1.Short-term outcome of patients after transcatheter aortic valve replacement receiving different anticoagulants.
Ying Hao SUN ; Jie LI ; Song Yuan LUO ; Sheng Neng ZHENG ; Jiao Hua CHEN ; Ming FU ; Guang LI ; Rui Xin FAN ; Jian Fang LUO
Chinese Journal of Cardiology 2023;51(8):838-843
		                        		
		                        			
		                        			Objective: To compare the safety and efficacy of different anticoagulants in patients with indications for anticoagulation after transcatheter aortic valve replacement (TAVR). Methods: This is a retrospective study. Patients who underwent TAVR from April 2016 to February 2022 in Guangdong Provincial People's Hospital and had indications for anticoagulation were included and divided into two groups according to the type of anticoagulants, i.e. non-vitamin K antagonist oral anticoagulant (NOAC) and warfarin, and patients were followed up for 30 days. The primary endpoint was the combination of death, stroke, myocardial infarction, valve thrombosis, intracardiac thrombosis and major bleeding. The incidence of endpoints was compared between two groups, and multivariate logistic regression analysis was applied to adjust the bias of potential confounders. Results: A total of 80 patients were included. Mean age was (74.4±7.1) years, 43 (53.8%) were male. Forty-nine (61.3%) patients used NOAC, 31 used warfarin, and major indication for anticoagulants was atrial fibrillation (76/80, 95.0%). The adjusted risks of the primary endpoint (OR=0.23, 95%CI 0.06-0.94, P=0.040) of NOAC were lower than that of warfarin, mainly driven by a lower risk of major bleeding (OR=0.19, 95%CI 0.04-0.92, P=0.039). Conclusions: The short-term outcome of NOAC is better than that of warfarin in patients with indications for anticoagulation after TAVR. Randomized controlled trials of large sample size with long-term follow-up are needed to further testify this finding.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Aged, 80 and over
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Anticoagulants/therapeutic use*
		                        			;
		                        		
		                        			Warfarin/therapeutic use*
		                        			;
		                        		
		                        			Transcatheter Aortic Valve Replacement
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Hemorrhage
		                        			;
		                        		
		                        			Stroke/epidemiology*
		                        			;
		                        		
		                        			Atrial Fibrillation/drug therapy*
		                        			;
		                        		
		                        			Treatment Outcome
		                        			;
		                        		
		                        			Administration, Oral
		                        			
		                        		
		                        	
2.Short-term outcome of patients after transcatheter aortic valve replacement receiving different anticoagulants.
Ying Hao SUN ; Jie LI ; Song Yuan LUO ; Sheng Neng ZHENG ; Jiao Hua CHEN ; Ming FU ; Guang LI ; Rui Xin FAN ; Jian Fang LUO
Chinese Journal of Cardiology 2023;51(8):838-843
		                        		
		                        			
		                        			Objective: To compare the safety and efficacy of different anticoagulants in patients with indications for anticoagulation after transcatheter aortic valve replacement (TAVR). Methods: This is a retrospective study. Patients who underwent TAVR from April 2016 to February 2022 in Guangdong Provincial People's Hospital and had indications for anticoagulation were included and divided into two groups according to the type of anticoagulants, i.e. non-vitamin K antagonist oral anticoagulant (NOAC) and warfarin, and patients were followed up for 30 days. The primary endpoint was the combination of death, stroke, myocardial infarction, valve thrombosis, intracardiac thrombosis and major bleeding. The incidence of endpoints was compared between two groups, and multivariate logistic regression analysis was applied to adjust the bias of potential confounders. Results: A total of 80 patients were included. Mean age was (74.4±7.1) years, 43 (53.8%) were male. Forty-nine (61.3%) patients used NOAC, 31 used warfarin, and major indication for anticoagulants was atrial fibrillation (76/80, 95.0%). The adjusted risks of the primary endpoint (OR=0.23, 95%CI 0.06-0.94, P=0.040) of NOAC were lower than that of warfarin, mainly driven by a lower risk of major bleeding (OR=0.19, 95%CI 0.04-0.92, P=0.039). Conclusions: The short-term outcome of NOAC is better than that of warfarin in patients with indications for anticoagulation after TAVR. Randomized controlled trials of large sample size with long-term follow-up are needed to further testify this finding.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Aged, 80 and over
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Anticoagulants/therapeutic use*
		                        			;
		                        		
		                        			Warfarin/therapeutic use*
		                        			;
		                        		
		                        			Transcatheter Aortic Valve Replacement
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Hemorrhage
		                        			;
		                        		
		                        			Stroke/epidemiology*
		                        			;
		                        		
		                        			Atrial Fibrillation/drug therapy*
		                        			;
		                        		
		                        			Treatment Outcome
		                        			;
		                        		
		                        			Administration, Oral
		                        			
		                        		
		                        	
4.Verification of accuracy of warfarin stable dose prediction models in Shandong population.
Yiping GE ; Fengxia QU ; Songtao WANG ; Xiao GUO ; Cuicui WANG ; Shiyun LIU ; Aiqing MA ; Xianyan JIANG ; Kai TAN
Chinese Journal of Medical Genetics 2020;37(4):401-404
		                        		
		                        			OBJECTIVE:
		                        			To compare the accuracy of five warfarin-dosing algorithms and warfarin stable dose model (2.5 mg/day) for Shandong population.
		                        		
		                        			METHODS:
		                        			One hundred and twenty five patients who achieved stable warfarin dose were enrolled. Clinical and genetic data were used to evaluate the value of each algorithm by calculating the percentage of patients whose predicted warfarin dose was within 20% of the actual stable therapeutic dose and mean absolute error (MAE).
		                        		
		                        			RESULTS:
		                        			The frequency of patients with CYP2C9*1/*1, CYP2C9*1/*3 and CYP2C9*1/*2 genotype was 92.00%, 7.20%, 0.80%, respectively. That of VKORC1-1639 AA, AG and GG genotype was 82.40%, 15.20%, 2.40%, respectively. CYP4F2*1/*1, *1/*3, *3/*3 genotype was 50.40%, 39.20%, 10.40%, respectively. With the same genotypes for other loci, patients who carried at least one VKORC1-16398G mutant allele had increased warfarin stable daily dose compared with VKORC1-1639AA. Compared with CYP4F2*1/*1, those carrying at least one CYP4F2*3 mutant allele had warfarin stable daily dose increased by 5.9%-13.00%. The percentage of ideal prediction calculated from IWPC model (59.20%), Huang model (57.60%) and Ohno model (52.80%) were higher than others. The MAE were 0.35 (95%CI: 0.11-0.49), 0.15 (95%CI: 0.10-0.32), 0.39 (95%CI: 0.12-0.51), respectively.
		                        		
		                        			CONCLUSION
		                        			The polymorphisms of CYP2C9, VKORC1 and CYP4F2 genes can influence the stable dose of warfarin in Shandong population. IWPC algorithm is suitable for guiding the use of warfarin in this population.
		                        		
		                        		
		                        		
		                        			Anticoagulants
		                        			;
		                        		
		                        			administration & dosage
		                        			;
		                        		
		                        			Aryl Hydrocarbon Hydroxylases
		                        			;
		                        		
		                        			Cytochrome P-450 CYP2C9
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			Cytochrome P450 Family 4
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			Dose-Response Relationship, Drug
		                        			;
		                        		
		                        			Genotype
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Models, Theoretical
		                        			;
		                        		
		                        			Polymorphism, Genetic
		                        			;
		                        		
		                        			Vitamin K Epoxide Reductases
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			Warfarin
		                        			;
		                        		
		                        			administration & dosage
		                        			
		                        		
		                        	
5.Development and Comparison of Warfarin Dosing Algorithms in Stroke Patients.
Sun Mi CHO ; Kyung Yul LEE ; Jong Rak CHOI ; Kyung A LEE
Yonsei Medical Journal 2016;57(3):635-640
		                        		
		                        			
		                        			PURPOSE: The genes for cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) have been identified as important genetic determinants of warfarin dosing and have been studied. We developed warfarin algorithm for Korean patients with stroke and compared the accuracy of warfarin dose prediction algorithms based on the pharmacogenetics. MATERIALS AND METHODS: A total of 101 patients on stable maintenance dose of warfarin were enrolled. Warfarin dosing algorithm was developed using multiple linear regression analysis. The performance of all the algorithms was characterized with coefficient of determination, determined by linear regression, and the mean of percent deviation was used to predict doses from the actual dose. In addition, we compared the performance of the algorithms using percentage of predicted dose falling within ±20% of clinically observed doses and dividing the patients into a low-dose group (≤3 mg/day), an intermediate-dose group (3-7 mg/day), and high-dose group (≥7 mg/day). RESULTS: A new developed algorithms including the variables of age, body weight, and CYP2C9 and VKORC1 genotype. Our algorithm accounted for 51% of variation in the warfarin stable dose, and performed best in predicting dose within 20% of actual dose and intermediate-dose group. CONCLUSION: Our warfarin dosing algorithm may be useful for Korean patients with stroke. Further studies to elucidate clinical utility of genotype-guided dosing and find the additional genetic association are necessary.
		                        		
		                        		
		                        		
		                        			Aged
		                        			;
		                        		
		                        			*Algorithms
		                        			;
		                        		
		                        			Anticoagulants/*administration & dosage/therapeutic use
		                        			;
		                        		
		                        			Cytochrome P-450 CYP2C9/*genetics
		                        			;
		                        		
		                        			Dose-Response Relationship, Drug
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Genotype
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			International Normalized Ratio
		                        			;
		                        		
		                        			Linear Models
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Multivariate Analysis
		                        			;
		                        		
		                        			Pharmacogenetics
		                        			;
		                        		
		                        			Regression Analysis
		                        			;
		                        		
		                        			Republic of Korea
		                        			;
		                        		
		                        			Stroke/*drug therapy/ethnology
		                        			;
		                        		
		                        			Vitamin K Epoxide Reductases/*genetics
		                        			;
		                        		
		                        			Warfarin/*administration & dosage/therapeutic use
		                        			
		                        		
		                        	
6.Early Experience of Novel Oral Anticoagulants in Catheter Ablation for Atrial Fibrillation: Efficacy and Safety Comparison to Warfarin.
Dong Geum SHIN ; Tae Hoon KIM ; Jae Sun UHM ; Joung Youn KIM ; Boyoung JOUNG ; Moon Hyoung LEE ; Hui Nam PAK
Yonsei Medical Journal 2016;57(2):342-349
		                        		
		                        			
		                        			PURPOSE: Compared with warfarin, novel oral anticoagulants (NOACs) are convenient to use, although they require a blanking period immediately before radiofrequency catheter ablation for atrial fibrillation (AF). We compared NOACs and uninterrupted warfarin in the peri-procedural period of AF ablation. MATERIALS AND METHODS: We compared 141 patients treated with peri-procedural NOACs (72% men; 58+/-11 years old; 71% with paroxysmal AF) and 281 age-, sex-, AF type-, and history of stroke-matched patients treated with uninterrupted warfarin. NOACs were stopped 24 hours before the procedure and restarted on the same procedure day after hemostasis was achieved. RESULTS: We found no difference in the CHA2DS2-VASc (p=0.376) and HAS-BLED scores (p=0.175) between the groups. The preprocedural anticoagulation duration was significantly shorter in the NOAC group (76.3+/-110.7 days) than in the warfarin group (274.7+/-582.7 days, p<0.001). The intra-procedural total heparin requirement was higher (p<0.001), although mean activated clotting time was shorter (350.0+/-25.0 s vs. 367.4+/-42.9 s, p<0.001), in the NOAC group than in the warfarin group. There was no significant difference in thromboembolic events (1.4% vs. 0%, p=0.111) or major bleeding (1.4% vs. 3.9%, p=0.235) between the NOAC and warfarin groups. Minor stroke occurred in two cases within 10 hours of the procedure (underlying CHA2DS2-VASc scores 0 and 1) in the NOAC group. CONCLUSION: Pre-procedural anticoagulation duration was shorter and intra-procedural heparin requirement was higher with NOAC than with uninterrupted warfarin during AF ablation. Although the peri-procedural thromboembolism and bleeding incidences did not differ, minor stroke occurred in two cases in the NOAC group.
		                        		
		                        		
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Anticoagulants/*therapeutic use
		                        			;
		                        		
		                        			Atrial Fibrillation/complications/*drug therapy/*surgery
		                        			;
		                        		
		                        			Catheter Ablation/*methods
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Follow-Up Studies
		                        			;
		                        		
		                        			Hemorrhage/epidemiology
		                        			;
		                        		
		                        			Heparin
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Incidence
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Postoperative Complications/epidemiology
		                        			;
		                        		
		                        			Stroke/epidemiology
		                        			;
		                        		
		                        			Thromboembolism/epidemiology
		                        			;
		                        		
		                        			Treatment Outcome
		                        			;
		                        		
		                        			Warfarin/administration & dosage/*therapeutic use
		                        			
		                        		
		                        	
7.Influence of genetic polymorphisms and non-genetic factors on the maintenance dose of warfarin.
Jianglong HOU ; Xin DONG ; Yuqing WANG ; Gang WANG ; Li DONG ; Jesse LI-LING
Chinese Journal of Medical Genetics 2015;32(5):629-634
		                        		
		                        			
		                        			OBJECTIVE To assess the influence of genetic polymorphisms and non-genetic factors on warfarin maintenance dose variations in order to provide guidance for personalized use of warfarin. METHODS Two hundred patients from outpatient and inpatient with stable international normalized ratio(INR) were recruited. Clinical data and blood samples were collected. Genotypes of 4 genes involved in warfarin metabolic pathways were determined with Sanger sequencing. Based on statistical analysis of warfarin maintenance dosage, a mathematical model was established. RESULTS Among non-genetic factors, the age and height have significant influence in warfarin dosage. The dosage is negatively correlated with age but positively correlated with height. The difference in dosage for between the 20-year-old group and 60-year-old group has reached 1.81 mg/day, and that for between the 140 cm in height and 180 cm in height groups has reached 1.06 mg/day. VKORC1 -1639G/A, CYP2C9 430C/T, CYP2C9 1075A/C and CYP4F2 V433M polymorphisms have significant influence on stable warfarin dosage. The dosage for patients with wild type and mutant genotypes has varied from 0.35 mg/day to 0.84 mg/day. CONCLUSION Non-genetic factors and genetic polymorphisms play important roles in personalized variations of warfarin maintenance dose. The establishment of mathematical models considering multiple factors is helpful in evaluating the safety and effectiveness of warfarin dosage.
		                        		
		                        		
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Anticoagulants
		                        			;
		                        		
		                        			administration & dosage
		                        			;
		                        		
		                        			Cytochrome P-450 CYP2C9
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			Cytochrome P-450 Enzyme System
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			Cytochrome P450 Family 4
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Polymorphism, Genetic
		                        			;
		                        		
		                        			Vitamin K Epoxide Reductases
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			Warfarin
		                        			;
		                        		
		                        			administration & dosage
		                        			
		                        		
		                        	
8.Interaction between warfarin and Chinese herbal medicines.
Yan Ting CHUA ; Xiang Ling ANG ; Xi Ming ZHONG ; Kei Siong KHOO
Singapore medical journal 2015;56(1):11-18
		                        		
		                        			
		                        			In traditional Chinese medicine (TCM), the human body is divided into Yin and Yang. Diseases occur when the Yin and Yang balance is disrupted. Different herbs are used to restore this balance, achieving the goal of treatment. However, inherent difficulties in designing experimental trials have left much of TCM yet to be substantiated by science. Despite that, TCM not only remains a popular form of medical treatment among the Chinese, but is also gaining popularity in the West. This phenomenon has brought along with it increasing reports on herb-drug interactions, beckoning the attention of Western physicians, who will find it increasingly difficult to ignore the impact of TCM on Western therapies. This paper aims to facilitate the education of Western physicians on common Chinese herbs and raise awareness about potential interactions between these herbs and warfarin, a drug that is especially susceptible to herb-drug interactions due to its narrow therapeutic range.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Carthamus tinctorius
		                        			;
		                        		
		                        			chemistry
		                        			;
		                        		
		                        			Clinical Trials as Topic
		                        			;
		                        		
		                        			Drugs, Chinese Herbal
		                        			;
		                        		
		                        			administration & dosage
		                        			;
		                        		
		                        			adverse effects
		                        			;
		                        		
		                        			therapeutic use
		                        			;
		                        		
		                        			Ginger
		                        			;
		                        		
		                        			chemistry
		                        			;
		                        		
		                        			Ginkgo biloba
		                        			;
		                        		
		                        			chemistry
		                        			;
		                        		
		                        			Glycyrrhiza
		                        			;
		                        		
		                        			chemistry
		                        			;
		                        		
		                        			Herb-Drug Interactions
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Lycium
		                        			;
		                        		
		                        			chemistry
		                        			;
		                        		
		                        			Medicine, Chinese Traditional
		                        			;
		                        		
		                        			methods
		                        			;
		                        		
		                        			Panax
		                        			;
		                        		
		                        			chemistry
		                        			;
		                        		
		                        			Prunus persica
		                        			;
		                        		
		                        			chemistry
		                        			;
		                        		
		                        			Salvia miltiorrhiza
		                        			;
		                        		
		                        			chemistry
		                        			;
		                        		
		                        			Singapore
		                        			;
		                        		
		                        			Warfarin
		                        			;
		                        		
		                        			administration & dosage
		                        			;
		                        		
		                        			adverse effects
		                        			;
		                        		
		                        			therapeutic use
		                        			
		                        		
		                        	
9.Obstructive Sleep Apnea Hypopnea Syndrome as a Reason for Active Management of Pulmonary Embolism.
Jiang XIE ; Yong-Xiang WEI ; Shuang LIU ; Wei ZHANG ; Xiang-Feng ZHANG ; Jie LI
Chinese Medical Journal 2015;128(16):2147-2153
BACKGROUNDObstructive sleep apnea hypopnea syndrome (OSAHS) constitutes an independent factor for high warfarin dose for patients with pulmonary embolism (PE). The aim of this study was to investigate whether the 6-month anticoagulation treatment by warfarin is enough for patients with PE complicated by OSAHS.
METHODSWe investigated 97 PE patients, 32 of them had OSAHS and 65 non-OSAHS. Warfarin was administered for 6-month if no abnormal circumstances occurred. All patients were followed up for 18 months. Adverse events (AE) included death, major bleeding, hospitalization due to heart failure or pulmonary hypertension, and recurrence or aggravation of PE (including deep vein thrombosis). Recurrence rate of PE after warfarin cessation was compared between the two groups.
RESULTSOSAHS patients required a significantly higher dose of warfarin than their non-OSAHS counterparts (4.73 mg vs. 3.61 mg, P < 0.001). During warfarin treatment, no major bleeding and aggravation of PE occurred among OSAHS patients, and the rates of various AE were not significantly different between the OSAHS and non-OSAHS groups. PE recurrence was higher in OSAHS than non-OSAHS groups after withdrawal of warfarin (21.43% vs. 6.78%, P = 0.047). Compared with non-OSAHS patients, OSAHS group had lower international normalized ratio (INR) value but higher plasminogen on baseline and INR resumed to a relatively low level after warfarin discontinuation.
CONCLUSIONSOSAHS patients may present with hypercoagulation and relatively high-risk of recurrence of PE after cessation of 6-month warfarin treatment.
Anticoagulants ; administration & dosage ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Pulmonary Embolism ; drug therapy ; Sleep Apnea, Obstructive ; complications ; Warfarin ; administration & dosage ; therapeutic use
10.Novel oral anticoagulants for atrial fibrillation.
Singapore medical journal 2015;56(12):657-quiz 659
		                        		
		                        			
		                        			Anticoagulation therapy is effective in preventing primary and secondary thromboembolic events due to atrial fibrillation. Warfarin, which was approved by the United States in 1954, was the only long-term oral anticoagulation therapy till the approval of dabigatran in 2010, and of rivaroxaban and other direct factor Xa inhibitors from 2011, forming a group known as novel oral anticoagulants (NOAC). NOAC have fewer food and drug interactions compared to warfarin; hence, the patient will require fewer clinic visits. However, the short half-life of NOAC means that twice-a-day dosing is needed and there is higher risk of a prothrombotic state when doses are missed. Other disadvantages are the lack of long-term data on NOAC, their high cost and the current lack of locally available antidotes.
		                        		
		                        		
		                        		
		                        			Administration, Oral
		                        			;
		                        		
		                        			Anticoagulants
		                        			;
		                        		
		                        			administration & dosage
		                        			;
		                        		
		                        			Atrial Fibrillation
		                        			;
		                        		
		                        			drug therapy
		                        			;
		                        		
		                        			Cardiology
		                        			;
		                        		
		                        			methods
		                        			;
		                        		
		                        			Dabigatran
		                        			;
		                        		
		                        			administration & dosage
		                        			;
		                        		
		                        			Family
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Professional-Patient Relations
		                        			;
		                        		
		                        			Rivaroxaban
		                        			;
		                        		
		                        			administration & dosage
		                        			;
		                        		
		                        			Stroke
		                        			;
		                        		
		                        			prevention & control
		                        			;
		                        		
		                        			Thromboembolism
		                        			;
		                        		
		                        			prevention & control
		                        			;
		                        		
		                        			Warfarin
		                        			;
		                        		
		                        			administration & dosage
		                        			
		                        		
		                        	
            
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