Gastrointestinal bleeding and the risk of colorectal cancer in anticoagulated patients with atrial fibrillation.

AIMS: Gastrointestinal bleeding (GI-bleeding) is frequent in patients with atrial fibrillation (AF) treated with oral anticoagulation (OAC) therapy. We sought to investigate to what extent lower GI-bleeding represents the unmasking of an occult colorectal cancer. METHODS AND RESULTS: A total of 125 418 Danish AF patients initiating OAC therapy were identified using Danish administrative registers. Non-parametric estimation and semi-parametric absolute risk regression were used to estimate the absolute risks of colorectal cancer in patients with and without lower GI-bleeding. During a maximum of 3 years of follow-up, we identified 2576 patients with lower GI-bleeding of whom 140 patients were subsequently diagnosed with colorectal cancer within the first year of lower GI-bleeding. In all age groups, we observed high risks of colorectal cancer after lower GI-bleeding. The absolute 1-year risk ranged from 3.7% [95% confidence interval (CI) 2.2-6.2] to 8.1% (95% CI 6.1-10.6) in the age groups ≤65 and 76-80 years of age, respectively. When comparing patients with and without lower GI-bleeding, we found increased risk ratios of colorectal cancer across all age groups with a risk ratio of 24.2 (95% CI 14.5-40.4) and 12.3 (95% CI 7.9-19.0) for the youngest and oldest age group of ≤65 and >85 years, respectively. CONCLUSION: In anticoagulated AF patients, lower GI-bleeding conferred high absolute risks of incident colorectal cancer. Lower GI-bleeding should not be dismissed as a benign consequence of OAC therapy but always examined for a potential underlying malignant cause.

Electrical cardioversion of atrial fibrillation and the risk of brady-arrhythmic events.

BACKGROUND: Electrical cardioversion (ECV) is a common procedure for terminating atrial fibrillation (AF). ECV is associated with brady-arrhythmic events, however, the age-specific risks of clinically significant brady-arrhythmic events are unknown. METHODS: Using Danish nationwide registers, we identified patients with AF at their first non-emergent ECV between 2005 and 2018 and estimated their 30-day risk of brady-arrhythmic events. Moreover, factors associated with increased risks of brady-arrhythmias were identified. Absolute risks were estimated using logistic regression models fitted with natural splines as well as standardization (G-formula). RESULTS: We identified 20,725 eligible patients with a median age of 66 years (IQR 60-72) and most males (73%). The 30-day risks of brady-arrhythmic events after ECV were highly dependent on age with estimated risks ranging from 0.5% (95% CI 0.2-1.7) and 1.2% (95% CI 0.99-1.5) to 2.7% (95% CI 2.1-3.3) and 5.1% (95% CI 2.6-9.7) in patients aged 40, 65, 80, and 90 years, respectively. Factors associated with brady-arrhythmias were generally related to cardiovascular disease (eg, ischemic heart disease, heart failure, valvular AF) or a history of syncope. We found no indications that pre-treatment with anti-arrhythmic drugs conferred increased risks of brady-arrhythmic events (standardized absolute risk difference -0.25% [95% CI -0.67 to 0.17]). CONCLUSIONS: ECV conferred clinically relevant 30-day risks of brady-arrhythmic events, especially in older patients. Anti-arrhythmic drug treatment was not found to increase the risk of brady-arrhythmias. Given the widespread use of ECV, these data should provide insights regarding the potential risks of brady-arrhythmic events.

Temporal trends in atrial fibrillation recurrence rates after ablation between 2005 and 2014: a nationwide Danish cohort study.

Aims: During the last decade, ablation has increasingly been used in rhythm control management of patients with atrial fibrillation (AF). Over time, experience and techniques have improved and indications for ablation have expanded. The purpose of this study was to investigate whether the recurrence rate of AF following ablation has improved during last decade. Methods and results: Through Danish nationwide registers, all patients with first-time AF ablation, between 2005 and 2014 in Denmark were identified. Recurrent AF after ablation was identified with 1 year follow-up. A total of 5425 patients undergoing first-time ablation were included. While patient median age increased over time the median AF duration prior to ablation decreased. The rates of recurrent AF decreased from 45% in 2005-2006 to 31% 2013-2014 with the relative risk of recurrent AF almost halved with an odds ratio of 0.57 [95% confidence intervals (95% CI) 0.47-0.68] in 2013-2014 compared with patients undergoing ablation in 2005-2006. Female gender, hypertension, AF duration >2 years, and cardioversion within 1 year prior to ablation were all associated with an increased risk of recurrent AF. Conclusion: One year risk of recurrent AF following first-time ablation has almost halved from 2006 to 2014. Hypertension, female sex, cardioversion 1 year prior to ablation, and AF duration for more than 2 years all increased the associated risk of recurrent AF.

YKL-40 in patients with end-stage renal disease receiving haemodialysis.

PURPOSE: This study aimed to determine serum YKL-40 in patients with end-stage renal disease (ESRD) on haemodialysis (HD) and to evaluate the prognostic value of serum YKL-40. METHODS: Patients >18 years on maintenance HD were included. Serum YKL-40 was measured using ELISA before and after a single HD treatment. RESULTS: A total of 306 patients were included. Median serum YKL-40 concentration was 238 µgL-1 (IQR: 193-291 µgL-1) before HD treatment and 198 µgL-1 (IQR: 147-258 µgL-1) after HD treatment, which corresponded to age-corrected 93th percentile in healthy subjects. All-cause mortality after 2.8 years was 35.9%. Patients with serum YKL-40 in the highest quartile compared with the lowest quartile had a univariate HR of 4.0 (95% CI: 2.2-7.3, p < 0.001) for all-cause mortality which decreased to 2.4 (95% CI: 1.1-4.5, p = 0.01) in multivariate analysis. Time-dependent receiver operating characteristic curves showed that serum YKL-40 after HD treatment had significant higher area under the curves from 90 d (p = 0.004) and throughout the rest of the follow-up period when compared to serum YKL-40 before HD treatment. CONCLUSION: YKL-40 was highly elevated in patients with ESRD on HD, and dialysis reduced serum YKL-40 concentrations approximately one-sixth. YKL-40 measured after dialysis was independently associated with mortality in HD patients.

Two decades of SVT ablation in Denmark: a trend towards higher age, more comorbidity, and less prior use of antiarrhythmic and rate-limiting pharmacotherapy-a nationwide registry-based Danish study.

BACKGROUND AND AIMS: Trends in patient selection and use of pharmacotherapy prior to catheter ablation (CA) for supraventricular tachycardia (SVT) are not well described. This study examined temporal trends in patients undergoing first-time CA for regular SVT, including atrioventricular nodal re-entry tachycardia (AVNRT), accessory pathways (APs), and ectopic atrial tachycardia (EAT) on a nationwide scale in Denmark in the period 2001-2018. METHODS AND RESULTS: Using Danish Nationwide registers, 9959 patients treated with first-time CA for SVT between 2001 and 2018 were identified, of which 6023 (61%) received CA for AVNRT, 2829 (28%) for AP, and 1107 (11%) for EAT. Median age was 55, 42, and 55 in the AVNRT, APs, and EAT group, respectively. The number of patients receiving CA increased from 1195 between 2001 and 2003 to 1914 between 2016 and 2018. The percentage of patients with a CHA2DS2-VASc score ≥ 2 increased in all patient groups. The number of patients who underwent CA with no prior use of antiarrhythmic- or rate limiting medicine increased significantly, though prior use of beta-blockers increased for AVNRT patients. Use of verapamil decreased in all three SVT groups (P < 0.05). Use of amiodarone and class 1C antiarrhythmics remained low, with the highest usage among EAT patients. CONCLUSION: Between 2001 and 2018, CA was increasingly performed in patients with SVT, primarily AVNRT- and EAT patients. The burden of comorbidities increased. Patients undergoing CA without prior antiarrhythmic- or rate-limiting drug therapy increased significantly. Use of beta-blockers increased and remained the most widely used drug.

Treatment patterns for oral anticoagulants in older patients with atrial fibrillation: a retrospective, cross-sectional, nationwide study from Denmark.

OBJECTIVES: Atrial fibrillation (AF) is a predominant risk factor of ischaemic stroke and treatment with oral anticoagulants (OACs) is recommended in all patients with risk factors. This study sought to examine treatment patterns of OACs in older patients with AF. DESIGN: Retrospective, cross-sectional study. SETTING: Danish nationwide administrative and clinical registers and databases. PARTICIPANTS: A total of 40 027 patients, >75 years of age, after their first hospital contact due to AF between 2010 and 2018. PRIMARY AND SECONDARY OUTCOMES MEASURES: The primary event of interest was claimed prescriptions for OACs within 180 days after first hospital contact due to AF. Proportions of patients treated with OACs were estimated and clinical factors associated with the probability of receiving OAC treatment were identified using adjusted logistic regression models. RESULTS: A total of 40 027 patients were included with a slight majority of women (54%). The median age was 81 years (IQR 78-86). We found that an overall 32 235 patients (81%) were prescribed an OAC after their first hospital contact due to AF with a marked increase in the proportion of patients treated from 2010 to 2018. Factors related to a decreased probability of receiving treatment were bleeding risk factors such as a history of haemorrhagic stroke (OR 0.21, 95% CI 0.16 to 0.27), any bleeding (OR 0.58, 95% CI 0.53 to 0.62) as well as markers of frailty such as osteoporosis (OR 0.78, 95% CI 0.71 to 0.85). CONCLUSION: In this large nationwide study, we found that in older patients with AF, the overall rates of OAC prescription were generally high (~80%) and increasing during the last decade. Factors associated with not receiving guideline recommended OAC treatment were generally related to bleeding risk factors or frailty.

Treatment of older patients with atrial fibrillation by morbidity burden.

AIMS: Older patients with atrial fibrillation (AF) are at risk of adverse outcomes, which is accentuated by comorbidities. We sought to examine the association between morbidity burden and the treatment of older AF patients. METHODS AND RESULTS: Using Danish nationwide registers we included patients ≥70 years of age between 2010 and 2017 at their first hospitalization due to AF. Using multiple logistic regression models we examined the association between morbidity burden and the odds of receiving oral anticoagulants (OACs), anti-arrhythmic drugs (AADs), and rhythm-control procedures (direct current cardioversions and catheter ablations). A total of 48 995 patients were included with a majority of women (54%), with a median age of 80 years [interquartile range (IQR) 75-85], and a median morbidity burden of 2 comorbidities (IQR 1-3). Increasing morbidity burden was associated with decreasing odds of OAC treatment with patients having >5 comorbidities having the lowest odds [odds ratio (OR) 0.38, 95% confidence interval (CI) 0.35-0.42] compared to patients with low morbidity burden (0-1 comorbidities). Having >5 comorbidities were associated with increased odds of AAD treatment (OR 1.90, 95% CI 1.64-2.21) and decreased odds of AF procedures (OR 0.39, 95% CI 0.31-0.48), compared to patients with a low morbidity burden (0-1 comorbidities). Examining morbidity burden continuously revealed similar results. CONCLUSIONS: In older AF patients, multimorbidity was associated with lower odds of receiving OACs and rhythm-control procedures but increased odds of AADs. This presents a clinical conundrum as multimorbid patients potentially benefit the most from treatment with OACs.

Haematuria and urinary tract cancers in patients with atrial fibrillation treated with oral anticoagulants.

AIMS: Patients with atrial fibrillation (AF) treated with oral anticoagulants (OACs) have an increased risk of bleeding including haematuria. In the general population, gross haematuria is associated with urinary tract cancer. Consequently, we aimed to investigate the potential association between gross haematuria and urinary tract cancer in anticoagulated patients with AF. METHODS AND RESULTS: Using Danish nationwide registers, we included Danish AF patients treated with OACs between 2001 and 2015. Non-parametric estimation and semi-parametric absolute risk regression were used to estimate the absolute risk of urinary tract cancer in patients with and without gross haematuria. We included 125 063 AF patients with a median age of 74 years (interquartile range 65-80) and a majority of males (57%). The absolute risk of gross haematuria 12 months after treatment initiation increased with age ranging from 0.37% [95% confidence interval (CI) 0.31-0.42] to 0.85% (95% CI 0.75-0.96) in the youngest and oldest age groups of ≤70 and >80 years of age, respectively. The 1-year risk of urinary tract cancer after haematuria ranged from 4.2% (95% CI 2.6-6.6) to 6.5% (95% CI 4.6-9.0) for patients in age group >80 and 71-80 years, respectively. Gross haematuria conferred large risk ratios of urinary tract cancer when comparing patients with and without haematuria across all age groups. CONCLUSION: Gross haematuria was associated with clinically relevant risks of urinary tract cancer in anticoagulated patients with AF. These findings underline the importance of meticulously examining anticoagulated patients with haematuria.

[Fatal outcome of coronavirus disease 2019 in a previously healthy 50-year-old man].

In this case report, a 50-year-old man who had no medical history, presented with multiple cardiac arrests following a week with progressing symptoms of pneumonia. After achieving return of spontaneous circulation he presented with respiratory failure with severe hypoxia, septic shock, and multiple organ failure. A chest X-ray showed signs of acute respiratory distress syndrome. Despite aggressive intensive care management, the patient died 7.5 hours after admission. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was later confirmed, and the presumed cause of death was SARS-CoV-2 pneumonia. In conclusion: coronavirus disease 2019 (COVID-19) can lead to a fatal outcome in younger healthy residents, who are not treated timely in case of severe symptoms like dyspnoea.

Risk factors and a 3-month risk score for predicting pacemaker implantation in patients with atrial fibrillations.

Objectives: To identify risk factors and to develop a predictive risk score for pacemaker implantation in patients with atrial fibrillation (AF). Methods: Using Danish nationwide registries, patients with newly diagnosed AF from 2000 to 2014 were identified. Cox proportional-hazards regression computed HRs for risk factors of pacemaker implantation. A logistic regression was used to fit a prediction model for 3-month risk of pacemaker implantation and derived a risk score using 80% of the data and its predictive accuracy estimated using the remaining 20%. Results: Among 155 934 AF patients included, the median age (IQR) was 75 (65-83) and 51.3% were men. During a median follow-up time of 3.4 (1.2-5.0) years, 8348 (5.4%) patients received a pacemaker implantation. Risk factors of pacemaker implantation were (in order of highest risk first) age above 60 years, congenital heart disease, heart failure at age under 60 years, prior syncope, valvular AF, hypertension, ischaemic heart disease, male sex and diabetes mellitus. The derived risk score assigns points ranging from 1 to 14 to each of these risk factors. The 3-month risk of pacemaker implantation increased from 0.4% (95% CI: 0.2 to 0.8) at 1 point to 2.6% (95% CI: 1.9 to 3.6) at 18 points. Area under the receiver operator characteristics curve was 62.9 (95% CI: 60.3 to 65.5). Conclusion: We highlighted risk factors of pacemaker implantation in newly diagnosed AF patients and created a risk score. The clinical utility of the risk score needs further investigation.

Amiodarone treatment in atrial fibrillation and the risk of incident cancers: A nationwide observational study.

BACKGROUND: In observational studies, case reports, and animal studies, amiodarone has been associated with incident cancer. OBJECTIVE: The purpose of this study was to examine whether a dose-response relationship between amiodarone use and the risk of cancer could be ascertained in a large nationwide study cohort. METHODS: Using nationwide registers, we included all Danish patients with atrial fibrillation (AF) treated with amiodarone from 1996 to 2014. Exposure was defined both by categories and as a continuous variable of the cumulative defined daily doses (cDDDs) of amiodarone. The associations between amiodarone cDDD and incident cancer, as well as organ-specific types of cancer (skin, liver, lung), were estimated using multivariable Cox regression models and reported as hazard ratios (HR) with 95% confidence intervals (CI) and using cubic restricted spline plots. RESULTS: We included 18,503 patients with a median follow-up time of 8.1 years (interquartile range [IQR] 4.3-12.4). Median age was 70 years (IQR 63-77). A total of 2974 individuals developed cancer during follow-up. We found no association between increasing amiodarone exposure (cDDD 181-400 and cDDD >400) and the hazard of incident cancer (HR 0.95; 95% CI 0.87-1.04; and HR 1.01; 95% CI 0.92-1.10) with reference to patients with cDDD <181. Similar results were found when investigating specific cancer types (skin, liver, and lung) as well as cDDD as a continuous variable. CONCLUSION: In a large nationwide cohort of AF patients treated with amiodarone, we found no evidence of a dose-response relationship between cumulative dose of amiodarone and incident cancer risk.

Catheter ablation and mortality, stroke and heart failure readmission with atrial fibrillation.

BACKGROUND: Recent randomised clinical trials have suggested prognostic benefits of catheter ablation in highly selected patients with atrial fibrillation (AF) and heart failure (HF). OBJECTIVES: This study sought to identify the treatment effect associated with catheter ablation in a broad population of patients with AF and HF. METHODS: Through nationwide administrative registers in Denmark, we estimated the 2-year average treatment effect (ATE) of catheter ablation for AF on a composite endpoint of HF readmission, stroke and all-cause mortality at 1-year and 5-year landmark analyses. The primary cohort was patients with AF before HF, and the second cohort of patients with HF before AF. RESULTS: A total of 13 756 patients were included with 9904 patients in the primary cohort, and 3852 in the secondary. An ATE (95% CI) reduction of the composite endpoint of 7.0% (4.5% to 9.5%) was observed in the primary cohort and 11.8% (6.0% to 17.6%) in the secondary in the 1-year landmark analysis with a reduction in all-cause mortality of 5.8% (3.7%-7.8%) and 6.3% (0.9%-11.7%), respectively. At the 5-year landmark, catheter ablation was associated with reductions in the composite endpoint and all-cause mortality in the primary (4.7% (2.3% to 7.2%), and 3.6% (1.0% to 6.3%), respectively), but not in the secondary cohort. CONCLUSIONS: Ablation was associated with decreased risk of HF readmission, stroke and all-cause mortality in patients with AF and HF. The effect is most substantial in patients with AF before HF and with catheter ablation after 1 year from the diagnosis of both conditions.

Risk of gastrointestinal bleeding associated with oral anticoagulation and non-steroidal anti-inflammatory drugs in patients with atrial fibrillation: a nationwide study.

AIMS: Non-vitamin K antagonist oral anticoagulants (NOACs) are displacing vitamin K antagonists (VKAs) for stroke prophylaxis in patients with atrial fibrillation (AF). Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) could increase gastrointestinal bleeding (GIB) risks among these patients. The aim of this study was to examine the risk of GIB among Danish AF patients taking oral anticoagulants (OACs) and NSAIDs. METHODS AND RESULTS: Using nationwide administrative registries, we determined concomitant NSAID use among anticoagulant-naïve patients with AF initiating OACs between August 2011 and June 2017. We calculated short-term absolute risks differences and hazard ratios (HRs) for GIB based on multiple adjusted cause-specific Cox regressions with time-dependent NSAID treatment. Among 41 183 patients [median age 70 years (interquartile range 64-78); 55% men], 21% of patients on NOACs and 18% on VKA were co-prescribed NSAIDs. The differences in absolute risk [95% confidence interval (CI)] of GIB within 14 days of commencing concomitant NSAID therapy (vs. no concomitant NSAID therapy) were 0.10% (0.04-0.18%) for NOACs and 0.13% (0.03-0.24%) for VKA. NOACs overall were associated with less GIB than VKA [HR 0.77 (95% CI 0.69-0.85)]. Compared with OACs alone, concomitant NSAIDs doubled the GIB risk associated with NOACs overall [HR 2.01 (95% CI 1.40-2.61)] and with VKA [HR 1.95 (95% CI 1.21-2.69)]. CONCLUSION: Among this nationwide AF population taking OACs, concomitant NSAID therapy increased the short-term absolute risk of GIB. Non-vitamin K antagonist oral anticoagulants alone were associated with lower GIB risks than VKA but concomitant NSAIDs abolished this advantage. The findings align with post hoc analyses from randomized studies. Physicians should exercise appropriate caution when prescribing NSAIDs for patients with AF taking NOACs or VKA.

Thiazolidinediones and Risk of Atrial Fibrillation Among Patients with Diabetes and Coronary Disease.

BACKGROUND: We sought to determine whether insulin-sensitizing therapy (thiazolidinediones or metformin) decreased the risk of developing atrial fibrillation compared with insulin-providing therapy (insulin, sulfonylurea, or a meglitinide). Thiazolidinediones are insulin sensitizers that also decrease the inflammatory response. Because inflammation is a risk factor for atrial fibrillation, we hypothesized that treating diabetes with thiazolidinediones might decrease the risk of developing atrial fibrillation. METHODS: The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial enrolled patients with type 2 diabetes and documented coronary artery disease. All patients were randomized to insulin-sensitizing therapy or insulin-providing therapy. RESULTS: A total of 2319 patients entered the study, with 1160 assigned to the insulin-sensitization strategy and 1159 assigned to the insulin-provision strategy. Over a median follow-up of 4.2 years, 90 patients (3.9%) developed new-onset atrial fibrillation. In the intention-to-treat analysis, the incidence of atrial fibrillation was 8.7 per 1000 person-years in patients assigned to insulin sensitization compared with 9.5 in patients assigned to insulin provision with a hazard ratio (HR) of 0.91 (95% confidence interval [CI], 0.60-1.38, P = .66). In a time-varying exposure analysis, the incidence rate per 1000 person-years was 7.2 while exposed to thiazolidinediones and 9.7 while not exposed to thiazolidinediones with an adjusted HR of 0.80 (95% CI, 0.33-1.94, P = .62). In a subset of patients matched on propensity to receive a thiazolidinediones, the HR was 0.75 (95% CI, 0.43-1.30, P = .30). CONCLUSIONS: We did not find a significant reduction of atrial fibrillation incidence with use of thiazolidinediones.

Combining Oral Anticoagulants With Platelet Inhibitors in Patients With Atrial Fibrillation and Coronary Disease.

BACKGROUND: The optimal treatment strategy when combining antiplatelets with oral anticoagulants in patients with atrial fibrillation (AF) and myocardial infarction (MI) or undergoing percutaneous coronary intervention (PCI) is unknown. OBJECTIVES: The authors investigated the risk of bleeding, ischemic stroke, MI, and all-cause mortality associated with direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) in combination with aspirin, clopidogrel, or both in patients with AF following MI and/or PCI. METHODS: Danish nationwide registries were used to identify patients with AF who were admitted with a MI and/or underwent PCI, between August 2011 and June 2017, treated with OAC in combination with antiplatelet(s). Patients were followed for 12 months or until an outcome, study end, or death. Standardized absolute risks were estimated on the basis of outcome-specific Cox regression models adjusted for potential confounders. Average treatment effects were obtained as standardized absolute risk differences (ARD) in risks at 3 and 12 months using the g-formula. RESULTS: Overall, 3,222 patients were included in the study population, of which 875 (27%) were treated with VKA+single antiplatelet therapy (SAPT), 595 (18%) were treated with DOAC+SAPT, 1,074 (33%) were treated with VKA+dual antiplatelet therapy (DAPT), and 678 (22%) were treated with DOAC+DAPT. At 3 months, there was a significant difference in the absolute risk of MI associated with DOAC+SAPT compared with VKA+SAPT (3-month ARD -1.53% (95% confidence interval: -3.08% to -0.11%), with no significant differences found regarding bleeding, ischemic stroke, and all-cause mortality. Compared with VKA+DAPT, DOAC+DAPT was associated with a significantly reduced risk of bleeding (3-month ARD -1.96%, 95% confidence interval: -3.46% to -0.88%), with no significant difference in the absolute risk of all-cause mortality, stroke, or MI. CONCLUSIONS: In a real-world population of AF patients with MI and/or after PCI, the authors found that DOAC in combination with DAPT was associated with a significantly decreased risk of bleeding and similar thromboembolic protection compared with VKA in combination with DAPT.

Risk of Myocardial Infarction in Anticoagulated Patients With Atrial Fibrillation.

BACKGROUND: Evidence is conflicting as to the efficacy of direct oral anticoagulation (DOAC) and vitamin K antagonist (VKA) for prevention of myocardial infarction (MI). OBJECTIVES: This study aimed to investigate the risk of MI associated with the use of apixaban, dabigatran, rivaroxaban, and VKA in patients with atrial fibrillation. METHODS: Patients with atrial fibrillation were identified using Danish health care registers and stratified by initial oral anticoagulant treatment. Standardized absolute 1-year risks were estimated based on Cox regression for hazard rates of MI hospitalizations and mortality. Reported were absolute risks separately for the oral anticoagulation treatments and standardized to the characteristics of the study population. RESULTS: Of the 31,739 patients included (median age, 74 years; 47% females), the standardized 1-year risk of MI for VKA was 1.6% (95% confidence interval [CI]: 1.3 to 1.8), apixaban was 1.2% (95% CI: 0.9 to 1.4), dabigatran was 1.2% (95% CI: 1.0 to 1.5), and rivaroxaban was 1.1% (95% CI: 0.8 to 1.3). No significant risk differences were observed in the standardized 1-year risks of MI among the DOACs: dabigatran versus apixaban (0.04%; 95% CI: -0.3 to 0.4), rivaroxaban versus apixaban (0.1%; 95% CI: -0.4 to 0.3), and rivaroxaban versus dabigatran (-0.1%; 95% CI: -0.5 to 0.2). The risk differences for DOACs versus VKA were all significant: -0.4% (95% CI: -0.7 to -0.1) for apixaban, -0.4% (95% CI: -0.7 to -0.03) for dabigatran, and -0.5% (95% CI: -0.8 to -0.2) for rivaroxaban. CONCLUSIONS: No significant risk differences of MI were found in the direct comparisons of DOACs, and DOACs were all associated with a significant risk reduction of MI compared with VKA.

Safety and effectiveness of rivaroxaban and apixaban in patients with venous thromboembolism: a nationwide study.

Aims: To investigate the risk of all-cause mortality, recurrent venous thromboembolism (VTE), and hospitalized bleeding in patients with VTE treated with either rivaroxaban or apixaban. Methods and results: Using Danish nationwide registries, patients with VTE treated with rivaroxaban or apixaban in the period from 1 January 2015 to 30 June 2017 were identified. Standardized absolute risks were estimated based on outcome-specific Cox regression models, adjusted for potential confounders. A total of 8187 patients were included in the study, of which 1504 (18%) were treated with apixaban [50% males, median age 70 years; interquartile range (IQR) 56-80] and 6683 (82%) were treated with rivaroxaban (55% males, median age 67 years; IQR 53-76). The 180 days risk of all-cause mortality was 5.08% [95% confidence interval (95% CI) 4.08% to 6.08%)] in the apixaban group and 4.60% (95% CI 4.13% to 5.18%) in the rivaroxaban group [absolute risk difference: -0.48% (95% CI -1.49% to 0.72%)]. The 180 days risk of recurrent VTE was 2.16% (95% CI 1.49% to 2.88%) in the apixaban group and 2.22% (95% CI 1.89% to 2.52%) in the rivaroxaban group [absolute risk difference of 0.06% (95% CI -0.72% to 0.79%)]. The 180 days risk of hospitalized bleeding was 1.73% (95% CI 1.22% to 2.35%) for patients in the apixaban group and 1.89% (95% CI 1.56% to 2.20%) in the rivaroxaban group [absolute risk difference: 0.16% (95% CI -0.59% to 0.81%)]. Conclusion: In a nationwide cohort of 8187 patients with VTE treated with rivaroxaban or apixaban, there were no significant differences in the risks of all-cause mortality, recurrent VTE, or hospitalized bleeding.

Temporal trends in initiation of VKA, rivaroxaban, apixaban and dabigatran for the treatment of venous thromboembolism - A Danish nationwide cohort study.

Danish nationwide registries were used to investigate temporal trends in initiation of rivaroxaban or apixaban or dabigatran versus vitamin K antagonists (VKA) in patients with venous thromboembolism (VTE). Patients treated with one of the NOACs (rivaroxaban, dabigatran, apixaban) or VKA were identified between February 2012 and September 2016. A total of 19,578 patients were included of which 10,844 (55.4%) were treated with VKA and 8,734 (44.6%) were treated with NOACs (rivaroxaban 7,572, apixaban 1,066, and dabigatran 96). Temporal trends showed a decrease in the initiation of VKA (p-value for decreasing trend, p < 0001) and an increase in the initiation of rivaroxaban and apixaban (p-value for increasing trend, p < 0001). By September 2016, 12%, 70%, 16%, and 2% of patients with VTE were initiated on VKA, rivaroxaban, apixaban, and dabigatran. Patients with previous VTE, chronic kidney disease, liver disease, cancer, and thrombophilia were more likely to be initiated on VKA compared with one of the NOACs. In conclusion the initiation of rivaroxaban and apixaban is increasing significantly over time in patients with VTE. Patients with previous VTE, chronic kidney disease, liver disease, cancer, and thrombophilia were more likely to be initiated on VKA compared with rivaroxaban or apixaban.

Thiazolidinediones are associated with a decreased risk of atrial fibrillation compared with other antidiabetic treatment: a nationwide cohort study.

Aim: The aim of this study was to investigate the association between thiazolidinediones (TZDs) vs. other antidiabetic drugs and risk of atrial fibrillation (AF) in diabetic patients. Method and results: Diabetes mellitus (diabetes) increases the risk of AF by approximately 34%. TZD is an insulin sensitizer that also has anti-inflammatory effects, which might decrease the risk of AF compared with other antidiabetic drugs. We used data from the Danish nationwide registries to study 108 624 patients with diabetes and without prior AF who were treated with metformin or sulfonylurea as first-line drugs. The incidence of AF was significantly lower with TZD as the second-line antidiabetic treatment compared with other second-line antidiabetic drugs (P < 0.001). The 10 year cumulative incidence [95% confidence interval (95% CI)] of AF was 6.2% (3.1-9.3%) with TZD vs. 10.2% (9.8-10.6%) with other antidiabetic drugs. The decreased risk of AF remained significant after adjusting for age, sex, and comorbidities with a hazard ratio (95% CI) of 0.76 (0.57-1.00), P = 0.047 associated with TZD treatment compared with other antidiabetic drugs. Conclusion: Use of a TZD to treat diabetes was associated with reduced risk of developing AF compared with other antidiabetic drugs as second-line treatment.

Risk of Ischemic Stroke, Hemorrhagic Stroke, Bleeding, and Death in Patients Switching from Vitamin K Antagonist to Dabigatran after an Ablation.

BACKGROUND: Safety regarding switching from vitamin K antagonist (VKA) to dabigatran therapy in post-ablation patients has never been investigated and safety data for this is urgently needed. The objective of this study was to examine if switch from VKA to dabigatran increased the risk of stroke, bleeding, and death in patients after ablation for atrial fibrillation. METHODS: Through the Danish nationwide registries, patients with non-valvular atrial fibrillation undergoing ablation were identified, in the period between August 22nd 2011 and December 31st 2015. The risk of ischemic stroke, hemorrhagic stroke, bleeding, and death, related to switching from VKA to dabigatran was examined using a multivariable Poisson regression model, where Incidence rate ratios (IRR) were estimated using VKA as reference. RESULTS: In total, 4,236 patients were included in the study cohort. The minority (n = 470, 11%) switched to dabigatran in the follow up period leaving the majority (n = 3,766, 89%) in VKA treatment. The patients in the dabigatran group were older, were more often males, and had higher CHA2DS2-VASc, and HAS-BLED scores. The incident rates of bleeding and death were almost twice as high in the dabigatran group compared with the VKA group. When adjusting for the individual components included in the CHA2DS2-VASc and HAS-BLED scores, the multivariable Poisson analyses yielded a non-significant IRR (95%CI) of 1.64 (0.72-3.75) for bleeding and of 1.41 (0.66-3.00) for death associated with the dabigatran group, compared to the VKA group. A significant increased risk of bleeding was found in the 110mg bid group with an IRR (95%CI) of 4.49(1.40-14.5). CONCLUSION: Shifting from VKA to dabigatran after ablation was associated with twice as high incidence of bleeding compared to the incidence in patients staying in VKA treatment. The only significant increased risk found in the adjusted analyses was for bleeding with 110mg bid dabigatran and not for 150mg bid. Since there was no dose-response for bleeding, the switch from VKA to dabigatran in itself was not a risk factor for bleeding.