Anticoagulation and population risk of stroke and death in incident atrial fibrillation: a population-based cohort study.
ABSTRACT: Atrial fibrillation increases the risk of stroke and death. Anticoagulation therapy is an effective treatment for stroke prevention, but remains underused in the community. We sought to determine the effectiveness and safety of anticoagulation therapy in an inception cohort with new-onset atrial fibrillation in the province of Alberta, Canada.We conducted a population-based cohort study of atrial fibrillation using an administrative database from Alberta's publicly funded and universally available health care system. All new-onset atrial fibrillation patients from Jan. 1, 2009, to Dec. 31, 2010, were included in the cohort and followed through Dec. 31, 2013. We assessed anticoagulation status as a predictor of stroke and death using time-to-event analysis and adjusted for sex and CHADS2 (congestive heart failure, hypertension, age ? 75 yr, diabetes mellitus and prior stroke or transient ischemic attack) score using Cox proportional hazards modelling.We identified 10?745 patients, 7358 (68.5%) of whom received anticoagulation therapy, principally with warfarin (n = 6997, 95.1%). Anticoagulation therapy was associated with significantly decreased risk of ischemic stroke (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.58-0.82), all stroke (HR 0.77, 95% CI 0.65-0.91), all stroke and death (HR 0.70, 95% CI 0.62-0.72) and all-cause mortality (HR 0.67, 95% CI 0.62-0.72), despite an association with increased risk of hemorrhagic stroke (HR 1.92, 95% CI 1.17-3.16). There was a neutral association with subdural (HR 1.01, 95% CI 0.53-1.93) and gastrointestinal (HR 0.96, 95% CI 0.70-1.31) hemorrhage.Anticoagulation therapy is effective and safe for stroke prevention and decreases mortality in patients with incident atrial fibrillation. These population data support an aggressive approach to screening for atrial fibrillation and treatment with anticoagulant medicines to prevent stroke and death.
Project description:Little is known about the clinical outcomes associated with posthemorrhage anticoagulation resumption for atrial fibrillation. This study had 2 objectives: first, to evaluate anticoagulation use after a first major bleed on warfarin or dabigatran and, second, to compare effectiveness and safety outcomes between patients discontinuing anticoagulation after a major bleed and patients restarting warfarin or dabigatran.Using 2010 to 2012 Medicare Part D data, we identified atrial fibrillation patients who experienced a major bleeding event while using warfarin (n=1135) or dabigatran (n=404) and categorized them by their posthemorrhage use of anticoagulation. We followed them until an ischemic stroke, recurrent hemorrhage, or death through December 31, 2012. We constructed logistic regression models to evaluate factors affecting anticoagulation resumption and Cox proportional hazard models to compare the combined risk of ischemic stroke and all-cause mortality and the risk of recurrent bleeding between treatment groups.Resumption of anticoagulation with warfarin (hazard ratio [HR] 0.76; 95% confidence interval [CI] 0.59-0.97) or dabigatran (HR 0.66; 95% CI 0.44-0.99) was associated with lower combined risk of ischemic stroke and all-cause mortality than anticoagulation discontinuation. The incidence of recurrent major bleeding was higher for patients prescribed warfarin after the event than for those prescribed dabigatran (HR 2.31; 95% CI 1.19-4.76) or whose anticoagulation ceased (HR 1.56; 95% CI 1.10-2.22), but did not differ between patients restarting dabigatran and those discontinuing anticoagulation (HR 0.65; 95% CI 0.32-1.33).Dabigatran was associated with a superior benefit/risk ratio than warfarin and anticoagulation discontinuation in the treatment of atrial fibrillation patients who have survived a major bleed.
Project description:Despite its lack of efficacy, aspirin is commonly used for stroke prevention in atrial fibrillation. Since prior studies have suggested a benefit of low-intensity anticoagulation over aspirin in the prevention of vascular events, the aim of this systematic review was to compare the outcomes of patients with non-valvular atrial fibrillation treated with low-intensity anticoagulation with Vitamin K antagonists or aspirin.We conducted a systematic review searching Ovid MEDLINE, Embase and the Cochrane Central Register of Controlled Trials, from 1946 to October 14th, 2015. Randomized controlled trials were included if they reported the outcomes of patients with non-valvular atrial fibrillation treated with a low-intensity anticoagulation compared to patients treated with aspirin. The primary outcome was a combination of ischemic stroke or systemic embolism. The random-effects model odds ratio was used as the outcome measure.Our initial search identified 6309relevant articles of which three satisfied our inclusion criteria and were included. Compared to low-intensity anticoagulation, aspirin alone did not reduce the incidence of ischemic stroke or systemic embolism OR 0.94 (95% CI 0.57-1.56), major bleeding OR 1.06 (95% CI 0.42-2.62) or vascular death OR 1.04 (95% CI 0.61-1.75). The use of aspirin was associated with a significant increase in all-cause mortality OR 1.66 (95% CI 1.12-2.48).In patients with non-valvular atrial fibrillation, aspirin provides no benefits over low-intensity anticoagulation. Furthermore, the use of aspirin appears to be associated with an increased risk in all-cause mortality. Our study provides more evidence against the use aspirin in patients with non-valvular atrial fibrillation.
Project description:BACKGROUND:We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing patent foramen ovale (PFO) closure, anticoagulation, and antiplatelet therapy to prevent stroke recurrence in patients with PFO-associated cryptogenic stroke. METHODS AND RESULTS:We searched Medline, Cochrane Library, and EMBASE through March 2018. The primary outcome was stroke recurrence. Pooled incidences, hazard ratios, and risk ratios (RRs) were calculated in random-effects meta-analyses. PFO closure was associated with a lower risk of recurrent stroke compared with antithrombotic therapy (antiplatelet therapy or anticoagulation: 3560 patients from 6 RCTs; RR=0.36, 95% CI: 0.17-0.79; I2=59%). The effect of PFO closure on stroke recurrence was larger in patients with atrial septal aneurysm or large shunt (RR=0.27, 95% CI, 0.11-0.70; I2=42%) compared with patients without these anatomical features (RR=0.80, 95% CI, 0.43-1.47; I2=12%). Major complications occurred in 2.40% (95% CI, 1.03-4.25; I2=77%) of procedures. New-onset atrial fibrillation was more frequent in patients randomized to PFO closure versus antithrombotic therapy (RR=4.33, 95% CI, 2.37-7.89; I2=14%). One RCT compared PFO closure versus anticoagulation (353 patients; hazard ratio=0.14, 95% CI, 0.00-1.45) and 2 RCTs compared PFO closure versus antiplatelet therapy (1137 patients; hazard ratio=0.18, 95% CI, 0.05-0.63; I2=12%). Three RCTs compared anticoagulation versus antiplatelet therapy, with none showing a significant difference. CONCLUSIONS:PFO closure is superior to antithrombotic therapy to prevent stroke recurrence after cryptogenic stroke. The annual absolute risk reduction of stroke was low, but it has to be tempered by a substantial time at risk (at least 5 years) in young and middle-aged patients. PFO closure was associated with an increased risk of atrial fibrillation.
Project description:Background We aimed to clarify associations between prior anticoagulation and short- or long-term clinical outcomes in ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation. Methods and Results A total of 1189 ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation who were hospitalized within 7 days after onset were analyzed. Of these, 813 patients (68.4%) received no prior anticoagulation, 310 (26.1%) received prior warfarin treatment with an international normalized ratio ( INR ) <2 on admission, 28 (2.4%) received prior warfarin treatment with an INR ?2 on admission, and the remaining 38 (3.2%) received prior direct oral anticoagulant treatment. Prior warfarin treatment was associated with a lower risk of death or disability at 3 months compared with no prior anticoagulation ( INR <2: adjusted odds ratio: 0.58; 95% CI, 0.42-0.81; P=0.001; INR ?2: adjusted odds ratio: 0.40; 95% CI, 0.16-0.97; P=0.043) but was not associated with a lower risk of death or disability at 2 years. Prior warfarin treatment with an INR ?2 on admission was associated with a higher risk of ischemic events within 2 years compared with no prior anticoagulation (adjusted hazard ratio: 2.94; 95% CI, 1.20-6.15; P=0.021). Conclusions Prior warfarin treatment was associated with a lower risk of death or disability at 3 months but was not associated with a lower risk of death or disability at 2 years in ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation. Prior warfarin treatment with an INR ?2 on admission was associated with a higher risk of ischemic events within 2 years. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01581502.
Project description:BACKGROUND:The role of anticoagulation therapy for stroke prevention in older atrial fibrillation (AF) patients with chronic kidney disease (CKD) remains unclear. Therefore, we conducted a meta-analysis to explore the efficacy and safety of anticoagulation therapy in this population. METHODS:The Cochrane Library, PubMed, and Embase databases were systematically searched for studies reporting the effect of anticoagulation therapy in older patients with AF and CKD. The risk ratios (RRs) and 95% confidence intervals (CIs) were regarded as the risk estimates. A random-effects model selected was to evaluate the treatment outcomes. The presentations were based on the Preferred Reporting Items for reporting systematic reviews and meta-analyses statement. RESULTS:A total of 7 studies with 24,794 older patients with AF and CKD were included. The follow-up of the included studies ranged from 0.9 to 9.0 years. In older patients with no dialysis, compared with nonanticoagulants, anticoagulants reduced the risk of all-cause death (RR 0.66, 95% CI 0.54-0.79), but had comparable risks of ischemic stroke/transient ischemic attack (TIA, RR 0.91, 95% CI 0.46-1.79) and bleeding (RR 1.17, 95% CI 0.86-1.60). In older patients with dialysis, compared with nonanticoagulants, anticoagulants increased the risk of bleeding (RR 1.37, 95% CI 1.09-1.74), but had similar risks of ischemic stroke/TIA (RR 1.18, 95% CI 0.88-1.58) and death (RR 0.87, 95% CI 0.60-1.27). CONCLUSION:Compared with nonanticoagulation, anticoagulation therapy is associated with a reduced risk of death in older AF patients with nondialysis, but an increased risk of bleeding in older patients with dialysis.
Project description:The characteristics of patients undergoing atrial fibrillation (AF) ablation and subsequent outcomes in community practice are not well described.Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF), we investigated the prevalence and impact of catheter ablation of AF. Among 9935 patients enrolled, 5.3% had previous AF ablation. Patients with AF ablation were significantly younger, more frequently male, and had less anemia, chronic obstructive pulmonary disease, and previous myocardial infarction (P<0.05 for all analyses) than those without previous catheter ablation of AF. Ablated patients were more likely to have a family history of AF, obstructive sleep apnea, paroxysmal AF, and moderate-to-severe symptoms (P<0.0001 for all analyses). Patients with previous ablation were more often in sinus rhythm on entry into the registry (52% vs. 32%; P<0.0001). Despite previous ablation, 46% in the ablation group were still on antiarrhythmic therapy. Oral anticoagulation was prescribed in 75% of those with previous ablation versus 76% in those without previous ablation (P=0.5). The adjusted risk of death (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.52 to 1.18; P=0.2) and cardiovascular (CV) hospitalization (HR, 1.06; 95% CI, 0.90 to 1.26; P=0.5) were similar in both groups. Patients with incident AF ablation had higher risk of subsequent CV hospitalization than matched patients without incident ablation (HR, 1.67; 95% CI, 1.24 to 2.26; P=0.0008).In U.S. clinical practice, a minority of patients with AF are managed with catheter ablation. Subsequent to ablation, there were no significant differences in oral anticoagulation use or outcomes, including stroke/non-central nervous system embolism/transient ischemic attack or death.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01165710.
Project description:Physical activity is of benefit for primary prevention of cardiovascular diseases, but it appears to increase the risk for atrial fibrillation. We aimed to study a cohort of patients following a first stroke in individuals with previous high physical activity, compare them to the general population with respect to recurrent stroke and death, and relate these to atrial fibrillation.From the participants of the Vasaloppet, the world's largest ski-race, and matched individuals from the general population (n=708,604), we identified 5964 patients hospitalized with a first-time stroke between 1994 and 2010. Individuals with severe diseases were excluded. One half percent of skiers and 1% of nonskiers were hospitalized due to stroke. The incidence rate was 8.3 per 100 person-years among skiers and 11.1 among nonskiers. The hazard ratio (HR) for recurrent stroke or death between the 2 groups was 0.76 (95% CI 0.67 to 0.86). The result was consistent in subgroups. The HR for death was 0.66 (95% CI 0.56 to 0.78) and for recurrent stroke 0.82 (95% CI 0.70 to 0.96). After adjustment for smoking and socioeconomic factors, the HR for death was consistent at 0.70 (95% CI 0.56 to 0.87) while the HR for recurrent stroke was not statistically significant. Outcomes for skiers with atrial fibrillation tended to show a lower risk than for nonskiers.This large cohort study supports the hypothesis that patients with a stroke and with prior regular physical activity have a lower risk of death, while their risk for recurrent stroke is similar to that of nonskiers. The skiers had a higher incidence of atrial fibrillation, but still no increased risk of recurring stroke.
Project description:Antiarrhythmic drugs (AADs) and anticoagulation are mainstays of atrial fibrillation (AF) treatment.To study the use and outcomes of AAD therapy in anticoagulated patients with AF.Patients in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation trial (N = 14,264) were stratified by AAD use at baseline: amiodarone, other AAD, or no AAD. Multivariable adjustment was performed to compare stroke, bleeding, and death across AAD groups as well as across treatment assignment (rivaroxaban or warfarin).Of 14,264 patients randomized, 1681 (11.8%) were treated with an AAD (1144 [8%] with amiodarone and 537 [3.8%] with other AADs). Amiodarone-treated patients were less often female (38% vs 48%), had more persistent AF (64% vs 40%), and more concomitant heart failure (71% vs 41%) than were patients receiving other AADs. Patients receiving no AAD more closely resembled amiodarone-treated patients. Time in therapeutic range was significantly lower in warfarin-treated patients receiving amiodarone than in those receiving no AAD (50% vs 58%; P < .0001). Compared with no AAD, neither amiodarone (adjusted hazard ratio [HR] 0.98; 95% confidence interval [CI] 0.74-1.31; P = .9) nor other AADs (adjusted HR 0.66; 95% CI 0.37-1.17; P = .15) were associated with increased mortality. Similar results were observed for embolic and bleeding outcomes. Treatment effects of rivaroxaban vs warfarin in patients receiving no AAD were consistent with results from the overall trial (primary end point: adjusted HR 0.82; 95% CI 0.68-0.98; Pinteraction = .06; safety end point: adjusted HR 1.12; 95% CI 0.90-1.24; Pinteraction = .33).Treatment with AADs was not associated with increased morbidity or mortality in anticoagulated patients with AF. The effect of amiodarone on outcomes in patients receiving rivaroxaban requires further investigation.
Project description:OBJECTIVE:To compare effectiveness and safety of warfarin and the direct oral anticoagulants (DOAC) dabigatran, rivaroxaban and apixaban in non-valvular atrial fibrillation in routine care. METHODS:From nationwide registries, we identified treatment-naïve patients initiating warfarin, dabigatran, rivaroxaban or apixaban for non-valvular atrial fibrillation from July 2013 to December 2015 in Norway. We assessed prescription duration using reverse waiting time distribution. Adjusting for confounding in a Cox proportional hazards model, we estimated one-year risks for ischemic stroke, transient ischemic attack (TIA) or systemic embolism, major or clinically relevant non-major bleeding; intracranial; gastrointestinal; and other bleeding. We censored at switch of treatment or 365 days of follow-up. RESULTS:We included 30,820 treatment-naïve patients. Compared to warfarin, the adjusted hazard ratios (HR) for ischemic stroke, TIA or systemic embolism were 0.96 (95% CI 0.71-1.28) for dabigatran, 1.12 (95% CI 0.87-1.45) for rivaroxaban and 0.97 (95% CI 0.75-1.26) for apixaban. Corresponding hazard ratios for major or clinically relevant non-major bleeding were 0.73 (95% CI 0.62-0.86) for dabigatran, 0.97 (95% CI 0.84-1.12) for rivaroxaban and 0.71 (95% CI 0.62-0.82) for apixaban. Statistically significant differences of other safety outcomes compared to warfarin were fewer intracranial bleedings with dabigatran (HR 0.28, 95% CI 0.14-0.56), rivaroxaban (HR 0.40, 95% CI 0.23-0.69) and apixaban (HR 0.56, 95% CI 0.34-0.92); fewer gastrointestinal bleedings with apixaban (HR 0.70, 95% CI 0.52-0.93); and fewer other bleedings with dabigatran (HR 0.67, 95% CI 0.55-0.81) and apixaban (HR 0.70, 95% CI 0.59-0.83). CONCLUSION:After 1 year follow-up in treatment-naïve patients initiating oral anticoagulation for non-valvular atrial fibrillation, all DOACs were similarly effective as warfarin in prevention of ischemic stroke, TIA or systemic embolism. Safety from bleedings was similar or better, including fewer intracranial bleedings with all direct oral anticoagulants, fewer gastrointestinal bleedings with apixaban and fewer other bleedings with dabigatran and apixaban.
Project description:Patients with liver cirrhosis have been excluded from randomized clinical trials of oral anticoagulation therapy for stroke prevention in atrial fibrillation. We hypothesized that patients with liver cirrhosis would have a positive net clinical benefit for oral anticoagulation when used for stroke prevention in atrial fibrillation.This study used the National Health Insurance Research Database in Taiwan. Among 289 559 atrial fibrillation patients aged ?20 years, there were 10 336 with liver cirrhosis, and 9056 of them having a CHA2DS2-VASc score ?2 were divided into 3 groups, that is, no treatment, antiplatelet therapy, and warfarin. Patients with liver cirrhosis had a higher risk of ischemic stroke (hazard ratio=1.10, P=0.046) and intracranial hemorrhage (hazard ratio=1.20, P=0.043) compared with those without. Among patients with liver cirrhosis, patients taking antiplatelet therapy had a similar risk of ischemic stroke (hazard ratio=1.02, 95%CI=0.88-1.18) compared to those without antithrombotic therapies, but the risk was significantly lowered among warfarin users (hazard ratio=0.76, 95%CI=0.58-0.99). For intracranial hemorrhage, there were no significant differences between those untreated and those taking antiplatelet therapy or warfarin. The use of warfarin was associated with a positive net clinical benefit compared with being untreated or receiving only antiplatelet therapy.For atrial fibrillation patients with liver cirrhosis in the current analysis of an observational study, warfarin use was associated with a lower risk of ischemic stroke and a positive net clinical benefit compared with nontreatment, and thus, thromboprophylaxis should be considered for such patients.