T) had an increased risk of OA incidence and progression (OR=4.18, 95% CI=2.69–6.50), while this relationship was not present in non-users of that group (OR=1.01, 95% CI=0.78–1.33).ConclusionsThese findings support the importance of vitamin K and vitamin K-dependent proteins, as MGP, in the pathogenesis of OA. Additionally, these results may have direct implications for the clinical prevention of OA, supporting the consideration of direct oral anticoagulants in favour of VKAs.

Non–Vitamin K Antagonist Oral Anticoagulants in the Treatment of Atrial Fibrillation

2019 ◽  
Vol 70 (1) ◽  
pp. 61-75 ◽  
Author(s):  
Alexander C. Fanaroff ◽  
E. Magnus Ohman
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Major Bleeding ◽  
Anticoagulant Activity ◽  
Oral Anticoagulants ◽  
Significant Risk ◽  
Vitamin K Antagonist ◽  
Therapeutic Window ◽  
Mechanical Valves ◽  
Frequent Monitoring

Atrial fibrillation (AF) increases a patient's stroke risk four- to five-fold. Anticoagulation with the vitamin K antagonist (VKA) warfarin reduces the risk of stroke by 67%, but warfarin carries a significant risk of major bleeding and has unpredictable pharmacodynamics with a narrow therapeutic window, necessitating frequent monitoring of its anticoagulant effect. The non–vitamin K antagonist oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, and edoxaban provide more predictable anticoagulant activity than warfarin with a lower risk of major bleeding, and each is noninferior to warfarin for the prevention of stroke. All have earned regulatory approval in the past eight years. At least one of the NOACs is approved for use in all patients with AF, except those with mechanical valves and rheumatic mitral valve disease, for whom warfarin remains the only option. Recent clinical trials have shown that antithrombotic regimens including NOACs are safe and effective in patients with AF who need potent antiplatelet therapy.

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

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.

scholarly journals The optimal drug adherence to maximize the efficacy and safety of non-vitamin K antagonist oral anticoagulant in real-world atrial fibrillation patients

EP Europace ◽  
2019 ◽  
Vol 22 (4) ◽  
pp. 547-557 ◽  
Author(s):  
Daehoon Kim ◽  
Pil-Sung Yang ◽  
Eunsun Jang ◽  
Hee Tae Yu ◽  
Tae-Hoon Kim ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Atrial Fibrillation ◽  
Ischaemic Stroke ◽  
Clinical Outcomes ◽  
Vitamin K ◽  
Major Bleeding ◽  
Oral Anticoagulant ◽  
Vitamin K Antagonist ◽  
Increased Risk ◽  
Optimal Drug

Abstract Aims To investigate the association between adherence to non-vitamin K antagonist oral anticoagulant (NOAC) and clinical outcomes and to determine the optimal cut-off level of NOAC adherence among patients with atrial fibrillation (AF). Methods and results Using the Korean National Health Insurance Service database, we identified 96 197 patients with non-valvular AF who initiated NOAC or warfarin in 2013–16. We compared clinical outcomes between adherent [proportion of days covered (PDC) ≥80%] vs. non-adherent (PDC &lt;80%) NOAC users, and further with warfarin users. We assessed the outcomes according to different levels of adherence. The proportion of adherent NOAC users was 64.0%. Compared with non-adherent NOAC users, adherent NOAC users were at lower risks of ischaemic stroke/systemic embolism (SE) [adjusted hazard ratio (aHR) 0.73, 95% confidence interval (CI) 0.69–0.79], and myocardial infarction (aHR 0.82, 95% CI 0.72–0.93), whereas there was no significant risk alteration for major bleeding (aHR 1.01, 95% CI 0.91–1.11). Compared with warfarin, non-adherent NOAC use failed to have better efficacy against ischaemic stroke/SE (aHR 0.99, 95% CI 0.93–1.05) and rather had increased risk of myocardial infarction (aHR 1.13, 95% CI 1.03–1.25). In NOAC users, the risks of adverse outcomes decreased according to gradual increase of adherence rates with the lowest risks in ≥90%, except for major bleeding in which there were no significant associations. Conclusions In an adherence level-dependent fashion, adherent use of NOAC showed better clinical outcomes without increasing bleeding risk. Maintaining ≥90% of adherence optimizes effectiveness of NOAC therapy without compromising its safety.

Factors associated with silent cerebral events during catheter ablation for atrial fibrillation in the era of uninterrupted oral anticoagulation therapy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Harada ◽  
Y Nomura ◽  
A Nishimura ◽  
Y Motoike ◽  
M Koshikawa ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Vitamin K ◽  
Oral Anticoagulation ◽  
Brain Mri ◽  
Anticoagulation Therapy ◽  
Surrogate Marker ◽  
Brain Magnetic Resonance Imaging ◽  
Vitamin K Antagonist ◽  
Factors Associated

Abstract Background A silent cerebral event (SCE), detected by brain magnetic resonance imaging (MRI), is defined as an acute new brain lesion without clinically apparent neurological deficit, and is frequently observed after catheter ablation in atrial fibrillation (AF) patients. Although the small number of SCEs does not cause neurocognitive dysfunction, the greater volume and/or larger number of SCE lesions are reportedly related to neuropsychological decline; SCE incidence may be a surrogate marker for the potential thromboembolic risk. Thus, strategies to reduce SCEs would be beneficial. Uninterrupted oral anticoagulation strategy for peri-procedural period reportedly reduced the risk of SCEs, but the incidence hovers at 10% to 30%. We sought factors associated with SCEs during catheter ablation for AF in patients with peri-procedural uninterrupted oral anticoagulation (OAC) therapy. Methods AF patients undergoing catheter ablation were eligible (n=255). All patients took non-vitamin K antagonist oral anticoagulants (NOACs) or vitamin K antagonist (VKA) for peri-procedural OAC (&gt;4 weeks) without interruption during the procedure. Brain MRI was performed within 2 days after the procedure to detect SCEs. Clinical characteristics and procedure-related parameters were compared between patients with and without SCEs. Results SCEs were detected in 59 patients (23%, SCE[+]) but not in 196 patients (77%, SCE[-]). Average age was higher in SCE[+] than SCE[-] (66±10 years vs. 62±12 years, p&lt;0.05). Persistent AF prevalence, CHADS2/CHA2DS2-VASc scores, and serum NT-ProBNP levels increased in SCE[+] vs. SCE[-]. In transthoracic/transesophageal echocardiography, left-atrial dimension (LAD) was larger and AF rhythm/spontaneous echo contrast were more frequently observed in SCE[+] than SCE[-]. SCE[+] had lower initial activated clotting time (ACT) before unfractionated heparin (UFH) injection and longer time to reach optimal ACT (&gt;300 sec) before trans-septal puncture than SCE [-]. In multivariate analysis, LAD, initial ACT before UFH injection, and time to reach optimal ACT were predictors for SCEs. Conclusions LAD and intra-procedural ACT kinetics affect SCEs during the procedure in patients with uninterrupted OAC for AF ablation. Shortening time to achieve optimal ACT during the procedure may reduce the risk of SCEs. Funding Acknowledgement Type of funding source: None

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

Healthcare ◽  
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.

scholarly journals Cardiovascular risks and bleeding with non-vitamin K antagonist oral anticoagulant versus warfarin in patients with type 2 diabetes: a tapered matching cohort study

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Dahai Yu ◽  
Zhanzheng Zhao ◽  
David Simmons
Keyword(s):  
Type 2 Diabetes ◽  
Vitamin K ◽  
Oral Anticoagulant ◽  
Large Scale ◽  
Vitamin K Antagonist ◽  
Exact Matching ◽  
Entropy Balancing ◽  
Risk Of Bleeding ◽  
Increased Risk

Abstract Background We compared the risk of bleeding and cardiovascular disease (CVD) events between non-vitamin K antagonist oral anticoagulant (NOAC) and warfarin in people with type 2 diabetes (T2DM). Methods 862 Incident NOAC users and 626 incident warfarin users with T2DM were identified from within 40 UK general practice (1/4/2017–30/9/2018). Outcomes included incident hospitalisation for bleeding, CVD and re-hospitalisation for CVD within 12 months since first anticoagulant prescription, identified from linked hospitalisation data. A tapered matching method was applied to form comparison cohorts: coarsened exact matching restricted the comparison to areas of sufficient overlap in missingness and characteristics: (i) demographic characteristics; (ii) clinical measurements; (iii) prior bleeding and CVD history; (iv) prescriptions with bleeding; (v) anti-hypertensive treatment(s); (vi) anti-diabetes treatment(s). Entropy balancing sequentially balanced NOAC and warfarin users on their distribution of (i–vi). Weighted logistic regression modelling estimated outcome odds ratios (ORs), using entropy balancing weights from steps i–vi. Results The 12-month ORs of bleeding with NOAC (n = 582) vs matched/balanced warfarin (n = 486) were 1.93 (95% confidence interval 0.97–3.84), 2.14 (1.03–4.44), 2.31 (1.10–4.85), 2.42 (1.14–5.14), 2.41 (1.12–5.18), and 2.51 (1.17–5.38) through steps i–vi. ORs for CVD re-hospitalisation was increased with NOAC treatment through steps i–vi: 2.21 (1.04–4.68), 2.13 (1.01–4.52), 2.47 (1.08–5.62), 2.46 (1.02–5.94), 2.51 (1.01–6.20), and 2.66 (1.02–6.94). Conclusions Incident NOAC use among T2DM is associated with increased risk of bleeding hospitalisation and CVD re-hospitalisation compared with incident warfarin use. For T2DM, caution is required in prescribing NOACs as first anticoagulant treatment. Further large-scale replication studies in external datasets are warranted.

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