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

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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175Bleeding and cardiovascular risk of New Oral Anti-Coagulants (NOACs) versus warfarin in type 2 diabetes

International Journal of Epidemiology ◽

10.1093/ije/dyab168.738 ◽

2021 ◽

Vol 50 (Supplement_1) ◽

Author(s):

Dahai Yu ◽

Julian Brown ◽

David Simmons

Keyword(s):

Type 2 Diabetes ◽

General Practice ◽

Oral Anticoagulants ◽

Exact Matching ◽

Bleeding Events ◽

Entropy Balancing ◽

Replication Studies ◽

Risk Of Bleeding ◽

Relative Risks

Abstract Background New oral anticoagulants (NOACs) (vs warfarin) in the general population are associated with 34% less major bleeding events. We compared the risk of bleeding and cardiovascular disease (CVD) events between NOACs and warfarin in people with type 2 diabetes (T2DM). Methods Incident NOAC users (cases) and matched controls (incident warfarin users) with T2DM were identified from within 40 UK general practice records (1/4/2017-31/3/2018). Coarsened Exact Matching restricted the comparison to areas of sufficient overlap in characteristics (i-iv) and missingness. Entropy Balancing sequentially balanced NOAC and warfarin users on their distribution of (i) age, sex, general practice, first anticoagulant prescription year, diabetes duration, (ii) body mass index, systolic blood pressure, total cholesterol, HbA1c, (iii) bleeding/CVD history, (iv) treatment (Antiplatelet, Corticosteroids, statins, anti-hypertensives, anti-diabetes treatment number). Continuous covariates were balanced for mean, variance, and skewness. Pre-processing/balancing occurred without reference to outcomes. Multivariable logistic regression modelling estimated bleeding and CVD relative risks (RRs: incident non-elective hospitalisation within 12 months since first anticoagulant prescription), identified from linked hospitalisation data (Secondary Uses Service dataset), using entropy balancing weights from steps i-iv. Results The twelve month RRs of bleeding with NOAC (n = 967) vs matched/balanced warfarin (n = 911) were 0.94(0.62-1.45), 0.95(0.62-1.46), 0.98(0.65-1.48) and 0.98(0.67-1.43) through steps i-iv. CVD RR was increased with NOAC treatment through steps i-iv: 1.15(1.00-1.31), 1.22(1.06-1.39), 1.34(1.13-1.60) and 1.43(1.20-1.70). Conclusion Among T2DM patients, risk of bleeding among NOAC and warfarin incident users was similar. However, NOAC use significantly increased the risk of CVD events. Further external replication studies are warranted.

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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 ◽

10.1093/europace/euz273 ◽

2019 ◽

Vol 22 (4) ◽

pp. 547-557 ◽

Cited By ~ 9

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 <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.

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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.

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