Effect of oral antiplatelet agents on major bleeding in users of coumarins

2008 ◽  
Vol 100 (12) ◽  
pp. 1076-1083 ◽  
Author(s):  
Olaf H. Klungel ◽  
Patrick C. Souverein ◽  
Anthonius de Boer ◽  
Tom Schalekamp
Keyword(s):  
Major Bleeding ◽  
Conditional Logistic Regression ◽  
Vitamin K Antagonists ◽  
Antiplatelet Agents ◽  
Bleeding Risk ◽  
Primary Diagnosis ◽  
Antiplatelet Drugs ◽  
Antiplatelet Drug ◽  
Concurrent Use ◽  
Increased Risk

SummaryTreatment with vitamin K antagonists (coumarins) is associated with an increased risk of bleeding. In order to elucidate the bleeding risk of users of antiplatelet drugs among users of coumarins, we assessed the odds ratio of major bleeding associated with use of antiplatelet drugs in users of the coumarins acenocoumarol and phenprocoumon. We used data froma Dutch record linkage system, including pharmacy and linked hospitalization records for approximately two million subjects, to conduct a nested case control study in a cohort of new users of coumarins. Cases were patients who were hospitalized with a primary diagnosis of major bleeding while taking coumarin and were matched with up to four control subjects. Conditional logistic regression analysis was used to determine ORs and 95% confidence intervals (CI).We identified 1848 case patients who were matched to 5818 controls. Users of clopidogrel or aspirin showed a significantly increased risk of hospitalization because of major bleeding (OR 2.9, 95% CI 1.2–6.9 and OR 1.6, 95% CI 1.3–1.9, respectively), whereas users of dipyridamole and combinations of antiplatelet drugs showed a strong trend (OR 1.5, 95% CI 1.0–2.3 and OR 1.8, 95 % CI 1.0–3.3, respectively). In all cases, the risks were greater for upper gastrointestinal bleedings than for other bleedings. In conclusion, the use of any antiplatelet drug increases the risk of hospitalization for major bleeding among users of coumarins. Concurrent use of clopidogrel or dipyridamole and coumarins is probably not safer than concurrent use of aspirin and coumarins.

scholarly journals Uncertain Associations of Major Bleeding and Concurrent Use of Antiplatelet Agents and Chinese Medications: A Nested Case-Crossover Study

2017 ◽  
Vol 2017 ◽  
pp. 1-9
Author(s):  
Hsin-Hui Tsai ◽  
Hsiang-Wen Lin ◽  
Chiu-Lin Tsai ◽  
Felix K. Yam ◽  
Sheng-Shing Lin
Keyword(s):  
Crossover Study ◽  
Major Bleeding ◽  
Conditional Logistic Regression ◽  
Antiplatelet Agents ◽  
Population Based ◽  
Antiplatelet Drugs ◽  
Bleeding Events ◽  
Case Crossover ◽  
Concurrent Use ◽  
Health Database

Despite the evidence that some commonly used Chinese medications (CMs) have antiplatelet/anticoagulant effects, many patients still used antiplatelets combined with CMs. We conducted a nested case-crossover study to examine the associations between the concomitant use of antiplatelets and CMs and major bleeding using population-based health database in Taiwan. Among the cohort of 79,463 outpatients prescribed antiplatelets (e.g., aspirin and clopidogrel) continuously, 1,209 patients hospitalized with new occurring bleeding in 2012 and 2013 were included. Those recruited patients served as their own controls to compare different times of exposure to prespecified CMs (e.g., Asian ginseng and dong quai) and antiplatelet agents. The periods of case, control 1, and control 2 were defined as 1–4 weeks, 6–9 weeks, and 13–16 weeks before hospitalization, respectively. Conditional logistic regression analyses found that concurrent use of antiplatelet drugs with any of the prespecified CMs in the case period might not significantly increase the risks of bleeding over that in the control periods (OR = 1.00, 95% CI 0.51 to 1.95 and OR = 1.13, 95% CI 0.65 to 1.97). The study showed no strong relationships between hospitalization for major bleeding events and concurrent use of antiplatelet drugs with the prespecified CMs.

Developments in Oral Antiplatelet Agents for the Treatment of Acute Coronary Syndromes

2015 ◽  
Vol 29 (3) ◽  
pp. 239-249 ◽  
Author(s):  
David S. Roffman
Keyword(s):  
Clinical Trials ◽  
Major Bleeding ◽  
Antiplatelet Agent ◽  
Antiplatelet Agents ◽  
Clinical History ◽  
Bleeding Risk ◽  
Phase Iii ◽  
Coronary Syndrome ◽  
Phase Iii Clinical Trials ◽  
Increased Risk

A review of the literature was conducted for clinical trials evaluating the antiplatelet P2Y12 receptor antagonists, clopidogrel, prasugrel, and ticagrelor, as well as the guidelines for the management of acute coronary syndrome (ACS) or myocardial infarction. Clinical guidelines recommend that patients with ACS be treated with dual oral antiplatelet therapy of aspirin plus clopidogrel, prasugrel, or ticagrelor. The selection of an appropriate antiplatelet agent depends on the treatment approach and a patient’s bleeding risk and clinical history. With respect to antiplatelet activity, prasugrel and ticagrelor demonstrate greater potency and less interpatient variability than clopidogrel. In phase III clinical trials, prasugrel and ticagrelor reduced the incidence of ischemic events in patients with ACS compared with clopidogrel. Ticagrelor and clopidogrel were associated with a similar risk of major bleeding, whereas patients receiving prasugrel had an increased risk of major bleeding versus those receiving clopidogrel. Pharmacists can provide guidance on the appropriate use of antiplatelet agents as well as the use of concomitant medications, while being vigilant for any potential drug interactions.

scholarly journals Selective serotonin reuptake inhibitor use is associated with major bleeding during treatment with vitamin K antagonists: results of a cohort study

2021 ◽  
Author(s):  
Sanne Bakker ◽  
Louise Burggraaf ◽  
MJHA Kruip ◽  
Felix van der Meer ◽  
WM Lijfering ◽  
...  
Keyword(s):  
Vitamin K ◽  
Major Bleeding ◽  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Cox Regression ◽  
Conditional Logistic Regression ◽  
Vitamin K Antagonists ◽  
Selective Serotonin ◽  
Bleeding Complications ◽  
Increased Risk

Aims: To determine whether Selective serotonin reuptake inhibitors (SSRIs) cause major bleeding during vitamin K antagonist (VKA) treatment and investigate the possible mechanisms behind this interaction. Methods: Information on SSRI use and bleeding complications was obtained from patient records at the Anticoagulation Clinics of Leiden and Rotterdam of VKA initiators between 2006 and 2018. Conditional logistic regression and time-dependent Cox regression were used to estimate the effect of SSRIs on a high INR (≥ 5) within 2 months after SSRI initiation and on major bleeding during the entire period of SSRI use, respectively. SSRI use was stratified for (non-)CYP2C9 inhibitors. Results: 58,918 patients were included, of whom 1504 were SSRI users. SSRI initiation versus non-use was associated with a 2.41-fold (95% confidence interval [CI] 2.01-2.89) increased risk for a high INR, which was 3.14-fold (95%CI 1.33-7.43) among CYP2C9 inhibiting SSRIs. SSRI use versus non-use was associated with a 1.22-fold (95%CI 0.99-1.50) increased risk for major bleeding in all SSRI users, which was 1.31-fold (95%CI 0.62-2.72) in CYP2C9 inhibiting SSRIs compared to non-users. Conclusion: SSRIs are associated with an increased risk of high INR and major bleeding. These risks were slightly more elevated for CYP2C9 inhibiting SSRI users, suggesting that this was due to a pharmacokinetic interaction (by CYP2C9 inhibition) as well as a pharmacodynamic effect of SSRIs on platelet activation.

Interaction between Traditional Chinese Medicine and Anticoagulant/Antiplatelet Drugs

2019 ◽  
Vol 20 (9) ◽  
pp. 701-713 ◽  
Author(s):  
Jiajia Li ◽  
Qing Liang ◽  
GuangChun Sun
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Drug Interactions ◽  
Adverse Reactions ◽  
Bleeding Risk ◽  
Antiplatelet Drugs ◽  
Pharmacokinetic Studies ◽  
Drug Databases ◽  
Concurrent Use ◽  
Anticoagulant Drugs

Background: Traditional Chinese medicine (TCM) has been used for medical purposes since the ancient time and has gradually gained recognition worldwide. Nowadays, patients with thrombus presiding to anticoagulant/ antiplatelet drugs prefer taking TCM. However, an increasing number of studies on herb–drug interactions have been shown. Nevertheless, findings are frequently conflicting and vague. In this review, we discuss the herb–drug interactions between TCM and anticoagulant/antiplatelet drugs to provide guidance on concomitant ingestion with anticoagulant/antiplatelet drugs. Methods: We undertook a structured search of medicine and drug databases for peer-reviewed literature using focused review questions. Results: Danshen, Ginkgo, Ginger, H. Perforatum, SMY and Puerarin injection had directional regulation effects on the efficacy of anticoagulant drugs by altering the CYPs, pharmacokinetic indexs and hemorheological parameters. H. Perforatum inhibited the efficacy of Clopidogrel by enhancing the CYP3A4 activity and Ginkgo increased the efficacy of Ticlopidine. Additionally, Renshen, the formulae except SMY and injections except Puerarin injection could increase or decrease the efficacy of anticoagulant/antiplatelet drugs via regulating the CYPs, platelet aggregation, hemorheological parameters and others. Conclusion: Some cases have reported that TCMs may increase the bleeding risk or has no effect on coagulation when anticoagulant/antiplatelet drugs are concurrently used. However, pharmacokinetic studies have presented either consistent or slightly varying results. So it is difficult to ascertain whether the concurrent use of TCM may increase or reduce the pharmacologic effects of anticoagulant/antiplatelet drugs with adverse reactions. Therefore, herb–drug interactions of TCM and anticoagulant/antiplatelet drugs should be further explored and defined.

Complex antithrombotic therapy and bleeding risk in patients with peripheral arterial disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Tseng ◽  
S Bhatt ◽  
M Girardo ◽  
D Liedl ◽  
P Wennberg ◽  
...  
Keyword(s):  
Peripheral Arterial Disease ◽  
Triple Therapy ◽  
Major Bleeding ◽  
Antithrombotic Therapy ◽  
Oral Anticoagulants ◽  
Bleeding Risk ◽  
Arterial Disease ◽  
Risk Of Bleeding ◽  
Increased Risk ◽  
Peripheral Arterial

Abstract Introduction Antiplatelet therapy is the cornerstone of treatment for many atherosclerotic vascular pathologies including peripheral arterial disease (PAD). Patients with PAD often have comorbid conditions that require complex antithrombotic therapy, i.e. combined antiplatelet and anticoagulation. Methods All adult patients undergoing ankle brachial index (ABI) measurements were included in the study. ABI values between 1.00 and 1.40 were considered normal, and values below 1.00 or above 1.40 were considered PAD. Demographic, comorbidity and outcome data were obtained using diagnostic codes from the electronic health record. Three medication classes were analyzed: aspirin, non-aspirin oral antiplatelets (e.g. P2Y12 inhibitors) and oral anticoagulants (warfarin and the direct oral anticoagulants). Medication use was determined for patients who had been on a medication for at least one year. Cox proportional hazard analysis for the time to first bleeding event was analyzed. Bleeding was defined as any bleeding requiring medical evaluation (including clinically-relevant non-major bleeding and major bleeding). Results In all, 40,144 patients were included in the analysis (mean age 66±15, 43% female). Patients with PAD were more likely to be on double therapy (one antiplatelet with anticoagulation) (28% vs 19%) and triple therapy (dual antiplatelet with anticoagulation) (10% vs 4%). Unadjusted hazard ratios for bleeding risk showed increased risk of bleeding for patients with PAD (1.18, 95% confidence interval [CI]: 1.08–1.29), though the association is no longer present after adjustment for antithrombotic therapy. Adjusting for age, sex and PAD class, compared to no antithrombotic therapy, there was increased risk of bleeding for monotherapy (1.91, 95% CI: 1.61–2.26), double therapy (3.40, 95% CI: 2.89–4.00) and triple therapy (5.00, 95% CI: 4.21–5.96). Among medications, aspirin and anticoagulant use was independently associated with the greatest increase in risk of bleeding. Conclusion Patients in PAD are at increased risk of bleeding secondary to antithrombotic therapy. Complex antithrombotic therapy with double or triple therapy confer additional bleeding risk, particularly regimens containing aspirin and oral anticoagulants. Funding Acknowledgement Type of funding source: None

scholarly journals Advances in Antiplatelet Therapy for Dentofacial Surgery Patients: Focus on Past and Present Strategies

Materials ◽  
2019 ◽  
Vol 12 (9) ◽  
pp. 1524 ◽  
Author(s):  
Gabriele Cervino ◽  
Luca Fiorillo ◽  
Ines Paola Monte ◽  
Rosa De Stefano ◽  
Luigi Laino ◽  
...  
Keyword(s):  
Antiplatelet Therapy ◽  
Oral Surgery ◽  
Case Reports ◽  
Case Series ◽  
Antiplatelet Agents ◽  
Preventive Therapy ◽  
Antiplatelet Drugs ◽  
Risk Of Bleeding ◽  
The Past ◽  
Increased Risk

Background: Nowadays, patients involved in antiplatelet therapy required special attention during oral surgery procedures, due to the antiplatelet drugs assumption. The motivations of the assumption may be different and related to the patient’s different systemic condition. For this reason, accordingly to the current international guidelines, different protocols can be followed. The aim of this work is to analyze how the dentist’s approach to these patients has changed from the past to the present, evaluating the risk exposure for the patients. Methods: This review paper considered different published papers in literature through quoted scientific channels, going in search of “ancient” works in such a way as to highlight the differences in the protocols undertaken. The analyzed manuscripts are in the English language, taking into consideration reviews, case reports, and case series in such a way as to extrapolate a sufficient amount of data and for evaluating the past therapeutic approaches compared to those of today. Results: Colleagues in the past preferred to subject patients to substitution therapy with low molecular weight anticoagulants, by suspending antiplatelet agents to treatment patients, often for an arbitrary number of days. The new guidelines clarify everything, without highlighting an increased risk of bleeding during simple oral surgery in patients undergoing antiplatelet therapy. Conclusion: Either patients take these medications for different reasons, because of cardiovascular pathologies, recent cardiovascular events, or even for simple prevention, although the latest research shows that there is no decrease of cardiovascular accidents in patients who carry out preventive therapy. Surely, it will be at the expense of the doctor to assess the patient’s situation and risk according to the guidelines. For simple oral surgery, it is not necessary to stop therapy with antiplatelet agents because the risk of bleeding has not increased, and is localized to a post-extraction alveolus or to an implant preparation, compared to patients who do not carry out this therapy. From an analysis of the results it emerges that the substitutive therapy should no longer be performed and that it is possible to perform oral surgery safely in patients who take antiplatelet drugs, after a thorough medical history. Furthermore, by suspending therapy, we expose our patients to more serious risks, concerning their main pathology, where present.

scholarly journals Tinzaparin in Cancer and Renal Impairment: A Systematic Review Focusing on Safety

2020 ◽  
Author(s):  
Ioannis Vathiotis ◽  
Nikolaos Syrigos ◽  
Evangelos Dimakakos
Keyword(s):  
Systematic Review ◽  
Renal Impairment ◽  
Creatinine Clearance ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Severe Renal Impairment ◽  
Vitamin K Antagonists ◽  
Bleeding Events ◽  
Increased Risk ◽  
Therapeutic Doses

Abstract Purpose: Low-molecular-weight heparins are approved for primary and secondary venous thromboembolism prevention. The purpose of this systematic review is to provide an update regarding the safety profile of tinzaparin sodium, prescribed either as a prophylactic or as a therapeutic regimen for VTE in cancer patients and individuals suffering from renal impairment. Method: We identified and studied clinical studies from 2000 until 2020, reporting safety outcomes for cancer patients and individuals with renal impairment receiving either prophylactic or therapeutic doses of tinzaparin. Results: In patients with cancer major bleeding rates fluctuate between 0.8% and 7%; reported major bleeding rates for non-cancer patients with renal impairment on prophylactic tinzaparin regimens were 0%. Non-cancer patients on therapeutic tinzaparin regimens exhibited major bleeding in 0 to 2.3% of cases; major bleeding rates were higher for cancer patients with renal impairment receiving therapeutic doses of tinzaparin (4.3 to 10%). Patients on tinzaparin exhibit significantly lower rates of clinically relevant nonmajor bleeding events in comparison with those on vitamin K antagonists. Bioaccumulation of tinzaparin is not correlated with age, body weight or creatinine clearance. Periodic administration of either prophylactic or therapeutic doses of tinzaparin does not result in bioaccumulation, even in patients with severe renal impairment and creatinine clearance < 20 ml/min. Conclusion: Tinzaparin is safe and can be used without dose adjustment in patients with severe renal impairment and creatinine clearance > 20 ml/min. Tinzaparin represents a thoroughly studied and safe choice for special populations at increased risk for thrombosis and bleeding.

Abstract 299: Association of Chronic Lung Disease with Treatments and Outcomes of Acute Coronary Syndromes: Results from the NCDR®

2012 ◽  
Vol 5 (suppl_1) ◽  
Author(s):  
Jonathan R Enriquez ◽  
James A de Lemos ◽  
Ramin Farzaneh-Far ◽  
Anand Rohatgi ◽  
S. A Peng ◽  
...  
Keyword(s):  
Hospital Mortality ◽  
Lung Disease ◽  
Major Bleeding ◽  
Chronic Lung Disease ◽  
Beta Blockers ◽  
Bleeding Risk ◽  
Bleeding Complications ◽  
Processes Of Care ◽  
Increased Risk ◽  
The Impact

Background: Previous reports are conflicting regarding outcomes, treatments, and processes of care after acute myocardial infarction (MI) for patients with chronic lung disease (CLD). Methods: Using the NCDR ACTION Registry ® -GWTG ™ (AR-G), demographics, clinical characteristics, treatments, processes of care, and in-hospital adverse events after NSTEMI and STEMI were compared between patients with (n= 22,624; 14.2%) and without (n= 136,266; 85.8%) CLD. CLD was defined by a history of COPD, chronic bronchitis, or emphysema. Multivariable adjustment using published AR-G in-hospital mortality and major bleeding risk adjustment models was performed to quantify the impact of CLD on treatments and outcomes. Results: CLD was present in 10.1% of STEMI patients and 17.0% of NSTEMI patients. In both STEMI and NSTEMI, CLD patients were older, more likely to be female, and had more comorbidities including diabetes, renal disease, prior MI and heart failure, compared to those without CLD. Although on admission CLD patients were more likely to be on cardiovascular medications, by discharge slightly fewer CLD patients received composite core measures (aspirin, beta-blockers, ACE-inhibitors, and statins) (table). In NSTEMI, CLD was also associated with less use of invasive procedures and with increased risk of both death and major bleeding. In STEMI, major bleeding but not mortality was increased. Conclusions: CLD is a common comorbidity and is independently associated with an increased risk for major bleeding after MI. In NSTEMI, CLD is also associated with receiving fewer evidence-based medications, less timely angiography and revascularization, and increased in-hospital mortality. Close attention should be given to this high-risk subgroup for the prevention and management of bleeding complications after MI, and further investigation is needed to determine the reasons for treatment and outcome disparities in NSTEMI.

Abstract 119: Risk of Intracerebral Hemorrhage with Combined Antiplatelet and Anticoagulant Use

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Matthew L Flaherty ◽  
Lili Ding ◽  
Jessica G Woo ◽  
Lisa Martin ◽  
Mary Haverbusch ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Antiplatelet Agents ◽  
Population Based ◽  
Careful Consideration ◽  
Antiplatelet Drug ◽  
Treatment Groups ◽  
Stroke Study ◽  
Increased Risk ◽  
Anticoagulant Drugs ◽  
Increase Risk

Context: Intracranial bleeding is the most feared complication of antithrombotic use. Antiplatelet and anticoagulant drugs increase risk of intracerebral hemorrhage (ICH), yet in some instances, combinations of antiplatelet agents and anticoagulants are used without firm evidence of efficacy. Few studies have compared the risks of different agents and their combinations in a single population. We determined the risk of ICH associated with the most commonly used antiplatelet and anticoagulant drugs and their combinations in a population-based case-control study. Methods: This report includes data from subjects recruited from the Greater Cincinnati/Northern Kentucky area by the Genetic and Environmental Risk Factors for Hemorrhagic Stroke Study from 1997 to 2009. We compared individuals in different treatment groups to identify any differences in baseline covariates that could be associated with treatment assignment. As there were a number of statistically significant differences, we used multivariate matching to analyze risk for ICH conferred by different antithrombotic agents. Treatment effects on ICH were estimated using the matched samples while accounting for the dependence between matched individuals. Results: There were 733 subjects with ICH and 2555 controls included in this study period. Results are shown in the table. Use of aspirin, clopidogrel, or their combination was associated with a trend toward increased risk. Warfarin increased risk compared with no antithrombotic use (OR 3.98, p < 0.0001). The combination of warfarin and either aspirin or clopidogrel produced the greatest risk, compared with no antithrombic therapy (OR 4.92 p<0.001) or compared with warfarin alone (OR 3.00 p=0.009). Conclusions: The combination of warfarin and an antiplatelet drug significantly increases risk of ICH compared with no antithrombotic therapy or warfarin monotherapy. The use of combination therapy requires careful consideration in clinical practice.

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