• Korean Journal of Clinical Pharmacy
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• v.15 no.1
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• pp.1-8
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• 2005

Clopidogrel is used to reduce the risk of cardiovascular events in patients with atherosclerosis documented by recent ischemic stroke, recent myocardial infarction (MI), or established peripheral arterial disease (secondary prevention). Clopidogrel is metabolized by CYP3A4, and the active metabolites inhibit platelet aggregation. The purpose of this study was to assess clopidogrel only versus clopidogrel + others (aspirin, CYP3A4 inhibitor, and CYPBA4 inducer) in terms of cardiovasculalr events and bleeding complications. We reviewed the charts of patients who visited between August 1, 2002 and August 31, 2003, retrospectively. Total 72 patients were included and they consisted of 5 groups; clopidogrel group (n=36), clopidogrel + aspirin group (n=11), clopidogrel + CYP3A4 inhibitor group (n=15), clopidogrel + aspirin + CYP3A4 inhibitor group (n=6), clopidorel + CYP3A4 inducer group (n=4). The primary endpoints at 6 months, 12 months were the composite of cardiovascular (CV) events. The secondary end-point was the incidence of bleeding events at 6months, and 12months. At 12months, the primary endpoint was not significantly different among the five groups (p=0.056). In comparison of two groups as clopidogrel only versus clopidogrel + others (aspirin, CYP3A4 inhibitor and CYP3A4 inducer), the primary endpoint was significantly different (p=0.02). The CV events were increased in the clopidogrel + others group. The secondary end point was not significantly different among the five groups (p=0.52). However, time to bleeding events was 230.8 in the clopidogrel group and 74.7 in the clopidogrel + others group (p = 0.046). In conclusion, clopidogrel interaction with aspirin, CYP3A4 inhibitor, and CYP3A4 inducer affected cardiovascular events and bleeding events. Drug interaction of clopidogrel with concurrent medications should be considered cautiously.

• Journal of Yeungnam Medical Science
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• v.40 no.3
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• pp.276-282
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• 2023

Background: Bleeding and thrombosis are major complications associated with high mortality in extracorporeal membrane oxygenation (ECMO) management. Anticoagulant therapy should be adequate to reduce thrombosis. However, related studies are limited. Methods: We retrospectively reviewed all patients supported with ECMO at a single institution between January 2014 and July 2022 and included those on all types of ECMO using the Permanent Life Support System. Patients were classified into two groups according to their measured mean activated partial thromboplastin time (aPTT) during ECMO management: a high-anticoagulation (AC) group (aPTT, ≥55 seconds; n=52) and a low-AC group (aPTT, <55 seconds; n=79). The primary outcome was thrombotic or bleeding events during ECMO. Results: We identified 10 patients with bleeding; significantly more of these patients were in the high-AC group (n=8) than in the low-AC group (15.4% vs. 2.5%, p=0.01). However, thrombus events and oxygenator change-free times were not significantly different between the two groups. Four patients in the high-AC group died of bleeding complications (brain hemorrhage, two; hemopericardium, one; and gastrointestinal bleeding, one). One patient in the low-AC group developed a thrombus and died of ECMO dysfunction due to circuit thrombosis. Conclusion: Heparin did not significantly improve thrombotic outcomes. However, maintaining an aPTT of ≥55 seconds was a significant risk factor for bleeding events, especially those associated with mortality.

• International journal of thyroidology
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• v.11 no.2
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• pp.71-74
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• 2018

Adverse events such as hemoptysis and gastrointestinal hemorrhage during tyrosine kinase inhibitor treatment are relatively rare, but the severity of the bleeding can be higher than other common adverse events. It is necessary to educate patients about its possibility so that they can be found early. In this case report of radioiodine refractory thyroid cancer patient, hemoptysis and gastrointestinal bleeding has occurred following lenvatinib administration. Drug interruption and dose modification and dose interruption were required in addition to management for bleeding itself. It is necessary to confirm the high risk of bleeding before the administration of tyrosine kinase inhibitors, and to appropriately control the follow-up interval and drug dosage accordingly.

• Journal of Acupuncture Research
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• v.31 no.4
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• pp.71-79
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• 2014

Objectives : The aim of this study is to evaluate the safety of acupuncture therapy when applied to patients who are undergoing anticoagulants / antiplatelet medication therapy combined with herbal medicine using a retrospective, case-control study. Methods : 428 charts of patients were reviewed in this study. Odds ratio between case of bleeding-related adverse event and control was calculated as main analysis. Exposures were anticoagulants / antiplatelet medication, Hwalhyeolgeoeo herbal medicine and combination of both drugs. Additionally, odds ratios were calculated according to the severity of bleeding-related adverse events. Results : The results were as following: 1. Analysis of all bleeding-related adverse events showed there was no increased risk of combined therapy compared with other exposures and control group. 2. Analysis of only clinically significant adverse events showed there was no increased risk of combined therapy compared with other exposure and control group. 3. Hwalhyeolgeoeo herbal medicine group showed a tendency of increased risk of bleeding-related adverse events in all analysis but was not statistically significant. Conclusions : The results suggest that Hwalhyeolgeoeo herbal medicine-anticoagulant / antiplatelet medication combined therapy may not increase risk of bleeding-related adverse events in acupuncture therapy. By executing various modules of analysis, it was possible to acquire useful data for possible future studies. Further research is needed to confirm such results.

• 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.

• Journal of Gastric Cancer
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• v.22 no.1
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• pp.47-55
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• 2022

Purpose: The use of direct oral Xa inhibitors (DXaIs) to prevent venothrombotic events is increasing. However, gastrointestinal bleeding, including that related to endoscopic resection, is a concern. In this study, we evaluated bleeding and coagulation times during the perioperative period of gastric endoscopic submucosal dissection (ESD). Materials and Methods: Patients who consecutively underwent gastric ESD from August 2016 to December 2018 were analyzed. Bleeding rates were compared among the 3 groups (antiplatelet, DXaIs, and control). DXaI administration was discontinued on the day of the procedure. Prothrombin time (PT), activated partial thromboplastin time, and the ratio of inhibited thrombin generation (RITG), which was based on dilute PT, were determined before and after ESD. Results: During the study period, 265 gastric ESDs were performed in 239 patients, where 23 and 50 patients received DXaIs and antiplatelets, respectively. Delayed bleeding occurred in 17 patients (7.4%) and 21 lesions (7.1%). The bleeding rate in the DXaI group was significantly higher than that in the other groups (30.4%, P<0.01), and the adjusted odds ratio of bleeding was 5.7 (95% confidence interval, 1.4-23.7; P=0.016). In patients using DXaIs, there was a significant (P=0.046) difference in the median RITG between bleeding cases (18.6%) and non-bleeding cases (3.8%). Conclusions: A one-day cessation of DXaIs was related to a high incidence of bleeding after gastric ESD, and monitoring of residual coagulation activity at trough levels might enable the predicted risk of delayed bleeding in patients using DXaIs.

• Journal of Preventive Medicine and Public Health
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• v.50 no.3
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• pp.165-176
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• 2017

Objectives: This study aimed to estimate the risk of bleeding following minor oral surgical procedures and uninterrupted aspirin therapy in high-risk patients or patients with existing chronic diseases compared to patients who did not use aspirin during minor oral surgery at a public hospital. Methods: This retrospective cohort study analyzed the data of 2912 patients, aged 20 years or older, who underwent 5251 minor oral surgical procedures at a district hospital in Thailand. The aspirin group was comprised of patients continuing aspirin therapy during oral surgery. The non-aspirin group (reference) included all those who did not use aspirin during surgery. Immediate and late-onset bleeding was evaluated in each procedure. The risk ratio of bleeding was estimated using a multilevel Poisson regression. Results: The overall cumulative incidence of immediate bleeding was 1.3% of total procedures. No late-onset bleeding was found. A significantly greater incidence of bleeding was found in the aspirin group (5.8% of procedures, p<0.001). After adjusting for covariates, a multilevel Poisson regression model estimated that the bleeding risk in the aspirin group was 4.5 times higher than that of the non-aspirin group (95% confidence interval, 2.0 to 10.0; p<0.001). However, all bleeding events were controlled by simple hemostatic measures. Conclusions: High-risk patients or patients with existing chronic diseases who continued aspirin therapy following minor oral surgery were at a higher risk of hemorrhage than general patients who had not used aspirin. Nonetheless, bleeding complications were not life-threatening and could be promptly managed by simple hemostatic measures. The procedures could therefore be provided with an awareness of increased bleeding risk, prepared hemostatic measures, and postoperative monitoring, without the need for discontinuing aspirin, which could lead to more serious complications.

• Journal of Yeungnam Medical Science
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• v.37 no.4
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• pp.321-328
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• 2020

Background: This study aimed to investigate the incidences of and risk factors for perioperative events following anticoagulant discontinuation in patients with non-valvular atrial fibrillation (NVAF) undergoing non-cardiac surgery. Methods: A total of 216 consecutive patients who underwent cardiac consultation for suspending perioperative anticoagulants were enrolled. A perioperative event was defined as a composite of thromboembolism and major bleeding. Results: The mean anticoagulant discontinuation duration was 5.7 (±4.2) days and was significantly longer in the warfarin group (p<0.001). Four perioperative thromboembolic (1.9%; three strokes and one systemic embolization) and three major bleeding events (1.4%) were observed. The high CHA₂DS₂-VASc and HAS-BLED scores and a prolonged preoperative anticoagulant discontinuation duration (4.4±2.1 vs. 2.9±1.8 days; p=0.028) were associated with perioperative events, whereas the anticoagulant type (non-vitamin K antagonist oral anticoagulants or warfarin) was not. The best cut-off levels of the HAS-BLED and CHA₂DS₂-VASc scores were 3.5 and 2.5, respectively, and the preoperative anticoagulant discontinuation duration for predicting perioperative events was 2.5 days. Significant differences in the perioperative event rates were observed among the four risk groups categorized according to the sum of these values: risk 0, 0%; risk 1, 0%; risk 2, 5.9%; and risk 3, 50.0% (p<0.001). Multivariate logistic regression analysis showed that the HAS-BLED score was an independent predictor for perioperative events. Conclusion: Thromboembolic events and major bleeding are not uncommon during perioperative anticoagulant discontinuation in patients with NVAF, and interrupted anticoagulation strategies are needed to minimize these.

• Journal of Chest Surgery
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• v.54 no.4
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• pp.263-265
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• 2021

Intraoperative events can occur during video-assisted thoracoscopic surgery (VATS) lobectomy due to unfavorable surgical anatomy, such as dense adhesions or calcifications around the pulmonary arteries. Troubleshooting intraoperative complications is essential for performing safe and successful VATS pulmonary resection and lymph node dissection. If continuous bleeding occurs or VATS does not proceed despite all measures, conversion to open thoracotomy should not be delayed.

• Korean Journal of Clinical Pharmacy
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• v.31 no.2
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• pp.87-95
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• 2021

Background: Patients with chronic kidney disease (CKD) are at a high risk of stroke-related morbidity, mortality, and bleeding. However, the overall risk/benefit of anticoagulant therapy among patients with CKD remains unclear. Methods: The MEDLINE, EMBASE, and CENTRAL databases were comprehensively searched until July 31, 2020, to investigate the safety and efficacy of apixaban in patients with stage 4 or 5 CKD, as compared with warfarin. The primary outcome was an incidence of major bleeding. Secondary outcomes included composite bleeding (major, clinically relevant, and minor bleeding), venous thromboembolism (VTE), stroke, and death. Results: In total, seven studies consisting of 10,816 patients were included. Compared with warfarin, apixaban was associated with a reduced risk of major bleeding (OR 0.49, 95% CI 0.41-0.58). In terms of composite bleeding, apixaban tended to pose a significantly lower risk than warfarin (OR 0.51, 95% CI 0.37-0.71). There was no difference between apixaban and warfarin with respect to the risk of stroke or death (stroke: OR 1.23, 95% CI 0.49-3.12; death: OR 0.73, 95% CI 0.45-1.18). Conclusion: Among patients with stage 4 or 5 CKD, the use of apixaban was associated with a lower risk of bleeding compared to warfarin and was also found to pose no excess risk of thromboembolic events.