Antithrombotics in HF and Associated AF and Vascular Disease
Antithrombotics in HF and Associated AF and Vascular Disease
Objectives. The aim of this study was to investigate the impact of atrial fibrillation (AF) and antithrombotic treatment on the prognosis in patients with heart failure (HF) as well as vascular disease.
Background. HF, vascular disease, and AF are pathophysiologically related, and understanding antithrombotic treatment for these conditions is crucial.
Methods. In hospitalized patients with HF and coexisting vascular disease (coronary artery disease or peripheral arterial disease) followed from 1997 to 2009, AF status was categorized as prevalent AF, incident AF, or no AF. Risk of thromboembolism (TE), myocardial infarction (MI), and serious bleeding was assessed by Cox regression models (hazard ratio [HR] with 95% confidence interval [CI]) with antithrombotic therapy and AF as time-dependent variables.
Results. A total of 37,464 patients were included (age, 74.5 ± 10.7 years; 36.3% females) with a mean follow-up of 3 years during which 20.7% were categorized as prevalent AF and 17.2% as incident AF. Compared with vitamin K antagonist (VKA) in prevalent AF, VKA plus antiplatelet was not associated with a decreased risk of TE (HR: 0.91; 95% CI: 0.73 to 1.12) or MI (HR: 1.11; 95% CI: 0.96 to 1.28), whereas bleeding risk was significantly increased (HR: 1.31; 95% CI: 1.09 to 1.57). Corresponding estimates for incident AF were HRs of 0.77 (95% CI: 0.56 to 1.06), 1.07 (95% CI: 0.89 to 1.28), and 2.71 (95% CI: 1.33 to 2.21) for TE, MI, and bleeding, respectively. In no AF patients, no statistical differences were seen between antithrombotic therapies in TE or MI risk, whereas bleeding risk was significantly increased for VKA with and without single-antiplatelet therapy.
Conclusions. In AF patients with coexisting HF and vascular disease, adding single-antiplatelet therapy to VKA therapy is not associated with additional benefit in thromboembolic or coronary risk, but notably increased bleeding risk.
Although systolic heart failure (HF) is associated with increased risk of thromboembolism (TE) and death, no firm evidence exists of the benefit of antithrombotic treatment in uncomplicated HF in sinus rhythm. For example, a recent Cochrane review found no convincing evidence that oral anticoagulant therapy modified mortality or vascular events in patients with HF in sinus rhythm.
Two conditions commonly related to HF are vascular disease and atrial fibrillation (AF), with both frequently requiring the use of antithrombotic therapy with antiplatelet drugs and oral anticoagulation, respectively. In patients with coronary or peripheral artery disease, antiplatelet therapy is recommended, although the benefits of antiplatelet therapy in patients with concomitant HF are less well defined in relation to mortality and vascular events. In HF patients with AF, oral anticoagulation is clearly indicated.
The use of antithrombotic therapy has to balance a reduction in TE against the potential increase in risk of bleeding. Bleeding while on antithrombotic therapy may have implications for subsequent adverse outcomes. Patients with HF may also be predisposed to more bleeding due to difficulties with warfarin and liver congestion, and in the recent WARCEF (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction) trial conducted in HF patients in sinus rhythm, the beneficial effects of reducing ischemic stroke were offset by an increase in major bleeding with warfarin therapy.
If patients with HF have both vascular disease and AF, a common practice is to concomitantly prescribe oral anticoagulation and antiplatelet therapy because such patients are considered high risk. Indeed, incident and prevalent AF may confer different risks. In general population studies, there is little evidence of a beneficial effect of such combination antithrombotic therapy on TE, given the increase in serious bleeding. Limited data are available for HF patients who have both vascular disease and AF.
In a real-life cohort of HF patients with vascular disease, our objective was to assess the relationship of incident or prevalent AF to TE and serious bleeding. Second, we also assessed the effectiveness and safety of ongoing antithrombotic treatment in such patients.
Abstract and Introduction
Abstract
Objectives. The aim of this study was to investigate the impact of atrial fibrillation (AF) and antithrombotic treatment on the prognosis in patients with heart failure (HF) as well as vascular disease.
Background. HF, vascular disease, and AF are pathophysiologically related, and understanding antithrombotic treatment for these conditions is crucial.
Methods. In hospitalized patients with HF and coexisting vascular disease (coronary artery disease or peripheral arterial disease) followed from 1997 to 2009, AF status was categorized as prevalent AF, incident AF, or no AF. Risk of thromboembolism (TE), myocardial infarction (MI), and serious bleeding was assessed by Cox regression models (hazard ratio [HR] with 95% confidence interval [CI]) with antithrombotic therapy and AF as time-dependent variables.
Results. A total of 37,464 patients were included (age, 74.5 ± 10.7 years; 36.3% females) with a mean follow-up of 3 years during which 20.7% were categorized as prevalent AF and 17.2% as incident AF. Compared with vitamin K antagonist (VKA) in prevalent AF, VKA plus antiplatelet was not associated with a decreased risk of TE (HR: 0.91; 95% CI: 0.73 to 1.12) or MI (HR: 1.11; 95% CI: 0.96 to 1.28), whereas bleeding risk was significantly increased (HR: 1.31; 95% CI: 1.09 to 1.57). Corresponding estimates for incident AF were HRs of 0.77 (95% CI: 0.56 to 1.06), 1.07 (95% CI: 0.89 to 1.28), and 2.71 (95% CI: 1.33 to 2.21) for TE, MI, and bleeding, respectively. In no AF patients, no statistical differences were seen between antithrombotic therapies in TE or MI risk, whereas bleeding risk was significantly increased for VKA with and without single-antiplatelet therapy.
Conclusions. In AF patients with coexisting HF and vascular disease, adding single-antiplatelet therapy to VKA therapy is not associated with additional benefit in thromboembolic or coronary risk, but notably increased bleeding risk.
Introduction
Although systolic heart failure (HF) is associated with increased risk of thromboembolism (TE) and death, no firm evidence exists of the benefit of antithrombotic treatment in uncomplicated HF in sinus rhythm. For example, a recent Cochrane review found no convincing evidence that oral anticoagulant therapy modified mortality or vascular events in patients with HF in sinus rhythm.
Two conditions commonly related to HF are vascular disease and atrial fibrillation (AF), with both frequently requiring the use of antithrombotic therapy with antiplatelet drugs and oral anticoagulation, respectively. In patients with coronary or peripheral artery disease, antiplatelet therapy is recommended, although the benefits of antiplatelet therapy in patients with concomitant HF are less well defined in relation to mortality and vascular events. In HF patients with AF, oral anticoagulation is clearly indicated.
The use of antithrombotic therapy has to balance a reduction in TE against the potential increase in risk of bleeding. Bleeding while on antithrombotic therapy may have implications for subsequent adverse outcomes. Patients with HF may also be predisposed to more bleeding due to difficulties with warfarin and liver congestion, and in the recent WARCEF (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction) trial conducted in HF patients in sinus rhythm, the beneficial effects of reducing ischemic stroke were offset by an increase in major bleeding with warfarin therapy.
If patients with HF have both vascular disease and AF, a common practice is to concomitantly prescribe oral anticoagulation and antiplatelet therapy because such patients are considered high risk. Indeed, incident and prevalent AF may confer different risks. In general population studies, there is little evidence of a beneficial effect of such combination antithrombotic therapy on TE, given the increase in serious bleeding. Limited data are available for HF patients who have both vascular disease and AF.
In a real-life cohort of HF patients with vascular disease, our objective was to assess the relationship of incident or prevalent AF to TE and serious bleeding. Second, we also assessed the effectiveness and safety of ongoing antithrombotic treatment in such patients.
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