Kim, Anthony S. MD, MAS
Cardioembolic stroke accounts for a substantial proportion of the overall burden of disease from stroke. This disproportionate burden reflects the overall prevalence of cardioembolic stroke combined with the greater severity, less favorable prognosis, and high recurrence risk of this stroke subtype.1
The potential for cardioembolism directly affects primary prevention, acute management, and secondary prevention of stroke. Recent advances in diagnosis, risk stratification, and management developed from clinical research, as well as the availability of new therapeutic options, have had an impact on current clinical decision making.
Initial Clinical Evaluation
Cardioembolic stroke typically occurs suddenly, with neurologic symptoms that are maximal at onset. A stroke syndrome that localizes to a large artery territory, particularly when there is clinical evidence of cortical involvement, also suggests a cardioembolic source. Evidence of multiple foci of concurrent or sequential ischemia, particularly in multiple cerebrovascular or systemic vascular beds, is also strongly suggestive of a cardioembolic source, although cardioembolism can initially present with a single ischemic lesion. Certain examination and laboratory findings can be informative in the diagnosis of cardioembolic stroke, as outlined in Table 3-1.
Neuroimaging studies can help to confirm or establish the vascular distribution of both clinically evident and subclinical ischemic lesions. Occlusion of a large- to medium-sized artery with an otherwise normal appearance of the parent vessel may suggest cardioembolic stroke rather than stroke due to intrinsic atherosclerotic disease. Carotid studies may help to define an alternative artery-to-artery mechanism.
Transthoracic echocardiography (TTE) provides a noninvasive assessment of the structure and function of the heart that is essential to the cardioembolic stroke evaluation. Transesophageal echocardiography (TEE) has higher procedural risks but is more sensitive than TTE for evaluating the aortic arch, the aortic valve, the atrial septum, and left atrial appendage.2 Bubble-contrast echocardiography, which involves the injection of agitated saline as a contrast agent, can identify an intracardiac (eg, septal defect or patent foramen ovale) or extracardiac shunt.
An estimated 2.7 million Americans, including approximately 8% of the population more than 80 years of age, have atrial fibrillation (AF).3 Given the increased risk of AF with age and the aging of the US population, the overall burden of AF and consequently stroke from AF is expected to surge in the coming decades.3,4 Because AF is responsible for nearly half of all cardioembolic strokes, and because strokes from AF are more severe and result in greater disability and mortality than other stroke subtypes, preventing stroke in patients with AF has a considerable impact on both individual patient outcomes and population health.
Most AF-related strokes are caused by embolization from the left atrium and atrial appendage, which have direct access to the cerebral arteries. AF is also associated with enlargement of the left atrium, which contributes to relative stasis, clot formation, and subsequent embolization. Relatively short periods of AF may be sufficient to form thrombus because paroxysmal AF appears to present a similar risk for stroke as permanent or persistent AF, but whether there is a threshold burden of paroxysmal AF that confers this risk is uncertain.
Risk Stratification in Atrial Fibrillation
AF confers a 5% annual risk of stroke overall. However, the estimated risk of stroke for a particular patient may vary substantially depending on other risk factors. Risk stratification scores have been developed to estimate this risk and to inform the choice of antithrombotic therapy. As illustrated in Case 3-1, CHADS2 (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke/TIA symptoms previously) and CHA2DS2VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke, vascular disease, age 65–74 years, sex category)—a refinement of CHADS2—combine readily available clinical factors into simple scores that provide estimates of annual stroke risk (Table 3-2, Table 3-3).5,6
For each of these scores, a history of stroke or TIA is typically sufficient to justify anticoagulation therapy in isolation. Nonetheless, neurologists may find utility by applying these scores in more complex cases, particularly when the estimated stroke risk is weighed against other risks such as the risk of bleeding.
An 80-year-old man with a history of hypertension suddenly developed left face and arm weakness and neglect. Head CT showed no hemorrhage, a neck CT angiogram showed no carotid stenosis, and an MRI demonstrated a small infarct in the distal right middle cerebral artery territory. His initial ECG showed sinus rhythm, but he had a 2-minute episode of atrial fibrillation (AF) captured on telemetry on the first hospital day. A transthoracic echocardiogram showed moderate left atrial enlargement. His primary care provider expressed some concern about initiating anticoagulation given this patient’s age and risk of falls. The patient’s wife was concerned about his taking “rat poison” because a family friend had sustained a warfarin-associated intracranial hemorrhage. After an extensive discussion, warfarin was initiated during the initial hospitalization given that a large infarct was not present, with a plan for close outpatient follow-up. Bridging aspirin therapy was stopped once an international normalized ratio (INR) of 2 was achieved several days later.
Comment. This case illustrates the clear indication for anticoagulation conferred by atrial fibrillation and stroke. Simple risk scores can provide recommendations based on estimated stroke risk, but a history of stroke and AF is typically sufficient to justify anticoagulation on its own. This patient’s CHADS2 (congestive heart failure, hypertension, age ≥ 75 years, Diabetes mellitus, Stroke/TIA symptoms previously) score was 4 (8.5% annual stroke risk), and his CHA2D2-Vasc (Congestive heart failure, age ≥ 75 years, Diabetes mellitus, Stroke, Vascular disease, Age 65–74 years, Sex category) score was 5 (9.3% risk). Concerns about falls, advanced age, and bleeding risks, while relevant, are likely to be outweighed by the benefits of anticoagulation. (This patient’s HAS-BLED [hypertension, abnormal liver or renal function, stroke, bleeding, labile INR, elderly age, drug or alcohol use] score was 3 [5.8% annual risk]—a threshold at which caution is warranted.)
Electrocardiogram and Cardiac Monitoring
Detecting an irregularly irregular heartbeat on examination or by ECG may establish the diagnosis of AF. However, since paroxysmal AF is often asymptomatic, at least 24 hours of cardiac monitoring after an ischemic stroke is recommended. An initial ECG demonstrating sinus rhythm does not exclude the possibility of a transient episode of new-onset paroxysmal AF that may have preceded the onset of stroke.7
AF is likely to be systematically underdiagnosed in patients with cryptogenic stroke. Extended cardiac monitoring with ambulatory electrocardiograms (Holter monitors), real-time continuous heart monitors, external loop recorders, or implantable loop recorders all allow for a longer sampling period to detect transient episodes of AF after stroke. The 30-Day Cardiac Event Monitor Belt for Recording Atrial Fibrillation After a Cerebral Ischemic Event (EMBRACE) study evaluated 572 patients with cryptogenic ischemic stroke or TIA who were randomized to either 30 days of home-based cardiac monitoring or repeat Holter monitoring.8 Significantly more patients were diagnosed with new AF in the 30-day monitoring group compared with the repeat Holter monitoring group (16% versus 3%, P<.001). However, the appropriate candidates for monitoring, the optimal duration and mode of monitoring, and the clinical significance of fleeting episodes of AF that can now be detected with prolonged monitoring have not been established.
The mainstay of stroke prevention in AF has been oral anticoagulation with warfarin to an international normalized ratio (INR) goal of 2.0 to 3.0 (Figure 3-19). Warfarin can effectively reduce the risk of stroke by up to 68% (95% CI 50% to 79%), which corresponds to an absolute reduction in the annual risk of stroke from 4.5% to 1.4%.10 In contrast, aspirin is substantially less effective (21% relative risk reduction; 95% CI 0% to 38%) and is reserved for patients who are unable to take oral anticoagulants. Adding aspirin to warfarin increases bleeding risk and does not provide clear additional benefits, and therefore is generally discouraged.11 The use of medications for rate control or rhythm control for AF does not obviate the need for appropriate antithrombotic therapy to prevent stroke.
For patients deemed unsuitable for oral anticoagulation because of a specific bleeding risk or patient preference, adding clopidogrel to aspirin provides additional efficacy for stroke prevention in AF (2.4% annual risk) over aspirin alone (3.3% annual risk; relative risk of stroke for aspirin compared with aspirin and clopidogrel is 1.6; 95% CI 1.3 to 1.9), but this benefit appears to be offset by a higher risk of major bleeding (2.0% versus 1.3% annual risk) that is similar to warfarin.12 Therefore, national guidelines recommend aspirin alone rather than the combination of aspirin and clopidogrel for patients with AF and clear contraindications to oral anticoagulation therapy, particularly in patients with hemorrhagic risks.11 Apixaban 5 mg twice daily may be a potential alterative for high-risk patients (see the section on novel oral anticoagulants).13
For patients with AF and ischemic stroke despite therapeutic anticoagulation, the optimal management strategy is not defined. Most patients with ischemic stroke while on warfarin therapy are found to have a subtherapeutic INR. The risk of ischemic stroke rapidly rises as the INR drops below 2 (Figure 3-19),14 and the percentage of time that patients spend in the therapeutic range may be 60% to 70% at most. For selected patients, an increased INR goal could be considered, but bleeding risks are increased and direct evidence of benefit is lacking.
Timing of Initiating Anticoagulation After Acute Stroke
During the first few weeks after a new ischemic stroke, the risks of hemorrhagic transformation, particularly for patients with large-territory infarcts or with evidence of associated hemorrhage, likely outweigh the potential benefits of anticoagulation to prevent early recurrent cardioembolic events for most patients. For high-risk patients with smaller strokes, well-controlled blood pressure, and no evidence of bleeding, earlier initiation of anticoagulation can be considered, particularly with warfarin since the achieving a full therapeutic effect typically takes several days anyway.
Novel Oral Anticoagulants
The intensive laboratory monitoring, narrow therapeutic range, and numerous drug interactions associated with warfarin have prompted the development of alternative oral anticoagulants. As of December 2013, the US Food and Drug Administration (FDA) has approved the direct thrombin inhibitor dabigatran15,16 and two factor Xa inhibitors (rivaroxaban17,18 and apixaban19,20) for prevention of stroke in nonvalvular AF (Table 3-4).
These agents have fixed dosing, do not require frequent laboratory monitoring, have a rapid onset of anticoagulant effect, and have fewer drug interactions than warfarin. All were found to be noninferior to warfarin for stroke and systemic embolism (Rivaroxaban Versus Warfarin in Nonvalvular Atrial Fibrillation [ROCKET-AF],18 Randomized Evaluation of Long-Term Anticoagulant Therapy [RE-LY],15 and Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation [ARISTOTLE]20). Dabigatran (150 mg dose) and apixaban also met superiority end points. Apixaban showed a mortality benefit over warfarin. Intracranial hemorrhage rates were lower for all three agents compared with warfarin, but major gastrointestinal bleeding was higher with dabigatran and rivaroxaban compared with warfarin.
As illustrated in Case 3-2, these agents can be considered as an alternative to warfarin in most patients with AF and stroke, particularly given the lower intracranial hemorrhage rates seen in these initial studies. But patients with renal impairment, liver disease, mechanical valves or other valvular disease, or an anticipated need for reversal of anticoagulant effect for gastrointestinal bleeding (for dabigatran and rivaroxaban) may be well served to remain on warfarin.
A validated reversal strategy and a laboratory test of anticoagulant effect are not yet available for these novel anticoagulants. Poor adherence to a twice-daily dosing schedule could result in a subtherapeutic anticoagulant effect more quickly compared with warfarin. Higher drug costs and controversy regarding whether patients on these agents could be candidates for acute thrombolytic therapy are also relevant considerations.
A 65-year-old man with a history of paroxysmal atrial fibrillation and a right middle cerebral artery stroke 1 year ago had been maintained on warfarin therapy. He reported good medication adherence, and his international normalized ratio was usually between 2 and 3 at his follow-up visits to the anticoagulation clinic. Renal function was normal. He would like to discuss whether he is a candidate for a novel oral anticoagulant.
Comment. For patients who are already well managed on warfarin, continuing warfarin therapy may be reasonable. However, the lower risks of intracranial hemorrhage that have been reported with the novel oral anticoagulants could justify making the transition from warfarin to a novel oral anticoagulant in carefully selected patients. Renal disease, liver disease, medication interactions, medication adherence, availability of reversal agents, and cost are all considerations when choosing an oral anticoagulant.
Underutilization of Anticoagulation
Up to two-thirds of patients with AF, particularly those at highest risk of stroke, are not on appropriate anticoagulation therapy.21 The underuse of anticoagulation for AF is based, in part, on the challenges of warfarin therapy; however, other significant barriers remain.
The bleeding risks associated with frequent falls or advanced age are often outweighed by the stroke-prevention benefits of anticoagulation. Patients at risk for falls with a CHADS2 score of 2 or higher generally benefit from anticoagulation therapy, even when there is an increased risk of hemorrhage from falls.22 Although elderly patients have higher risks for both ischemic and hemorrhagic stroke, a meta-analysis of 12 clinical trials found that the benefits of anticoagulation appear to extend to elderly patients. This benefit was driven by hemorrhage rates that were similar with aspirin and with warfarin therapy.23 Ultimately though, the decision to initiate anticoagulation is often complex and should incorporate patient preferences.
The HAS-BLED (Hypertension, Abnormal liver or renal function, Stroke, Bleeding, Labile INR, Elderly age, Drug or alcohol use) scale was developed to estimate the risk of hemorrhage with anticoagulation and to highlight modifiable factors that are associated with increased risk such as concomitant antiplatelet therapy or alcohol intake (Table 3-524,25).24 HAS-BLED can provide additional information for clinical decision making, but should not be used as the sole reason to withhold anticoagulation therapy for patients who have other indications for anticoagulation for stroke secondary prevention.
Surgical Procedures for Atrial Fibrillation
Left atrial appendage closure devices and left atrial appendage excision or exclusion procedures as well as Cox maze procedures (a series of surgical incisions to the atria to interrupt atrial reentry) and radioablation have been developed to treat AF. For most patients, these procedures do not obviate the need for long-term anticoagulation therapy because a continued risk for recurrent AF remains even after treatment, and the risk of recurrent stroke for patients with AF who have already had a stroke or TIA is high. Therefore, the precise role for these procedural approaches to prevent stroke with AF has not been established.
Stroke is often the primary presenting symptom of infective endocarditis. Although direct infection of normal valves can occur, the risk of endocarditis is much higher when the native valve is compromised. Although rheumatic heart disease is uncommon in developed counties, it is still the most common cause of valvular disease globally. Bicuspid aortic valve and prosthetic valve implantation confer higher risks for infection as well. IV drug use is more commonly associated with right-sided valvular disease (eg, tricuspid valve) and typically results in septic embolization to the lungs rather than ischemic stroke, but IV drug use still confers a higher risk for left-sided endocarditis. Staphylococcus aureus, Streptococcus viridans, and Enterococcus are the most common organisms.26
Endocarditis is suggested by fever, weight loss, a history of IV drug use or other source of bacteremia, a new murmur on physical examination, or evidence of systemic embolization to other vascular territories. Multiple blood cultures, serial ECG (to evaluate for myocardial infarction, heart block, or conduction delay), and TEE are critical elements of the diagnostic workup. TTE is not adequate to exclude the possibility of valvular vegetations when endocarditis is suspected.27 An elevated erythrocyte sedimentation rate or C-reactive protein, and a leukocytosis, which is not always present, support this diagnosis but are relatively nonspecific.
Brain MRI is better suited than head CT for demonstrating the multiple foci of ischemia and cerebral microbleeds that are typical for endocarditis. The lesions in endocarditis are classically of differing ages and in multiple vascular distributions or in a watershed distribution; subclinical brain lesions are common.
Antibiotic therapy may reduce the risk of continued embolization. Antithrombotic therapy in the acute setting is associated with an increased risk of hemorrhage. For patients with AF or mechanical heart valve prostheses who present with endocarditis and stroke, short-term interruption of anticoagulation therapy may be necessary in some cases, despite the high risks of thrombosis and recurrent stroke during the period that anticoagulation is withheld.
Nonbacterial Thrombotic Endocarditis
Nonbacterial thrombotic endocarditis (marantic endocarditis) involves the aggregation of sterile vegetations along the edge of heart valves and is primarily associated with systemic malignancy. Heparin or low-molecular-weight heparin rather than warfarin is generally recommended.28 Libman-Sacks endocarditis, which is associated with systemic lupus erythematosus and the antiphospholipid antibody syndrome, involves a similar deposition of immune complexes that result in small inflammatory vegetations. Direct evidence is lacking, but antiplatelet therapy for primary prevention or anticoagulation for secondary prevention is reasonable.
Rheumatic Heart Disease
Rheumatic heart disease, a complication of Group A streptococcal infection, most commonly affects the mitral valve. Concurrent AF is common.11 The risk of stroke remains even after successful valvuloplasty, so continued anticoagulation to a goal INR of 2.0 to 3.0 is recommended.
Prosthetic Mechanical Valves and Bioprosthetic Valves
Prosthetic mechanical valves present a high risk for thromboembolization, especially for devices with caged-ball or tilting-disc mechanisms and for devices in the mitral position. Anticoagulation is indicated for all patients with mechanical valves; the intensity of anticoagulation therapy and the specific indications for concomitant antiplatelet therapy are based on the type and position of the prosthetic valve.
For patients with prosthetic valves that present with embolic events such as stroke despite adequate antithrombotic therapy, national guidelines provide comprehensive suggestions on intensifying antithrombotic therapy for various clinical scenarios, although definitive data to support these recommendations are admittedly sparse (Table 3-629). Bioprosthetic valves do not present the same degree of embolic risk as mechanical valves and can generally be managed with antiplatelet therapy. However, warfarin is recommended for the first 3 months after implantation of a mitral bioprosthetic valve.
Dabigatran is not recommended for use in patients with mechanical heart valves, and rivaroxaban and apixaban have not been evaluated for this indication. Therefore, warfarin remains the preferred treatment for this indication.
Mitral Valve Prolapse
Mitral valve prolapse is a largely echocardiographic diagnosis that is characterized by abnormal movement of one or more valve leaflets into the left atrium during systole. Data on the relationship between mitral valve prolapse and stroke are conflicting. Most patients with stroke and mitral valve prolapse can be managed with antiplatelet therapy.30
CARDIOMYOPATHY AND STRUCTURAL HEART LESIONS
Heart failure is associated with an increased risk of stroke from altered flow within dilated heart chambers, relative stasis of blood, increased risk of concomitant AF, and an associated relative prothrombotic state. For patients with associated AF or left ventricular thrombus, anticoagulation is generally preferred over antiplatelet therapy.
As illustrated in Case 3-3, for patients with heart failure and sinus rhythm, the optimal choice of antiplatelet or anticoagulation therapy is uncertain. In the Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) study, patients with symptomatic heart failure, sinus rhythm, and a left ventricular ejection fraction of 35% or less were randomized to aspirin (162 mg/d), clopidogrel (75 mg/d), or warfarin (INR 2.5 to 3.0).32 There were no significant differences between the three treatment arms for the risk of the composite primary end point of death, myocardial infarction, or stroke. Similarly, in the Warfarin and Aspirin in Patients With Heart Failure and Sinus Rhythm (WARCEF) study, patients with an ejection fraction below 35% with sinus rhythm were randomized to aspirin 325 mg/d or adjusted-dose warfarin (goal INR of 2.75; range 2.0 to 3.5).31 Anticoagulation did not provide an overall benefit: a reduction in ischemic stroke was offset by an increase in major hemorrhage. For secondary prevention, warfarin, aspirin, clopidogrel, or aspirin plus extended dipyridamole are all reasonable options, but comparative data are lacking. Data on the use of novel oral anticoagulants in this setting are not available.
A 64-year-old woman with a history of congestive heart failure presented with an acute right middle cerebral stroke. Her echocardiogram showed biatrial enlargement and a left ventricular ejection fraction of 30%; no thrombus or valvular disease was seen. ECG showed sinus rhythm. A brain MRI showed multiple foci of restricted diffusion in the right middle cerebral artery territory, as well as three small foci of restricted diffusion in the left hemisphere. The patient was discharged home on antiplatelet therapy, but, given the suspicion for a cardioembolic source, she was referred for extended cardiac monitoring. One week later, she had an asymptomatic 5-minute episode of atrial fibrillation noted on cardiac monitoring and returned to clinic to transition to anticoagulation therapy.
Comment. This case illustrates the initial management of a stroke patient with a history of congestive heart failure with a reduced ejection fraction and sinus rhythm with antiplatelet therapy based on the Warfarin and Aspirin in Patients With Heart Failure and Sinus Rhythm (WARCEF) study.31 However, the distribution of the infarcts suggested a cardioembolic source, and the documented paroxysmal atrial fibrillation demonstrated in follow-up provided a clear justification for anticoagulation therapy.
Myocardial Infarction and Left Ventricular Thrombus
Left ventricular thrombus, a complication of myocardial infarction, presents a high risk for embolization and subsequent stroke. Left ventricular thrombus is more common with anterior ST-segment elevation myocardial infarction because of the relative stasis of blood within the ventricle. Therefore, for patients at high risk of developing left ventricular thrombus, a screening TTE is recommended. For patients with documented left ventricular thrombus and myocardial infarction, at least 3 months of anticoagulation is recommended.11 Follow-up TTE to evaluate left ventricular ejection fraction and residual thrombus may help with individualized decisions on the optimal duration of anticoagulation therapy. Again, novel oral anticoagulants have not been evaluated in this setting and are not recommended.
Other Cardiac Lesions
Atrial myxoma, a tumor of mesenchymal cells of the heart, is a rare cause of cardioembolic stroke that is seen most often in younger patients. An atrial mass is seen on echocardiography and can be present even without a mitral stenosis murmur or a tumor plop on auscultation. Papillary fibroelastoma is a rare cause of stroke that is also apparent on echocardiography. For both lesions, the ongoing risk of embolization typically warrants surgical resection.
AORTIC ARCH ATHEROSCLEROSIS
Aortic arch atherosclerosis confers a risk for both systemic and cerebrovascular embolization. This commonly occurs via thromboembolism of larger clots that lodge and fragment in medium and large vessels. However, cholesterol embolization from the plaque itself may also occur and typically showers much smaller emboli into the arterioles in multiple vascular territories. Cholesterol embolization from the plaque itself can shower much smaller emboli into arterioles in multiple vascular territories.
TEE is generally preferred over TTE for assessing the aortic arch. Plaque thickness greater than 4 mm, ulceration, and actively mobile elements have been implicated as potential risk factors for embolization.33–35
Increased plaque thickness suggests a complex plaque with overlying thrombus. Ulceration is thought to increase the risk of thrombus formation. Mobile elements suggest that a thrombus is superimposed on an unstable plaque.
Aortic arch atherosclerosis shares risk factors in common with stroke more generally, so these patients often have clear indications for aggressive risk factor modification and antiplatelet therapy for secondary prevention irrespective of aortic arch disease. Statins may have the potential to stabilize or even regress plaques. The Aortic Arch Related Cerebral Hazard Trial (ARCH) trial compared the combination of aspirin and clopidogrel with adjusted-dose warfarin to prevent recurrent vascular events in patients with significant aortic arch disease and a recent TIA or minor stroke.36 The final results of this study are not yet available; however, the trial was recently and prematurely terminated for futility.
Cardioembolism is an important cause of stroke that requires an initial clinical suspicion, a tailored diagnostic workup, particularly for atrial fibrillation, and a prevention strategy that draws upon current clinical evidence and therapeutic options.
- Cardioembolic strokes are often more severe than other stroke subtypes and have a high recurrence risk.
- The suspicion for cardioembolic stroke is raised with large artery occlusions or strokes in multiple vascular territories.
- Transesophageal echocardiography is helpful for evaluating the aortic arch, aortic valve, atrial septum, and left atrial appendage.
- The incidence of stroke from atrial fibrillation is expected to surge in the coming decades as the US population ages.
- Relatively short and asymptomatic periods of atrial fibrillation may be sufficient to form thrombus and cause stroke.
- Patients with atrial fibrillation and a history of stroke or TIA are in a high-risk category that typically justifies anticoagulation.
- The absence of symptoms of atrial fibrillation such as reduced exercise tolerance, shortness of breath, or palpitations, or an initial ECG showing sinus rhythm is not sufficient to exclude the possibility of paroxysmal atrial fibrillation as a cause of stroke.
- Extended cardiac monitoring increases the sampling period for detecting paroxysmal atrial fibrillation, but the appropriate candidates for monitoring, the optimal duration and mode of monitoring, and the clinical significance of fleeting episodes of atrial fibrillation have not been established.
- Anticoagulation is preferred over antiplatelet agents for secondary stroke prevention in most patients with atrial fibrillation.
- Medications for rate or rhythm control for atrial fibrillation do not obviate the need for antithrombotic therapy in patients with atrial fibrillation.
- Potential benefits of novel oral anticoagulants compared to warfarin include noninferior (rivaroxaban) or superior efficacy (dabigatran and apixaban), lower intracranial bleeding, fixed dosing, fewer drug-drug interactions, rapid onset of anticoagulant effect, and a mortality benefit (apixaban).
- Potential drawbacks of novel oral anticoagulants compared to warfarin include the lack of a validated reversal strategy or laboratory test of anticoagulant effect, uncertainty about candidacy for acute thrombolytic therapy, and cost.
- A significant proportion of patients with atrial fibrillation who would benefit from anticoagulation are not on anticoagulation therapy.
- Overestimating the bleeding risk associated with falls and advanced age and underappreciating the benefits of anticoagulation with age contribute to the underuse of anticoagulation for atrial fibrillation.
- A transthoracic echocardiogram is not adequate to exclude the possibility of valvular vegetations when endocarditis is suspected. Rather, a transesophageal echocardiogram is critical to the diagnostic workup of possible endocarditis.
- Anticoagulation with warfarin is strongly indicated for all patients with mechanical heart valves.
- For patients with congestive heart failure with sinus rhythm, the choice of anticoagulation or antiplatelet agent for secondary stroke prevention is uncertain.
- Patients with left ventricular thrombus should generally be treated with anticoagulation for at least 3 months.
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