-
1.
Comparison of Anticoagulation Quality between Acenocoumarol and Warfarin in Patients with Mechanical Prosthetic Heart Valves: Insights from the Nationwide PLECTRUM Study.
Menichelli, D, Poli, D, Antonucci, E, Cammisotto, V, Testa, S, Pignatelli, P, Palareti, G, Pastori, D, The Italian Federation Of Anticoagulation Clinics Fcsa,
Molecules (Basel, Switzerland). 2021;(5)
Abstract
Vitamin K antagonists are indicated for the thromboprophylaxis in patients with mechanical prosthetic heart valves (MPHV). However, it is unclear whether some differences between acenocoumarol and warfarin in terms of anticoagulation quality do exist. We included 2111 MPHV patients included in the nationwide PLECTRUM registry. We evaluated anticoagulation quality by the time in therapeutic range (TiTR). Factors associated with acenocoumarol use and with low TiTR were investigated by multivariable logistic regression analysis. Mean age was 56.8 ± 12.3 years; 44.6% of patients were women and 395 patients were on acenocoumarol. A multivariable logistic regression analysis showed that patients on acenocoumarol had more comorbidities (i.e., ≥3, odds ratio (OR) 1.443, 95% confidence interval (CI) 1.081-1.927, p = 0.013). The mean TiTR was lower in the acenocoumarol than in the warfarin group (56.1 ± 19.2% vs. 61.6 ± 19.4%, p < 0.001). A higher prevalence of TiTR (<60%, <65%, or <70%) was found in acenocoumarol users than in warfarin ones (p < 0.001 for all comparisons). Acenocoumarol use was associated with low TiTR regardless of the cutoff used at multivariable analysis. A lower TiTR on acenocoumarol was found in all subgroups of patients analyzed according to sex, hypertension, diabetes, age, valve site, atrial fibrillation, and INR range. In conclusion, anticoagulation quality was consistently lower in MPHV patients on acenocoumarol compared to those on warfarin.
-
2.
The effect of genetic and nongenetic factors on warfarin dose variability in Qatari population.
Bader, L, Mahfouz, A, Kasem, M, Mohammed, S, Alsaadi, S, Abdelsamad, O, Elenani, R, Soaly, E, Elzouki, A, Rizk, N, et al
The pharmacogenomics journal. 2020;(2):277-284
Abstract
The objective of this study is to estimate the prevalence of VKORC1, CYP2C9, and CYP4F2 genetic variants and their contribution to warfarin dose variability in Qataris. One hundred and fifty warfarin-treated Qatari patients on a stable dose and with a therapeutic INR for at least three consecutive clinic visits were recruited. Saliva samples were collected using Oragene DNA self-collection kit, followed by DNA purification and genotyping via TaqMan Real-Time-PCR assay. The population was stratified into derivation and validation cohorts for the dosing model. The minor allele frequency (MAF) of VKORC1 (-1639G>A) was A (0.47), while the MAF's for the CYP2C9*2 and *3 and CYP4F2*3 were T (0.12), C (0.04) and T (0.43), respectively. Carriers of at least one CYP2C9 decreased function allele (*2 or *3) required lower median (IQR) warfarin doses compared to noncarriers [24.5 (14.5) mg/week vs. 35 (21) mg/week, p < 0.001]. Similarly, carriers of each additional copy of (A) variant in VKORC1 (-1639G>A) led to reduction in warfarin dose requirement compared to noncarriers [21(7.5) vs. 31.5(18.7) vs. 43.7(15), p < 0.0001]. CYP4F2*3 polymorphism on the other hand was not associated with warfarin dose. Multivariate analysis on the derivation cohort (n = 104) showed that a dosing model consisting of hypertension (HTN), heart failure (HF), VKORC1 (-1639G>A), CYP2C9*2 & *3, and smoking could explain 39.2% of warfarin dose variability in Qataris (P < 0.001). In the validation cohort (n = 45), correlation between predicted and actual warfarin doses was moderate (Spearman's rho correlation coefficient = 0.711, p < 0.001). This study concluded that VKORC1 (-1639G>A), CYP2C9*2 & *3 are the most significant predictors of warfarin dose along with HTN, HF and smoking.
-
3.
ABCA1 Polymorphism Is Associated With the Warfarin-Induced Aortic Stiffness After Coronary Artery Bypass Surgery in the Chinese Population.
Liao, S, Zhou, Q, Zhang, Y
Journal of cardiovascular pharmacology. 2020;(3):360-366
Abstract
Warfarin is the most widely prescribed oral anticoagulant and is recommended for patients recovering from coronary artery bypass graft (CABG) with atrial fibrillation. Increasing evidence suggested that warfarin increased arterial stiffness in those patients. We aimed to examine the effect of warfarin therapy on aortic stiffness in patients who underwent CABG with or without postoperative warfarin treatment and explored the potential relationships of warfarin therapy with ABCA1 polymorphisms. This was a retrospect observational study of 24 patients who were continuously treated with warfarin were selected as the warfarin group and matched them by age (±3 years) and gender to 48 patients with nonuse of warfarin as the control group. The aortic stiffness, cholesterol efflux capacity, and plasma level of PIVKA-II were measured. Two ABCA1 polymorphisms were genotyped. Compared with baseline, treatment with warfarin for 1 year significantly increased the plasma level of PIVKA-II and aortic stiffness in pulse pressure and pulse wave velocity in patients after CABG. The increase of pulse wave velocity and plasma PIVKA-II level in the TT genotype was significantly greater than the CC genotype when comparing the -565C/T genotypes. The capacity of cholesterol efflux was significantly lower in the TT genotype at baseline and 1-year follow-up than the CC genotype. Postoperative treatment of warfarin for 1 year significantly increased aortic stiffness in patients who underwent CABG. ABCA1 -565C/T polymorphisms affected the cholesterol efflux capacity and were associated with the vitamin K status and the increased aortic stiffness after warfarin treatment in those patients.
-
4.
Quantitative Volumetric Comparison of Direct Oral Anticoagulant and Vitamin K Antagonist Treatment for Pulmonary Thrombus Reduction During the Acute Phase in Symptomatic Patients.
Jujo, K, Yoshida, A, Fukushima, K, Kikuchi, Y, Minami, Y, Murasaki, K, Haruki, S, Sekiguchi, H, Tanaka, H, Ogawa, H, et al
The American journal of the medical sciences. 2020;(2):153-160
Abstract
BACKGROUND Recent clinical trials' findings have revealed the therapeutic noninferiority of direct oral anticoagulant (DOAC) to standard therapy with vitamin K antagonist (VKA) in patients with pulmonary thromboembolism (PTE). However, few studies have quantitatively analyzed thrombus reduction in the pulmonary artery. METHODS This observational study included 38 symptomatic PTE patients with stable hemodynamics. All patients received an intravenous heparin bolus followed by continual heparin injections immediately after the PTE diagnosis. The heparin was discontinued after edoxaban therapy began in the DOAC group (n = 22) or after the therapeutic range for the prothrombin time-international normalized ratio was achieved in the VKA group (n = 16). The thrombus volumes in the pulmonary arteries were quantitatively analyzed using contrast-enhanced computed tomography scans, and they were compared at baseline and at 2 weeks after admission. RESULTS The pulmonary thrombus volumes declined in the VKA and DOAC groups from 7.9 to 4.2 cm3 (P = 0.048) and from 7.1 to 3.7 cm3 (P < 0.01), respectively, and the thrombus reduction rates did not differ significantly between the groups (-34% vs. -64%, respectively; P = 0.38). The fibrinogenolysis parameter changes during the14 days after admission were similar in both groups. Compared with the VKAgroup, the average hospital stay was 9days shorter in the DOAC group. There were no in-hospital deaths, and 1 case experienced major bleeding in the VKA group. CONCLUSIONS In relation to pulmonary artery thrombus volume reduction, DOAC monotherapy for PTE may be comparable with standard therapy involving VKAs.
-
5.
Oral Anticoagulation in Asian Patients With Atrial Fibrillation and a History of Intracranial Hemorrhage.
Lee, SR, Choi, EK, Kwon, S, Jung, JH, Han, KD, Cha, MJ, Oh, S, Lip, GYH
Stroke. 2020;(2):416-423
Abstract
Background and Purpose- Warfarin is associated with a better net clinical benefit compared with no treatment in patients with nonvalvular atrial fibrillation (AF) and history of intracranial hemorrhage (ICH). There are limited data on nonvitamin K antagonist oral anticoagulants (NOACs) in these patients, especially in the Asian population. We aimed to compare the effectiveness and safety of NOACs to warfarin in a large-scale nationwide Asian population with AF and a history of ICH. Methods- Using the Korean Health Insurance Review and Assessment database from January 2010 to April 2018, we identified patients with oral anticoagulant naïve nonvalvular AF with a prior spontaneous ICH. For the comparisons, warfarin and NOAC groups were balanced using propensity score weighting. Ischemic stroke, ICH, composite outcome (ischemic stroke+ICH), fatal ischemic stroke, fatal ICH, death from composite outcome, and all-cause death were evaluated as clinical outcomes. Results- Among 5712 patients with AF with prior ICH, 2434 were treated with warfarin and 3278 were treated with NOAC. Baseline characteristics were well-balanced after propensity score weighting (mean age 72.5 years and CHA2DS2-VASc score 4.0). Compared with warfarin, NOAC was associated with lower risks of ischemic stroke (hazard ratio [HR], 0.77 [95% CI, 0.61-0.97]), ICH (HR, 0.66 [95% CI, 0.47-0.92]), and composite outcome (HR, 0.73 [95% CI, 0.60-0.88]). NOAC was associated with lower risks of fatal stroke (HR, 0.54 [95% CI, 0.32-0.89]), death from composite outcome (HR, 0.53 [95% CI, 0.34-0.81]), and all-cause death (HR, 0.83 [95% CI, 0.69-0.99]) than warfarin. NOAC showed nonsignificant trends toward to reduce fatal ICH compared with warfarin (HR, 0.47 [95% CI, 0.20-1.03]). Conclusions- NOAC was associated with a significant lower risk of ICH and ischemic stroke compared with warfarin. NOAC might be a more effective and safer treatment option for Asian patients with nonvalvular AF and a prior history of ICH.
-
6.
Effects of fasting on warfarin sensitivity index in patients undergoing cardiovascular surgery.
Katada, Y, Nakagawa, S, Nishimura, A, Sato, YK, Taue, H, Matsumura, K, Yamazaki, K, Minakata, K, Yano, I, Omura, T, et al
European journal of clinical pharmacology. 2019;(4):561-568
Abstract
PURPOSE Warfarin shows large inter- and intra-individual variabilities in its pharmacokinetics and pharmacodynamics. Sufficient understanding of factors affecting the response to warfarin is necessary to achieve improved outcomes for warfarin therapy. In this study, we evaluated effects of fasting on the anticoagulant properties of warfarin. METHODS We conducted a retrospective observational study involving a total of 58 patients, who received cardiovascular surgeries and subsequent warfarin therapy. The effect of dietary intake on the anticoagulant properties with warfarin was assessed by measurement of the international normalized ratio of prothrombin time (PT-INR): the anticoagulant activities of warfarin were expressed as the warfarin sensitivity index (WSI). Additionally, fluctuations in WSI during the study period were obtained as differences between the maximum and minimum WSI. RESULTS The maximum PT-INR and WSI values were significantly higher for patients who were fasting for different reasons during the postoperative period than those in the group without reduced dietary intake. The differences between maximum and minimum WSI in the fasting group significantly increased compared with those in the groups with moderate or no reduced dietary intake. Meanwhile, effects of other markers of clinical conditions including the baseline Child-Pugh score and Charlson Comorbidity Index on WSI were not significant. CONCLUSIONS Our results indicate that postoperative fasting was significantly associated with the anticoagulation activity of warfarin. In patients fasting for different reasons during the postoperative period, closer control of PT-INR values and warfarin adjustments may be required to avoid adverse effects such as bleeding in warfarin treatment.
-
7.
Impact of genetic and clinical factors on warfarin therapy in patients early after heart valve replacement surgery.
Li, B, Liu, R, Wang, C, Ren, C, Zhang, S, Zhang, F, Zhang, J, Liu, S, Wei, Y, Liu, W, et al
European journal of clinical pharmacology. 2019;(12):1685-1693
Abstract
PURPOSE Factors influencing responsiveness to warfarin at treatment onset time were not well identified in Chinese patients undergoing heart valve replacement. We sought to select the most relevant factors that associated with patient response to warfarin early after heart valve surgery. METHODS In this observational study, 289 patients starting warfarin therapy early after heart valve replacement surgery were enrolled. CYP2C9 *1, *2, *3, and *5; VKORC1-1639 G>A, CYP4F2 V433M, and GGCX rs11676382 genotypes; clinical characteristics, response to therapy, and bleeding and thrombosis events were collected. The primary outcomes were the time to the first INR equal to or more than lower limit of therapeutic range and the warfarin dose requirements. Stepwise multiple linear regression was performed to develop a dosing algorithm to predict the warfarin dose requirements. RESULTS The results of univariate analysis showed lone VKORC1-1639 G>A, CYP2C9 *1/*3, cefazolin, cefoperazone-sulbactam, increased BMI, Δhemoglobin, and white blood cell count could significantly affect patient responsiveness to warfarin in the initial period of anticoagulation. Multivariate analysis resulted in an equation: Accumulated warfarin doses (mg) = 17.068 VKORC1-1639 G>A - 4.261 hypertension + 0.593 BMI - 0.115 age - 4.852 CYP2C9 *1/*3 - 2.617 cefazolin - 4.902 cefoperazone-sulbactam - 4.537, which could explain 40.2% of the variability in warfarin dose needed to reach the first INR equal to or more than lower limit of therapeutic range. CONCLUSIONS Both genetic and clinical factors contributed to anticoagulation effect of warfarin in the initial period of treatment. Our findings could provide a basis for the personalized management of warfarin use in the early stage of anticoagulation in northern Chinese patients.
-
8.
Traditional thromboprophylaxis in elderlies with atrial fibrillation: What we can achieve in real life.
Dubrava, M, Nemeth, F, Drobna, T, Gerlich, L
Bratislavske lekarske listy. 2019;(10):764-768
Abstract
OBJECTIVES To investigate real-world data on warfarinisation rates and results in the elderly patients with atrial fibrillation (AF). BACKGROUND AF is the most frequent arrhythmia in the elderlies with considerable risk of devastating stroke-related consequences. Guidelines prefer non-vitamin K antagonist oral anticoagulants (NOAC) to warfarin for thromboprophylaxis. Nevertheless, warfarin is still widely used, even if it is challenging, especially in polymorbid elderlies, to achieve the therapeutic international normalised ratio (INR). There are only scarce real-world data on INR in warfarinised elderly AF patients. METHODS The study was based on multicentric observational Slovak audit of atrial fibrillation in seniors (SAFIS) performed on 4,252 hospitalised AF patients aged over 64 years (mean age 80.9 yrs.). INR data from warfarinised patients were analysed (955 at admission and 870 at discharge). RESULTS At hospital admission and discharge, the warfarin medication rates were 22.6 % and 23.5 %, respectively, INR lower than 2 was present in 41.8 % and 30.6 % of patients, respectively, and INR higher than 3 was in 27.0 % and 7.7 %, respectively and altogether, 68.8 % and 38.3 % of warfarinised patients, respectively, were out of therapeutic range. CONCLUSION Warfarin is still frequently used in the elderlies with AF, but the success rates are unsatisfactory in a huge number of patients. It is urgent to improve seniors' access to NOAC (Fig. 2, Ref. 34).
-
9.
Evaluation of the Bleeding Intensity of Patients Anticoagulated with Warfarin or Dabigatran Undergoing Dental Procedures.
Andrade, MVS, Andrade, LAP, Bispo, AF, Freitas, LA, Andrade, MQS, Feitosa, GS, Feitosa-Filho, GS
Arquivos brasileiros de cardiologia. 2018;(3):394-399
Abstract
BACKGROUND Thrombotic disorders remain one of the leading causes of death in the Western world. Dabigatran appeared as an alternative to warfarin for anticoagulation in the treatment of atrial fibrillation (AF). The risk associated with bleeding due to its use has been documented in several randomized clinical trials, but no large study has examined in detail the risk of bleeding during dental extraction and other dental procedures involving bleeding. OBJECTIVE To compare the intensity of bleeding in individuals taking dabigatran or vitamin K antagonist (warfarin) and undergoing dental procedures. METHODS Prospective, single-center, controlled study with one single observer. Patients diagnosed with nonvalvular AF, on warfarin or dabigatran, cared for at a cardiology referral center, and requiring single or multiple dental extractions, were evaluated up to seven days post-extraction. The following outcomes were assessed: bleeding time between the beginning and the end of suture and complete hemostasis; bleeding before the procedure, after 24 hours, 48 hours, 7 days, during and after suture removal (late); p<0.05 was defined as of statistical relevance. RESULTS We evaluated 37 individuals, 25 in the warfarin group and 12 in the dabigatran group. Age, sex, weight, height, blood pressure, color, schooling, family income and comorbidities were similar between the two groups. Regarding bleeding after 24 hours of the procedure, no one in the dabigatran group had bleeding, whereas 32% in the warfarin group had documented bleeding (p = 0.028). The other variables analyzed did not differ between the groups. CONCLUSIONS This study suggests that, regarding dental extraction, there is no statistically significant difference in the intensity of bleeding of patients taking dabigatran as compared to those taking warfarin. Bleeding 24 hours after the procedure was less frequent among patients on dabigatran.
-
10.
Patient Satisfaction with Direct Oral Anticoagulants and Warfarin.
Okumura, Y, Yokoyama, K, Matsumoto, N, Tachibana, E, Kuronuma, K, Oiwa, K, Matsumoto, M, Kojima, T, Arima, K, Kotani, T, et al
International heart journal. 2018;(6):1266-1274
Abstract
The burden of anticoagulation treatment affects patient satisfaction, which in turn affects adherence to treatment. Thus, we must thoroughly understand the advantages of direct oral anticoagulants (DOACs) over vitamin K antagonists (VKAs)/warfarin given for stroke prevention in patients with atrial fibrillation (AF). We compared satisfaction with anticoagulation therapy between 654 DOAC and 821 warfarin users enrolled in the SAKURA AF Registry. Satisfaction was assessed by means of the Anti-Clot Treatment Scale (ACTS), which includes 12-item burdens and 3-item benefits scales, and the treatment satisfaction questionnaire for medication II (TSQM II), which includes 2-item effectiveness, 3-item side effects, 3-item convenience, and 2-item global satisfaction domains. There were no significant between-group differences in TSQM II convenience (67.6 ± 14.5 versus 68.9 ± 14.5, P = 0.280), effectiveness (65.0 ± 13.3 versus 66.0 ± 15.0, P = 0.422), side effects (93.6 ± 13.7 versus 92.8 ± 14.4, P = 0.067), and global satisfaction (64.7 ± 14.9 versus 66.0 ± 14.6, P = 0.407) scores. In contrast, although there was no significant between-group difference in the ACTS benefits scores (9.8 ± 3.1 versus 10.1 ± 3.2, P = 0.051), the ACTS burdens scores (54.5 ± 6.3 versus 52.7 ± 6.9, P < 0.0001) were significantly higher in the DOAC users, independent of age, sex, and DOAC type. We can expect greater burden satisfaction with anticoagulation treatment in patients given a DOAC versus VKA/warfarin. The reduced burden of treatment will translate to greater patient adherence to their treatment plans and a positive effect on clinical outcomes.