Anticoagulation represents the mainstay of therapy for most patients with atrial fibrillation. Patients on oral anticoagulation often require concomitant antiplatelet therapy, mostly because of coronary artery disease. After coronary stent implantation, dual antiplatelet therapy is necessary. However, the combination of oral anticoagulation and antiplatelet therapy increases the bleeding risk. Risk scores such as the CHA2DS2-Vasc score and the HAS-BLED score help to identify both bleeding and stroke risk in individual patients. The guidelines of the European Society of Cardiology provide a rather detailed recommendation for patients on oral anticoagulation after coronary stent implantation. However, robust evidence is lacking for some of the recommendations, and especially for new oral anticoagulants and new antiplatelets few or no data are available. This review addresses some of the critical points of the guidelines and discusses potential advantages of new anticoagulants in patients with atrial fibrillation after stent implantation.
Atrial fibrillation (AF) is strongly associated with cardioembolic stroke, and thromboprophylaxis is an established means of reducing stroke risk in patients with AF. Oral vitamin K antagonists such as warfarin have been the mainstay of therapy for stroke prevention in patients with AF. However, they are associated with a number of limitations, including excessive bleeding when not adequately controlled. Antiplatelet agents do not match vitamin K antagonists in terms of their preventive efficacy. Dual-antiplatelet therapy (clopidogrel and acetylsalicylic acid) or combined antiplatelet–vitamin K antagonist therapy in AF has also failed to provide convincing evidence of their additional benefit over vitamin K antagonists alone. Novel oral anticoagulants, including the direct thrombin inhibitor dabigatran and direct Factor Xa inhibitors such as rivaroxaban, apixaban, and edoxaban, have now been approved or are currently in late-stage clinical development in AF. These newer agents may provide a breakthrough in the optimal management of stroke risk.
Anticoagulants; Apixaban; Aspirin; Atrial fibrillation; Clopidogrel; Dabigatran; Drug discovery; Rivaroxaban; Stroke; Warfarin
The thromboembolic risk of atrial fibrillation varies with the underlying cause, associated heart disease, and history of previous embolism. Decisions regarding warfarin anticoagulation therapy require a careful assessment of relative risks of thromboembolism and bleeding. Anticoagulation is strongly indicated for valvular atrial fibrillation and to prevent recurrent stroke in patients with atrial fibrillation and previous stroke or transient ischemic attack. Several randomized trials have consistently shown a reduction of the risk with the use of warfarin in nonvalvular atrial fibrillation, and anticoagulation is recommended. With a careful selection of patients, the risk of major bleeding on warfarin therapy is 2% to 4% per year. Aspirin therapy is less efficacious but also less risky than warfarin. Patients younger than 60 with lone atrial fibrillation do not require anticoagulation.
Atrial fibrillation, the commonest cardiac arrhythmia, predisposes to thrombus formation and consequently increases risk of ischaemic stroke. Recent years have seen approval of a number of novel oral anticoagulants. Nevertheless, warfarin and aspirin remain the mainstays of therapy. It is widely appreciated that both these agents increase the likelihood of bleeding: there is a popular conception that this risk is greater with warfarin. In fact, well-managed warfarin therapy (INR 2-3) has little effect on bleeding risk and is twice as effective as aspirin at preventing stroke. Patients with atrial fibrillation and a further risk factor for stroke (CHA2DS2-VASc >0) should therefore either receive warfarin or a novel oral agent. The remainder who are at the very lowest risk of stroke are better not prescribed antithrombotic therapy. For stroke prevention in atrial fibrillation; aspirin is rarely the right choice.
Atrial Fibrillation; Aspirin; Antithrombotic; Anticoagulant; Warfarin
Antithrombotic medications (anticoagulants and antiplatelets) are often withheld in the periprocedural period and after bleeding complications to limit the risk of new or recurrent bleeding. These medications are also stopped by patients for various reasons such as cost, side effects, or unwillingness to take medication.
Methods and Results
Patient records from the population-based Greater Cincinnati / Northern Kentucky Stroke Study were reviewed to identify cases of ischemic stroke in 2005 and determine the temporal association of strokes with withdrawal of antithrombotic medication. Ischemic strokes and reasons for medication withdrawal were identified by study nurses for subsequent physician review.
In 2005, 2,197 cases of ischemic stroke among residents of the region were identified via hospital discharge records. Of the 2,197 ischemic strokes, 114 (5.2%) occurred within 60 days of an antithrombotic medication withdrawal: 61 (53.5%) of these after stoppage of warfarin and the remainder after stoppage of an antiplatelet medication. Of the strokes following withdrawal, 71 (62.3%) were first-ever, and 43 (37.7%) were recurrent; 54 (47.4%) occurred after withdrawal of medication by a physician in the periprocedural period.
The withdrawal of antiplatelet and antithrombotic medications in the 60 days preceding an acute ischemic stroke was associated with 5.2% of ischemic strokes in our study population. This finding emphasizes the need for thoughtful decision making concerning antithrombotic medication use in the periprocedural period and efforts to improve patient compliance.
Ischemic stroke; antiplatelet therapy; anticoagulant therapy
The use of antithrombotic medications after ischemic stroke is recommended for deep vein thrombosis (DVT) prophylaxis and secondary stroke prevention. We assessed the rate of receipt of these therapies among eligible ischemic stroke patients aged ≥65 years and determined the effects of age and other patient characteristics on treatment.
Methods and Results
The analysis included Medicare fee-for-service beneficiaries discharged with ischemic stroke (ICD-9 433, 434, 436) randomly selected for inclusion in the Medicare Health Care Quality Improvement Program’s National Stroke Project 1998–1999, 2000–2001. Patients discharged from non-acute facilities, transferred, or terminally ill were excluded. Receipt of in-hospital pharmacological DVT prophylaxis, antiplatelet medication, anticoagulants for atrial fibrillation, and antithrombotic medications at discharge were assessed in eligible patients, stratified by age (65–74, 75–84, 85+ yrs). Descriptive models identified characteristics associated with treatment. Among 31,554 patients, 14.9% of those eligible received pharmacologic DVT prophylaxis, 83.9% antiplatelet drugs, 82.8% anticoagulants for atrial fibrillation, and 74.2% were discharged on an antithrombotic medication. Rates of treatment decreased with age, and were lowest for patients aged 85 years or older. Admission from a skilled nursing facility and functional dependence were associated with lower treatment rates.
There was substantial underuse of antithrombotic therapies among elderly ischemic stroke patients, particularly among the very elderly, those admitted from skilled nursing facilities, and patients with functional dependence. The reasons for low use of antithrombotic therapies, including the apparent underuse of DVT prophylaxis in otherwise eligible patients, require further investigation.
stroke; prevention; medical care; deep vein thrombosis; elderly
The rate of ischemic stroke associated with traditional risk factors for patients with atrial fibrillation has declined over the past two decades. Further, new and potentially safer anticoagulants are on the horizon. Thus, the balance between risk factors for stroke and benefit of anticoagulation may be shifting.
Methods and Results
Markov state transition decision model to analyze the CHADS2 score above which anticoagulation is preferred, first using the stroke rate predicted for the CHADS2 derivation cohort, and then using the stroke rate from the more contemporary ATRIA cohort for any CHADS2 score. Base case was a 69-year-old man with atrial fibrillation. Interventions included: oral anticoagulant therapy with warfarin or a hypothetical “new and safer” anticoagulant (based on dabigatran), no antithrombotic therapy, or aspirin.
Warfarin is preferred above a stroke rate of 1.7%/year, while aspirin is preferred at lower rates of stroke. Anticoagulation with warfarin is preferred even for a score of 0 using the higher rates of the older CHADS2 derivation cohort. Using more contemporary and lower estimates of stroke risk, raises the threshold for use of warfarin to a CHADS2 score ≥ 2. However, anticoagulation with a “new, safer” agent, modeled on the results of the RE-LY trial of dabigatran, leads to a lowering of the threshold for anticoagulation to a stroke rate of just 0.9%/year.
Use of a more contemporary estimate of stroke risk shifts the “tipping point” such that anticoagulation is preferred at a higher CHADS2 score, reducing the number of patients for whom anticoagulation is recommended. The introduction of “new, safer” agents, however, would shift the tipping point in the opposite direction.
anticoagulants; atrial fibrillation; health services research; stroke prevention; decision analysis
Patients with acute coronary syndrome (ACS) continue to be at risk for recurrent ischemic events, despite an early invasive strategy and the use of dual antiplatelet therapy. The anticoagulant pathway remains activated for a prolonged period after ACS and, consequently, has been a target for treatment. Early studies with warfarin indicated its benefit, but the risk of bleeding and the complexities of warfarin anticoagulation resulted in little use of this strategy. Rivaroxaban, apixaban, and dabigatran are new specific inhibitors of anticoagulant factors (Xa or IIa) currently available for the prevention of thrombosis and/or thromboembolism. Thus far, studies with dabigatran and apixaban in ACS have shown no clinical benefit and bleeding has been increased. The ATLAS ACS 2-TIMI 51 trial observed the impact of rivaroxaban 2.5 mg and 5 mg twice daily in patients with recent ACS receiving current management (both early invasive strategy and dual antiplatelet therapy with aspirin and clopidogrel) over a follow-up period of over 1 year. Rivaroxaban 2.5 mg twice daily reduced cardiovascular death, myocardial infarction, or stroke by 16%, and both cardiovascular and all-cause mortality by approximately 20%. Although major bleeding increased from 0.6% to 2.1% and intracranial hemorrhage from 0.2% to 0.6%, there was no increase in fatal bleeding. The role of rivaroxaban in the management of ACS is discussed in this review. The reduction in mortality is the main finding that could lead to the use of rivaroxaban in the management of ACS in high-risk individuals with a low bleeding risk.
cardiovascular death; myocardial infarction; stroke; anticoagulation; bleeding risk
Atrial fibrillation (AF) is the most common adult arrhythmia, and significantly increases the risk of ischemic stroke. Oral anticoagulation may be underused and may be less effective in community settings than clinical trial settings.
To determine the rates of thromboembolism and bleeding in an ambulatory cohort of patients with AF.
Observational study of Nova Scotian residents with AF identified by electrocardiogram in ambulatory settings between November 1999 and January 2001. Main outcome measures were rates of thromboembolism and bleeding over two years.
Four hundred twenty-five patients were included in the study. The mean (±SD) age was 70.6±11.1 years, and 40% were women. Warfarin therapy was used by 68% of patients. Sixty-two per cent of patients had hypertension, 21% had a previous stroke or transient ischemic attack, 44% had congestive heart failure and 20% were diabetic. The overall rate of thromboembolic events was 2.7% in warfarin users and 8.5% in nonwarfarin users over two years, with an RR reduction of 68% (OR 0.31, 95% CI 0.09 to 0.91; P=0.047). The annual rate of ischemic stroke was 1.2% and 3.1% in warfarin and nonwarfarin users, respectively, with an RR reduction of 62% (OR 0.29, 95% CI 0.08 to 1.04; P=0.057). The overall rate of major bleeding was 2.6% in warfarin users and 1.4% in nonwarfarin users (P=0.667). The annual mortality rate was 7.79% in warfarin users and 9.93% in nonwarfarin users (P=0.192).
Warfarin use was found to significantly reduce the rate of thromboembolic events without a concomitant increase in hemorrhagic events. The present study confirms the effectiveness of warfarin therapy in a population-based cohort.
Atrial fibrillation; Hemorrhage; Mortality; Stroke
Anticoagulation therapy significantly reduces the incidence of thromboembolic events in patients with atrial fibrillation (AF), and warfarin therapy at discharge is a class I–indicated drug in patients with ischemic stroke with persistent or paroxysmal AF without contraindications. The aim was to determine whether participation in the Get With The Guidelines-Stroke (GWTG-S) quality improvement program would be associated with improved adherence to anticoagulation guidelines for patients with all types of AF. Adherence to warfarin treatment at hospital discharge was assessed in eligible patients with AF who presented with stroke or transient ischemic attack, based on type of AF. Of patients with stroke, 10.5% presented with some form of AF. When AF was documented using electrocardiography or telemetry (ECG) during the present admission, eligible patients were more likely to receive warfarin compared with patients for whom AF was reported using medical history only (78.8% vs 49.4%; p <0.0001). Improvement after GWTG-S participation in warfarin use was observed in patients with ECG-documented AF (73.8% at baseline vs 88.5% after the intervention; p <0.0001), but not patients using history only. Women and elderly patients were less likely to receive warfarin, and these gaps in treatment did not narrow during the quality improvement program for patients with ECG-documented AF and those with history only. In conclusion, anticoagulation for stroke prevention was underused in general for patients with AF, even in such high-risk groups as patients with stroke. GWTG-S was associated with improved adherence for patients with ECG-documented AF, but patients with a history of AF alone were largely untreated.
Atrial fibrillation is the commonest arrhythmia worldwide and is a growing problem. AF is responsible for 25% of all strokes, and these patients suffer greater mortality and disability. Warfarin has traditionally been the only successful therapy for stroke prevention, but its limitations have resulted in underutilisation. Major progress has been made in AF research, leading to improved management strategies. Better risk stratification permits identification of truly low-risk patients who do not require anticoagulation and we are able to simplify ourevaluation of a patient’s bleeding risk.
The advent of novel anticoagulants means warfarin is no longer the only choice for stroke prophylaxis. These drugs circumvent many of warfarin’s inconveniences, but onlylong-term study and use will conclusively demonstrate how they compare to warfarin. The landscape of stroke prevention in AF has changed with effective alternatives to warfarin available for the first time in 60 years—but each new option brings new considerations.
atrial fibrillation; warfarin; stroke prevention; oral anticoagulants
In patients with nonvalvular atrial fibrillation oral anticoagulation with the vitamin K antagonists acenocoumarol, phenprocoumon and warfarin reduces the risk of stroke by more than 60%, whereas single or double antiplatelet therapy is much less effective and sometimes associated with a similar bleeding risk as vitamin K antagonists. Besides bleeding, INR monitoring and high interindividual variability remain the largest drawbacks of vitamin K antagonists. In the last decade oral agents have been developed that directly block the activity of thrombin (factor IIa), as well as drugs that directly inhibit activated factor X (Xa), which is the first protein in the final common pathway to the activation of thrombin. These agents have huge advantages in that they do not need monitoring and have a fast onset and offset of action. This survey addresses the role of classical and modern anticoagulation in stroke prevention in atrial fibrillation. (Neth Heart J 2010;18:314–8.)
Anticoagulants, Administration, Oral; Atrial Fibrillation; Warfarin; Drug Discovery; Stroke
Older patients with atrial fibrillation (AF) and coronary artery disease (CAD) face high risk of stroke and bleeding with antithrombotic therapy. Balancing safe and effective use of aspirin, clopidogrel, and warfarin in this population is important.
From the Duke Databank for Cardiovascular Disease, we identified patients with AF ≥65 years old with angiographically confirmed CAD from 2000 to 2010. Antithrombotic use was described across age and Congestive heart failure, Hypertension, Age >75 years, Diabetes, prior Stroke/transient ischemic attack (CHADS2) stroke risk and Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) bleeding scores. Death and the composite of death, myocardial infarction, and stroke by antithrombotic strategy were reported.
Of 2,122 patients ≥65 years old with AF and CAD, 477 (22.5%) were ≥80 years old; 1,133 (53.4%) had acute coronary syndromes. Overall rates of aspirin, clopidogrel, and warfarin use were 83.4%, 34.6%, and 38.9%, respectively. Compared with patients 65 to 79 years old, more patients ≥80 years old were at high stroke risk (CHADS2 ≥2, 84.7% vs 57.8%) and high bleeding risk (ATRIA 5-10, 55.8% vs 23.3%). Warfarin use in both age groups increased with higher CHADS2 scores and decreased with higher ATRIA scores. Of patients ≥80 years old with CHADS2 ≥2, 150 (38.2%) received warfarin. Antithrombotic strategy was not associated with improved 1-year adjusted outcomes.
Among older patients with AF and CAD, overall warfarin use was low. Patients ≥80 years old at highest stroke risk received warfarin in similar proportions to the overall cohort. Further investigation into optimizing antithrombotic strategies in this population is warranted.
As the management of patients treated with anticoagulants and antiplatelet drugs entails balancing coagulation levels, we evaluated the net clinical benefit of warfarin and aspirin on stroke in a large cohort of patients with atrial fibrillation (AF).
A population-based cohort study of all patients at least 18 years of age with a first-ever diagnosis of chronic AF during the period 1993–2008 was conducted within the United Kingdom General Practice Research Database. A nested case–control analysis was conducted to estimate the risk of ischemic stroke and intracranial hemorrhage associated with the use of warfarin and aspirin. Cases were matched up to 10 controls on age, sex, and date of cohort entry. The adjusted net clinical benefit of warfarin and aspirin (expressed as the number of strokes prevented per 100 persons per year) was calculated by subtracting the ischemic stroke rate (prevented by therapy) from the intracranial hemorrhage (ICH) rate (increased by therapy).
The cohort included 70,766 patients newly-diagnosed with chronic AF, of whom 5519 experienced an ischemic stroke and 689 an ICH during follow-up. The adjusted net clinical benefit of warfarin was 0.59 (95% CI: 0.45, 0.73). However, the benefit was not seen for patients below (0.08, 95%: -0.38, 0.54) and above (−0.49, 95% CI: -1.13, 0.15) therapeutic range. The net clinical benefit of warfarin, apparent after 3 months of continuous use, increased as a function of CHADS2 score. The net clinical benefit was not significant with aspirin (−0.07, 95% CI: -0.22, 0.08), though it was seen in certain subgroups.
Warfarin provides a net clinical benefit in patients with atrial fibrillation, which is maintained with longer duration of use, particularly when used within therapeutic range. A similar net effect is not as clear with aspirin.
Atrial fibrillation; stroke; intracranial hemorrhage; warfarin; aspirin; net clinical benefit
Nonvalvular atrial fibrillation is an increasingly common condition. It may cause disabling symptoms and is an important risk factor for stroke. The goals of treatment include the relief and prevention of rate- and rhythm-related symptoms and the prevention of stroke and systemic emboli. Three principal treatments should be considered: pharmacologic rate control, cardioversion and antiarrhythmic therapy to restore and maintain sinus rhythm, and prophylactic anticoagulation or antiplatelet therapy to reduce the risk of stroke. The risks and benefits of each of these therapies have been reviewed. Symptoms, if present, can often be managed safely with rate-directed therapy alone. Until issues regarding safety and long-term efficacy are resolved, cardioversion and antiarrhythmic therapy should be limited to those patients whose symptoms cannot otherwise be controlled. The benefits of warfarin anticoagulation for the primary and secondary prevention of stroke in nonvalvular atrial fibrillation have been demonstrated convincingly by several randomized clinical trials. These benefits must be weighed against the real risk of major hemorrhage. For patients at low risk of stroke, the use of aspirin may be an acceptable alternative to warfarin sodium therapy.
(AF) can be cured by pulmonary vein antrum
isolation (PVAI) in a substantial proportion of
patients. The high efficacy of PVAI is partially
undermined by a small but concrete
periprocedural risk of complications, such as
thromboembolic events and bleeding. A correct
management of anticoagulation is essential to
prevent such complications. Performing PVAI
without interruption of oral anticoagulation has
been demonstrated feasible by our group in
previous studies. Recently, we reported that
continuation of therapeutic warfarin during
radiofrequency catheter ablation consistently
reduces the risk of periprocedural
stroke/transient ischemic attack without
increasing the risk of hemorrhagic events. Of
note, interrupting warfarin anticoagulation may
actually increase the risk of stroke even when
bridged with heparin. The latter strategy is
also associated with an increased risk of minor
bleeding. With regard to major bleeding, we
found no significant difference between patients
with a therapeutic INR and those who were
bridged with heparin. Therefore, continuation of
therapeutic warfarin during ablation of AF
appears to be the best anticoagulation strategy.
In this paper we summarize our experience with
AF ablation without interruption of
Clinical presentations of atherothrombotic vascular disease, such as acute coronary syndromes, ischemic stroke or transient ischemic attack, and symptomatic peripheral arterial disease, are major causes of morbidity and mortality worldwide. Platelet activation and aggregation play a seminal role in the arterial thrombus formation that precipitates acute manifestations of atherothrombotic disease. As a result, antiplatelet therapy has become the cornerstone of therapy for the prevention and treatment of atherothrombotic disease. Dual antiplatelet therapy with aspirin and a P2Y12 adenosine diphosphate (ADP) receptor inhibitor, such as clopidogrel or prasugrel, is the current standard-of-care antiplatelet therapy in patients with acute coronary syndromes managed with an early invasive strategy. However, these agents are associated with several important clinical limitations, including significant residual risk for ischemic events, bleeding risk, and variability in the degree of platelet inhibition. The residual risk can be attributed to the fact that aspirin and P2Y12 inhibitors block only the thromboxane A2 and ADP platelet activation pathways but do not affect the other pathways that lead to thrombosis, such as the protease-activated receptor-1 pathway stimulated by thrombin, the most potent platelet agonist. Bleeding risk associated with aspirin and P2Y12 inhibitors can be explained by their inhibitory effects on the thromboxane A2 and ADP pathways, which are critical for protective hemostasis. Interpatient variability in the degree of platelet inhibition in response to antiplatelet therapy may have a genetic component and contribute to poor clinical outcomes. These considerations underscore the clinical need for therapies with a novel mechanism of action that may reduce ischemic events without increasing the bleeding risk.
acute coronary syndromes; antiplatelet therapy; ADP; thromboxane A2; PAR-1; bleeding
Atrial fibrillation is the most common cardiac arrhythmias, and a major cause of morbidity and mortality due to cardioembolic stroke. The left atrial appendage is the major site of thrombus formation in non-valvular atrial fibrillation. Loss of atrial systole in atrial fibrillation and increased relative risk of associated stroke point strongly toward a role for stasis of blood in left atrial thrombosis, although thrombus formation is multifactorial, and much more than blood flow irregularities are implicated. Oral anticoagulation with vitamin-K-antagonists is currently the most effective prophylaxis for stroke in atrial fibrillation. Unfortunately, this treatment is often contraindicated, particularly in the elderly, in whom risk of stroke is high. Moreover, given the risk of major bleeding, there is reason to be skeptical of the net benefit when warfarin is used in those patients. This work reviews the pathophysiology of cardioembolic stroke and critically spotlights the current status of preventive anticoagulation therapy. Various techniques to exclude the left atrial appendage from circulation were discussed as a considerable alternative for stroke prophylaxis.
Atrial appendage; Atrial fibrillation; Thromboembolism; Stroke; Prostheses and implants; Prognosis
Oral anticoagulant therapy (OAT) with warfarin is the standard of stroke prevention in patients with atrial fibrillation. Approximately 30% of patients with cardioembolic strokes are on OAT at the time of symptom onset. We investigated whether warfarin exacerbates the risk of thrombolysis-associated hemorrhagic transformation (HT) in a mouse model of ischemic stroke.
62 C57BL/6 mice were used for this study. To achieve effective anticoagulation, warfarin was administered orally. We performed right middle cerebral artery occlusion (MCAO) for 3 h and assessed functional deficit and HT blood volume after 24 h.
In non-anticoagulated mice, treatment with rt-PA (10 mg/kg i.v.) after 3 h MCAO led to a 5-fold higher degree of HT compared to vehicle-treated controls (4.0±0.5 µl vs. 0.8±0.1, p<0.001). Mice on warfarin revealed larger amounts of HT after rt-PA treatment in comparison to non-anticoagulated mice (9.2±3.2 µl vs. 2.8±1.0, p<0.05). The rapid reversal of anticoagulation by means of prothrombin complex concentrates (PCC, 100 IU/kg) at the end of the 3 h MCAO period, but prior to rt-PA administration, neutralized the exacerbated risk of HT as compared to sham-treated controls (3.8±0.7 µl vs. 15.0±3.8, p<0.001).
In view of the vastly increased risk of HT, it seems to be justified to withhold tPA therapy in effectively anticoagulated patients with acute ischemic stroke. The rapid reversal of anticoagulation with PCC prior to tPA application reduces the risk attributed to warfarin pretreatment and may constitute an interesting therapeutic option.
In patients with nonvalvular atrial fibrillation, oral anticoagulation with the vitamin K antagonists acenocoumarol, phenprocoumon and warfarin reduces the risk of stroke by more than 60 %, whereas single or double antiplatelet therapy is much less effective and sometimes associated with a similar bleeding risk as vitamin K antagonists. Besides bleeding, and intracranial haemorrhage in particular, INR monitoring remains the largest drawback of vitamin K antagonists. In the last decade oral agents have been developed that directly block the activity of thrombin (factor IIa), as well as drugs that directly inhibit activated factor X (Xa), which is the first compound in the final common pathway to the activation of thrombin. These agents have been approved for stroke prevention in atrial fibrillation and are now reimbursed under a national guideline for their safe use. They have advantages in that they do not need monitoring and have a fast onset and offset of action, but lack an established specific antidote. This survey addresses the role of modern anticoagulation for stroke prevention in atrial fibrillation.
Atrial fibrillation; Stroke; Prevention; Warfarin; Dabigatran; Rivaroxaban; Apixaban
Despite the indisputable role of anticoagulation therapy for atrial fibrillation (AF) patients at risk for stroke, anticoagulants remain under-used in everyday clinical practice. We assumed that by performing trans-oesophageal echocardiography (TEE) on patients with AF who were not on anticoagulation treatment prior to the procedure, and by explaining to them the TEE images obtained, as well as the possible consequences of these findings, we could convince patients to start anticoagulation therapy. The main objective of the study was to assess the examined patients’ adherence to warfarin therapy over a two-year period.
Methods and results
We conducted a prospective TEE study from February 2006 to December 2008 on 70 patients with chronic AF who were not on anticoagulation treatment. Mean patient age was 65.85 ± 10.02 years and 68.57% were women. Thrombus in the left atrial appendage was found in 25 (35.71%) patients. Fifty-four (77.14%) patients had thrombi or spontaneous echo contrast in at least one of their supraventricular cavities.
Following the procedure and with detailed explanation to the patients of their TEE findings, we managed to start anticoagulation therapy on 60 (85.71%) patients. At the end of the follow-up period of 23.76 ± 2.8 months, 53 (75.71%) patients remained on warfarin therapy. The rest of the surviving patients settled for thrombo-prophylaxis with aspirin.
TEE is a valuable method that, in addition to its diagnostic possibilities, could also serve as a convincing visual method of putting atrial fibrillation patients onto an anticoagulation regimen.
atrial fibrillation; trans-oesophageal echocardiography; left atrial appendage thrombus
Warfarin therapy is effective for the prevention of stroke in patients with atrial fibrillation. However, warfarin therapy is underutilized even among ideal anticoagulation candidates. The purpose of this study was to examine the use of warfarin in both inpatients and outpatients with atrial fibrillation within a Veterans Affairs (VA) hospital system.
This retrospective medical record review included outpatients and inpatients with atrial fibrillation. The outpatient cohort included all patients seen in the outpatient clinics of the VA Connecticut Healthcare System during June 2000 with a diagnosis of atrial fibrillation. The inpatient cohort included all patients discharged from the VA Connecticut Healthcare System West Haven Medical Center with a diagnosis of atrial fibrillation during October 1999 – March 2000. The outcome measure was the rate of warfarin prescription in patients with atrial fibrillation.
A total of 538 outpatients had a diagnosis of atrial fibrillation and 73 of these had a documented contraindication to anticoagulation. Among the 465 eligible outpatients, 455 (98%) were prescribed warfarin. For the inpatients, a total of 212 individual patients were discharged with a diagnosis of atrial fibrillation and 97 were not eligible for warfarin therapy. Among the 115 eligible inpatients, 106 (92%) were discharged on warfarin.
Ideal anticoagulation candidates with atrial fibrillation are being prescribed warfarin at very high rates within one VA system, in both the inpatient and outpatient settings; we found warfarin use within our VA was much higher than that observed for Medicare beneficiaries in our state.
Atrial fibrillation; warfarin; anticoagulation; preventive medicine; guideline adherence
Warfarin prescribing patterns for hemodialysis patients with atrial fibrillation vary widely amongst nephrologists. This may be due to a paucity of guiding evidence, but also due to concerns of increased risks of warfarin use in this population. The literature lacks clarity on the balance of warfarin therapy between prevention of thrombotic strokes and the increased risks of bleeding in hemodialysis patients with atrial fibrillation.
We performed a survey of Canadian Nephrologists, assessing warfarin prescribing practice, and measured the certainty in making these choices.
Respondents were consistently uncertain about warfarin use for atrial fibrillation. This uncertainty increased with a history of falls or starting hemodialysis, even when a high CHADS2 or CHA2DS2VASc score was present. The majority of respondents agreed that clinical equipoise existed about the use of oral anticoagulation in hemodialysis patients with atrial fibrillation (72.2%) and that the results of a randomized controlled trial would be relevant to their practice (98.2%).
A randomized controlled trial of warfarin use in hemodialysis patients with atrial fibrillation would clarify the risks and benefits of warfarin use in this population.
Warfarin; Anticoagulation; Atrial fibrillation; Hemodialysis; Stroke; CKD; Bleeding
Patients with Atrial Fibrillation (AF) and prior stroke are classified as high risk in all risk stratification schemes. A systematic review and meta-analysis was performed to compare the efficacy and safety of New Oral Anticoagulants (NOACs) to warfarin in patients with AF and previous stroke or transient ischemic attack (TIA).
Three randomized controlled trials (RCTs), including total 14527 patients, comparing NOACs (apixaban, dabigatran and rivaroxaban) with warfarin were included in the analysis. Primary efficacy endpoint was ischemic stroke, and primary safety endpoint was intracranial bleeding. Random-effects models were used to pool efficacy and safety data across RCTs. RevMan and Stata software were used for direct and indirect comparisons, respectively.
In patients with AF and previous stroke or TIA, effects of NOACs were not statistically different from that of warfarin, in reduction of stroke (Odds Ratio [OR] 0.86, 95% confidence interval [CI] 0.73- 1.01), disabling and fatal stroke (OR 0.85, 95% CI 0.71-1.04), and all-cause mortality (OR 0.90, 95% CI 0.79 -1.02). Randomization to NOACs was associated with a significantly lower risk of intracranial bleeding (OR 0.42, 95% CI 0.25-0.70). There were no major differences in efficacy between apixaban, dabigatran (110 mg BID and 150 mg BID) and rivaroxaban. Major bleeding was significantly lower with apixaban and dabigatran (110 mg BID) compared with dabigatran (150 mg BID) and rivaroxaban.
NOACs may not be more effective than warfarin in the secondary prevention of ischemic stroke in patients with a prior history of cerebrovascular ischemia, but have a lower risk of intracranial bleeding.
Stroke is one of the leading causes of disability and death. Ischemic stroke is a syndrome with heterogeneous mechanisms and multiple etiologies, rather than a singularly defined disease. Approximately one third of ischemic strokes are preceded by another cerebrovascular ischemic event. Stroke survivors are at high risk of vascular events (i.e., cerebrovascular and cardiovascular events), particularly during the first several months after the ischemic event. The use of antiplatelet agents remains the fundamental component of secondary stroke prevention. Based on the available data, antiplatelet agents should be used for patients with noncardioembolic stroke. The use of combination therapy (aspirin plus clopidogrel) has not been proven to be effective or safe to use for prevention of early stroke recurrence or in long-term treatment. There is no convincing evidence that any of the available antiplatelet agents are superior for a given stroke subtype. Currently, the uses of aspirin, clopidogrel, or aspirin combined with extended release dipyridamole are all valid alternatives after an ischemic stroke or transient ischemic attack. However, to maximize the effects of these agents, the treatment should be initiated as early as possible and be continued on a lifelong basis.
Electronic supplementary material
The online version of this article (doi:10.1007/s13311-011-0060-2) contains supplementary material, which is available to authorized users.
Stoke; Prevention; Antiplatelets; Clinical trials; Aspirin; Clopidogrel; Dipyridamole