Anja Katholing

Therapy persistence in newly diagnosed non-valvular atrial fibrillation treated with warfarin or NOAC. A cohort study.

Efforts to reduce stroke in atrial fibrillation (AF) have focused on increasing physician adherence to oral anticoagulant (OAC) guidelines, but high early vitamin K antagonist (VKA) discontinuation is a limitation. We compared persistence of non-VKA OAC (NOAC) with VKA treatment in the first year after OAC inception for incident AF in real-world practice. We studied 27,514 anticoagulant-naïve patients with incident non-valvular AF between January 2011 and May 2014 in the UK primary care Clinical Practice Research Datalink, with full medication use linkage: mean age 74.2 ± 12.4, 45.7% female, mean follow-up 1.9 ± 1.1 years. After treatment initiation and follow-up until 1/2015, the proportion remaining on OAC at one year (persistence) was estimated using competing risk survival analyses. OAC was commenced ≤ 90 days after incident AF in 13,221 patients (48.1%): 12,307 VKA and 914 NOAC (apixaban, dabigatran, rivaroxaban). Amongst those treated with OAC, the proportion commencing NOAC increased from zero in 1/2011 to 27.0% in 5/2014, and OAC prescriptions for CHA2DS2VASc score ≥ 2 (guideline adherence) increased from 41.2% to 65.5%. Persistence with OAC declined over 12 months to 63.6% for VKA and 79.2% for NOAC (p< 0.0001). Persistence for those with CHA2DS2VASc ≥ 2 was significantly greater for NOAC (83.0%) than VKA (65.3%, p< 0.0001) at one year and all earlier time points. Comparison of VKA and NOAC cohorts matched on individual CHA2DS2VASc components showed consistent results. In conclusion, persistence was significantly higher with NOAC than VKA, and could alone lead to fewer cardioembolic strokes. Increased guideline adherence following NOAC introduction could further decrease AF stroke burden.

Adverse prognosis of incidentally detected ambulatory atrial fibrillation

It was the aim of this study to determine prognosis of incidentally detected ambulatory atrial fibrillation (IA-AF) and its response to antithrombotic therapy. We performed a cohort study of 5,555 patients with IA-AF (mean age 70.9 ± 10.1, 38.4% female) and 24,705 age- and gender-matched controls without AF followed three years using UK Clinical Practice Research Datalink. We measured incidence rates of stroke, all-cause mortality, myocardial infarction, major bleeding, and effect of antithrombotic therapy. Patients with IA-AF had mean CHA2DS2VASc score 2.5 ± 1.5, 73% with score ≥2. The stroke incidence rate (IR) was 19.4 (95% confidence interval 17.1 - 21.9)/1,000 person-years vs 8.4 (7.7 - 9.1) in controls (p<0.001), mortality 40.1 (36.8 - 43.6)/1,000 person-years vs 20.9 (19.8 - 22.0) in controls (p<0.001), and myocardial infarction 9.0 (7.5 - 10.8)/1,000 person-years vs 6.5 (5.9 - 7.2) in controls (p<0.001). IRs of all endpoints increased with age. Oral anticoagulant ± antiplatelet therapy received by 51.0% in year following IA-AF was associated with adjusted hazard ratio (HR) of 0.35 (0.17 - 0.71) for stroke, and 0.56 (0.36 - 0.85) for death compared to no therapy, while antiplatelet treatment was associated with a non-significant reduction of HR: 0.81 (0.51 - 1.29) for stroke, and 0.80 (0.55 - 1.15) for death, though both carried a similar small non-significant adjusted excess IR of major bleeding. In conclusion, asymptomatic AF detected incidentally is associated with a significant adverse effect on stroke and death, with reduction in both associated with oral anticoagulant but not antiplatelet treatment. This provides justification to assess cost-effectiveness of community screening to detect unknown AF.

Testosterone treatment and risk of venous thromboembolism: population based case-control study

Objective To determine the risk of venous thromboembolism associated with use of testosterone treatment in men, focusing particularly on the timing of the risk. Design Population based case-control study Setting 370 general practices in UK primary care with linked hospital discharge diagnoses and in-hospital procedures and information on all cause mortality. Participants 19 215 patients with confirmed venous thromboembolism (comprising deep venous thrombosis and pulmonary embolism) and 909 530 age matched controls from source population including more than 2.22 million men between January 2001 and May 2013. Exposure of interest Three mutually exclusive testosterone exposure groups were identified: current treatment, recent (but not current) treatment, and no treatment in the previous two years. Current treatment was subdivided into duration of more or less than six months. Main outcome measure Rate ratios of venous thromboembolism in association with current testosterone treatment compared with no treatment were estimated using conditional logistic regression and adjusted for comorbidities and all matching factors. Results The adjusted rate ratio of venous thromboembolism was 1.25 (95% confidence interval 0.94 to 1.66) for current versus no testosterone treatment. In the first six months of testosterone treatment, the rate ratio of venous thromboembolism was 1.63 (1.12 to 2.37), corresponding to 10.0 (1.9 to 21.6) additional venous thromboembolisms above the base rate of 15.8 per 10 000 person years. The rate ratio after more than six months’ treatment was 1.00 (0.68 to 1.47), and after treatment cessation it was 0.68 (0.43 to 1.07). Increased rate ratios within the first six months of treatment were observed in all strata: the rate ratio was 1.52 (0.94 to 2.46) for patients with pathological hypogonadism and 1.88 (1.02 to 3.45) for those without it, and 1.41 (0.82 to 2.41) for those with a known risk factor for venous thromboembolism and 1.91 (1.13 to 3.23) for those without one. Conclusions Starting testosterone treatment was associated with an increased risk of venous thromboembolism, which peaked within six months and declined thereafter.

Increasing incidence of non-valvular atrial fibrillation in the UK from 2001 to 2013

Objective To determine whether the incidence of atrial fibrillation (AF) is static or rising in the UK. Design Among the cohort of all individuals aged ≥45 years in the UK Clinical Practice Research Datalink (CPRD) (linked to hospital discharges) we identified incident non-valvular AF cases between 2001 and 2013. Overall and annual AF incidence rates were calculated and standardised to the UK population. Results The cohort of 2.23 million individuals included 91 707 patients with incident AF. The overall standardised AF incidence rate was 6.7 (95% CI 6.7 to 6.8) per 1000 person-years, increasing exponentially with age and higher in men of all ages. There was a small increase in the standardised incidence of AF in the last decade from 5.9 (5.8 to 6.1)/1000 person-years in 2001 to 6.9 (6.8 to 7.1)/1000 person-years in 2013, mostly attributable to subjects aged >80 years with a non-primary hospital discharge diagnosis of AF. Standardised incidence rates of AF among white patients was 8.1 (8.1 to 8.2)/1000 person-years, compared with 5.4 (4.6 to 6.3) for Asians and 4.6 (4.0 to 5.3) for black patients. AF diagnosis was first made in general practice in 39% of incident AF. Conclusions The incidence of AF in the UK has increased gradually in the last decade, with more than 200 000 first-ever non-valvular AF cases expected in 2015. This increase is only partly due to population ageing, though the principal increase has been in the elderly hospitalised for a reason other than AF.

Residual Risk of Stroke and Death in Anticoagulant-Treated Patients With Atrial Fibrillation

Residual Risk of Stroke and Death in AnticoagulantTreated Patients With Atrial Fibrillation Despite the impressive reduction of risk of stroke and death in patients with atrial fibrillation (AF) conferred by anticoagulation with warfarin or non–vitamin K antagonist oral anticoagulants,1,2 there is still an appreciable stroke risk during anticoagulant treatment, approximating 1.7% per year for warfarin and 1.4% per year for non–vitamin K antagonist oral anticoagulants at 2.2 years’ follow-up.2 This residual stroke rate is often regarded as treatment failure, but, to our knowledge, it has not been compared with a matched control population and could instead reflect the stroke rate in people of a comparable baseline risk without AF.

Risk of recurrent venous thromboembolism after discontinuation of vitamin K antagonist treatment: a nested case-control study.

Essentials Vitamin K antagonists (VKA) in venous thromboembolism (VTE) lower the risk of recurrences. 41 841 VKA‐treated VTE patients had 1242 recurrent VTEs on therapy or early after cessation. An increased risk of recurrence was found in the first 120 days after VKA cessation. Patient education for the early detection of recurrent VTE after VKA cessation is recommended.

ADVERSE PROGNOSIS OF ASYMPTOMATIC ATRIAL FIBRILLATION DETECTED INCIDENTALLY: A CASE FOR SCREENING

Stroke is not uncommonly the first clinical manifestation of atrial fibrillation (AF). Although ACC guidelines do not mention screening, ESC 2012 guidelines now recommend opportunistic screening for AF in patients ≥ 65, but the prognosis of incidentally detected asymptomatic AF that might be

Thirteen-year trend in the persistence with vitamin K antagonists for venous thromboembolism in the UK: a cohort study

Abstract Background: Venous thromboembolism (VTE) comprises deep vein thrombosis (DVT) and pulmonary embolism (PE) and is associated with significant recurrence and mortality risk. Standard VTE treatment includes at least 3 months anticoagulation. The objective was to describe time trends in the duration of oral anticoagulation in patients initially treated with vitamin K antagonists (VKAs). Methods: A retrospective cohort study was conducted on patients with first VTE and VKA treatment initiation within 30 days, identified from the UK Clinical Practice Research Datalink from 2001 to 2014. VKA users were followed for the duration of oral anticoagulation which included switching to non-VKA oral anticoagulants. The probability of remaining on anticoagulation treatment (persistence) was estimated using Kaplan–Meier survival functions. Results: A total of 16,018 patients with VTE initiated VKA; 48.2% males, mean age 62.1 years, median VKA treatment duration 6.5 months. The 90-day persistence increased from 75.6% in 2001 to 91.2% in 2013 (p < .0001) and the 180-day persistence from 39.3% in 2001 to 61.1% in 2013 (p < .0001). This time trend was also shown for patients with DVT, PE, provoked VTE, unprovoked VTE, provoked DVT, unprovoked DVT, provoked PE and unprovoked PE. There were no major differences in persistence between patients with provoked and unprovoked VTE, but persistence was lower following DVT than PE (p < .0001). Conclusions: The increase in persistence was independent of the presentation of the first VTE (provoked or unprovoked), but higher for first PE. Whether the increasing persistence resulted in decreasing risk of recurrent VTE needs to be confirmed.