Anna Gundlund

Stroke and recurrent haemorrhage associated with antithrombotic treatment after gastrointestinal bleeding in patients with atrial fibrillation: nationwide cohort study.

Study question What are the risks of all cause mortality, thromboembolism, major bleeding, and recurrent gastrointestinal bleeding associated with restarting antithrombotic treatment after gastrointestinal bleeding in patients with atrial fibrillation? Methods This Danish cohort study (1996-2012) included all patients with atrial fibrillation discharged from hospital after gastrointestinal bleeding while receiving antithrombotic treatment. Restarted treatment regimens were single or combined antithrombotic drugs with oral anticoagulation and antiplatelets. Follow-up started 90 days after discharge to avoid confounding from use of previously prescribed drugs on discharge. Risks of all cause mortality, thromboembolism, major bleeding, and recurrent gastrointestinal bleeding were estimated with competing risks models and time dependent multiple Cox regression models. Study answer and limitations 4602 patients (mean age 78 years) were included. Within two years, 39.9% (95% confidence interval 38.4% to 41.3%, n=1745) of the patients had died, 12.0% (11.0% to 13.0%, n=526) had experienced thromboembolism, 17.7% (16.5% to 18.8%, n=788) major bleeding, and 12.1% (11.1% to 13.1%, n=546) recurrent gastrointestinal bleeding. 27.1% (n=924) of patients did not resume antithrombotic treatment. Compared with non-resumption of treatment, a reduced risk of all cause mortality was found in association with restart of oral anticoagulation (hazard ratio 0.39, 95% confidence interval 0.34 to 0.46), an antiplatelet agent (0.76, 0.68 to 0.86), and oral anticoagulation plus an antiplatelet agent (0.41, 0.32 to 0.52), and a reduced risk of thromboembolism was found in association with restart of oral anticoagulation (0.41, 0.31 to 0.54), an antiplatelet agent (0.76, 0.61 to 0.95), and oral anticoagulation plus an antiplatelet agent (0.54, 0.36 to 0.82). Restarting oral anticoagulation alone was the only regimen with an increased risk of major bleeding (1.37, 1.06 to 1.77) compared with non-resumption of treatment; however, the difference in risk of recurrent gastrointestinal bleeding was not significant between patients who restarted an antithrombotic treatment regimen and those who did not resume treatment. What this study adds Among patients with atrial fibrillation who experience gastrointestinal bleeding while receiving antithrombotic treatment; subsequent restart of oral anticoagulation alone was associated with better outcomes for all cause mortality and thromboembolism compared with patients who did not resume treatment. This was despite an increased longitudinal associated risk of bleeding. Funding, competing interests, data sharing This study was supported by a grant from Boehringer-Ingelheim. Competing interests are available in the full paper on bmj.com. The authors have no additional data to share.

Familial clustering and subsequent incidence of atrial fibrillation among first-degree relatives in Denmark

AIMS Atrial fibrillation (AF) is associated with increased morbidity and mortality. Determination and quantification of familial risk may help identify high-risk patients. METHODS AND RESULTS Using Danish nationwide registry data (1978-2012), we identified all first-time AF patients (probands) in Denmark. Relatives to these probands were grouped according to proband-relation: offspring from either maternal or paternal proband, and siblings to proband. Age-specific incidence of AF for these three groups of relatives and for the general Danish population was estimated. Using the general population as reference, we calculated adjusted rate ratios (RRs) of AF in the three groups of relatives. We identified 67 310, 103 822, and 11 800 AF probands who were mothers (median age 74 years, IQR 66-81), fathers (70 years, IQR 62-78), and siblings (46 years, IQR 38-52), respectively. Among those, 133 516, 221 774, and 21 448 offspring from a maternal proband, offspring from a paternal proband, and siblings, respectively, were screened for incident AF. This was recorded in 2536 (1.9%), 2906 (1.3%), and 292 (1.4%) relatives, respectively. Compared with the general Danish population, the adjusted RRs for incident AF were 3.37 [95% confidence interval (CI) 3.21-3.53] for offspring from maternal probands, 2.81 (95% CI 2.69-2.93) for offspring from paternal probands, and 5.20 (95% CI 4.61-5.85) for siblings to sibling probands. Subgroup analyses showed increased RRs with younger aged probands. CONCLUSION Familial AF was associated with an increased RR of AF in first-degree relatives compared with the general Danish population. This suggests that familial AF is a major risk factor for developing AF in relatives.

Family history of atrial fibrillation is associated with earlier-onset and more symptomatic atrial fibrillation: Results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry

BACKGROUND We addressed whether patients with a family history of atrial fibrillation (AF) were diagnosed as having AF earlier in life, were more symptomatic, and had worse outcomes compared with those without a family history of AF. METHODS Using the ORBIT-AF, we compared symptoms and disease characteristics in those with and without a family history of AF. A family history of AF was defined as AF in a first-degree family member and obtained by patient self-reporting. Multivariable Cox proportional hazard analyses were performed to compare the incidence of cardiovascular outcomes, AF progression, all-cause hospitalization, and all-cause death. RESULTS Among 9,999 patients with AF from 176 US outpatient clinics, 1,481 (14.8%) had a family history of AF. Relative to those without, those with a family history of AF developed AF 5 years earlier on average (median age 65 vs 70 years, P < .01), with less comorbidity, and had more severe AF-related symptoms. No differences were found between the 2 groups in the risk of AF progression (adjusted hazard ratio [HR] 0.98, 95% CI 0.85-1.14), stroke, non-central nervous system embolism, or transient ischemic attack (adjusted HR 0.95, 95% CI 0.67-1.34), all-cause hospitalization (adjusted HR 1.03, 95% CI 0.94-1.12), and all-cause death (adjusted HR 1.05, 95% CI 0.86-1.27). CONCLUSIONS Patients with a family history of AF developed AF at a younger age, had less comorbidity, and were more symptomatic. Once AF developed, no significantly increased risks of AF progression and thromboembolism were associated with a family history of AF compared with no family history.

Outcomes Associated With Familial Versus Nonfamilial Atrial Fibrillation: A Matched Nationwide Cohort Study

Background We examined all‐cause mortality and long‐term thromboembolic risk (ischemic stroke, transient ischemic attack, systemic thromboembolism) in patients with and without familial atrial fibrillation (AF). Methods and Results Using Danish nationwide registry data, we identified all patients diagnosed with AF (1995–2012) and divided them into those with familial AF (having a first‐degree family member with a prior AF admission) and those with nonfamilial AF. We paired those with and without familial AF according to age, year of AF diagnosis, and sex in a 1:1 match. Using cumulative incidence and multivariable Cox models, we examined the risk of long‐term outcomes. We identified 8658 AF patients (4329 matched pairs) with and without familial AF. The median age was 50 years (interquartile range 43–54 years), and 21.4% were women. Compared with nonfamilial AF patients, those with familial AF had slightly less comorbid illness but similar overall CHA 2 DS 2‐VASc score (P=0.155). Median follow‐up was 3.4 years (interquartile range 1.5–6.5 years). Patients with familial AF had risk of death and thromboembolism similar to those with nonfamilial AF (adjusted hazard ratio 0.91 [95% CI 0.79–1.04] for death and 0.90 [95% CI 0.71–1.14] for thromboembolism). Conclusions Although family history of AF is associated with increased likelihood for development of AF, once AF developed, long‐term risks of death and thromboembolic complications were similar in familial and nonfamilial AF patients.

Shifting to a non-Vitamin K antagonist oral anticoagulation agent from Vitamin K antagonist in atrial fibrillation

Aims After non-vitamin K antagonist (VKA) oral anticoagulation agents (NOAC) have been approved for thrombo-embolic prophylaxis in non-valvular atrial fibrillation (NVAF), utilization of oral anticoagulants (OAC) in NVAF has changed. Contemporary shifting from a VKA to a NOAC (dabigatran, rivaroxaban, or apixaban) has not been quantified, and could help assess whether these drugs are used according to recommendations. Methods and results Using Danish nationwide registries, we identified all VKA-experienced NVAF patients initiating a NOAC from 22 August 2011 to 31 December 2015 (shifters) and all VKA-experienced NVAF patients who were not switched to NOACs (non-shifters). Baseline characteristics and temporal utilization trends were examined. We included 62 065 patients with NVAF; of these, 19 386 (29.6%) shifted from a VKA to a NOAC (9973 (54.2%) shifted to dabigatran, 4775 (26.0%) to rivaroxaban, and 3638 (19.8%) to apixaban). Shifting was associated with lower age [odds ratio (OR) 0.95, 95% confidence interval (95% CI) 0.94-0.96 per 5 year increments], female gender (OR 1.33, 95% CI 1.28-1.38), and certain co-morbidities: more often stroke, bleeding, heart failure, and alcohol abuse, and less often hypertension, ischaemic heart disease, and diabetes. Shifting was common and initially dominated by shifting from VKA to dabigatran, but at the end of 2015, most shifters were shifted to rivaroxaban (45%) or apixaban (45%) whereas shifting to dabigatran decreased (to 10%). Conclusion In a contemporary setting among VKA-experienced NVAF patients; VKA is still prevalent although about 30% by December 2015 had shifted to a NOAC.

Long-term thromboembolic risk in patients with postoperative atrial fibrillation after coronary artery bypass graft surgery and patients with nonvalvular atrial fibrillation

Importance New-onset postoperative atrial fibrillation (POAF) is a common complication of coronary artery bypass graft (CABG) surgery. However, the long-term risk of thromboembolism in patients who develop POAF after CABG surgery remains unknown. In addition, information on stroke prophylaxis in this setting is lacking. Objective To examine stroke prophylaxis and the long-term risk of thromboembolism in patients with new-onset POAF after first-time isolated CABG surgery compared with patients with nonsurgical, nonvalvular atrial fibrillation (NVAF). Design, Setting, and Participants This cohort study used data from a clinical cardiac surgery database and Danish nationwide registries to identify patients undergoing first-time isolated CABG surgery who developed new-onset POAF from January 1, 2000, through June 30, 2015. These patients were matched by age, sex, CHA2DS2-VASc score, and year of diagnosis to patients with nonsurgical NVAF in a 1 to 4 ratio. Data analysis was completed from February 2017 to January 2018. Main Outcomes and Measures The proportion of patients initiating oral anticoagulation therapy within 30 days and the rates of thromboembolism. Results A total of 2108 patients who developed POAF after CABG surgery were matched with 8432 patients with NVAF. In the full population of 10 540 patients, the median (interquartile range) age was 69.2 (63.7-74.7) years; 8675 patients (82.3%) were men. Oral anticoagulation therapy was initiated within 30 days postdischarge in 175 patients with POAF (8.4%) and 3549 patients with NVAF (42.9%). The risk of thromboembolism was lower in the POAF group than in the NVAF group (18.3 vs 29.7 events per 1000 person-years; adjusted hazard ratio [HR], 0.67; 95% CI, 0.55-0.81; P < .001). Anticoagulation therapy during follow-up was associated with a lower risk of thromboembolic events in both patients with POAF (adjusted HR, 0.55; 95% CI, 0.32-0.95; P = .03) and NVAF (adjusted HR, 0.59; 95% CI, 0.51-0.68; P < .001) compared with patients who did not receive any anticoagulation therapy. Further, the risk of thromboembolism was not significantly higher in patients with POAF compared with those who did not develop POAF after CABG surgery (adjusted HR, 1.11; 95% CI, 0.94-1.32; P < .24). Conclusions and Relevance New-onset POAF in patients who had undergone CABG surgery was associated with a lower long-term thromboembolic risk than that of patients who had NVAF. These data do not support the notion that new-onset POAF should be regarded as equivalent to primary NVAF in terms of long-term thromboembolic risk.

Comparative thromboembolic risk in atrial fibrillation patients with and without a concurrent infection

Background The aim of this study was to compare long‐term thromboembolic risk in infection‐related and non‐infection‐related atrial fibrillation (AF). Methods Using Danish nationwide registries, we identified patients with first‐time AF from 1996–2015 and performed a retrospective cohort study. We did a 1:1 match (upon sex, age, calendar year, and oral anticoagulation (OAC) status at the beginning of follow‐up) of patients with infection‐related (concurrent discharge diagnosis code for infection) and non‐infection‐related AF. Long‐term outcomes were examined using multivariable Cox regression analyses. Results Our study population comprised 48,644 patients equally distributed on infection‐related and non‐infection‐related AF. In both groups, those initiated on OAC therapy were younger than those not initiated on OAC therapy (median age 77 years, interquartile range 69–83 versus median age 79 years, interquartile range 71–86). During the 1st year of follow up, infection‐related AF was associated with an increased risk of thromboembolic events compared with non‐infection‐related AF: adjusted hazard ratio (HR) 1.44 (95% confidence interval (CI) 1.16–1.78) for those initiated on OAC therapy and HR 1.17 (95% CI 1.06–1.28) for those not initiated on OAC therapy. In both groups, OAC therapy was associated with better outcomes than no OAC therapy (HR of thromboembolic events 0.75 (95% CI 0.68–0.83) and HR 0.70 (95% CI 0.63–0.78) for patients with infection‐related and non‐infection‐related AF, respectively). Conclusion Infection was associated with an increased thromboembolic risk in patients with first‐time AF. OAC therapy was associated with a similar risk‐reduction in AF patients with and without a concurrent infection.

Familial clustering of atrial fibrillation and comparative longitudinal outcomes of familial and non-familial atrial fibrillation

Several studies have suggested that family history of atrial fibrillation (AF) is an important risk factor for AF, with several specific genetic regions now implicated through Genome Wide Association Studies. In addition, familial AF is associated with earlier age of onset and affects patients with fewer comorbid conditions than their non-familial counterparts. While those with familial AF have worse symptoms, all-cause mortality and risk of thromboembolic complications are similar among familial and non-familial AF patients.

Familial Clustering of Venous Thromboembolism - A Danish Nationwide Cohort Study.

Background Identification of risk factors for venous thromboembolism (VTE) is of utmost importance to improve current prophylactic regimes and treatment guidelines. The extent to which a family history contributes to the risk of VTE needs further exploration. Objectives To examine the relative rate of VTE in first-degree relatives compared with the general population. Methods By crosslinking Danish nationwide registries we identified patients with VTE between 1978 and 2012, and their familial relations. The first member in a family to acquire VTE was defined as the proband. All first-degree relatives to probands were followed from the VTE date of the proband and until an event (VTE), death, emigration, 100 year birthday or end of study: 31st of December 2012, whichever came first. The relative rate of VTE was estimated by standardized incidence ratios (SIR) using time-dependent Poisson regression models, with the general population as a fixed reference. Results We identified 70,767 children of maternal probands, 66,065 children of paternal probands, and 29,183 siblings to sibling probands. Having a maternal proband or a paternal proband were associated with a significantly increased VTE rate of 2.15 (CI: 2.00–2.30) and 2.06 (CI: 1.92–2.21), respectively. The highest estimate of VTE was observed among siblings (adjusted SIR of 2.60 [CI: 2.38–2.83]). Noteworthy, the rate of VTE increased for all first-degree relatives when the proband was diagnosed with VTE in a young age (≤ 50 years). Conclusion A family history of VTE was associated with a significantly increased rate of VTE among first-degree relatives compared with the general population.