Reviewing the reality: why we need to change

Lin, Peter

doi:10.1093/eurheartj/sui031

Cited by 38 publications

(28 citation statements)

References 38 publications

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“…However, its narrow therapeutic window and numerous food and drug interactions affect its safety, efficacy, and patient compliance. In addition, its slow onset of action and variable pharmacologic effects make it difficult to maintain the appropriate antithrombotic effect 45. A meta-analysis reported that 44% of bleeding complications with warfarin were associated with supratherapeutic INRs, and 48% of thromboembolic events occurred in the subtherapeutic range 46.…”

Section: Emergence Of New Anticoagulantsmentioning

confidence: 99%

Practical Issues to Prevent Stroke Associated with Non-valvular Atrial Fibrillation

2013

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Stroke associated with non-valvular atrial fibrillation (NVAF) is one of the most important subtypes of ischemic stroke, and its importance is becoming even more apparent in an aging population. To assess the risk of stroke associated with NVAF, the CHADS2 and CHA2DS2-VASc scores are mainly used. Such scores can be used to predict the recurrence and prognosis of ischemic stroke. In addition, new oral anticoagulants (NOACs) and devices are being evaluated in the prevention of stroke associated with NVAF in addition to treatment with the conventional oral anticoagulant, warfarin. Since clinical experience with NOACs is not globally sufficient, a cautious approach is needed.

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Section: Emergence Of New Anticoagulantsmentioning

confidence: 99%

Practical Issues to Prevent Stroke Associated with Non-valvular Atrial Fibrillation

2013

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“…[6] Despite the rapid market uptake of the direct oral anticoagulants, warfarin remains the most widely-prescribed anticoagulant. [7] DDIs involving warfarin are of major concern, since the drug: is commonly-used;[7,8] has a narrow therapeutic index; may interact with almost every therapeutic class;[9] and is the leading cause of adverse drug event-related hospitalizations in older adults. [10] Further, clinical sequelae resulting from over-anticoagulation—particularly gastrointestinal bleeding (GIB) and intracranial hemorrhage (ICH), the vast majority of serious bleeds in warfarin-treated persons[11]—are common and can be fatal.…”

Section: Introductionmentioning

confidence: 99%

Gastrointestinal bleeding and intracranial hemorrhage in concomitant users of warfarin and antihyperlipidemics

Leonard

Brensinger

Bilker

et al. 2017

International Journal of Cardiology

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Background Drug interactions, particularly those involving warfarin, are a major clinical and public health problem. Minimizing serious bleeding caused by anticoagulants is a recent major focus of the United States (US) Department of Health and Human Services. This study quantified the risk of gastrointestinal bleeding (GIB) and intracranial hemorrhage (ICH) among concomitant users of warfarin and individual antihyperlipidemics. Methods The authors conducted a high-dimensional propensity score-adjusted cohort study of new concomitant users of warfarin and an antihyperlipidemic, among US Medicaid beneficiaries from five states during 1999–2011. Exposure was defined by concomitant use of warfarin plus one of eight antihyperlipidemics. The primary outcome measure was a composite of GIB/ICH within the first 30 days of concomitant use. As a secondary outcome measure, GIB/ICH was examined within the first 180 days of concomitant use. Results Among 236,691 persons newly-exposed to warfarin and an antihyperlipidemic, the crude incidence of GIB/ICH was 13.2 (95% confidence interval 12.7 to 13.8) per 100 person-years. Users were predominantly older, female, and Caucasian. Adjusted hazard ratios (aHRs) for warfarin and individual statins were consistent with no association. Warfarin + gemfibrozil was associated with an 80% increased risk of GIB/ICH within the first month of concomitant use (aHR = 1.8, 1.4 to 2.4). Warfarin + fenofibrate was associated with a similar increased risk (aHR = 1.8, 1.2 to 2.7), yet with an onset during the second month of concomitant use. Conclusions Among warfarin-treated persons, the use of fibrates—but not statins—increases the risk of hospital presentation for GIB/ICH.

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“…By preventing the recycling of vitamin K, VKAs inhibit synthesis of several vitamin K-dependent coagulation factors, meaning dietary vitamin K fluctuations can both amplify or diminish VKA effect. 23 Also, like many other drugs, VKAs are metabolized by cytochrome P450 enzymes, and their metabolism is affected by pharmacokinetic interactions with other drugs. 23 Initial VKA dose response also varies individually as a result of cytochrome P450 genetic polymorphisms 23 and comorbidities such as hepatic or renal disease, or heart failure.…”

Section: Current Thromboprophylaxis and Its Limitations In Routine Prmentioning

confidence: 99%

“…23 Also, like many other drugs, VKAs are metabolized by cytochrome P450 enzymes, and their metabolism is affected by pharmacokinetic interactions with other drugs. 23 Initial VKA dose response also varies individually as a result of cytochrome P450 genetic polymorphisms 23 and comorbidities such as hepatic or renal disease, or heart failure. 24,25 These interactions, coupled with the fact that VKAs have a narrow therapeutic window (INR: 2-3), mean that patients must be monitored regularly and have their dose adjusted accordingly.…”

Section: Current Thromboprophylaxis and Its Limitations In Routine Prmentioning

confidence: 99%

Advances in Stroke Prevention in Atrial Fibrillation: Enhanced Risk Stratification Combined With the Newer Oral Anticoagulants

Verheugt

2013

Clinical Cardiology

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Patients with atrial fibrillation (AF) have an increased stroke risk compared with those in sinus rhythm, although the absolute risk for individual patients is modulated by the presence of various additional risk factors. Patient selection for oral anticoagulation for stroke prevention is based on risks of stroke and bleeding. Although CHADS 2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack) is the most widely used scheme for evaluating stroke risk in patients with AF, several other stroke risk factors are not included; therefore, many patients' stroke risk may be underestimated, contributing to the underuse of anticoagulants. Furthermore, a substantial proportion of patients are categorized as being at moderate risk (CHADS 2 = 1), and there has been some ambiguity regarding optimum thromboprophylaxis in this group. -VASc = 0), who are unlikely to benefit from antithrombotic therapy. For all others, an oral anticoagulant may be the preferred approach, simplifying clinical decision making. Implementation of CHA 2 DS 2 -VASc may also result in an increased proportion of patients receiving anticoagulation. The emergence of newer oral anticoagulants that can be given without routine coagulation monitoring, with improved benefit-risk profiles vs vitamin K antagonists, promises to simplify therapy for patients with AF at risk of stroke. This, coupled with advances in stroke risk stratification, is expected to improve patient outcomes and reduce the burden of AF-related stroke. IntroductionAtrial fibrillation (AF) is the most frequent clinically relevant cardiac arrhythmia encountered in the outpatient clinic, 1 affecting ∼ 1% of the US population and up to 10% of individuals age ≥80 years, with a higher prevalence among men than among women at all ages. 2 It is predicted that the prevalence of AF will continue to rise in the coming decades. 3 Patients with AF are at an increased risk of cardioembolic stroke; their risk is approximately 5-fold greater than for patients in sinus rhythm, 4 although the absolute risk for individual patients is highly variable depending on the presence or absence of various risk factors. 5,6

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Reviewing the reality: why we need to change

Cited by 38 publications

References 38 publications

Practical Issues to Prevent Stroke Associated with Non-valvular Atrial Fibrillation

Practical Issues to Prevent Stroke Associated with Non-valvular Atrial Fibrillation

Gastrointestinal bleeding and intracranial hemorrhage in concomitant users of warfarin and antihyperlipidemics

Advances in Stroke Prevention in Atrial Fibrillation: Enhanced Risk Stratification Combined With the Newer Oral Anticoagulants

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