Should We Reintroduce Previous Venous Thromboembolism Into Decision-Making for Anticoagulation in Atrial Fibrillation?

BackgroundWe aimed to investigate whether history of venous thromboembolism should be considered a prognostic factor for future thromboembolic events in patients with atrial fibrillation.MethodsThis was a nationwide cohort study of patients with incident atrial fibrillation from 2000-2017, defined and characterized using Danish health registries. Cox regression analyses were used to calculate hazard ratios and 95% confidence intervals for the outcomes ischemic stroke or systemic embolism, and ischemic stroke, systemic embolism, or venous thromboembolism, according to history of venous thromboembolism. Analyses were adjusted for components of the CHA₂DS₂-VASc score and time-varying use of oral anticoagulation.ResultsThe study included 246,313 patients with incident atrial fibrillation, of which 6,516 (2.6%) had previous venous thromboembolism. Patients with previous venous thromboembolism carried an overall similar adjusted risk of ischemic stroke or systemic embolism compared with patients without previous venous thromboembolism (reference; hazard ratio 0.99; 95% confidence interval, 0.90-1.09). When analyzing a composite thromboembolic outcome of ischemic stroke, systemic embolism, or venous thromboembolism, patients with previous venous thromboembolism were at high-risk (hazard ratio 1.76; 95% confidence interval, 1.64-1.90). Similar conclusions were drawn when stratifying by venous thromboembolism subtype, and when restricting to patients with low CHA₂DS₂-VASc scores or the non-anticoagulated subset of the study population.ConclusionPatients with atrial fibrillation and previous venous thromboembolism carried similar risk of ischemic stroke or systemic embolism compared with patients with atrial fibrillation without previous venous thromboembolism. Nonetheless, patients with previous venous thromboembolism remain a high-risk population due to an excess risk of future venous thromboembolism. Patients and physicians should keep this excess thromboembolic risk in mind when weighing the expected risks and benefits of oral anticoagulation in patients with atrial fibrillation.     

Effectiveness and Safety of Anticoagulants in Adults with Non-valvular Atrial Fibrillation and Concomitant Coronary/Peripheral Artery Disease

Background

Direct oral anticoagulants (DOAC) are at least non-inferior to warfarin in efficacy and safety among patients with nonvalvular atrial fibrillation. Limited evidence is available regarding outcomes for nonvalvular atrial fibrillation patients with coronary/peripheral artery disease.

Clinical characteristics and outcomes of Japanese atrial fibrillation patients with poor medication adherence: A sub-analysis of the GENERAL study

BackgroundOral anticoagulation therapy is essential for preventing stroke in patients with atrial fibrillation (AF). However, poor anticoagulant adherence may hamper medication safety and effective prevention of stroke.MethodsGENERAL is a prospective cohort study of AF patients taking rivaroxaban prescribed by general practitioners in Japan. In this study, anticoagulant adherence was calculated as the proportion of days covered (PDC), and patients were retrospectively divided into two groups: good adherence (PDC ≥80 %) and poor adherence (<80 %).ResultsOf 5680 patients in the GENERAL study, the poor adherence group consisted of 223 patients (3.9 %). Baseline clinical characteristics were almost comparable regarding age (PDC ≥80 % vs. <80 %: 73.9 vs. 74.0 years, p = 0.92) and sex (male 64.6 % vs. 66.8 %, p = 0.52). The PDC <80 % group more often had various co-morbidities, and had significantly higher CHADS₂ (2.14 vs. 2.28, p = 0.04) and CHA₂DS₂-VASc scores (3.12 vs. 3.31, p = 0.045). There was no significant difference in HAS-BLED score (1.41 vs. 1.47, p = 0.39).During 2-year follow-up, the incidences of stroke or systemic embolism (1.14 vs. 3.56 % per patient-year, p < 0.01), major bleeding (0.59 vs. 1.78 % per patient-year, p < 0.01), and net clinical outcome (the composite of stroke, systemic embolism, major bleeding, or death) (3.49 vs. 7.78 % per patient-year, p < 0.01) were significantly higher in the poor adherence group; however, there was no significant difference in all-cause (1.89 vs. 2.73 % per patient-year, p = 0.23) and cardiovascular mortality (0.86 vs. 1.49 % per patient-year, p = 0.18). Multivariate analysis revealed that the poor adherence group was independently associated with stroke or systemic embolism (adjusted hazard ratio 3.12, 95 % confidence interval 1.79–5.47), major bleeding (2.87, 1.31–6.34), and net clinical outcome, (2.02, 1.39–2.93), but not with all-cause (1.18, 0.64–2.17) or cardiovascular death (1.39, 0.60–2.93).ConclusionsPoor anticoagulant adherence, as measured by PDC <80 %, was associated with higher incidence of stroke or systemic embolism and major bleeding in the GENERAL study.     

Outcomes in Newly Diagnosed Atrial Fibrillation and History of Acute Coronary Syndromes: Insights from GARFIELD-AF

BackgroundMany patients with atrial fibrillation have concomitant coronary artery disease with or without acute coronary syndromes and are in need of additional antithrombotic therapy. There are few data on the long-term clinical outcome of atrial fibrillation patients with a history of acute coronary syndrome. This is a 2-year study of atrial fibrillation patients with or without a history of acute coronary syndromes.MethodsAdults with newly diagnosed atrial fibrillation and ≥ 1 investigator-defined stroke risk factor were enrolled in GARFIELD-AF between March 2010 and September 2015. The association between prior acute coronary syndromes and long-term outcomes was determined using a Cox proportional hazards model, adjusting for baseline risk factors, oral anticoagulation (OAC) ± antiplatelet (AP) therapy, and usual care.ResultsOf 39,679 patients, 10.5% had a history of acute coronary syndromes. At 2-year follow-up, patients with prior acute coronary syndromes had higher adjusted risks of stroke/systemic embolism (hazard ratio [HR] 1.39; 95% confidence interval [CI], 1.08-1.78), major bleeding (HR 1.30; 95% CI, 0.95 -1.79), all-cause mortality (HR 1.34; 95% CI, 1.21 -1.49), cardiovascular mortality (HR 1.85; 95% CI, 1.51-2.26), and new acute coronary syndromes (HR 3.42; 95% CI, 2.62-4.45). Comparing antithrombotic therapy in the acute coronary syndromes vs no acute coronary syndromes groups, most patients received OAC ± AP: 60.8% vs 66.1%, but AP therapy was more likely in the acute coronary syndromes group (68.1% vs 32.9%), either alone (34.9% vs 20.8%) or with OAC (33.2% vs 12.1%). Overall, 17.8% in the acute coronary syndromes group received dual AP therapy with (5.3%) or without OAC (12.5%). Among patients with moderate/high risk for stroke/systemic embolism, fewer in the acute coronary syndromes group received OAC with or without AP therapy (Congestive heart failure, Hypertension, Age 75 years, Diabetes mellitus, prior Stroke, TIA, or thromboembolism, Vascular disease, Age 65-74 years, Sex category [CHA₂DS₂-VASc] 2: 52.1% vs 64.6%; CHA₂DS₂-VASc ≥ 3: 62.0% vs 70.7%), and the majority with a Hypertension (uncontrolled systolic blood pressure > 160 mm Hg), Abnormal renal or liver function, previous Stroke, Bleeding history or predisposition, Labile international normalized ratios, Elderly, and concomitant Drugs or alcohol excess (HAS-BLED) score ≥ 3 were on AP therapy (83.8% vs 65.5%).ConclusionsIn GARFIELD-AF, previous acute coronary syndromes are associated with worse 2-year outcomes and a greater likelihood of under-treatment with OAC, while two-thirds of patients receive AP therapy. Major bleeding was more common with previous acute coronary syndromes, even after adjusting for all risk factors.     

Long-Term Clinical Outcomes of Underdosed Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Atrial Flutter

BackgroundAlthough direct oral anticoagulants (DOACs) have been shown to be effective at reducing the risk of stroke in patients with atrial fibrillation/flutter (AF), they are sometimes underdosed off-label to mitigate their associated higher bleeding risk. We sought to evaluate frequency and clinical outcomes of inappropriate underdosing of DOACS in patients with AF.MethodsWe conducted a study of subjects with AF who had a clinical indication for stroke prophylaxis (with a congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65 to 47 years, sex category [CHA₂DS₂-VASc] of 2 or greater) and were prescribed 1 of the 4 clinically approved DOACs (apixaban, rivaroxaban, dabigatran, or edoxaban). We compared all-cause mortality, composite of stroke and systemic embolism, composite of myocardial infarction (MI), acute coronary syndromes (ACS), and coronary revascularization, and major bleeding between patients appropriately dosed and inappropriately underdosed.ResultsA total of 8125 patients met inclusion criteria, with a mean follow up of 2.2 ± 2 years. Of those, 1724 patients (21.2%) were inappropriately dosed. After adjusting for baseline variables, there was no difference in all-cause mortality, risk of stroke or systemic embolism, International Society on Thrombosis and Haemostasis (ISTH) major bleeding, or composite of myocardial infarction, acute coronary syndromes, or coronary revascularization between patients appropriately dosed and inappropriately underdosed. In subgroup analysis, only apixaban demonstrated an increased incidence all-cause mortality (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.03-1.49) with inappropriate underdosing. There was no difference in the remaining clinical outcomes noted on subgroup analysis.ConclusionUnderdosing of DOACs did not minimize risk of bleeding, systemic embolization or all-cause mortality in patients with AF. Inappropriate underdosing with apixaban in particular was associated with increased all-cause mortality.     

Evolution of clinical and electrophysiologic data in patients with a preexcitation syndrome

The purpose of the study is to report the natural changes of preexcitation syndrome (PS).MethodsElectrophysiologic study was performed for syncope (n = 8), atrioventricular reentrant tachycardia (AVRT) (n = 42), atrial fibrillation (n = 3), adverse presentation (n = 4), or for asymptomatic PS (n = 22) and was repeated 1 to 21 years later.ResultsClinically, 12 patients initially asymptomatic became symptomatic (54.5%), and 12 symptomatic patients became asymptomatic (21%). At electrophysiologic study 2, maximal rate conducted over accessory pathway (AP) was slower. Anterograde conduction disappeared in 22 patients, but 10 of them had inducible AVRT. Among 27 patients with initially rapid conduction over AP, 7 had a benign form; 20 had always a rapid conduction over AP, and 3 of them initially asymptomatic developed rapid atrial fibrillation.ConclusionsAsymptomatic patients with a PS frequently became symptomatic (54.5%), whereas symptomatic patients rarely became asymptomatic (21%). Maximal rate conducted over AP decreased during life, but AVRT remained inducible.     

SAMe-TT2R2 Score,Time in Therapeutic Range,and Outcomes in Anticoagulated Patients with Atrial Fibrillation

BackgroundOral anticoagulation is highly effective in preventing stroke and mortality in nonvalvular atrial fibrillation patients. However, the efficacy and safety of vitamin K antagonists (the main oral anticoagulation drug used) strongly depends upon the quantity of anticoagulation control, as reflected by the average percentage of the time in therapeutic range of international normalized ratio 2.0-3.0. An easy, simple prediction of which atrial fibrillation patients are likely to do well on vitamin K antagonists (with good average time in therapeutic range) could guide decision-making between using vitamin K antagonists (eg, warfarin) and non-vitamin K antagonist oral anticoagulants.Methods and ResultsIn a consecutive cohort of nonvalvular atrial fibrillation patients attending our anticoagulation clinic, we tested the hypothesis that the new Sex, Race, Medical history, Tobacco use, Race (SAMe-TT₂R₂) score was a predictor for good average time in therapeutic range, and second, this would translate into adverse events in a “real world” cohort of patients with nonvalvular atrial fibrillation. The incidence of bleeding, adverse cardiovascular events (including stroke/thromboembolism), and mortality during the follow-up was higher with increasing SAMe-TT₂R₂ score. The SAMe-TT₂R₂ score was predictive for the composite of all adverse events (hazard ratio 1.32 [95% Confidence Interval 1.17-1.50]; P <.001), adverse cardiovascular events (1.52 [1.28-1.83]; P <.001), and all-cause mortality (1.41 [1.16-1.67]; P = .001). A trend was also observed for major bleeding events (1.23 [0.99-1.53]; P = .059).ConclusionIn a “real world” cohort of consecutive patients with nonvalvular atrial fibrillation, a high SAMe-TT₂R₂ score (reflecting poor anticoagulation control with poor time in therapeutic range) was associated with more bleeding, adverse cardiovascular events, and mortality during follow-up.     

Prior History of Falls and Risk of Outcomes in Atrial Fibrillation: The Loire Valley Atrial Fibrillation Project

BackgroundPatients with nonvalvular atrial fibrillation are often denied oral anticoagulation due to falls risk. The latter is variably defined, and existing studies have not compared the associated risk of bleeding with other cardiovascular events. There are no data about outcomes in individuals with nonvalvular atrial fibrillation with a prior history of (actual) falls, rather than being “at risk of falls.” Our objective was to evaluate the risk of cardiovascular outcomes associated with prior history of falls in patients with atrial fibrillation in a contemporary “real world” cohort.MethodsPatients with nonvalvular atrial fibrillation in a 4-hospital institution between 2000 and 2010 were included. Stroke/thromboembolism event rates were calculated according to prior history of falls. Risk factors were investigated by Cox regression.ResultsAmong 7156 atrial fibrillation patients, prior history of falls/trauma was uncommon (n = 76; 1.1%). Compared with patients without history of falls, those patients were older and less likely to be on oral anticoagulation; they also had higher risk scores for stroke/thromboembolism but not for bleeding. Compared with no prior history of falls, rates of stroke/thromboembolism (P = .01) and all-cause mortality (P < .0001) were significantly higher in patients with previous falls. In multivariable analyses, prior history of falls was independently associated with stroke/thromboembolism (hazard ratio [HR] 5.19; 95% confidence interval [CI], 2.1-12.6; P < .0001), major bleeding (HR 3.32 [1.23-8.91]; P = .02), and all-cause mortality (HR 3.69; 95% CI, 1.52-8.95; P = .04), but not hemorrhagic stroke (HR 4.20; 95% CI, 0.58-30.48; P = .16) in patients on oral anticoagulation.ConclusionIn this large “real world” atrial fibrillation cohort, prior history of falls was uncommon but independently increased risk of stroke/thromboembolism, bleeding, and mortality, but not hemorrhagic stroke in the presence of anticoagulation. Prior history of (actual) falls may be a more clinically useful risk prognosticator than “being at risk of falls.”     

La fibrillation atriale asymptomatique

Asymptomatic atrial fibrillation (AF) is common, may adversely affect quality of life, and above all can be as serious as symptomatic AF. The prevalence of AF reported in epidemiological studies is significantly underestimated, as asymptomatic AF is often not known about. The efficacy of pharmacological or non-pharmacological treatment is often overestimated if the only aim considered is symptomatic recurrences. Like symptomatic AF, asymptomatic AF justifies anticoagulation, depending on the risk of embolism. Estimating the risk of embolism only from symptomatic episodes may result in unjustified discontinuation of antithrombotic treatment. Finally, frequent asymptomatic episodes may worsen atrial or even ventricular remodelling and result in tachycardia-induced cardiomyopathy.     

Non-Vitamin K Antagonists Versus Warfarin in Patients with Atrial Fibrillation and Bioprosthetic Valves: A Systematic Review and Meta-Analysis

BackgroundPatients with atrial fibrillation and bioprosthetic valves are at high risk for thromboembolic events. The pooled efficacy and safety of non-vitamin K oral anticoagulants (NOACs), as a class, relative to warfarin in this population is not well-known. We aimed to compare the efficacy and safety of NOACs relative to warfarin in patients with bioprosthetic valves or valve repair.MethodsWe systematically searched EMBASE, PubMed, and Cochrane databases for randomized controlled trials comparing NOACs to warfarin in patients with atrial fibrillation and bioprosthetic valves or valve repair. We pooled outcomes for stroke or systemic embolism, ischemic stroke, hemorrhagic stroke, and major bleeding.ResultsWe included 4 trials with 1379 patients, of whom 723 (52.4%) received a NOAC. Mean follow-up ranged from 90 days to 2.8 years. In the pooled analysis, stroke or systemic embolism was significantly lower in patients treated with NOACs (1.9%) compared with warfarin (3.7%) (odds ratio [OR] 0.43; 95% confidence interval [CI] 0.22-0.85; P = .02). Ischemic stroke (OR 0.72; 95% CI 0.18-2.93), hemorrhagic stroke (OR 0.18; 95% CI 0.03-1.05), cardiovascular death (OR 0.78; 95% CI 0.38-1.62), and all-cause mortality (OR 0.94; 95% CI 0.55-1.62) were not significantly different among groups. Major bleeding was significantly lower in patients treated with NOAC (2.8%) compared with warfarin (4.7%) (OR 0.49; 95% CI 0.28-0.88; P = .02).ConclusionsIn patients with atrial fibrillation and bioprosthetic valves or valve repair, NOACs are associated with a reduced incidence of thromboembolic events and major bleeding as compared with warfarin. Thus, NOACs may be considered a preferred option for this patient population.     

Atrial fibrillation is associated with an increased risk for mortality and heart failure progression in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: a retrospective analysis of the SOLVD trials

Objective. This study undertook to determine if the presence of atrial fibrillation in patients with asymptomatic and symptomatic left ventricular dysfunction was associated with increased mortality and, if so, whether the increase could be attributed to progressive heart failure or arrhythmic death.Background. Atrial fibrillation is a common condition in heart failure with the potential to impact hemodynamics and progression of left ventricular systolic dysfunction as well as the electrophysiologic substrate for arrhythmias. The available data do not conclusively define the effect of atrial fibrillation on prognosis in heart failure.Methods. A retrospective analysis of the Studies of Left Ventricular Dysfunction Prevention and Treatment Trials was conducted that compared patients with atrial fibrillation to those in sinus rhythm at baseline for the risk of all-cause mortality, progressive pump-failure death and arrhythmic death.Results. The patients with atrial fibrillation at baseline, compared to those in sinus rhythm, had greater all-cause mortality (34% vs. 23%, p < 0.001), death attributed to pump-failure (16.7% vs. 9.4%, p < 0.001) and were more likely to reach the composite end point of death or hospitalization for heart failure (45% vs. 33%, p < 0.001), but there was no significant difference between the groups in arrhythmic deaths. After multivariate analysis, atrial fibrillation remained significantly associated with all-cause mortality (relative risk [RR] 1.34, 95% confidence interval [CI] 1.12 to 1.62, p = 0.002), progressive pump-failure death (RR 1.42, 95% CI 1.09 to 1.85, p = 0.01), the composite end point of death or hospitalization for heart failure (RR 1.26, 95% CI 1.03 to 1.42, p = 0.02), but not arrhythmic death (RR 1.13; 95% CI 0.75 to 1.71; p = 0.55).Conclusions. The presence of atrial fibrillation in patients with asymptomatic and symptomatic left ventricular systolic dysfunction is associated with an increased risk for all-cause mortality, largely explained by an increased risk for pump-failure death. These data suggest that atrial fibrillation is associated with progression of left ventricular systolic dysfunction.     

An observational study of the management practices and outcomes of patients with new onset atrial fibrillation in non-cardiothoracic surgeries

Background and objectiveLimited data exist on characteristics and management of patients with postoperative atrial fibrillation (POAF) after noncardiothoracic surgeries and on the relationship between symptoms and outcomes. We sought to describe clinical features, in-hospital practices and outcomes in patients with new POAF by the presence or absence of clinical symptoms.MethodsRetrospective cohort study of adults with POAF in one tertiary center.ResultsAmong the 99 patients who fulfilled the eligibility criteria, median age was 75 years (IQR 64–83) and 57.6% were male. Only thirty percent of patients with POAF were symptomatic. Rate control/conversion to sinus rhythm was achieved in ≤ 4 h in 56% of the patients and in 80% was maintained for ≥ 24 h. Anticoagulation was prescribed in 50% of those discharged in AF; the CHADS2-VASc score was not associated with anticoagulation prescribed. One third of patients were readmitted and half of them were in AF. Asymptomatic patients had lower median heart rate than symptomatic patients but no other clinical characteristics, or outcomes were different.ConclusionsMost patients with POAF were asymptomatic but their presentation or outcomes were similar with symptomatic patients. One in four discharged patients was prescribed anticoagulation and the CHADS2-VASC score was not associated with this decision. These findings have important implications for practice and future research. There is a need to better delineate the risk associated with transient versus persistent POAF, symptomatic versus asymptomatic POAF, as well as for clinical trials to determine optimal strategies to improve their outcomes.     

Efficacy and Safety of Oral Anticoagulants in Patients With Atrial Fibrillation and Stages 4 or 5 Chronic Kidney Disease

PurposeThe aim of this study was to investigate whether oral anticoagulants can provide efficacy and safety profiles better than no anticoagulant in patients with stages 4 or 5 chronic kidney disease and atrial fibrillation.MethodsFrom 2001 to 2017, a cohort of patients with stages 4 or 5 chronic kidney disease and atrial fibrillation based on electronic medical records were selected from Chang Gung Memorial Hospital system in Taiwan. Patients were divided into nonvitamin K antagonist oral anticoagulants (NOACs), warfarin, and nonanticoagulated groups. They were followed from the index date to the occurrence of the study outcomes or for 5 years, whichever occurred first. The outcomes were admissions due to ischemic stroke or systemic embolism or major bleedings. Survival analyses were conducted to estimate the incidence rates of outcomes.ResultsA total of 3771 patients with atrial fibrillation and estimated glomerular filtration rate less than 30 mL/min/1.73m² were enrolled, of whom 2971 were in the nonanticoagulated group, 280 in the NOAC group, and 520 in the warfarin group. About 25% of all subjects (940 patients) were on dialysis. The mean follow-up was 3.2 years. After adjusting for sex, age, comorbidities, and comedication, the warfarin group had a significantly higher risk of ischemic stroke or systemic embolism (adjusted hazard ratio [aHR] 3.1, 95% confidence interval [CI] 2.1-4.6) than the nonanticoagulated group. The NOAC group had a similar risk of ischemic stroke or systemic embolism (aHR 1.1; 95% CI 0.3-3.4) to that of the nonanticoagulated group. Both the warfarin and the NOAC groups had a significantly higher major bleeding risk than the noncoagulated group (aHR 2.8 [95% CI 2.0-3.8] for warfarin; aHR 3.1 [95% CI 1.9-5.2] for NOAC).ConclusionThe use of NOACs or warfarin is not more effective than using no anticoagulants at all in reducing the risk of ischemic stroke or systemic embolism. Both NOACs and warfarin are associated with increased risk of major bleeding. Our results do not support the use of anticoagulants in patients with atrial fibrillation and stages 4-5 chronic kidney disease.     

Non-vitamin K antagonist oral anticoagulation versus left atrial appendage occlusion for primary and secondary stroke prevention after cardioembolic stroke

IntroductionThis study aimed to evaluate the performance of non-vitamin K antagonist oral anticoagulation (NOAC) in patients with previous stroke and non-valvular atrial fibrillation (AF) compared with left atrial appendage occlusion (LAAO) in primary and secondary stroke prevention settings.MethodsThis was a prospective, single-center, non-randomized cohort study of 302 consecutive patients with non-valvular AF and at high risk for stroke. Two treatment strategies were compared: LAAO (n=91) and long-term treatment with NOAC (n=149). The primary outcome was the composite endpoint of death, stroke and major bleeding. Propensity score and cause-of-death analyses were performed to compare outcomes.ResultsIn a mean follow-up of 13 months, there were 30 deaths (LAAO 8.8% vs. NOAC 14.8%), five strokes (LAAO 1.1% vs. NOAC 2.7%) and six major bleeds (LAAO 1.1% vs. NOAC 3.4%). There was a non-significant trend for a lower incidence of the primary endpoint in the LAAO group (11.0% vs. 20.9%; HR 0.42, 95% CI 0.17-1.05, p=0.064). Considering only secondary prevention LAAO patients (34.1% of the LAAO group), there was also a non-significant lower incidence of the primary endpoint (LAAO 6.5% vs. 20.9%; HR 0.30, 95% CI 0.07-1.39, p=0.12). While about a fifth of LAAO patients stopped antiplatelet treatment six months after device implantation due to recurrent minor bleeding, no adverse cardiovascular event or major bleeding occurred in this subset of patients.ConclusionIn this registry-based study, LAAO was a reasonable alternative to NOAC for the prevention of a composite endpoint of all-cause mortality, stroke and major bleeding in patients at high risk for stroke.     

Clinical Effectiveness of Anticoagulation Therapy Among Older Patients With Heart Failure and Without Atrial Fibrillation: Findings From the ADHERE Registry Linked to Medicare Claims

BackgroundPatients with heart failure are at higher risk for thromboembolic events, even in the absence of atrial fibrillation, but the effect of anticoagulation therapy on outcomes is uncertain.Methods and ResultsWith data from a clinical registry linked to Medicare claims, we estimated the adjusted associations between anticoagulation and 1-year outcomes with the use of inverse probability of treatment weighting. Eligible patients had an ejection fraction ≤35%, had no concurrent atrial fibrillation, were alive at discharge, and had not received anticoagulation therapy before admission. Of 13,217 patients in 276 hospitals, 1,140 (8.6%) received anticoagulation therapy at discharge. Unadjusted rates of thromboembolic events and major adverse cardiovascular events did not differ by receipt of anticoagulation therapy. Patients discharged on anticoagulation therapy had lower unadjusted rates of all-cause mortality (27.2% vs 32.3%; P < .001) and readmission for heart failure (29.4% vs 35.4%; P < .001) and higher rates of bleeding events (5.2% vs 2.8%; P < .001). After adjustment for probability of treatment and discharge medications, there were no differences in all-cause mortality (hazard ratio 0.92; 95% confidence interval 0.80–1.06) or readmission for heart failure (0.91, 0.81–1.02), but patients receiving anticoagulation therapy were at higher risk for bleeding events (2.09, 1.47–2.97).ConclusionsAnticoagulation therapy at discharge is infrequent among older patients with heart failure and without atrial fibrillation. There were no statistically significant propensity-weighted associations between anticoagulation therapy and 1-year outcomes, except for a higher risk of bleeding.     

Risk factors for systemic embolism in patients with paroxysmal atrial fibrillation.

The purpose of this study was to define the risk factors for systemic embolism in patients with recently diagnosed paroxysmal atrial fibrillation. We therefore studied 63 consecutive patients with symptomatic nonvalvular paroxysmal atrial fibrillation and performed a clinical and noninvasive cardiac, peripheral vascular, and neurologic evaluation that included two-dimensional echocardiography, 24-hour Holter monitoring, and computed tomographic brain scan. Patients with predisposing clinical conditions for systemic embolism (valvular heart or coronary artery disease) or paroxysmal atrial fibrillation (sick sinus disease, preexcitation, or thyroid dysfunction) were excluded. At entry 34 patients had idiopathic paroxysmal atrial fibrillation and 29 had hypertension. Fourteen patients had a recent systemic embolic complication: nine had a recent occlusive nonlacunar cerebrovascular accident, two had transient ischemic attacks, and three had peripheral systemic emboli that required surgery. In addition, five patients had evidence of old cerebrovascular accident on the computed tomographic scan (group 1). Forty-four patients had no systemic embolism (group 2). Results of univariate analysis showed that patients in group 1 were older (72 +/- 9 vs 63 +/- 13 years, p less than 0.05), had a higher incidence of hypertension (70% vs 35%, p less than 0.01), and had an increased left atrial diameter (4.1 +/- 0.7 vs 3.6 +/- 0.5 cm, p less than 0.05). Multiple stepwise logistic regression analysis showed that a history of hypertension and left atrial enlargement on two-dimensional echocardiography were significant independent risk factors for systemic embolism in patients with symptomatic nonvalvular paroxysmal atrial fibrillation.     

Anticoagulación oral en la fibrilación auricular no valvular: ¿son efectivas y seguras las recomendaciones científicas en la práctica clínica diaria?

INTRODUCTION AND OBJECTIVES: To study the efficacy and safety of an oral anticoagulation protocol for the treatment of nonvalvular atrial fibrillation, based on scientific associations' recommendations, in unselected patients seen in daily clinical practice. METHODS: The study included all consecutive patients with permanent nonvalvular atrial fibrillation who attended two outpatient cardiology clinics between February 1, 2000 and February 1, 2002. They were treated according to an anticoagulation protocol based on Spanish Society of Cardiology and American College of Cardiology/American Heart Association/European Society of Cardiology guidelines. Patients were followed up prospectively for major events, such as death, stroke, transient ischemic attack, peripheral embolism and severe hemorrhage, which were recorded by treatment group. RESULTS: A total of 624 patients were included in the study. Those receiving anticoagulation therapy (n=425; 68%) more frequently had hypertension, diabetes and previous embolism as well as a greater number of cardioembolic risk factors (P< .001). Overall, 93% of non-anticoagulated patients received platelet aggregation inhibitors (92% received aspirin). After a median follow-up of 21 months, the probability of an embolic event was lower in anticoagulated patients (0.81% vs 14.04%; P< .001), as was all-cause mortality (3.27% vs 6.42%; P=.003). However, there was no significant difference in the probability of severe bleeding (2.75% vs 2.93%; P=.96). Results were unchanged after adjustment for age, sex, and previous embolic events. CONCLUSIONS: Oral anticoagulation therapy for nonvalvular atrial fibrillation implemented according to scientific associations' recommendations is effective and safe in daily clinical practice.     

Oral Anticoagulation and Adverse Outcomes after Ischemic Stroke in Heart Failure Patients without Atrial Fibrillation

BackgroundThe safety and effectiveness of oral anticoagulation (OAC) after an ischemic stroke in older patients with heart failure (HF) without atrial fibrillation remains uncertain.MethodsUtilizing Get With The Guidelines Stroke national clinical registry data linked to Medicare claims from 2009-2014, we assessed the outcomes of eligible patients with a history of HF who were initiated on OAC during a hospitalization for an acute ischemic stroke. The cumulative incidences of adverse events were calculated using Kaplan-Meier curves and adjusted Cox proportional hazard ratios were compared between patients discharged on or off OAC.ResultsA total of 8,261 patients from 1,370 sites were discharged alive after an acute ischemic stroke and met eligibility criteria. Of those, 747 (9.0%) were initiated on OAC.  Patients on OAC were younger (77.2±8.0 vs. 80.5±8.9 years, p<0.01). After adjustment for clinical covariates, the likelihood of 1 year mortality was higher in those on OAC (aHR: 1.22, 95% CI 1.05-1.41, p<0.01), while no significant differences were noted for ICH (aHR: 1.34, 95% CI 0.69-2.59, p=0.38) and recurrent ischemic stroke (aHR: 0.78, 95% CI 0.54-1.15, p = 0.21).  The likelihood of all-cause bleeding (aHR: 1.59, 95% CI 1.29-1.96, p<0.01) and all-cause re-hospitalization (aHR: 1.14, 95% CI 1.02-1.27, p = 0.02) was higher for those on OAC.ConclusionInitiation of OAC after an ischemic stroke in older patients with HF in the absence of atrial fibrillation is associated with death, bleeding and re-hospitalization without an associated reduction in recurrent ischemic stroke. If validated, these findings raise caution for prescribing OAC to such patients.     

Comparison of Transcatheter Aortic Valve Implantation Outcomes Between Normal-Flow,Low-Gradient Severe Aortic Stenosis and Normal-Flow,High-Gradient Severe Aortic Stenosis

BackgroundNormal flow low gradient severe aortic stenosis (NFLG-AS) with preserved ejection fraction is the most prevalent form of low gradient severe aortic stenosis. Despite the increased prevalence, the clinical outcomes and management strategy of NFLG-AS remain controversial. Therefore, our study aimed to evaluate transcatheter aortic valve implantation (TAVI) outcomes of patients with NFLG-AS compared with normal flow high gradient severe aortic stenosis (NFHG-AS).MethodsWe performed a retrospective analysis of 394 patients who underwent TAVI between January 2011 to September 2020. Among 394 patients, 232 patients had NFLG-AS, and 162 patients had NFHG-AS. The primary outcomes included all-cause mortality and cardiovascular mortality. In addition, multiple secondary outcomes were evaluated, including stroke, myocardial infarction, duration of hospital stay, new-onset atrial fibrillation, temporary or permanent pacemaker requirement, major bleeding, blood transfusion, vascular complications, acute kidney injury, hemodialysis requirement, symptom improvement, and repeat hospitalizations due to any cardiac disease.ResultsThe cumulative six months incidence of all-cause mortality and cardiovascular mortality were similar between and NFLG-AS and NFHG-AS (4.32% vs. 5.17%, P = 0.71 and 2.47% vs. 2.59%, P = 0.94 respectively). There was no difference in the rates of stroke, myocardial infarction, duration of hospital stay, new-onset atrial fibrillation, temporary or permanent pacemaker requirement, major bleeding, blood transfusion, vascular complications, acute kidney injury, hemodialysis requirement, and symptom improvement between the two groups. However, patients with NFLG-AS compared to NFHG-AS had more frequent cardiac-related repeat hospitalizations (19.14% vs. 11.64%, P = 0.04%).ConclusionThere was no significant difference in all-cause mortality and cardiovascular mortality between NFLG-AS and NGHG-AS six months post-TAVI. However, patients undergoing TAVI with NFLG-AS had significantly higher rates of cardiac-related repeat hospitalizations.     

Underuse of Oral Anticoagulants in Atrial Fibrillation: A Systematic Review

Background

Atrial fibrillation is associated with substantial mortality and morbidity from stroke and thromboembolism. Despite an efficacious oral anticoagulation therapy (warfarin), atrial fibrillation patients at high risk for stroke are often under-treated. This systematic review compares current treatment practices for stroke prevention in atrial fibrillation with published guidelines.

Methods

Literature searches (1997-2008) identified 98 studies concerning current treatment practices for stroke prevention in atrial fibrillation. The percentage of patients eligible for oral anticoagulation due to elevated stroke risk was compared with the percentage treated. Under-treatment was defined as treatment of <70% of high-risk patients.

Results

Of 54 studies that reported stroke risk levels and the percentage of patients treated, most showed underuse of oral anticoagulants for high-risk patients. From 29 studies of patients with prior stroke/transient ischemic attack who should all receive oral anticoagulation according to published guidelines, 25 studies reported under-treatment, with 21 of 29 studies reporting oral anticoagulation treatment levels below 60% (range 19%-81.3%). Subjects with a CHADS₂ (congestive heart failure, hypertension, age >75 years, diabetes mellitus, and prior stroke or transient ischemic attack) score ≥2 also were suboptimally treated, with 7 of 9 studies reporting treatment levels below 70% (range 39%-92.3%). Studies (21 of 54) using other stroke risk stratification schemes differ in the criteria they use to designate patients as “high risk,” such that direct comparison is not possible.

Conclusions

This systematic review demonstrates the underuse of oral anticoagulation therapy for real-world atrial fibrillation patients with an elevated risk of stroke, highlighting the need for improved therapies for stroke prevention in atrial fibrillation.