심방세동 환자의 연령별 와파린 초기용량 적정성 평가 및 새로운 용량조절 기준설정

권효정,정지은,민경아,이영미,손기호 한국병원약사회 2008 병원약사회지 Vol.25 No.2

There are limited data on the initial dose of warfarin therapy in outpatients. The Anti-coagulation Service(ACS) of the Samsung Medical Center(SMC) confirmed that patient age is the most important determinant of warfarin requirement in Korean, and has set up age-related warfarin initial dosage guideline: warfarin 3.5 mg/day for under 50-year-old, 3 mg/day for age between 51~60, 2.5 mg/day for age between 61~70, 2 mg/day for over 71-year-old patients, followed by checking INR weekly. In the context, the purpose of this study is to analyze the appropriateness of age-related warfarin initial dosage guideline and propose a new dosage protocol. Study was processed as follows. First, targeted patients who initiated warfarin therapy with age-related warfarin initial dosage guideline(target INR 2.0-3.0) in ACS of our out-patient medical center and had indication of atrial fibrillation were investigated. For the study, 81 patients' records were analysed retrospectively. Before age-related warfarin initial dosage guideline was applied, the average period of achieving therapeutic levels was 32.42 days, on the other hands, 18.07 days for age-related warfarin initial dosage guideline. No patient suffered any thrombotic or hemorrhagic complications during taking age-related warfarin initial dose. The age-related initial warfarin dosage guideline has proposed safe and effective in out-patient warfarinization. But the group of age between 61~70, it took 5 days longer than other group, and needs increase in initial warfarin dose. The INR checked within 1 week and the ratio of the warfarin dose of maintaining therapeutic level to initial dose was analysed. The less INR checked within 1 week, need the more warfarin dose to maintain therapeutic level(p<0.0001). All things considered, this study allowed new protocol for warfarin dose regulation like followings; 100% increase of initial warfarin dose for checked INR under 1.2, 50% increase for INR 1.2~1.4, 30% increase for INR 1.4~1.6, 10~20% increase for INR 1.6~1.8, 10% increase for INR 1.8~1.9, maintain initial dose for INR 1.9~2.0, decrease 10% for INR over 2.0. The study was designed to the appropriateness of age-related warfarin initial dosage guideline. The guideline was shortened required period of achieving therapeutic levels. And based on the results, this study proposed a new dosage protocol.

과도한 항응고 효과에 대한 치료현황 평가 및 이후 치료범위 INR로의 전환을 위한 예후인자 분석

박가영,김형숙,정영미,최경숙,이은숙,이병구 한국병원약사회 2012 병원약사회지 Vol.29 No.4

Warfarin, a widely used oral anticoagulant, has a narrow therapeutic index; the side effect is typically monitored according to the international normalized ratio (INR). While the American College of Chest Physicians (ACCP) has proposed the guidelines for the management of excessive use of warfarin as anticoagulation, few data were published for the patient-specific factors that influence the return of the INR within the therapeutic range after the adjusted warfarin doses. Therefore, the aim of this study is to assess the treatment of excessive anticoagulation and prognostic factors that influence the return of the INR within the therapeutic range after the adjusted warfarin doses. Patients who were on warfarin therapy and were presented with an INR greater than 5.0 from Jan 1, 2007 and May 31, 2010 at Seoul National University Bundang Hospital (SNUBH), were included and observed retrospectively by reviewing electronic medical records (EMRs), such as causes of excessive anticoagulation, treatments, adjusted warfarin maintenance doses, and return of the INR within the therapeutic range after the adjusted warfarin doses. A total of 164 cases in 142 patients were analyzed. Common causes of elevated INR were excessive warfarin dose (17.8 %) and drug interaction (15.5 %). A total of 80.1 % was treated by adjusting warfarin dose, such as hold or reduction, and 67.1 % were treated appropriately according to the ACCP guidelines. Seventy-six cases found to have INR value within the therapeutic range [INR 1.7~3.3] by the adjustment and restarted warfarin therapy with adjusted dosage. However, 69 cases had INR values that were not with the range by the adjustment. Nineteen cases were excluded by warfarin discontinuation, death or follow up loss. The variables, which were associated with INR values returned within the therapeutic range by warfarin dosage adjustment, were age (P = 0.004), maintenance doses of warfarin (P = 0.004), and reduced % of adjusted dosage of warfarin (P < 0.001). By means of a multiple logistic regression model suggested that prognostic factors are associated with maintenance dosage (odds ratio, 0.47 [Cl, 0.31 to 0.93]), and reduced % of dosage (odds ratio, 1.06 [Cl, 1.01 to 1.12]). Therefore, these observations suggested that patients who take lower weekly maintenance doses of warfarin have to monitor their INR carefully, and, if anticoagulation is excessive, appropriately reduce the doses of warfarin. Furthermore, prospective, randomized trials might help the safety and efficacy management of excessive anticoagulation.

Warfarin과 Propafenone 병용 시 용량 조절 기준 설정

박선미,민경아,인용원,이영미 한국병원약사회 2013 病院藥師會誌 Vol.30 No.1

Oral anticoagulation therapy with warfarin is effective in the prevention of stroke during atrial fibrillation, but it needs careful monitoring because of its narrow therapeutic range and complexity of interaction with other medications. Propafenone is an antiarrhythmic agent classified in the class I c category. A previous study provided clinical evidence for a possible interaction between warfarin and propafenone. The addition of propafenone can potentiate the anticoagulant effect of warfarin so the previous study recommended a close monitoring and reduction of warfarin dosage when co-administered with propafenone. However, no reports have established an appropriate warfarin dosage guideline. Therefore, this study was conducted to determine the appropriate dosage of warfarin when co-administered with propafenone in regards to developing a practical guideline. A retrospective analysis was done for all patients who received propafenone, seen by the anticoagulation service (ACS) at Samsung Medical Center from January 1, 2008 to January 31, 2011. Patients who had consistent therapeutic INR values (1.8-3.2) with the same dose of warfarin for at least 1 month and who had not received any drugs known to alter INR values or interact with warfarin were included in the study. A total of twenty four patients met the inclusion criteria. The 1st ACS follow-ups were performed on day 7.63±3.85 and increases in INR were observed. The reduction rate in the warfarin dose for maintaining therapeutic INR was 10.08±6.79%. There was a significant difference in the reduction of the warfarin dose between the baseline and the 1st ACS follow-up. No significant differences were observed in the reduction of warfarin dose between the 1st ACS follow-up and 2nd ACS follow-up. Although no major bleeding was observed in the study group, 2 cases of minor bleeding (bruise and gingival bleeding) occurred during the study period. Based on these findings, we recommend a 10-15% reduction in the dose of warfarin at the time propafenone treatment is started and INR values should be determined on day 7-10 to ensure that therapeutic INR levels are maintained. This study provides a clinically available warfarin dosage guideline in the concomitant use of propafenone and warfarin. In addition, based on the results of this study, additional prospective study should be needed.

Determination of Plasma Warfarin Concentrations in Korean Patients and Its Potential for Clinical Application

권민정,김희진,김종원,이경훈,손기호,조현정,온영근,김준수,이수연 대한진단검사의학회 2009 Annals of Laboratory Medicine Vol.29 No.6

Background : Warfarin is a widely used oral anticoagulant with broad within- and between-individual dose requirements. Warfarin concentrations can be monitored by assessing its pharmacologic effects on International Normalized Ratio (INR). However, this approach has not been applied in the routine clinical management of patients receiving warfarin therapy. We performed a plasma warfarin assay using high-performance liquid chromatography tandem mass spectrometry (HPLCMS/ MS) to determine if such an assay can be utilized in routine clinical practice. Methods : We included a total of 105 patients with atrial fibrillation, and who were receiving warfarin for more than 1 yr. The plasma concentrations of total warfarin and 7-hydroxywarfarin were determined by HPLC-MS/MS (Waters, UK). We assessed the association between warfarin dose, concentration, and INR as well as the effects of these factors on warfarin concentrations. Results : The mean maintenance dose of warfarin in 105 patients was 4.1±1.3 mg/day (range, 1.7-8.0 mg/day) and their mean plasma warfarin concentration was 1.3±0.5 mg/L. We defined a concentration range of 0.6-2.6 mg/L (corresponding to the 2.5th to 97.5th percentile range of the serum warfarin levels in the 74 patients showing INR within target range) as the therapeutic range for warfarin. The correlation of warfarin dose with warfarin concentration (r2=0.259, P<0.001) was higher than that with INR (r2=0.029, P=0.072). Conclusions : There was a significant correlation between warfarin dose and plasma warfarin concentrations in Korean patients with atrial fibrillation. Hence, plasma warfarin monitoring can help determine dose adjustments and improve our understanding of individual patient response to warfarin treatment. Background : Warfarin is a widely used oral anticoagulant with broad within- and between-individual dose requirements. Warfarin concentrations can be monitored by assessing its pharmacologic effects on International Normalized Ratio (INR). However, this approach has not been applied in the routine clinical management of patients receiving warfarin therapy. We performed a plasma warfarin assay using high-performance liquid chromatography tandem mass spectrometry (HPLCMS/ MS) to determine if such an assay can be utilized in routine clinical practice. Methods : We included a total of 105 patients with atrial fibrillation, and who were receiving warfarin for more than 1 yr. The plasma concentrations of total warfarin and 7-hydroxywarfarin were determined by HPLC-MS/MS (Waters, UK). We assessed the association between warfarin dose, concentration, and INR as well as the effects of these factors on warfarin concentrations. Results : The mean maintenance dose of warfarin in 105 patients was 4.1±1.3 mg/day (range, 1.7-8.0 mg/day) and their mean plasma warfarin concentration was 1.3±0.5 mg/L. We defined a concentration range of 0.6-2.6 mg/L (corresponding to the 2.5th to 97.5th percentile range of the serum warfarin levels in the 74 patients showing INR within target range) as the therapeutic range for warfarin. The correlation of warfarin dose with warfarin concentration (r2=0.259, P<0.001) was higher than that with INR (r2=0.029, P=0.072). Conclusions : There was a significant correlation between warfarin dose and plasma warfarin concentrations in Korean patients with atrial fibrillation. Hence, plasma warfarin monitoring can help determine dose adjustments and improve our understanding of individual patient response to warfarin treatment.

Warfarin과 Baclofen 간의 약물 상호 작용의 검증

고현윤,박재홍,신용범 大韓再活醫學會 1999 Annals of Rehabilitation Medicine Vol.23 No.6

Warfarin과 Baclofen 간의 약물 상호 작용 가능성

고현윤,박재흥,김훈 大韓再活醫學會 1998 Annals of Rehabilitation Medicine Vol.22 No.3

심방세동 환자에서 Warfarin 단일요법과 Warfarin-Aspirin 병용요법 간의 출혈경향 발생과 뇌졸중 예방효과 고찰

박지은,이정은,서인아,고종희,안지현,손은선,김성은,석현주 한국병원약사회 2013 병원약사회지 Vol.30 No.1

Atrial fibrillation (AF), the most common sustained arrhythmia, confers an independent risk factor for stoke. If the disease is not treated, stroke risk will increase more than five times, and about one in three people will experience a stroke during their life time. Therefore, AF needs active management, and anticoagulation therapy is effective in the prevention of stroke. Warfarin and aspirin, the medicines for the prevention and treatment of thromboembolism, are effective in the prevention of stroke in AF. Medication is determined by stroke risk, generally classified by CHADS2 score. Warfarin is recommended primarily for high-risk patients, and aspirin is recommended for low-risk patients and those unable to take warfarin. Despite the combined warfarin-aspirin therapy is not recommended in general, complementary effects are expected due to different mechanisms of the drug. However, some cases have been reported that the combination of these medications just administered to increase bleeding risks and did not represent a remarkable therapeutic effect. Therefore, this study is in 2011, Jan. 1 to Oct. 31 in outpatients with AF who underwent the anticoagulation therapy, and patients were classified according to medication uses. This study was analyzed cardiovascular diseases, medical treatments, and hematologic data. In addition, this study retrospectively analyze the status of anticoagulation therapy in patients with AF. The warfarin group and warfarin+aspirin group were 54 and 51 patients and average duration of drug administration were 4.7 and 3.6 months, respectively. Bleeding events occurred in 5 and 6 patients in warfarin group and warfarin+aspirn group, respectively. Retrospective analysis of the two drugs showed no significant differences between the bleeding risk and stroke prevention, additional research is needed for the clinical evaluation of the combination therapy of warfarin and aspirin.

Effect of warfarin discontinuation on the incidence of postoperative bleeding in tooth extraction

Jung-Soo Lee,Moon-Key Kim,Sang-Hoon Kang 대한구강악안면외과학회 2020 대한구강악안면외과학회지 Vol.46 No.4

Objectives: The number of patients undergoing oral anticoagulant therapy for cardiovascular and cerebrovascular disease is increasing. However, the risk of bleeding after tooth extraction in patients receiving warfarin is unclear. Here, we assess the risk of bleeding after tooth extraction in patients on warfarin. Materials and Methods: The study included 260 patients taking warfarin who underwent tooth extraction (694 teeth). The patients were divided into those whose teeth were extracted while they were taking warfarin, those who discontinued warfarin before extraction, and those who underwent extraction while receiving heparin bridging therapy. Bleeding complications in the two groups were compared. Results: Of the 260 patients, 156 underwent extraction while taking warfarin, 70 stopped taking warfarin before extractions, and 34 received heparin bridging therapy and stopped taking either medication before extractions. Bleeding complications occurred in 9 patients (3.5%) and 9 tooth sites (1.3%). Among the 9 patients with bleeding complications, 6 underwent extraction while taking warfarin, 2 stopped warfarin before extraction, and 1 underwent extraction after receiving heparin bridging therapy. No significant difference was seen between patient groups regarding bleeding after extractions (P=0.917). Conclusion: Warfarin use does not increase the risk of post-extraction bleeding and can therefore be continued during tooth extraction.

Gastrointestinal bleeding risk of non-vitamin K antagonist oral anticoagulants versus warfarin in general and after polypectomy: a population-based study with propensity score matching analysis

Jong Yop Pae,김은수,김성국,정민규,허준,이장훈,Min Ae Park 대한장연구학회 2022 Intestinal Research Vol.20 No.4

Background/Aims: Gastrointestinal bleeding (GIB) risk for non-vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin is largely unknown. We aimed to determine the risk of overall and post-polypectomy GIB for NOACs and warfarin. Methods: Using the Korean National Health Insurance database, we created a cohort of patients who were newly prescribed NOACs or warfarin between July 2015 and December 2017 using propensity score matching (PSM). Kaplan-Meier analysis with log-rank test was performed to compare the risk of overall and post-polypectomy GIB between NOACs (apixaban, dabigatran, and rivaroxaban) and warfarin. Post-polypectomy GIB was defined as bleeding within 1 month after gastrointestinal endoscopic polypectomy.Results: Out of 234,206 patients taking anticoagulants (187,687 NOACs and 46,519 warfarin), we selected 39,764 pairs of NOACs and warfarin users after PSM. NOACs patients showed significantly lower risk of overall GIB than warfarin patients (log-rank <i>P</i><0.001, hazard ratio, 0.86; 95% confidence interval, 0.78–0.94; <i>P</i>=0.001). Among NOACs, apixaban showed the lowest risk of GIB. In the subgroup of 7,525 patients who underwent gastrointestinal polypectomy (lower gastrointestinal polypectomy 93.1%), 1,546 pairs were chosen for each group after PSM. The NOACs group showed a high risk of post-polypectomy GIB compared with the warfarin group (log-rank <i>P</i>=0.001, hazard ratio, 1.97; 95% confidence interval, 1.16–3.33; <i>P</i>=0.012).Conclusions: This nationwide, population-based study demonstrates that risk of overall GIB is lower for NOACs than for warfarin, while risk of post-polypectomy GIB is higher for NOACs than for warfarin.

고령의 심방세동 환자의 Warfarin 치료 시, 출혈 발생률과 위험인자 분석

조현복,민경아,인용원,이영미,손기호 한국병원약사회 2011 병원약사회지 Vol.28 No.2

Atrial fibrillation is an independent risk factor for stroke, and oral anticoagulation therapy with warfarin is effective in the prevention of stroke in atrial fibrillation. It has been reported that the prevalence of atrial fibrillation increases with age, and numbers of elderly patients who take warfarin is also increasing. As a result, increasing rate of bleeding associated with warfarin in elderly patients has been reported in previous studies. This study was designed to evaluate the incidence rate of bleeding in relation to age, and the factor associated with bleeding. In this retrospective study, baseline characteristics, anticoagulant control (target INR of 2-3)and the incidence of bleeding were assessed in an elderly population (≥75 years) compared with a younger population (between 65 and 74 years). All patients were new warfarin users, attending anticoagulation service (ACS) at Samsung Medical Center from January 1, 2008 to August 31,2009. Each patient was followed up by 1 year after starting taking warfarin. A total of 155 patients were studied, and 100 patients in the younger group providing 83.1 person-years of follow-up and 55 patients in the elderly group providing 39.5 person-years of follow up. Between younger and elderly group, average of duration of INR within target range is 57.5% and 61.5% respectively, and there is no significant difference (p=0.269). No difference of incidence of minor bleedings was found between the elderly group and the elderly group(p=0.395). Major bleedings were developed 1 event in younger group and 2 events in the elderly group. Incidence rate of major bleeding in the elderly group was higher than the younger group in 4.21folds, but it was not statistically significant (95% CI, 0.38-46.4). 42.6% of all bleeding and 33.3%of major bleeding were developed in first 90 days after starting warfarin therapy. Male (p=0.031)was analyzed as a risk factor for bleeding associated with warfarin in the all 155 patient, and history of cancer was analyzed that had effect on the analyzing sex as a risk factor for bleeding. However, we couldn't find the risk factors of bleeding for the elderly group. These findings suggest that older age and early period of warfarin therapy were related to increasing of bleeding caused by warfarin, and needed much care for anticoagulation therapy. Further studies to analyse risk factors for bleeding and there results may be help provide better anticoagulation therapy to elderly atrial fibrillation patients for prevention of stroke.