Prevalence of atrial fibrillation and reasons for undertreatment with oral anticoagulants

Objectives: To investigate the prevalence of atrial fibrillation (AF), the proportion of AF patients not receiving oral anticoagulation (OAC) and reasons for abstaining from OAC treatment. Methods: A retrospective cross-sectional study of patients aged 18 years or older with an AF diagnosis on June 1st 2020 in Västernorrland County, Sweden. AF diagnosis was retrieved using the ICD10 code I.48, and medical records were reviewed for comorbidities and documented reasons to abstain OAC treatment. Results: Of 197 274 residents in Västernorrland County, 4.7% (9 304/197 274) had a documented AF diagnosis. Of these, 19% (1 768/9 304) had no OAC treatment, including 4.2% (393/9 304) with no indication, 2.5% (233/9 304) with a questionable and 2.5% (231/9 304) with a documented clear contraindication for OAC. In total 9.8% (911/9 304) were not treated with OAC despite indication and no reasonable documented contraindication, thus 90.8% (8 447/9 304) of all AF-patients were eligible for OAC treatment. Common reasons for abstaining treatment without reasonable contraindication were present sinus rhythm in 13.7% (125/911), perceived not an OAC candidate in 10.6% (97/911) and anemia in the past in 4.3% (39/911). Conclusions: In the population of Västernorrland County, a very high AF prevalence of 4.7% was found, of which just over 90% would theoretically benefit from OAC treatment. This is higher than previously reported and stresses the importance of stroke prevention in this large patient group

Dabigatran, rivaroxaban and apixaban vs. high TTR warfarin in atrial fibrillation

Introduction: New oral anticoagulants are non-inferior compared with warfarin regarding stroke prevention in atrial fibrillation, with similar or decreased risk of bleeding. However, it is unclear whether high TTR warfarin is as effective and safe as NOACs. Our objective was to investigate efficacy and safety of apixaban, dabigatran or rivaroxaban compared with warfarin in clinical practice. Materials and methods: Nationwide retrospective cohort study based on Swedish quality registries. Atrial fibrillation patients initiated on apixaban, dabigatran, rivaroxaban or warfarin between 2013-01-01 and 2015-12-31 were included. Main outcome measures were all-cause stroke and systemic embolism, all-cause stroke, ischemic stroke, hemorrhagic stroke; major bleeding, intracranial bleeding, gastrointestinal bleeding, other bleeding (fatal or requiring hospital care); all-cause mortality; myocardial infarction. Results: The study included 64,382 patients corresponding to 81,176 treatment years. Of these, 37,174 patients were instituted on warfarin, 6574 on dabigatran, 8323 on rivaroxaban and 12,311 on apixaban. In warfarin treated patients, the time in therapeutic range was 71.4%. After propensity score matching, there was no significant difference in risk of stroke or systemic embolism between NOAC and warfarin treated patients. Hazard ratios for major bleeding events were 0.63(95%CI 0.52–0.75) for apixaban, 0.74(0.62–0.87) for dabigatran and 1.06(0.92–1.23) for rivaroxaban, compared with warfarin. Conclusions: This study showed no difference between apixaban, dabigatran, or rivaroxaban compared to high TTR warfarin treatment regarding stroke prevention. However, fewer bleeding events were seen for apixaban and dabigatran, but not for rivaroxaban. Further studies are needed on the comparability of individual NOACs with respect to bleeding risks

Predictors for INR-control in a well-managed warfarin treatment setting

Warfarin is well studied in patients with non-valvular atrial fibrillation (AF). It has low complication rates for patients achieving individual Time in Therapeutic Range (iTTR)>70%. The risk scores SAMe-TT2R2 and PROSPER are designed to predict future TTR, but are derived from a heterogeneous population with generally low iTTR. The aim of this study was to evaluate predictors for high and low iTTR in an AF population in Sweden, where there is a generally good anticoagulation control. A retrospective register study based on Swedish warfarin dosing system AuriculA, including 28,011 AF patients starting treatment during 1 January 2006 to 31 December 2011. Complications and risk factors were analysed and related to iTTR. Mean age was 73.7 (SD +/- 9.5) years, with 42.0% women. Mean CHA(2)DS(2)-VASc score (SD) was 3.6 (+/- 1.7). For patients with iTTR<60% there were over three times higher prevalence of excessive alcohol consumption than for patients with iTTR>70% (3.7% vs. 1.1%). Previous stroke were more prevalent for patients with high than low iTTR (17.1% vs. 20.3%). Concomitant comorbidities were associated with increased risk of poor iTTR. In Swedish AF patients, excessive alcohol use is clearly associated with iTTR below 60%. Patients with previous stroke are more likely to get iTTR above 70%, unlike those with concomitant disorders who more often have poor anticoagulation control. The SAMe-TT2R2-score cannot be applied in Sweden

Bleeding risk in patients with venous thromboembolic events treated with new oral anticoagulants

New oral anticoagulants (NOACs) is the preferred treatment in secondary prophylaxis of venous thromboembolic events (VTE). The aim of this study was to investigate possible risk factors associated with major bleeding in VTE-patients treated with NOACs. In this retrospective register-based study we screened the Swedish anticoagulation register Auricula (during 2012.01.01-2017.12.31) to find patients and used other national registers for outcomes. Primary endpoint was major bleeding defined as bleeding leading to hospital care. Multivariate Cox-regression analysis was used to reveal risk factors. 18 219 patients with NOAC due to VTE were included. 85.6% had their first VTE, mean age was 69.4 years and median follow-up time was 183 days. The most common NOAC was rivaroxaban (54.8%), followed by apixaban (42.0%), dabigatran (3.2%) and edoxaban (0.1%). The rate of major bleeding was 6.62 (95% CI 6.19-7.06) per 100 treatment years in all patients and 11.27 (CI 9.96-12.57) in patients above 80 years of age. Statistically independent risk factors associated with major bleeding were age (normalized HR 1.38, CI 1.27-1.50), earlier major bleeding (HR 1.58, Cl 1.09-2.30), COPD (HR 1.28, CI 1.04-1.60) and previous stroke (HR 1.28, Cl 1.03-1.58) or transient ischemic attack (TIA) (HR 1.33, Cl 1.01-1.76). Prior warfarin treatment was protective (HR 0.67, CI 0.58-0.78). This real world cohort shows a high bleeding rate especially among the elderly and in patients with previous major bleeding, COPD and previous stroke or TIA. This should be considered when deciding on treatment duration and NOAC dose in these patients.First published online: 2 November 2020</p

Direct oral anticoagulants : patient reported adherence and minor bleedings

Data regarding adherence and minor bleeding on direct oral anticoagulants in everyday life are still sparse. Inclusion criteria: treatment initiated with dabigatran, rivaroxaban or apixaban in non-valvular atrial fibrillation patients from a center in northern Sweden between 2011 and 2019 (n = 668). Exclusion criteria: cognitive impairment, dose dispensing, need of interpreter or hospital admission (n = 67). By a telephone interview adherence was measured in 569 patients (response rate 94.8%) using the 8-item Morisky medication adherence scale and minor bleeding was asked for. CHA2DS2-VASc and HAS-BLED scores were collected from medical records. The number (n), mean age, mean treatment duration, mean (points) CHA2DS2-VASc and HAS-BLED scores was with dabigatran (n = 175, 73.3 years, 17.8 months, 3.6 p and 2.2 p), rivaroxaban (n = 198, 73.7 years, 21months, 3.8 p and 2.1 p) and apixaban (n = 196, 72.7 years, 15.2 months, 3.4 p and 2.1 p). Adherence was high for dabigatran, rivaroxaban and apixaban in 54%, 76% and 53%; intermediate in 37%, 20% and 37% or low in 9%, 4% and 10% respectively. High adherence (Morisky score 8) distinguished rivaroxaban (p &lt; 0.0001) and in patients with CHA2DS2-VASc ≥ 4 p, (p &lt; 0.0001). Patients on rivaroxaban/apixaban reported more minor bleedings (37% / 28%) compared to dabigatran (13%), (p &lt; 0.001). Only 61% of the patients followed prescription. Adherence to rivaroxaban was significantly better, maybe due to the once daily dosing regimen, and furthermore among patients with higher risk for stroke. Minor bleedings were less common in the dabigatran group. The impact of minor bleedings on adherence and a possible relationship to clinical outcomes need to be further studied

Venous thromboembolism and cancer risk

Cancer increases the risk of venous thromboembolism (VTE) and about 20 % of all VTE are associated with cancer. VTE can also be used as a marker for occult cancer. The objective was to examine the correlation between VTE and cancer regarding predictors for a subsequent cancer diagnosis. Patients treated for VTE between January 1st 2006 and December 31th 2011 were extracted from the Swedish national quality register AuriculA and crossmatched with the Swedish National Patient Register. In total 7854 patients corresponding to 14284 treatments years were examined. Primary VTE was found in 6451 patients, with 3936 first and 2515 recurrent VTE. There were 1403 patients with secondary VTE. After a first or recurrent primary VTE the incidence of cancer diagnose was high being 9.4-10.0 % the first year compared to 2.7-2.5 % during the second year. Cancer in the digestive organs was the most common type of cancer among those with first primary VTE with 19.2 % of diagnoses. In multivariable analysis age was found to increase the risk of cancer diagnosis after both first and recurrent primary VTE HR 1.02 (CI 1.02-1.03) and HR 1.02 (CI 1.01-1.03). For a first primary VTE anemia HR 2.13 (CI 1.48-3.08) and male sex HR 1.38 (CI 1.09-1.76) increased the risk while hypertension HR 0.74 (0.57-0.96), dementia HR 0.30 (CI 0.10-0.95) and history of major bleeding HR 0.52 (CI 0.28-0.97) reduced the risk of a subsequent cancer diagnosis. There is a substantial proportion of patients being diagnosed with cancer the first year after a primary VTE, anaemia and male sex confers an increased risk

Incidence and risk factors for thromboembolism and major bleeding in patients with mechanical valve prosthesis : A nationwide population-based study

Risk factors of stroke/thromboembolism (TE) and major bleeding, and incidence of these events in specific age categories in warfarin-treated patients with mechanical heart valves (MHV) are uncertain. Our objective was to calculate event rates in specific age categories and identify risk factors for adverse events. Methods and results We identified 4,810 treatment periods with MHV between January 2006 and December 2011 in the Auricula and Swedish Web system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registries. There were 3,751 treatment periods with aortic valve replacements (AVR) and 866 with mitral valve replacements (MVR). Median follow-up time was 4.5 years (IQR, 1.5-6.0). Time in therapeutic range with warfarin for patients with AVR was 74.2% for international normalized ratio of 2.0 to 3.0, with 72% of the patients having this target range. Rate of stroke/TE for AVR and MVR was 1.3 and 1.6 per 100 patient years, respectively (P = .20). The rate of first major bleeding was 2.6 and 3.9 per 100 patient years with AVR and MVR, respectively (P < .001). By multivariate analysis for AVR, age (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.01-1.03 per year) and previous stroke (HR, 2.4; 95% CI, 1.7-3.5) emerged as independent risk factors for stroke/TE. Heart failure (HR, 0.9; 95% CI, 0.6-1.4) and atrial fibrillation (HR, 1.0; 95% CI, 0.7-1.4) were not associated to stroke/TE. For major bleeding events, age (HR, 1.02; 95% CI, 1.01-1.03 per year) and previous major bleeding (HR, 2.5; 95% CI, 1.9-3.3) emerged as independent risk factors for AVR. Conclusions In a nationwide cohort study with MHV and high time in therapeutic range, heart failure and atrial fibrillation did not appear as risk factors of stroke/TE

INR variability and outcomes in patients with mechanical heart valve prosthesis.

The quality of treatment with warfarin is mainly assessed by the time in therapeutic range (TTR) in patients with mechanical heart valve prosthesis (MHV). Our aim was to evaluate if International Normalized Ratio (INR) variability predicted a combined endpoint of thromboembolism, major bleeding and death better than TTR

Reduced dose direct oral anticoagulants compared with warfarin with high time in therapeutic range in nonvalvular atrial fibrillation

Direct oral anticoagulants (DOACs) used in nonvalvular atrial fibrillation (NVAF) are dose-reduced in elderly and patients with impaired renal function. Only reduced dose dabigatran is concluded as having similar stroke risk reduction and lower risk of major bleeding than warfarin in the pivotal studies. In clinical practice, reduced dose is prescribed more often than expected making this an important issue. The objective of this study was to compare effectiveness and safety between reduced dose DOACs and high TTR warfarin treatment (TTR ≥ 70%) in NVAF. A Swedish anticoagulation registry was used in identifying eligible patients from July 2011 to December 2017. The study cohort consisted of 40,564 patients with newly initiated DOAC (apixaban, dabigatran, or rivaroxaban) (11,083 patients) or warfarin treatment (29,481 patients) after exclusion of 374,135 patients due to not being warfarin or DOAC naïve, not being prescribed reduced dose, having previous mechanical heart valve (MHV), or being under 18 years old. The median durations of follow up were 365, 419, 432 and 473 days for apixaban, dabigatran, rivaroxaban and warfarin, respectively. Warfarin TTR identified from Auricula was 70.0%. Endpoints (stroke and major bleeding) and baseline characteristics were collected from hospital administrative registers using ICD-10 codes. Cohorts were compared using weighted adjusted Cox regression after full optimal matching based on propensity scores. DOACs are associated with lower risk of major bleeding (HR with 95% CI) 0.85 (0.78–0.93), intracranial bleeding HR 0.64 (0.51–0.80), hemorrhagic stroke HR 0.68 (0.50–0.92), gastrointestinal bleeding HR 0.81 (0.69–0.96) and all-cause stroke HR 0.87 (0.76–0.99), than warfarin. Apixaban and dabigatran are associated with lower risk of major bleeding, HR 0.70 (0.63–0.78) and HR 0.80 (0.69–0.94), and rivaroxaban is associated with lower risk of ischemic stroke, HR 0.73 (0.59–0.96), with higher major bleeding risk, HR 1.31 (1.15–1.48), compared to warfarin. Apixaban is associated with higher all-cause mortality compared to warfarin, HR 1.12 (1.03–1.21). DOACs are associated with lower risk of major bleeding and all-cause stroke, than high quality warfarin treatment, with exception of rivaroxaban that carried higher risk of major bleeding and lower risk of stroke or systemic embolism. In this large observational registry-based NVAF cohort, DOACs are preferred treatment in patients with indication for DOAC dose reduction, even in a high TTR setting