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 studySetting 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.

SummaryIt 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 ageand 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 CHA 2 DS 2 VASc 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 personyears 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.

SummaryEfforts 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.Supplementary Material to this article is available online at www.thrombosis-online.com.

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associated with family history leads to greater adherence to treatment and improved outcomes. Disclosure of CHD risk that includes discussion of family history influences shared decision making regarding statin therapy in individuals at intermediate risk for CHD.