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European Journal of Heart Failure 2000 2(4):355-363; doi:10.1016/S1388-9842(00)00126-4
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© 2000 European Society of Cardiology

Thromboembolism in heart failure: who should be treated?

Frank Diet* and Erland Erdmann

Klinik III für Innere Medizin, Universität zu Köln Joseph-Stelzmann-Str. 9, 50924 Köln, Germany

* Corresponding author. Tel.: +49-221-478 6205; fax: +49-221-478 6490. E-mail address: f.diet{at}uni-koeln.de (F. Diet).


   Abstract
Top
 Abstract
1. Introduction
 2. Incidence of thromboembolism
 3. Thromboembolic risk factors
 4. Treatment
 5. Conclusions and...
 References
 
The risk of thromboembolic complications in patients with heart failure and/or chronic left-ventricular systolic dysfunction is increased. Nevertheless, anticoagulant therapy in these patients is still a subject of debate. Atrial fibrillation is the only prospectively evaluated, proven thromboembolic risk factor and patients with atrial fibrillation benefit from long term anticoagulant therapy. The significance of other proposed thromboembolic risk factors in heart failure and/or chronic left-ventricular dysfunction such as gender, cause of myocardial disease, severity of heart failure, left-ventricular ejection fraction, left-ventricular thrombus, left ventricular aneurysm and history of previous thromboembolic event is less clear. This article summarizes key studies, assesses the incidence of thromboembolism, evaluates risk factors and proposes guidelines for anticoagulation of patients with heart failure and/or left ventricular systolic dysfunction.

Key Words: Thromboembolism • Anticoagulant • Atrial fibrillation

Received January 25, 2000; Accepted September 12, 2000


   1. Introduction
Top
 Abstract
 1. Introduction
2. Incidence of thromboembolism
 3. Thromboembolic risk factors
 4. Treatment
 5. Conclusions and...
 References
 
Anticoagulant therapy in patients with heart failure has been the subject of considerable debate. Patients with severe chronic left-ventricular systolic dysfunction are thought to be at an increased risk of developing arterial and venous thromboembolic complications, but reports of the incidence of thromboembolic events in this population vary widely.

Hypercoagulability, stasis and vascular damage were proposed nearly 150 years ago by Virchow as the pathogenesis of thrombus formation. Patients with heart failure do show evidence of activation of platelets [1,2] and of the coagulation system [3,4], and these hemostatic abnormalities seem to be more pronounced in patients with severe left-ventricular dysfunction [1,4]. Dilated cardiac chambers, poor contractility, regional wall motion abnormalities and concomitant atrial fibrillation may predispose to thromboembolism by facilitating stasis of intracardiac blood flow [5]. Endothelial and epicardial dysfunction as shown in heart failure [6] may also contribute to thrombus formation.

While there is good evidence to support anticoagulant therapy in patients with atrial fibrillation, anticoagulation in patients with sinus rhythm is controversial. The lack of a controlled large trial assessing the efficacy of anticoagulation and antiplatelet agents for patients with heart failure outside the hospital setting is the main reason for the absence of a consensus recommendation for systemic anticoagulation. The purpose of this article is to summarize key studies, assess the incidence of thromboembolism, evaluate risk factors and propose guidelines for anticoagulation of patients with heart failure and/or left ventricular systolic dysfunction.


   2. Incidence of thromboembolism
Top
 Abstract
 1. Introduction
 2. Incidence of thromboembolism
3. Thromboembolic risk factors
 4. Treatment
 5. Conclusions and...
 References
 
A number of studies reporting the incidence of thromboembolism — stroke, including transient ischemic events, and pulmonary and peripheral arterial embolism — in patients with heart failure and/or left ventricular systolic dysfunction have been published and discussed in earlier review articles [7–10]. Smaller longitudinal studies [11–19] mainly investigating patients with non-ischemic dilative cardiomyopathy vary widely in their reported incidence of thromboembolic events (Table 1). Referral bias (in some studies patients were referred to tertiary care centers or to echocardiographic studies), sampling error due to small study populations, the retrospective nature of some studies, uncontrolled therapy with anticoagulants and antiplatelet drugs and prevalence of atrial fibrillation in the studied population may all have influenced the results and contributed to the variation in reported thromboembolic events. More recent prospective studies, with a larger and heterogeneous study population, report thromboembolic incidences of less than 2 events per 100 patient-years [17,19]. A second source to estimate the incidence of thromboembolism in patients with heart failure and/or left ventricular dysfunction is the analysis of patients in large therapeutic trials of heart failure and left-ventricular systolic dysfunction [20–25] (Table 2). These studies reported an annual thromboembolic incidence between 1.5 and 3.5%, with the highest incidence in a population with severe heart failure [24]. Studies that report the incidences for pulmonary emboli, stroke and peripheral arterial embolic events separately identify stroke as the leading event [20,22]. In the analysis of the ‘vasodilator heart-failure trial’ (V-HeFT) studies, the rates of stroke, peripheral arterial embolism and pulmonary embolism were 1.8, 0.1–0.3 and 0.3 events per 100 patient-years of follow up, respectively. Similar distributions were reported in the studies of left-ventricular dysfunction (SOLVD) trial [22]. The ‘survival and ventricular enlargement’ (SAVE) and ‘prospective randomized milrinone survival evaluation’ (PROMISE) trials only report the incidence of stroke [23,24]. In all studies, all ischemic strokes were classified to be of embolic origin, not considering primary thrombotic cerebrovascular disease. It has been suggested that a substantial number of strokes detected in patients with heart failure may have been related to primary cerebrovascular disease rather than to cardiogenic emboli [7]. In a recent study, all patients suffering a stroke had at least one of the known risk factors for a cerebrovascular accident [17]. On the other hand, embolic stroke, myocardial infarction and pulmonary emboli may have been the cause of sudden deaths, resulting in underestimation of the incidence of thromboembolic events. It has been discussed that the major cause of sudden death in patients with heart failure is not arrhythmic, but vascular occlusion [25]. However, due to the rather low incidence of thromboembolism in an unselected population of patients with chronic heart failure and/or left-ventricular systolic dysfunction, the data available at present do not support routine antithrombotic therapy in all patients. Specific subgroups of patients at high thromboembolic risk need to be identified in whom the risk/benefit ratio of oral anticoagulation is particularly favorable.


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  		Table 1 Incidence of thromboembolism in observational studies of heart failure (modified from [9])e

 


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  		Table 2 Incidence of thromboembolism and cerebrovascular accident in selected large therapeutic trials of heart failure and left ventricular dysfunction (modified from [9])e

 

   3. Thromboembolic risk factors
Top
 Abstract
 1. Introduction
 2. Incidence of thromboembolism
 3. Thromboembolic risk factors
4. Treatment
 5. Conclusions and...
 References
 
No prospective trial large enough to evaluate thromboembolic risk factors in patients with chronic heart failure has been published yet. At present, only retrospective analyses of the V-HeFT studies [20], SOLVD [22] and SAVE [23] trials included a population large enough to allow multivariate analysis of clinical risk factors for thromboembolism.

3.1. Atrial fibrillation
People with atrial fibrillation do have, on average, approximately six times the stroke risk of people without atrial fibrillation [26,27]. The risk of stroke varies greatly, depending upon age and coexisting cardiovascular disease [28]. Several studies identified a history of heart failure and chronic left-ventricular dysfunction as independent risk factors for stroke in patients with non-valvular atrial fibrillation [29–31]. Patients with heart failure and/or impaired left-ventricular function on echocardiography and atrial fibrillation have been classified as high-risk patients. The annual risk of cerebrovascular accidents has been estimated to be 8–12% [32]. The benefits of oral anticoagulation in patients with atrial fibrillation is well established, with an overall stroke risk reduction of 68% [32].

Surprisingly, retrospective analysis of heart failure studies has only inconsistently identified atrial fibrillation as a thromboembolic risk factor. In the V-HeFT studies, the incidence of thromboembolism did not differ in patients with and without atrial fibrillation, and atrial fibrillation was not a thromboembolic risk factor [20]. In the SAVE trial, patients with stroke had more frequent atrial fibrillation or flutter before randomization than patients without stroke (7.4 vs. 4.3%, P=0.03) [23]. However, in the multivariate analysis, the presence of atrial fibrillation or flutter before randomization was not identified as a risk factor for stroke [23]. Similar results were reported in smaller studies [19]. These negative results have to be discussed with regard to the study limitations. The SAVE trial and the V-HeFT studies were not primarily designed to determine the incidence of thromboembolic complications. Criteria for diagnosis of thromboembolic events were not established by protocol. Misclassification of events may have occurred. Although retrospective analyses attempted to control for anticoagulant use, the use of these agents has always been greater in patients with atrial arrhythmias. Importantly, in all retrospective studies, atrial arrhythmias were only assessed at baseline.

On balance the evidence from randomized controlled trials in atrial fibrillation indicates that patients with atrial fibrillation and flutter and heart failure and/or significant left ventricular dysfunction benefit from anticoagulation.

3.2. Gender
There are data supporting an increased thromboembolic risk in women with chronic left-ventricular dysfunction. In a retrospective analysis of patients of the SOLVD trials with left-ventricular systolic dysfunction and sinus rhythm at the time of randomization, the left-ventricular ejection fraction appeared to be independently associated with thromboembolic risk in women, but not in men [22]. The overall annual incidence of thromboembolic events, including stroke, pulmonary and peripheral arterial embolism, was 2.4% in women and 1.8% in men (P= 0.04). This difference was mainly driven by a greater proportion of pulmonary emboli in women (24%) compared with the men (14%) (P=0.01). Not considering pulmonary embolism, the incidence of stroke and peripheral embolism was similar for men and women. In a cohort of the Framingham Study, atrial fibrillation in the presence of clinically evident cardiac failure was associated with an excess risk of stroke in women compared to men (2.8 vs. 1.7%; P<0.01) [27]. However, the clinical relevance of these correlations remains unclear. Recent studies even suggest that women with advanced heart failure have a better survival rate than men [33].

3.3. Ischemic/non-ischemic cardiomyopathy
Comparison of natural history studies in populations of patients with either ischemic heart disease or idiopathic dilated cardiomyopathy suggest an increased thromboembolic risk in the latter group. However, studies that have included patients with chronic heart-failure of mixed origins did not find different thromboembolic incidences due to the cause of myocardial disease [19,20,24].

3.4. Severity of heart failure
An association between the clinical severity of heart failure in ambulatory patients and the incidence of thromboembolic complications has rarely been studied. A retrospective analysis of patients from the V-HeFT studies suggests that patients with more severe heart failure have a higher risk of thromboembolic events. Peak exercise oxygen consumption as a marker of clinical severity of heart failure was associated with the rate of thromboembolic events [20]. In V-HeFT I, the peak oxygen consumption in patients with events in comparison to those without was 13.4±3.1 vs. 14.7±4.0 ml kg–1 min–1 (P<0.03), and in V-HeFT II it was 11.9±3.4 vs. 13.8±3.5 ml kg–1 min–1 (P<0.001). Similarly, low exercise-capacity was associated with an increased thromboembolic risk in a recent longitudinal prospective study in 406 patients [19].

3.5. Left-ventricular ejection fraction
A severely reduced left-ventricular ejection fraction is often proposed as an indication for anticoagulation. Although the risk of stroke is increased after acute myocardial infarction and correlates with the extent of infarction [34], data in chronic left-ventricular dysfunction, with or without congestive heart failure, are not conclusive. While some smaller studies reported an association between increased thromboembolic risk and more severe left-ventricular dysfunction [14,16], others did not [15,17,19]. In the SAVE trial evaluating post-myocardial infarction patients with left-ventricular ejection fractions of 40% or less, a decreased ejection fraction and greater age were both independent predictors of an increased risk of stroke [23]. In patients with a left-ventricular ejection fraction of 28% or less, the risk of stroke was increased nearly two-fold compared to patients with a left-ventricular ejection fraction of more than 28% [relative risk (RR) 1.86, 95% confidence interval (CI) 1.15–3.04, P=0.01]. For every absolute decrease of 5 percentage points in the left-ventricular ejection fraction, the risk of stroke increased by 18% in that study. Anticoagulant or aspirin therapy reduced the total stroke risk by 81 and 56%, respectively [23]. In contrast, in patients with sinus rhythm at the time of randomization of the SOLVD trial, left-ventricular ejection fraction was only associated with increased thromboembolic risk in women, and not in men (86% of the study population) [22]. While in women a 10% decline in left-ventricular ejection fraction was associated with a 53% increase in thromboembolic risk (RR 1.53, 95% CI 1.06–2.20, P=0.02), no association was found in men (RR 1.08, 95% CI 0.89–1.31, P=0.42). When specific types of embolic events — stroke, pulmonary embolism, and peripheral arterial embolism — were studied separately, the only significant difference between the genders was the greater proportion of pulmonary emboli (24% in women vs. 14% in men, P=0.01). When only stroke and peripheral arterial embolism were analyzed, the association between left-ventricular ejection fraction and thromboembolic risk was no longer statistically significant. A trend remained, suggesting that a lower left-ventricular ejection fraction was associated with an increased thromboembolic risk for stroke and peripheral arterial embolism in women (RR per 10% decrease in EF 1.47%, P=0.07) but not in men (RR per 10% decrease in EF 0.99, P=0.95). Similarly, in patients of the V-HeFT studies, left-ventricular ejection fraction did not differ between patients with or without stroke or thromboembolism [20].

These retrospective analyses of large therapeutic trials [20,22,23] were limited by the lack of follow-up data on the presence or absence of atrial fibrillation, which might have influenced the results. New onset of atrial fibrillation, rather than the decreased left-ventricular ejection fraction, might have caused a thromboembolic event. Furthermore, different study populations in the SAVE and SOLVD trials might have affected thromboembolic risk (Table 2). In the SAVE trial exclusively, post-myocardial infarction patients — randomization was 3–16 days after myocardial infarction — were included [35], while in the analysis of the SOLVD trial [22] only 79% of men and 65% of women had a past history of myocardial infarction.

3.6. Left-ventricular thrombus
Intraventricular mural thrombosis occurs as a complication of acute myocardial infarction, or of chronic left-ventricular aneurysm, and with severe ventricular dysfunction. The prevalence of left-ventricular thrombus in patients with chronic left-ventricular dysfunction varies markedly in different studies. Echocardiographic and autopsy studies report incidences of up to 50% [12,16,17,36]. Technical difficulties in the interpretation of the echocardiographic images, as well as differences in the studied populations, may have contributed to the high prevalence [9]. More recent studies have reported a prevalence of less than 10% [18,19]. The development of ventricular thrombi has not been shown to be significantly different based on the etiology of chronic heart failure. Thrombus formation and endogenous thrombus resolution seem to be a dynamic process, and have been reported in a longitudinal echocardiographic study [16]. Thrombus formation seems to be more common in poor left-ventricular function and in the presence of ventricular aneurysm. The embolic potential of a left-ventricular thrombus seems to differ. A protruding shape, mobility of the thrombus and morphologic changes over time have been identified as predictors of thromboembolic events [16,37–40].

After acute myocardial infarction and diagnosis of a left-ventricular thrombus, an anticoagulation of at least 3 months duration is recommended [41]. Although studies show fairly consistently a higher mortality rate in patients with left-ventricular thrombus and severe left-ventricular dysfunction, there is controversy about the benefit of routine anticoagulation in patients with chronic systolic dysfunction and a left-ventricular thrombus. Several studies have failed to find a correlation between the presence of left-ventricular thrombus and an increased incidence of thromboembolic complications [12,14,19,42]. It has not been established yet that antithrombotic therapy can significantly influence thromboembolic risk in the presence of a left-ventricular thrombus in chronic heart failure. A number of reasons for the poor relationship between the presence of a ventricular thrombus and thromboembolic complications have been discussed, including: flat thrombus morphology with low embolic risk [43,44]; methodological problems in detecting thrombi [45]; clinically silent thromboembolic episodes [46]; anticoagulant therapy in patients with thrombus [9]; and the importance of atrial thrombi as a source of cardiac emboli [9].

3.7. Left-ventricular aneurysm
A left-ventricular aneurysm is a risk factor for the persistence of a left-ventricular thrombus after myocardial infarction, as well as for development of a new mural thrombus [47]. Layers of thrombus are commonly found in left-ventricular aneurysms, and intra-aneurysmal thrombi have been reported in more than 50% of patients undergoing surgery [49–51] and in approximately 50% of patients at autopsy [43]. Although the thromboembolic risk in patients with a left-ventricular aneurysm and thrombus after acute myocardial infarction is increased during the first 3 months [47,48], it is not clear whether this also applies in chronic left-ventricular aneurysm. A retrospective study, which investigated the incidence of clinically evident embolic events in 69 patients with chronic left-ventricular aneurysm, suggested a very low incidence of thromboembolic events of 0.35% year–1, not supporting the use of long-term anticoagulant therapy [51]. However, this study did not report the left ventricular function in the study population. The risk of patients with severely compromised left-ventricular dysfunction and aneurysm may be higher.

3.8. History of thromboembolic event
Few studies reported data on the risk of thromboembolic events in the presence of previous thromboembolism. In the V-HeFT studies, patients with a history of stroke before entry into the study were more likely than the study population as a whole to have a second stroke during follow-up [20]. In V-HeFT I and II, 3 of 44 (6.8%) and 7 of 82 (8.5%) patients with a prior stroke experienced a second event, respectively. Previous pulmonary and peripheral arterial embolism did not seem to increase the risk of further events in those studies. However, in the SOLVD trial, in patients with a sinus rhythm at the time of randomization, a history of cerebrovascular accident was independently associated with an increased thromboembolic risk only in men (RR 2.31, 95% CI 1.61–3.31, P=0.0001), but not in women (RR 1.66, 95% CI 0.69–3.94, P=0.26) [22]. Prospective data on the risk of previous thromboembolism on further events in patients with heart failure are not available at present.


   4. Treatment
Top
 Abstract
 1. Introduction
 2. Incidence of thromboembolism
 3. Thromboembolic risk factors
 4. Treatment
5. Conclusions and...
 References
 
4.1. Effectiveness of antiplatelet agents
Aspirin is widely used in patients with coronary disease and reduces the rate of death and myocardial infarction in unstable angina [52]. The efficacy of aspirin as an antithrombotic agent used to reduce the risk of stroke and death is established in patients with transient ischemic attacks [53] and in patients with non-valvular atrial fibrillation [54], but not in patients with heart failure and/or left-ventricular dysfunction.

In the V-HeFT studies, there was a statistically non-significant trend towards a reduction in thromboembolic events for patients treated with antiplatelet agents (aspirin, dipyridamol, or both). The incidence of thromboembolism in patients receiving antiplatelet therapy in V-HeFT I and II was 0.5 and 1.6 events per 100 patient-years, compared to 2.7 and 2.1 events per 100 patient-years in patients who not been treated, respectively [20]. In the SOLVD trials, the use of antiplatelet agents was associated with a risk reduction for thromboembolic events of 23% (RR 0.77, 95% CI 0.59–1.00, P=0.06) in men and 53% (RR 0.47, 95% CI 0.24–0.92, P=0.03) in women, compared to those not using antiplatelet therapy at baseline [22]. Similarly, in the SAVE trial, aspirin use during follow-up was associated with a 56% risk reduction for stroke (RR 0.44, 95% CI 0.29–0.65, P<0.001) [23]. Interpreting these results, the retrospective nature of those studies has to be kept in mind, and the fact that the allocation of antiplatelet agents was not randomized.

Recently, the preliminary results of a prospective pilot study called ‘warfarin/aspirin study of heart failure’ (WASH) comparing the effect of aspirin (300 mg day–1), warfarin [target international normalized ratio (INR) 2.5], or no antithrombotic in patients with left-ventricular systolic dysfunction were reported [55]. WASH was a multicenter, prospective, open-label, blind endpoint pilot study involving 279 patients with a mean follow-up of 27 months. The primary outcome measure was the combined endpoint of all-cause mortality, non-fatal myocardial infarction, and non-fatal stroke. Mortality was higher in the aspirin group (30%), compared to warfarin (25%) and no antithrombotic treatment (21%). Incidence of stroke and myocardial infarction did not differ between the aspirin and no-antithrombotic-therapy groups.

In a retrospective analysis of patients of the SOLVD trials evaluating the relation between antiplatelet and survival and morbidity from cardiac disease, the use of antiplatelet agents was associated with a reduced mortality from all causes [adjusted hazard ratio (HR) 0.82, 95% CI 0.73–0.92, P=0.0005], and reduced risk of death or hospital admission for heart failure (adjusted HR 0.81, 95% CI 0.74–0.89) [56]. Interestingly, antiplatelet-therapy use was associated with retained, but reduced, benefit from enalapril. Aspirin has been discussed to adversely effect the benefit of angiotensin-converting enzyme (ACE) inhibitors on reducing mortality in heart-failure patients [57,58]. It has been suggested that long-term aspirin therapy may be helpful in patients with well preserved ventricular function, but possibly harmful in high risk patients with significantly compromised left-ventricular function [9]. However, the clinical significance of a possible interaction between aspirin and ACE inhibitors are presently unresolved. Besides interacting with ACE-inhibitor therapy, aspirin can result in dose-dependent gastrointestinal symptoms. Patients taking aspirin are at an increased risk of gastrointestinal hemorrhage [59]. In WASH (see above), serious adverse events were lowest for warfarin and highest for aspirin, driven primarily by an excess in gastrointestinal side effects with aspirin [55].

At present, the available data do not support an antithrombotic therapy with aspirin in all patients with heart failure and/or left ventricular dysfunction. In the future, new antiplatelet agents might be another option. For example, clopidogrel was marginally more effective than aspirin in reducing the combined risk of ischemic stroke, myocardial infarction, or vascular death in the CAPRIE study [60]. In the upcoming ‘warfarin and antiplatelet therapy study in chronic heart failure’ (WATCH), a large prospective study randomizing a total of 4500 patients, clopidogrel will be compared to aspirin and warfarin.

4.2. Effectiveness of oral anticoagulation
Oral anticoagulation is frequently used for patients with heart failure and/or left-ventricular dysfunction to prevent thromboembolism. This practice is often empirical, or based on retrospective analysis of referral populations [61]. A large prospective study is currently not available and the retrospective analyses of large therapeutic trials are inconclusive. In the V-HeFT studies, the rates of systemic or pulmonary emboli in patients not anticoagulated were similar to those in patients receiving anticoagulant therapy [20]. In patients with sinus rhythm at the time of randomization in the SOLVD trial, anticoagulant therapy was not associated with a risk reduction of thromboembolic events, either in women or men [22]. Contrary data were reported by the SAVE and PROMISE trials. Anticoagulant therapy reduced the risk of stroke by 83% (RR 0.19, 95% CI 0.13–0.28, P<0.001) in the SAVE trial [23]. In the PROMISE trial, the incidence of stroke in patients with a left-ventricular ejection fraction (LVEF) <20% was significantly higher without anticoagulant therapy than with therapy [24]. These seemingly contradictory results have to be discussed in the light of the study limitations. Stroke, peripheral arterial and pulmonary embolism were not primary study-endpoints. Atrial fibrillation was only assessed at baseline, and during the trial, newly developed atrial fibrillation was not documented. Treatment with anticoagulant drugs was neither randomized nor blinded, and a target international normalized ratio (INR) was not specified.

In the WASH study [55], the primary endpoint of combined all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke did not differ for the warfarin group (target INR 2.5) and control group without antithrombotic therapy. However, warfarin therapy was associated with a reduction in total bed-days and a reduced risk of non-fatal vascular events (stroke, myocardial infarction). In a retrospective trial evaluating the relation between warfarin anticoagulation and survival and morbidity from cardiac disease of the patients of the SOLVD trial, the use of warfarin was significantly associated with improved survival and reduced risk of death or hospital admission for heart failure [62]. However, anticoagulation is not without a risk, and therefore available data do not generally support anticoagulant therapy in all patients with heart failure and/or left-ventricular systolic dysfunction.

The major complication of anticoagulant therapy is the precipitation of hemorrhagic events. The most important determinants of oral anticoagulant-induced bleeding are the intensity of anticoagulation, the use of drugs that interfere with hemostasis, the length of therapy, and patient characteristics [63]. The highest bleeding rates were seen in patients with cerebrovascular disease [63]. Serious heart disease has also been suggested to be a condition with increased risk of bleeding during oral anticoagulation [64]. The annual risk of anticoagulant-induced bleeding in a diverse variety of indications and intensities of anticoagulation has been reported to be 1–2.7% for major bleeding and 0.17–0.25% for lethal bleeding [65–67]. Bleeding rates during long-term anticoagulant therapy are substantial with high-intensity therapy, and are lower with anticoagulation with a INR of 2.0–3.0, as recommended in atrial fibrillation. However, at present the risk of long-term anticoagulation in patients with heart failure and/or left-ventricular dysfunction can only be estimated, since no controlled, large-scale clinical trial has been published.


   5. Conclusions and recommendations
Top
 Abstract
 1. Introduction
 2. Incidence of thromboembolism
 3. Thromboembolic risk factors
 4. Treatment
 5. Conclusions and...
References
 
The annual incidence of thromboembolic events in a large unselected group of patients with heart failure and/or left-ventricular systolic dysfunction is in the region of 2%. Atrial fibrillation is the only prospectively evaluated, proven thromboembolic risk factor. A mobile left-ventricular thrombus, previous thromboembolic events and a severely decreased left-ventricular ejection fraction seem to be risk factors for thromboembolic events, but have not yet been evaluated prospectively. Female gender may be a risk factor, especially for pulmonary embolism, but sound data are limited.

Patients with atrial fibrillation benefit from long-term oral anticoagulant therapy, and anticoagulation with an INR of 2–3 is indicated in patients with atrial fibrillation and heart failure and/or left-ventricular systolic dysfunction.

Although there is the suggestion from retrospective and smaller prospective studies that warfarin improves survival and reduces morbidity in patients with chronic left-ventricular dysfunction, at present it remains unclear whether all patients with heart failure and/or left-ventricular systolic dysfunction in sinus rhythm benefit from oral anticoagulant therapy. Empirically, oral anticoagulation is recommended in patients with previous thromboembolic events with a target INR of 3 [68]. Long-term anticoagulation in patients with a low left-ventricular ejection fraction or thrombus is controversial, and should be decided on an individual base. Anticoagulation in patients with mobile LV thrombus seems reasonable until resolution of the thrombus. The benefit of aspirin to prevent thromboembolic complications in patients without a clear indication for anticoagulant therapy is even less clear. Hopefully, planned and ongoing large-scale trials investigating the effects of warfarin and anti-platelet agents on mortality, stroke, pulmonary and peripheral embolism will help identify thromboembolic risk factors and guide anticoagulant therapy in patients with chronic heart failure and/or left-ventricular systolic dysfunction in the future.


   References
Top
 Abstract
 1. Introduction
 2. Incidence of thromboembolism
 3. Thromboembolic risk factors
 4. Treatment
 5. Conclusions and...
 References
 

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