Oral Anticoagulants: Mechanism of Action, Clinical Effectiveness, and Optimal Therapeutic Range

Hirsh, Jack; Dalen, James E.; Anderson, David R.; Poller, L.; Bussey, Henry I.; Ansell, Jack; Deykin, Daniel

doi:10.1378/chest.119.1_suppl.8s

Cited by 879 publications

(455 citation statements)

References 151 publications

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“…In our study, we examined whether the increased risk of adverse events in patients with diagnosed anxiety may have been related to anticoagulation control, which is potentially modifiable. Anticoagulation quality depends on multiple factors, including age, sex, the targeted INR,24 the frequency of INR monitoring,25 medication adherence,26 diet, comorbidities,24 and drug‐drug interactions27; some of these factors may be negatively affected by mental health disorders 28, 29, 30. However, adjustment for patient‐level time in therapeutic INR range did not materially affect the strength of association for anxiety and outcomes.…”

Section: Discussionmentioning

confidence: 97%

Anxiety, Depression, and Adverse Clinical Outcomes in Patients With Atrial Fibrillation Starting Warfarin: Cardiovascular Research Network WAVE Study

Baumgartner

Fan

Fang

et al. 2018

JAHA

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BackgroundAnxiety and depression are associated with worse outcomes in several cardiovascular conditions, but it is unclear whether they affect outcomes in atrial fibrillation (AF). In a large diverse population of adults with AF, we evaluated the association of diagnosed anxiety and/or depression with stroke and bleeding outcomes.Methods and ResultsThe Cardiovascular Research Network WAVE (Community‐Based Control and Persistence of Warfarin Therapy and Associated Rates and Predictors of Adverse Clinical Events in Atrial Fibrillation and Venous Thromboembolism) Study included adults with AF newly starting warfarin between 2004 and 2007 within 5 health delivery systems in the United States. Diagnosed anxiety and depression and other patient characteristics were identified from electronic health records. We identified stroke and bleeding outcomes from hospitalization databases using validated International Classification of Diseases, Ninth Revision (ICD‐9), codes. We used multivariable Cox regression to assess the relation between anxiety and/or depression with outcomes after adjustment for stroke and bleeding risk factors. In 25 570 adults with AF initiating warfarin, 490 had an ischemic stroke or intracranial hemorrhage (1.52 events per 100 person‐years). In multivariable analyses, diagnosed anxiety was associated with a higher adjusted rate of combined ischemic stroke and intracranial hemorrhage (hazard ratio, 1.52; 95% confidence interval, 1.01–2.28). Results were not materially changed after additional adjustment for patient‐level percentage of time in therapeutic anticoagulation range on warfarin (hazard ratio, 1.56; 95% confidence interval, 1.03–2.36). In contrast, neither isolated depression nor combined depression and anxiety were significantly associated with outcomes.ConclusionsDiagnosed anxiety was independently associated with increased risk of combined ischemic stroke and intracranial hemorrhage in adults with AF initiating warfarin that was not explained by differences in risk factors or achieved anticoagulation quality.

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Section: Discussionmentioning

confidence: 97%

Anxiety, Depression, and Adverse Clinical Outcomes in Patients With Atrial Fibrillation Starting Warfarin: Cardiovascular Research Network WAVE Study

Baumgartner

Fan

Fang

et al. 2018

JAHA

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“…If patient opts to switch to UFH, then she should do so under hospital care as chances of valve thrombosis are higher. INR range should be kept around 2.5 [6]. If valve thrombosis is suspected, echocardiography is the best diagnostic modality as fluoroscopy involves risks of radiation.…”

Section: Mechanicalmentioning

confidence: 99%

“…Measuring activated partial thromboplastin time (aPTT) remains the most frequently used method for monitoring the anticoagulant response of unfractionated heparin (UFH) and should be measured Table 1 Guidelines for anticoagulation therapy in pregnant women with mechanical heart valves ACC/AHA [6] ACCP [6,7] ESC [5,6] Oral anticoagulants LMWH LMWH has a better bioavailability and has a lower risk of bleeding, thrombocytopenia and osteoporosis, but has a longer half-life. In 2004, it was rephrased that its use for thromboprophylaxis in pregnant women with mechanical prosthetic heart valves has not been adequately studied.…”

Section: Unfractionated Heparinmentioning

confidence: 99%

Pregnancy After Cardiac Surgery

Kanhere

2016

J Obstet Gynecol India

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Heart disease is one of the common, indirect obstetric causes of maternal death. Management of these cases may challenge the entire team providing care to the mother and fetus. Advances in cardiac surgery has improved quality of life and level of functioning of cardiovascular system of patients with congenital or acquired heart disease. These diseases complicate 0.1-4 % pregnancies. Maternal complications in the form of thromboembolic, hemorrhagic episode and heart failure may occur. The fetus is in danger of effects of oral anticoagulation therapy and other medications given to the patient in order to support cardiovascular system, intrauterine growth restriction and danger of hypoxia. In recent era, we are facing more pregnant patients with previous history of surgical correction of congenital or rheumatic heart disease. 123In this review, we have attempted to draw a management protocol of such patients based on the available literature and various international guidelines. In pregnant women with mechanical heart valves, recent data support warfarin use throughout pregnancy, followed by a switch to heparin and planned induction of labor. However, the complexity of this situation demands a cafeteria approach where the patient herself can choose from the available options that are supported by evidence-based information. Preconception counseling, evaluation and antenatal high-risk management protocol with the help of cardiologist and cardiac surgeon improves maternal and neonatal outcome.

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“…Orthopedic surgery, orthopedic trauma, acute coronary syndromes, and atrial fibrillation are well documented risk factors for thromboembolic events, such as deep vein thrombosis, pulmonary embolism, and stroke 1. Prophylaxis with an anticoagulant drug can reduce these risks.…”

mentioning

confidence: 99%

“…However, these anticoagulant therapies have some drawbacks. Warfarin can be administered orally; however, blood monitoring is required, it has a slow onset and offset of action thus rapid intervention is difficult, and is prone to have extensive food and drug interactions 1, 2, 3. Heparins have a rapid onset of action but must be administered parenterally and are thus neither convenient nor cost‐effective for administration after hospital discharge.…”

mentioning

confidence: 99%

A Systems Pharmacology Model for Predicting Effects of Factor Xa Inhibitors in Healthy Subjects: Assessment of Pharmacokinetics and Binding Kinetics

Zhou

Huntjens

Gilissen

2015

CPT Pharmacometrics Syst. Pharmacol.

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Factor Xa (FXa) emerged as a promising target for effective anticoagulation and several FXa inhibitors are now available for the prevention of venous thromboembolism. However, in previously reported pharmacokinetic/pharmacodynamic (PK/PD) models, the complex coagulation processes and detailed information of drug action are usually unclear, which makes it difficult to predict clinical outcome at the drug discovery stage. In this study, a large‐scale systems pharmacology model was developed based on several published models and clinical data. It takes into account all pathways of the coagulation network, and captures drug‐specific features: plasma pharmacokinetics and drug‐target binding kinetics (BKs). We aimed to predict the anticoagulation effects of FXa inhibitors in healthy subjects, and to use this model to compare the effects of compounds with different binding properties. Our model predicts the clotting time and anti‐FXa effects and could thus serve as a predictive tool for the anticoagulant potential of a new compound.

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Oral Anticoagulants: Mechanism of Action, Clinical Effectiveness, and Optimal Therapeutic Range

Cited by 879 publications

References 151 publications

Anxiety, Depression, and Adverse Clinical Outcomes in Patients With Atrial Fibrillation Starting Warfarin: Cardiovascular Research Network WAVE Study

Anxiety, Depression, and Adverse Clinical Outcomes in Patients With Atrial Fibrillation Starting Warfarin: Cardiovascular Research Network WAVE Study

Pregnancy After Cardiac Surgery

A Systems Pharmacology Model for Predicting Effects of Factor Xa Inhibitors in Healthy Subjects: Assessment of Pharmacokinetics and Binding Kinetics

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