• Korean Journal of Clinical Pharmacy
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• v.26 no.3
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• pp.207-212
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• 2016

Objective: Prescription rate of dabigatran and rivaroxaban, which are the direct oral anticoagulants (DOAC), has increased. We have analyzed the prescription trend and medication use of dabigatran and rivaroxaban in patients with non-valvular atrial fibrillation (NVAF). Methods: It was retrospectively studied from September 2012 to April 2014 using the electronic medical records and the progress notes. Patients with NVAF (n=424) were evaluated on the medication use, prescribing preferences, adverse drug reactions (ADRs) and the availability of prescription reimbursement of dabigatran (n=210) and rivaroxaban (n=214). Results: Dabigatran was prescribed higher than rivaroxaban (23.3% versus 7.5%, p<0.001) in the neurology department, but rivaroxaban was prescribed higher compared to dabigatran in the cardiology department (87.4% versus 74.3%, p<0.001). Dabigatran was prescribed more than rivaroxaban in high risk patients with CHADS2 score ${\geq}3$ (44.3% versus 31.3%, p=0.006). Dabigatran patients seemed to have more ADRs than patients with rivaroxaban (25.2% versus 11.2%, p<0.001), but no serious thrombotic events and bleeding were found. Only 35.6% (n=151) were eligible for prescription reimbursement by the National Health Insurance (NHI). Bridging therapy (86, 31.5%) and direct-current cardioversion (57, 20.2%) were main reasons of ineligibility for reimbursement. Conclusion: Prescription preferences were present in choosing either dabigatran or rivaroxaban for patients with NVAF. Inpatient protocols and procedures considering patient-factors in NVAF need to be developed.

• Journal of The Korean Society of Clinical Toxicology
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• v.12 no.2
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• pp.92-96
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• 2014

Dabigatran is the first oral direct thrombin inhibitor approved by the US Food and Drug Administration (FDA) for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Because dabigatran is excreted mainly by the kidneys, serum levels of dabigatran can be elevated to a supratherapeutic range in patients with renal failure, predisposing to emergent bleeding. We describe the case of a 66-year-old man taking dabigatran 150 mg twice daily for atrial fibrillation and cerebral infarction who presented with hematochezia and disseminated intravascular coagulation. Laboratory evaluation showed a hemoglobin level of 6.3 g/dL, platelets of $138,000/mm^3$, activated partial thromboplastin time (aPTT) of 10 s, and an international normalized ratio (INR) of 8.17. Colonoscopy showed a bleeding anal fissure. Hemostasis was provided by hemoclips and packed red blood cells and fresh frozen plasma were transfused. Since then, there was no further hematochezia, however, bleeding including oral mucosal bleeding, hematuria, and intravenous site bleeding persisted. At presentation, his serum creatinine was 4.96 mg/dL (baseline creatinine, 0.9 mg/dL). Dabigatran toxicity secondary to acute kidney injury was presumed. Because acute kidney injury of unknown cause was progressing after admission, he was treated with hemodialysis. Fresh frozen plasma transfusion was provided with hemodialysis. At 15 days from admission, there was no further bleeding, and laboratory values, including hemoglobin, partial thromboplastin time, and prothrombin time were normalized. He was discharged without bleeding. After 2 months, he undergoes dialysis three times per week and no recurrence of bleeding has been observed.

• Korean Journal of Clinical Pharmacy
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• v.32 no.1
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• pp.37-46
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• 2022

Background: Non-valvular atrial fibrillation (NVAF) is associated with ischemic stroke risk in the aging population. Observational studies have indicated beneficial effects of direct-acting oral anticoagulant (DOAC) against ischemic stroke compared to warfarin. This study aimed to investigate ischemic stroke incidence and bleeding risk in patients on DOAC therapy. Methods: Using the database of Korean Health Insurance Review and Assessment-Aged Patient Sample 2015, we conducted a retrospective cohort study. Study subjects with NVAF diagnosis and prescribed anticoagulants were enrolled. Propensity score (PS) matching by age, sex, comorbidities, and medications were used. The clinical outcomes were major adverse cerebro-cardiovascular events (MACCEs, ischemic stroke/systemic embolism, myocardial infarction, cardiac death) and bleeding events. A cox proportional hazard model analysis was performed to compare the outcomes with hazard ratio (HR) and 95% confidence interval (CI). Results: Total 4,773 elderly patients with NVAF were initially included. Four PS-matched groups including rivaroxaban vs. warfarin-only (n=1,079), dabigatran vs. warfarin-only (n=721), rivaroxaban vs. dabigatran (n=721), and switchers of warfarin to rivaroxaban vs. warfarin-only (n=287) were analyzed. Every group showed statistically similar results of MACCEs and bleeding events, except for the group of rivaroxaban vs. dabigatran. Rivaroxaban users showed higher risks of bleeding events than dabigatran users (HR 2.25, 95% CI 1.01-4.99). Conclusion: In the elderly patients with NVAF, efficacy and safety outcomes among oral anticoagulants including DOACs and warfarin were similar, while rivaroxaban are more likely to have higher bleeding risks than dabigatran. Further research using large size sample is needed.

• The Korean journal of helicobacter and upper gastrointestinal research
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• v.18 no.4
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• pp.219-224
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• 2018

New oral anticoagulants (NOACs) are now widely used for the prevention and treatment of venous thrombosis, and for the prevention of stroke and systemic embolism in patients with atrial fibrillation. As compared with warfarin, NOACs have the advantage of rapid onset of action and less drug interaction. However, they carry a higher risk of gastrointestinal (GI) bleeding than warfarin. The risk of GI bleeding in patients using NOACs varies according to the type and dose of the drug. By contrast, apixaban and edoxaban are reported to carry similar risks as warfarin, and the risks with dabigatran and rivaroxaban are higher than that with warfarin. In patients using NOACs, old age, impaired renal function, impaired liver function, concurrent use of antiplatelet agents, and nonsteroidal anti-inflammatory drugs are considered major risk factors of GI bleeding, and gastroprotective agents such as histamine-2 receptor antagonist and proton pump inhibitor have preventive effects. To prevent GI bleeding associated with NOACs, the characteristics of each NOAC and the risk factors of bleeding should be recognized.

• The Journal of the Korean life insurance medical association
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• v.32 no.2
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• pp.33-38
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• 2013

Coronary artery diseases are very important agenda in the insurance medicine. Insurance medicine is defined as using medical knowledge for insurance administration such as underwriting, claims, and customer satisfaction. This review article contains review of coronary artery disease in terms of insurance medicine. Estimation of extra-risks for acute myocardial infarction are MR of 349% and EDR of 41‰. In medical underwriting, individual life applicants can be assessed by Framingham's CHD risk assessment model. In claims, medical claims review is a useful method of consulting for claims staffs. Several diagnostic criteria of acute myocardial infarction are introduced in time. The universal definition of myocardial infarction by ESC/ACCF/WHF was demonstrated the most valuable predictor of 10-year mortality. Contents for State-Of-The-Art of the coronary artery disease are current antithrombotics. There are many novel anti-thrombotic agents such as ticagrelol, dabigatran, rivaroxaban, and pegnivacogin.

• Tuberculosis and Respiratory Diseases
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• v.77 no.3
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• pp.105-110
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• 2014

Venous thromboembolism (VTE), which includes pulmonary embolism and deep vein thrombosis, is an important cause of morbidity and mortality. The aim of this review is to summarize the findings from clinically important publications over the last year in the area of VTE. In this review, we discuss 11 randomized controlled trials published from March 2013 to April 2014. The COAG and the EU-PACT trials indicate that pharmacogenetic testing has either no usefulness in the initial dosing of vitamin K antagonists or marginal usefulness in the Caucasian population. Recent clinical trials with novel oral anticoagulants (NOACs) have demonstrated that the efficacy and safety of rivaroxaban, apixaban, edoxaban, and dabigatran are not inferior to those of conventional anticoagulants for the treatment of VTE. The PEITHO and ULTIMA trials suggested that rescue thrombolysis or catheter-directed thrombolysis may maximize the clinical benefits and minimize the bleeding risk. Lastly, riociguat has a proven efficacy in treating chronic thromboembolic pulmonary hypertension. In the future, NOACs, riociguat, and catheter-directed thrombolysis have the potential to revolutionize the management of patients with VTE.

• The Journal of the Korean dental association
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• v.57 no.10
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• pp.613-622
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• 2019

The vitamin K antagonist (VKA), cumadin, or warfarin, is the only antithrombotic drug that can be orally administered and has excellent effective for decades. However, it is cumbersome to periodically inspect the prothrombin time (PT) order to maintain adequate concentrations that do not cause bleeding, takes a few days to indicate therapeutic effects, gets affected by several factors such as food and drugs etc, and narrow in the therapeutic range. Although recently in development, the non-vitamin K antagonist anticoagulants(NOACs) exhibit a rapid onset of action and have relatively short half- lives compared to Coumadin. Because of these pharmacokinetic properties, it is possible to modify an individual's anticoagulation status quite rapidly, minimizing the period where the anticoagulation activity is therapeutically suboptimal. And the short half -lives of these drug allow for the relatively rapid reduction of their anticoagulation effects. There are currently no published clinical trials specifically assessing the bleeding risks associated with dental procedures for patients taking the NOACs. It is not necessary to interrupt NOAC medication for dental procedures that are likely to cause bleeding, but which have a low risk of bleeding complications. Because the bleeding risk for these procedures is considered to be low, the balance of effects is in favour of continuing the NOAC treatment without modification, to avoid increasing the risk of a thromboembolic event. The patients should be advised to miss(apixaban or dabigatran) or delay(rivaroxaban) a dose of their NOAC prior to dental procedures that are likely to cause bleeding and which have a higher risk of bleeding complications. Because the risk of bleeding complications for these procedures is considered to be higher, the balance effects is in favour of missing or delaying the pretreatment NOAC dose. The interruption is only for a short time to minimize the effect on thromboembolic risk.

• Journal of Chest Surgery
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• v.56 no.2
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• pp.90-98
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• 2023

Background: Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. Totally thoracoscopic ablation (TTA) is a surgical treatment showing a high success rate as a hybrid procedure with radiofrequency catheter ablation to control AF. This study compared the early complications of warfarin and non-vitamin K antagonist oral anticoagulants (NOACs) in patients who underwent TTA. Methods: This single-center retrospective cohort study enrolled patients who underwent planned TTA for AF from February 2012 to October 2020. All patients received postoperative anticoagulation, either with warfarin or a NOAC (apixaban, rivaroxaban, dabigatran, or edoxaban). Propensity score matching was performed for both groups. Early complications were assessed at 12 weeks after TTA and were divided into efficacy and safety outcomes. Both efficacy and safety outcomes were compared in the propensity score-matched groups. Results: Early complications involving efficacy outcomes, such as stroke and transient ischemic attack, were seen in 5 patients in the warfarin group and none in the NOAC group. Although the 2 groups differed in the incidence of efficacy outcomes, it was not statistically significant. In safety outcomes, 11 patients in the warfarin group and 24 patients in the NOAC group had complications, but likewise, the between-group difference was not statistically significant. Conclusion: Among patients who underwent TTA, those who received NOACs had a lower incidence of thromboembolic complications than those who received warfarin; however, both groups showed a similar bleeding complication rate. Using a NOAC after TTA does not reduce efficacy and safety when compared to warfarin.

• The Korean journal of internal medicine
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• v.39 no.1
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• pp.77-85
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• 2024

Background/Aims: There may be many predictors of anticoagulation-related gastrointestinal bleeding (GIB), but until now, systematic reviews and assessments of the certainty of the evidence have not been published. We conducted a systematic review to identify all risk factors for anticoagulant-associated GIB to inform risk prediction in the management of anticoagulation-related GIB. Methods: A systematic review and meta-analysis were conducted to search PubMed, EMBASE, Web of Science, and Cochrane Library databases (from inception through January 21, 2022) using the following search terms: anticoagulants, heparin, warfarin, dabigatran, rivaroxaban, apixaban, DOACs, gastrointestinal hemorrhage, risk factors. According to inclusion and exclusion criteria, studies of risk factors for anticoagulation-related GIB were identified. Risk factors for anticoagulant-associated GIB were used as the outcome index of this review. Results: We included 34 studies in our analysis. For anticoagulant-associated GIB, moderate-certainty evidence showed a probable association with older age, kidney disease, concomitant use of aspirin, concomitant use of the antiplatelet agent, heart failure, myocardial infarction, hematochezia, renal failure, coronary artery disease, helicobacter pylori infection, social risk factors, alcohol use, smoking, anemia, history of sleep apnea, chronic obstructive pulmonary disease, international normalized ratio (INR), obesity et al. Some of these factors are not included in current GIB risk prediction models. such as anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction, etc. Conclusions: The study found that anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction et al. were associated with anticoagulation-related GIB, and these factors were not in the existing prediction models. This study informs risk prediction for anticoagulant-associated GIB, it also informs guidelines for GIB prevention and future research.

• The Korean Journal of Gastroenterology
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• v.72 no.5
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• pp.271-273
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• 2018

내시경 시술 전 일시적으로 항응고제를 중단하는 것은 위장관 출혈의 위험과 혈전색전증의 위험 사이에 적절한 균형을 잡기 어렵기 때문에 논란의 여지가 많다. 와파린은 새로운 경구용 항응고제(direct oral anticoagulant agent, DOAC)보다 임상의에게 더 친숙하고, 효과를 쉽고 빠르게 전환시킬 수 있다는 장점이 있지만 복잡한 약역동학 특징과 좁은 치료적 범위 때문에 관리가 어렵다. 반면, DOAC는 약물의 모니터링 및 용량 조절 없이 정해진 용량으로 처방이 가능하며, 빠르게 작용하고, 반감기가 짧아 관리가 쉽지만 해독제가 없다는 단점이 있다. 이전 연구들에서 DOAC를 복용한 환자들은 와파린을 복용한 환자들보다 시술과 관련되지 않은 위장관 출혈의 위험이 높았다고 보고한 바 있다. 하지만 시술과 관련된 위장관 출혈 위험에 대하여는 알려진 바가 없는 실정이다. 미국이나 유럽 내시경 가이드라인들에서는 저위험 내시경 시술을 받는 환자들에서는 와파린과 DOAC를 유지하도록 권고하고 있으며, 고위험 시술의 경우에는 와파린를 사용하는 환자들에서 헤파린 교량 요법(heparin bridging)을 시행하도록 권고하고 있다. 임상적으로 DOAC를 사용하는 환자들 또한 혈전색전증을 예방하기 위하여 헤파린 교량 요법을 시행해볼 수 있는데, 와파린 및 DOAC의 헤파린 교량 요법과 관련된 출혈 및 혈전색전증 위험의 차이 또한 명확하지 않다. 따라서 저자들은 1) 와파린과 DOAC 치료를 받는 환자들에서의 출혈, 혈전색전증 및 사망의 위험을 비교하고자 하였으며, 2) 13종류의 고위험 내시경 시술 중에서 시술별 위험을 비교하고, 3) 헤파린 교량 요법이 합병증의 발생을 증가시키지 않는지 확인하고자 본 연구를 진행하였다. 일본 대규모 국가 입원 환자 데이터베이스를 이용하여 2014년 4월부터 2015년 5월까지 시술 전 와파린 또는 DOAC(rivaroxaban, apixaban, dabigatran, edoxaban)를 복용하고, 13종류의 고위험 내시경 시술을 시행받은 20세 이상의 성인 환자 총 16,977명을 확인하였다. 고위험 시술은 용종 절제술, 내시경 점막절제술, 내시경 점막하박리술, 협착 부위의 풍선확장술, 내시경 지혈술, 내시경 정맥결찰술, 내시경 주사 경화요법, 내시경 괄약근절개술, 내시경 초음파 유도하 미세침 흡인 검사, 경피적 위루술을 포함하였다. 일대일 성향 점수 매칭 분석(propensity score matching, 나이, 성별, 체질량 지수, 기저 질환, 병원의 규모, 시술의 종류, 약물의 종류를 매칭)을 시행하여 와파린군과 DOAC군에서 시술 위장관 출혈 및 혈전색전증, 사망의 발생을 비교하였다. 또한 경구항혈전제와 헤파린 교량 치료 시행 유무에 따라, DOAC 단독군, 와파린 단독군, DOAC와 헤파린 교량 요법군, 와파린과 헤파린 교량요법군으로 나누어, 하위군(subgroup) 분석을 시행하였다. 5,046쌍이 성향 점수 매칭 분석에 포함되었으며, 와파린군에서 DOAC군보다 통계적으로 의미 있게 위장관 출혈의 비율이 높았다(12.0% vs. 9.9% p=0.02). 혈전색전증 발생률(5.4% vs. 4.7%)과 입원중 사망률(5.4% vs. 4.7%)은 양 군에서 의미 있는 차이는 없었다. DOAC 종류별로 나누어 하위군 분석을 시행하였을 때, 와파린군은 rivaroxaban군에 비하여 위장관 출혈의 비율이 높았으며, rivaroxaban군, dabigatran군에 비하여 혈전색전증의 비율이 높았고, 입원 중 사망률에서는 의미 있는 차이는 없었다. 내시경 시술의 종류로 보정하였을 때 위장관 출혈 및 혈전색전증, 사망률은 DOAC 단독으로 치료한 환자에서보다 와파린과 헤파린 교량 요법(bridging) 또는 DOAC과 헤파린 교량 요법을 시행한 환자에서 높았다. 시술 종류 중에서는 위루관 삽입술에 비하여 내시경 점막하박리술, 내시경 점막절제술 및 내시경 정맥류결찰술, 내시경 주사경화요법을 시행한 환자에서 위장관 출혈의 위험이 가장 높았으며, 하부 내시경 점막절제술, 하부 용종 절제술, 내시경적 유두괄약근절제술 또는 내시경 초음파 유도하 미세침 흡인 검사는 중등도 위험을 보였다.