Association of risk factors and bleeding complications in Asian patients taking edoxaban.

AIMS: Asian patients are known to be more prone to bleeding complications than patients of other ethnicities. Therefore, there are possibilities of other risk factors that should be given special consideration for dosage adjustment in this specific ethnic group. This study aimed to investigate the risk factors for bleeding complications in Asian patients under appropriate edoxaban dosage regimens. METHODS: Data on patients taking proper dosages, based on the Lixiana package insert, were analysed. Univariate and multivariable analyses were conducted to evaluate associations between risk factors and bleeding outcomes. Subgroup analysis was performed on high-risk patients for bleeding complications whose edoxaban dose was reduced according to the package insert. RESULTS: In total, 346 patients were included. Among them, 32 patients experienced bleeding complications. Patients with weight ≤60 kg and with cancer showed around 3.3- and 3.4-fold increased risk of bleeding complications compared to heavier patients (>60 kg) and those without cancer, respectively. In subgroup analysis with high-risk patients who took low-dose edoxaban (15 and 30 mg), weight ≤60 kg remained a significant factor for bleeding outcomes. CONCLUSION: This study showed that weight ≤60 kg and the presence of cancers could affect bleeding complications, which occurred despite proper edoxaban treatment in Asian patients. Therefore, more strict dosage guideline could be considered in populations with high proportions of Asian ethnicities.

Effect of post-operative anticoagulation management in patients who have undergone On-X mechanical heart valve replacement surgery on post-discharge warfarin therapy.

WHAT IS KNOWN AND OBJECTIVE: We evaluated the effect of the proportion of time maintained within the target international normalized ratio (INR) postoperatively in hospitalized patients who underwent On-X mechanical heart valve replacement on warfarin therapy after discharge. METHODS: Inclusion was patients who were ≥18 years, received warfarin for a minimum of 10 days without any interruptions during hospitalization and followed by the anticoagulation service (ACS) clinic after discharge between June 2006 and June 2016. Patients were excluded if they had incomplete medical records, INR goal changes, known as warfarin resistance, transferred to another facility or expired during the study. The patients were divided into 3 groups according to the proportion of time maintained within therapeutic INR range (TTR) from day 4 to 10 of warfarin initiation (low: <30%, moderate: ≥30% to <70%, and high: ≥70%). The number of days needed to reach target INR for 2 consecutive measurements after discharge and the number of ACS visits was compared among the groups. RESULTS AND DISCUSSION: Among 539 postoperative patients, 273 were included. The baseline demographics were similar among the 3 groups. The mean time needed to reach target INR for 2 consecutive measurements was 68.6 ± 106.1 days. The low group required time needed to reach target INR for 2 consecutive measurements of 94.0 ± 140.9 days compared with 44.8 ± 57.1 days in the high group (P = .007). Additionally, the low group had more ACS visits than the high group (low, 6.6 ± 5.2 vs high, 4.6 ± 3.9; P = .025). Patient compliance affected the time needed to reach target INR for 2 consecutive measurements (compliant, 42.36 ± 58.5 days vs non-compliant, 132.0 ± 157.1 days, P < .001). WHAT IS NEW AND CONCLUSION: The study implicated that high postoperative TTR would reduce the time to require post-discharge target INR and the number of ACS visits.

Factors related to inappropriate edoxaban use.

WHAT IS KNOWN AND OBJECTIVE: The aim of this study was to evaluate the appropriateness and clinical outcomes of edoxaban use, and to determine the role of clinical pharmacists in improving the efficacy and safety of edoxaban use. METHODS: A retrospective study was performed by using an electronic medical record and anticoagulation clinical data from 600 patients who received edoxaban from 1 March 2016 to 16 July 2017 at a tertiary teaching university hospital. The appropriateness of edoxaban use was assessed using eight criteria based on drug use evaluation criteria developed by the American Society of Health-System Pharmacists drug use evaluation guidelines, details in Korea Food and Drug Administration approval of edoxaban. Clinical outcomes were evaluated between the appropriately prescribed and inappropriately prescribed groups regarding the incidence of thrombosis and bleeding episodes. RESULTS AND DISCUSSION: After excluding 86 patients due to the inability to assess renal function, 514 were eligible. Appropriate use was found in 294 patients (57.2%). The most frequent inappropriate use of edoxaban was dose adjustment (60.8%) in accordance with the dosing recommendation in patients with renal insufficiency (creatinine clearance [CrCl] of 15-50 mL/min) and a low body weight of <60 kg. Moreover, there were three cases of edoxaban use in patients with prosthetic heart valves and moderate-to-severe mitral stenosis, and 15 cases of non-valvular atrial fibrillation in patients with CrCl >95 mL/min in whom edoxaban use is not recommended. Furthermore, we found that the factors related to the appropriateness of edoxaban use were <60 kg body weight (adjusted odds ratio [OR]: 0.310; confidence interval [CI]: 0.197-0.488) and CrCl <50 mL/min (adjusted OR: 0.629; CI: 0.404-0.980). There were 45 events (8.75%) of any bleeding, 9 (1.8%) of stroke/transient ischaemic attack (TIA) and four events (0.8%) of deep vein thrombosis (DVT)/pulmonary embolism (PE). However, there was no difference between the appropriately prescribed group (294 patients) and inappropriately prescribed group (220 patients) in the incidence of bleeding events (27 [9.2%] vs 18 [8.2%]), stroke/TIA (7 [2.4%] vs 2 [0.9%]) and DVT/PE (2 [0.7%] vs 2 [0.9%]), respectively. WHAT IS NEW AND CONCLUSION: Although edoxaban has a broad therapeutic window that does not require routine monitoring, it should be cautiously used in patients with renal insufficiency (CrCl <50 mL/min) and body weight <60 kg.

High-Intensity Statin Therapy Is "Too Much," Thus Not Indicated for Very Elderly Patients.

PURPOSE: Although moderate- to high-intensity statin therapy is increasingly recommended in cardiovascular disease patients, the efficacy and safety in elderly patients have not been proven clearly. Here, we compare the effect of various-intensity statins between elderly and very elderly patients. METHODS: 43,870 patients over 65 years old who were treated with statins were screened using electronic medical record data. RESULTS: We evaluated 451 patients in the elderly group aged 65-74 years and 159 patients in the very elderly group over 75 years old. Baseline cholesterol profiles were similar between the 2 groups, but the 10-year atherosclerotic cardiovascular disease (ASCVD) risk was significantly higher in the very elderly (20.9 ± 11.5$ vs. 37.2 ± 13.6$, p < 0.001). The reduction rate of low-density lipoprotein (LDL) (-40.2 ± 21.3$ vs. -39.3 ± 21.0$, p = 0.634) and the ratio of target LDL attainment (74.2 vs. 79.2$, p = 0.252) were similar between the 2 groups. Low-intensity statins showed comparable LDL cholesterol reduction with moderate-intensity statins both in the elderly and the very elderly groups. The 10-year ASCVD risk reduction was similar between the 2 groups (-3.5 ± 4.9$ vs. -3.0 ± 8.4$, p = 0.480), but in the very elderly group, no different ASCVD reduction rate was shown in low- to high-intensity statins (p = 0.784). Only the elderly group showed a significant correlation (r = 0.112, p = 0.017) with LDL reduction and 10-year ASCVD risk. Interestingly, the incidence of adverse drug reaction (ADR) was higher in the very elderly group (4.4$) than in the elderly group (2.7$) and was more frequent in high-intensity statin therapy. CONCLUSION: The efficacy of statins in LDL reduction was similar between the elderly and very elderly population. However, the benefit of moderate- to high-intensity statins is limited considering potential ADR. Therefore, the stepwise intensification of statin therapy might be necessary for the very elderly in spite of the higher cardiovascular risk.

Medication Adherence Improvement By Using Administration Timing Simplification Protocol (ATSP) in Cardiovascular Disease Patients.

AIMS: In chronic diseases, keeping adherence to medication is very difficult. The objective of this study was to evaluate the impact of administration timing simplification protocol (ATSP) on medication adherence and clinical parameters of cardiovascular diseases. METHODS: 210 out-patients with cardiovascular disease, who were taking two or more pills of any type of medication per day for more than one year, were enrolled and randomized. The intervention group followed the simplified administration schedule of ATSP with two main strategies: 1) moving medication from "pc" (30 minute after meal) to "stat. pc" (immediately after meal); and 2) moving medication time from "at evening" to "at morning." In contrast, the control group maintained the same medication schedule. Both patient groups were equally educated about the names and effects of the medication. RESULTS: The intervention group had more pills than the control group with marginal statistical significance (5.1±2.3 vs 4.6±1.8, p=0.05). The total frequency of administration was significantly higher in the intervention group than that of the control group (2.9±1.0 vs 2.6±0.9, p=0.03) at the baseline. In the intervention group, the frequency was significantly decreased to 1.5±0.6 times per day after following ATSP application (p＜0.01). In both patient groups, knowledge about the medication was significantly improved by education. However, medication adherence was only improved in the intervention group. Interestingly, total cholesterol was significantly decreased in the intervention group (p＜0.01). The decrease in serum cholesterol concentration was significantly correlated with the improvement in medication adherence evaluated with Morisky Medication Adherence Scale (MMAS)-8 items (r=0.507, p＜0.01). CONCLUSION: ATSP was shown to be an effective strategy to improve medication adherence in chronic cardiovascular disease patients.

Chitin from the Extract of Cuttlebone Induces Acute Inflammation and Enhances MMP1 Expression.

We previously reported that the extract from cuttlebone (CB) has wound healing effect in burned lesion of rat. In present study, the main component of CB extract was analyzed and its wound healing activity was evaluated by using in vitro acute inflammation model. The extract of CB stimulated macrophages to increase the production of TNF-α. The extract also enhanced the production of TGF-ß and VEGF, which were involved in angiogenesis and fibroblast activation. The treatment with CB extract enhanced proliferation of murine fibroblast. CB extract also induced the activation of fibroblast to increase the secretion of matrix metalloproteases 1 (MMP1). The constituent of CB extract which has wound healing activity was identified as chitin by HPLC analysis. The mechanism that the CB extract helps to promote healing of burned lesion is associated with that chitin in CB extracts stimulated wound skins to induce acute inflammation and to promoted cell proliferation and MMP expression in fibroblast. Our results suggest that CB or chitin can be a new candidate material for the treatment of skin wound such as ulcer and burn.

Comparative evaluation for the use of oral ibuprofen and intravenous indomethacin in Korean infants with patent ductus.

Ductus arteriosus is a normal connecting blood vessel between the pulmonary artery and aorta in the fetus. However, if the ductus arteriosus is not closed and maintained as the open state even after 72 h of the birth, this is called a patent ductus arteriosus (PDA). Intravenous indomethacin is the conventional treatment for PDA in immature infants, but remains controversial in mature infants. The purpose of this study was to compare intravenous indomethacin and oral ibuprofen with regard to efficacy and safety for treatment of PDA. 78 neonates treated for PDA were included and classified into immature (n = 49) and mature (n = 29) groups. Ductal closure occurred in immature infants treated with indomethacin (74.1%) and ibuprofen (90.9%). Ductal closure occurred in mature infants treated with indomethacin (66.7%) and ibuprofen (92.9%). Platelet counts were increased in immature infants treated with ibuprofen (p = 0.027). Hyponatremia occurred in immature infants treated with ibuprofen (p = 0.002) and in both groups of mature infants (p = 0.001 for both groups). Serum creatinine values were lowered in mature infants treated with ibuprofen (p = 0.032). Bleeding occurred in 5 immature infants treated with indomethacin. Administration of furosemide for urine output was more frequent in the mature groups than in the immature group. In conclusion, oral ibuprofen was as effective as intravenous indomethacin in the immature groups and more effective in the mature groups. Adverse effects of oral ibuprofen were less severe than intravenous indomethacin.