• 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.

• Korean Circulation Journal
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• v.54 no.7
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• pp.398-406
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• 2024

Background and Objectives: Optimal anticoagulation in very elderly patients is challenging due to the high risk of anticoagulant-induced bleeding. The aim of this study was to assess outcomes of on-label reduced-dose edoxaban (30 mg) in very elderly patients who had additional risk factors for bleeding. Methods: This was a multi-center, prospective, non-interventional observational study to evaluate the efficacy and safety of on-label reduced-dose edoxaban in atrial fibrillation (AF) patients 80 years of age or older and who had more than 1 risk factor for bleeding. Results: A total of 2448 patients (mean age 75.0±8.3 years, 801 [32.7%] males) was included in the present study, and 586 (23.9%) were 80 years of age or older with additional risk factors for bleeding. Major bleeding events occurred frequently among very elderly AF patients who had additional bleeding risk factors compared to other patients (unadjusted hazard ratio [HR], 2.16; 95% confidence interval [CI], 1.16-4.02); however, there were no significant differences in stroke incidence (HR, 1.86; 95% CI, 0.98-3.55). There were no significant differences for either factor after adjusting for age and sex (adjusted HR, 1.65; 95% CI, 0.75-3.62 for major bleeding; adjusted HR, 1.13; 95% CI, 0.51-2.50 for stroke). Conclusions: In very elderly AF patients with comorbidities associated with greater risk of bleeding, the incidence of major bleeding events was significantly increased. In addition, risk of stroke showed tendency to increase in same population. Effective anticoagulation therapy might be important in these high-risk population, and close observation of bleeding events might also be required.

• Clinical Endoscopy
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• v.57 no.4
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• pp.454-465
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• 2024

Background/Aims: Gastrointestinal bleeding is a significant and potentially lethal event. We aimed to review the efficiency and safety of self-assembling peptides for the treatment and prevention of gastrointestinal tract bleeding. Methods: We conducted a systematic search for studies describing the endoscopic use of self-assembling peptides for treatment or prevention of bleeding in the gastrointestinal tract in a parallel, independent fashion. The primary outcomes were rates of successful initial hemostasis, delayed bleeding, and rebleeding. The secondary outcomes were adverse events and ease and volume of gel used. Results: Seventeen studies were analyzed. Overall success rate of self-assembling peptides in gastrointestinal bleeding was 87.7% (38%-100%), regardless of etiology or associated treatments. Rebleeding rate ranged from 0% to 16.2%, with a mean of 4.7%, and overall delayed bleeding rate was 5% (range, 0%-15.9%). Only three adverse events were reported in a pooled number of 815 patients. The volume of gel used varied (0.43 to 3.7 mL) according to indication and type of bleeding. Conclusions: The limited available data on the use of self-assembling peptides in gastrointestinal endoscopy suggest a high efficiency and good safety profile.

• International Journal of Heart Failure
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• v.6 no.2
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• pp.76-81
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• 2024

Background and Objectives: Real-world clinical data, outside of clinical trials and expert centers, on adverse events related to the use of SyncCardia total artificial heart (TAH) remain limited. We aim to analyze adverse events related to the use of SynCardia TAH reported to the Food and Drug Administration (FDA)'s Manufacturers and User Defined Experience (MAUDE) database. Methods: We reviewed the FDA's MAUDE database for any adverse events involving the use of SynCardia TAH from 1/01/2012 to 9/30/2020. All the events were independently reviewed by three physicians. Results: A total of 1,512 adverse events were identified in 453 "injury and death" reports in the MAUDE database. The most common adverse events reported were infection (20.2%) and device malfunction (20.1%). These were followed by bleeding events (16.5%), respiratory failure (10.1%), cerebrovascular accident (CVA)/other neurological dysfunction (8.7%), renal dysfunction (7.5%), hepatic dysfunction (2.2%), thromboembolic events (1.8%), pericardial effusion (1.8%), and hemolysis (1%). Death was reported in 49.4% of all the reported cases (n=224/453). The most common cause of death was multiorgan failure (n=73, 32.6%), followed by CVA/other non-specific neurological dysfunction (n=44, 19.7%), sepsis (n=24, 10.7%), withdrawal of support (n=20, 8.9%), device malfunction (n=11, 4.9%), bleeding (n=7, 3.1%), respiratory failure (n=7, 3.1%), gastrointestinal disorder (n=6, 2.7%), and cardiomyopathy (n=3, 1.3%). Conclusions: Infection was the most common adverse event following the implantation of TAH. Most of the deaths reported were due to multiorgan failure. Early recognition and management of any possible adverse events after the TAH implantation are essential to improve the procedural outcome and patient survival.

• 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.