Improved adherence to statin treatment and differences in results between men and women after pictorial risk communication-a sub-study of the VIPVIZA RCT.

BACKGROUND: People with intermediate CVD risk constitute most of the population. Within this group, the proportion of events is lower compared to the high-risk group, but they contribute with the largest absolute number of events. Atherosclerosis is a dynamic process and progression can be slowed or even reversed with medication and lifestyle changes, but adherence to prescribed treatment is crucial. AIM: To investigate the long-term effects of interventions with pictorial risk communication of cardiovascular (CVD) risk on average adherence in a group of statin users. Compare response in adherence over time between men and women after intervention. METHODS: Participants on active statin treatment were followed up to 5 years after being randomly assigned to an intervention program aimed at raising CVD risk awareness among participants and their physicians. Merging prescribed medication databases with VIPVIZA study to study adherence over time. A moving average adherence was used to compare groups. RESULTS: Generally, the average adherence to statins among the 512 participants was high. Men had a higher average adherence over time, while women had a sharper increase in adherence in conjuncture with the intervention program. CONCLUSIONS: Both men and women were receptive to pictorial information regarding CVD risk, but the intervention effect was more pronounced in women. Sex differences are important when considering risk communication strategies. Periodically repeating the intervention was beneficial for maintaining the intervention effect over time. TRIAL REGISTRATION: The VIPVIZA study is registered with ClinicalTrials.gov , May 8, 2013, number NCT01849575.

ABO Blood Groups, RhD Factor and Their Association with Subclinical Atherosclerosis Assessed by Carotid Ultrasonography.

Background: The ABO blood group system has previously been associated with cardiovascular disease (CVD), where non-O blood group individuals have shown an increased risk. Studies assessing early atherosclerotic disease while also including RhD are few. We aimed to determine whether the ABO and RhD blood groups are associated with subclinical atherosclerosis in a healthy population. Methods: We included 3532 participants from the VIPVIZA trial with available carotid ultrasonography results to assess subclinical disease. Information about blood groups was obtained from the SCANDAT-3 database, where 85% of VIPVIZA participants were registered. Results: RhD- individuals aged 40 years showed increased carotid intima-media thickness (B 1.09 CI 95% 1.03; 1.14) compared to RhD+ individuals. For ABO, there were no differences in ultrasonography results when assessing the whole study population. However, 60-year-old individuals with heredity for CVD and a non-O blood group had decreased odds for carotid plaques (OR 0.54 CI 95% 0.33; 0.88). Conclusions: RhD blood group is associated with subclinical atherosclerosis in younger individuals, indicating a role as a mediator in the atherosclerotic process. In addition, a non-O blood group was associated with decreased subclinical atherosclerosis in individuals aged 60 and with heredity (corresponding to the group with the highest atherosclerotic burden).

Thromboembolic events, major bleeding and mortality in essential thrombocythaemia and polycythaemia vera-A matched nationwide population-based study.

Thromboembolic events and bleeding are known complications in essential thrombocythaemia (ET) and polycythaemia vera (PV). Using multiple Swedish health care registers, we assessed the rate of arterial and venous events, major bleeding, all-cause stroke and all-cause mortality in ET and PV compared to matched controls. For each patient with ET (n = 3141) and PV (n = 2604), five matched controls were randomly selected. In total, 327 and 405 arterial or venous events were seen in the group of ET and PV patients respectively. Compared to corresponding controls, the rate of venous thromboembolism, major bleeding and all-cause mortality per 100 treatment years was significantly increased among both ET (0.63, 0.79 and 3.70) and PV patients (0.94, 1.20 and 4.80). The PV patients also displayed a significantly higher rate of arterial events and all-cause stroke compared to controls. When dividing the cohort into age groups, we found a significantly higher rate of arterial and venous events in all age groups of PV patients, and the rate of all-cause mortality was significantly higher in both ET and PV patients in all ages above the age of 50. This study confirms that PV and ET are diseases truly marked by thromboembolic complications and bleeding.

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.

Entrustable professional activities (EPAs) for undergraduate medical education - development and exploration of social validity.

BACKGROUND: The development of entrustable professional activities (EPAs) as a framework for work-based training and assessment in undergraduate medical education has become popular. EPAs are defined as units of a professional activity requiring adequate knowledge, skills, and attitudes, with a recognized output of professional labor, independently executable within a time frame, observable and measurable in its process and outcome, and reflecting one or more competencies. Before a new framework is implemented in a specific context, it is valuable to explore social validity, that is, the acceptability by relevant stakeholders. AIM: The aim of our work was to define Core EPAs for undergraduate medical education and further explore the social validity of the constructs. METHOD AND MATERIAL: In a nationwide collaboration, EPAs were developed using a modified Delphi procedure and validated according to EQual by a group consisting of teachers nominated from each of the seven Swedish medical schools, two student representatives, and an educational developer (n = 16). In the next step, social validity was explored in a nationwide survey. The survey introduced the suggested EPAs. For each EPA, the importance of the EPA was rated, as was the rater's perception of the present graduates' required level of supervision when performing the activity. Free-text comments were also included and analyzed. RESULTS: Ten Core EPAs were defined and validated. The validation scores for EQual ranged from 4.1 to 4.9. The nationwide survey had 473 responders. All activities were rated as "important" by most responders, ranging from 54 to 96%. When asked how independent current graduates were in performing the ten activities, 6 to 35% reported "independent". The three themes of the free text comments were: 'relevant target areas and content'; 'definition of the activities'; and 'clinical practice and learning'. CONCLUSION: Ten Core EPAs were defined and assessed as relevant for Swedish undergraduate medical education. There was a consistent gap between the perceived importance and the certainty that the students could perform these professional activities independently at the time of graduation. These results indicate that the ten EPAs may have a role in undergraduate education by creating clarity for all stakeholders.

Warfarin treatment quality and outcomes in patients with non-valvular atrial fibrillation and CKD G3-G5D.

INTRODUCTION: Warfarin treatment quality is calculated as time in therapeutic range (TTR). TTR ≥ 70 % is considered reducing the risk of adverse events for patients with atrial fibrillation (AF). The association of TTR and adverse events in chronic kidney disease (CKD) is however poorly investigated. The aim is to explore this further. MATERIALS AND METHODS: Swedish cohort study based on national healthcare registers between 2009 and 2018, including Swedish Renal Registry, Swedish Stroke Register and AuriculA - the Swedish national quality register for AF and anticoagulation. Investigating the effect of individual TTR (iTTR) and iTTR ≥ 70 % versus <70 % on the risk of ischemic stroke, major bleeding and death for patients with CKD GFR category 3-5 (G3-G5) including patients on dialysis (G5D) and non-valvular AF (NVAF). RESULTS: Of 2379 included patients 21.9 % had G3, 47.5 % G4, 10.8 % G5 and 19.8 % G5D. TTR in G3 was 75.6 %, G4 72.2 %, G5 67.6 % and G5D 62.0 %. Increase by 10 percentage points iTTR conferred lower risk of major bleeding, ischemic stroke and death for all patients (hazard ratio 0.91 (95 % Confidence interval 0.87-0.94), 0.92 (0.85-0.99) and 0.88 (0.85-0.90)). iTTR≥ 70 % versus <70 % was associated with lower risk of bleeding and death in all patients (0.63 (0.51-0.77) and (0.51 (0.43-0.61)), and a non-significant tendency towards lower stroke risk (0.67 (0.43-1.06)). CONCLUSIONS: Warfarin treatment quality worsens with decreasing GFR. Higher iTTR confers lower risk of bleeding, ischemic stroke and death in patients with NVAF and G3-G5D. iTTR ≥ 70 % was associated with better safety profile. Close monitoring of patients with CKD on warfarin is recommended.

Direct oral anticoagulants versus warfarin in patients with non-valvular atrial fibrillation and CKD G3-G5D.

Background: The use of direct oral anticoagulants (DOAC) in patients with non-valvular atrial fibrillation (NVAF) and advanced chronic kidney disease (CKD) including dialysis is growing. Several studies have shown favorable results of DOAC compared with warfarin regarding bleeding risk but no difference in stroke protection. However, these studies had poor time in therapeutic range (TTR), in the warfarin comparison group. Methods: This was a Swedish national cohort study investigating the risk of ischemic stroke and major bleeding on DOAC compared with warfarin in patients with NVAF, glomerular filtration rate category 3-5D (G3-G5D), kidney transplant recipients excluded, between 2009 and 2018. Data extracted from high-quality national healthcare registries including the Swedish Renal Registry, AuriculA (the Swedish national quality register for AF and anticoagulation) and The Stroke Register. Results: At enrolment, of 2453 patients 59% were treated with warfarin (mean TTR 67%) and 41% with DOAC. Overall, 693 (28.3%) had G3, 1113 (45.4%) G4, 222 (9.1%) G5 and 425 (17.3%) G5D. DOAC compared with warfarin showed lower hazard of major bleeding [hazard ratio 0.71 (95% confidence interval 0.53-0.96)] but no difference in ischemic stroke risk. Mortality was increased during DOAC treatment [1.24 (1.01-1.53)], presumably not a causal association since fewer fatal bleedings occurred on DOAC. Conclusions: DOAC treatment, compared with warfarin, is associated with almost 30% lower risk of bleeding in patients with NVAF and CKD G3-G5D. The stroke risk is comparable between the treatments. This is the first study comparing DOAC and well-managed warfarin (TTR 67%) in advanced CKD. Ongoing and planned randomized controlled trials need to confirm the possible benefit of DOAC.

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 < 0.0001) and in patients with CHA2DS2-VASc ≥ 4 p, (p < 0.0001). Patients on rivaroxaban/apixaban reported more minor bleedings (37% / 28%) compared to dabigatran (13%), (p < 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.

Erythrocytosis, thrombocytosis, and rate of recurrent thromboembolic event-A population based cohort study.

INTRODUCTION: The management to reduce risk of thromboembolic complications in polycythemia vera and essential thrombocythemia are well established, but for other conditions with elevated hemoglobin, hematocrit, or platelets there are no consensus regarding treatment and follow up. AIMS: To assess frequency of elevated blood values in patients with thromboembolic event, how many of these should be investigated further regarding myeloproliferative neoplasm and if the risk of recurrent event is depending on underlying condition. METHODS: Retrospective cohort study of 3931 adult patients in the county of Norrbotten, Sweden, with thromboembolism during 2017 and 2018. RESULTS: Of the 3931 patients, 1195 had either elevated Hb, HCT, or platelets fulfilling the 2016 revised WHO criteria for PV and ET, and out of these 411 should be evaluated regarding underlying myeloproliferative neoplasms. Unexplained thrombocytosis and secondary erythrocytosis were associated with the highest rate of recurrent event as well as the most inferior restricted mean survival time. CONCLUSION: Elevated blood values are common in patients with thromboembolic event and the high risk of recurrent event and inferior restricted mean survival time in patients with unexplained thrombocytosis and secondary erythrocytosis implicates the importance of finding and managing the underlying condition.

Celiac disease and upper secondary school achievement in Sweden A retrospective cohort study.

BACKGROUND: Both undiagnosed celiac disease and some chronic childhood diseases are associated with lower academic achievement. However, there is little knowledge of achievements in those diagnosed with celiac disease. Our aim was to investigate school achievements in upper secondary school among Swedish adolescents with celiac disease. METHODS: We performed a retrospective cohort study using register data. We analyzed choice of upper secondary school program, completion of upper secondary school including achievements of basic eligibility for college/university, and final grade in individuals with celiac disease diagnosed before 15 years of age, born 1991-97. We compared with the Swedish population of the same birth years. Analyses were adjusted for sex, year of birth, living region at 17 years of age, and parental education as well as income. RESULTS: The cohort included 734 074 individuals, whereof 3 257 (62% females) with celiac disease. There was no significant difference in choice of upper secondary school program. No significant difference was found in completion or achieving basic eligibility for college/university in adjusted analyses. The mean final grade in the celiac disease group was 13.34 (standard deviation 4.85) compared to 12.78 (standard deviation 5.01) in the reference population (p < 0.001), out of a maximum of 20. The effect of celiac disease on final grade remained in adjusted analyses (p = 0.012). CONCLUSIONS: We found that diagnosed celiac disease does not negatively affect school achievements in upper secondary school. This finding suggests the diagnosis, treatment and follow-up programs of celiac disease could reverse potential deleterious academic processes.

Time to initiation of lipid-lowering drugs for subclinical atherosclerosis: sub-study of VIPVIZA randomized controlled trial, with single-arm cross-over.

Aims: Visual information about subclinical atherosclerosis was provided to physicians and participants in the VIPVIZA trial, inclusion 2013-16 in northern Sweden, aiming to improve adherence to cardiovascular disease (CVD) prevention guidelines. Pictorial risk information may be more actionable. The aim of this study was to investigate the effect of intervention with pictorial risk information on time to first dispensing of statins. Methods and results: Asymptomatic atherosclerotic disease was screened for by carotid ultrasound examination in 3532 participants enrolled in VIPVIZA, of those 3000 met the criteria for this study. Participants were randomly assigned to receive pictorial risk information consisting of graphical representation of atherosclerosis as compared to a control group without intervention. Time to initiation of statins was assessed during 5 years of follow-up through the National prescribed drug register. After 3 years, both groups were re-examined and received the intervention information. In the intervention group, initiation of statins increased considerably for the first 3 years and a smaller increase was also seen after re-intervention. After the cross-over, the control group showed a sharp increase in initiation of statins, almost reaching the same proportion treated at 5 years. The propensity to initiate statin treatment increased over the study period and there was no difference between men and women. Conclusions: The pictorial information had an effect on time to initiation of statins, both as original and repeated intervention and also in the control group after single-arm cross-over. The current study supports pictorial information as a tool to shorten time to initiation of statins for CVD prevention.The VIPVIZA study is registered with ClinicalTrials.gov, number NCT01849575.

Efficacy and safety of warfarin in patients with non-valvular atrial fibrillation and CKD G3-G5D.

Background: Observational data comparing warfarin with no treatment for patients with non-valvular atrial fibrillation (NVAF) and severely reduced glomerular filtration rate (GFR) are conflicting and randomized controlled trials (RCTs) are lacking. Most studies do not provide information on warfarin treatment quality, making them difficult to compare. Methods: This national cohort study investigates the risk of ischaemic stroke and major bleeding during warfarin treatment compared with no oral anticoagulants in patients with NVAF, GFR category 3-5 (G3-G5) or on dialysis (G5D), with kidney transplant recipients excluded, between 2009 and 2018. Data extracted from high-quality Swedish national healthcare registries, including the Swedish Renal Registry, AuriculA-the Swedish national quality registry for atrial fibrillation and anticoagulation-and the Stroke Registry. Results: At enrolment of 12 106 patients, 21.4% were G3, 43.5% were G4, 11.6% were G5 and 23.6% were G5D. The mean time in the therapeutic range was 70%. Warfarin compared with no treatment showed a lower risk for ischaemic stroke for G3 {hazard ratio [HR] 0.37 [95% confidence interval (CI) 0.18-0.76]}, G4 [0.53 (0.38-0.74)] and G5 [0.49 (0.30-0.79)] and an increased risk of major bleeding in G4 [HR 1.22 (1.02-1.46)], G5 [1.52 (1.15-2.01)] and G5D [1.23 (1.00-1.51)]. All-cause mortality was more than halved on warfarin compared with no treatment in all GFR categories. Conclusions: Warfarin treatment is associated with a lower risk of ischaemic stroke for patients with NVAF and G3, G4 and G5D at the cost of a higher risk of major bleeding for G4-G5D. Existing observational data are conflicting, stressing the need for RCTs on warfarin compared with no treatment in G4-G5D. Awaiting RCTs, it seems reasonable to treat selected patients on dialysis and NVAF with warfarin.

Incidence and risk factors of venous thromboembolism in men and women.

INTRODUCTION: Studies have indicated that men have a higher overall risk of VTE than women. In previous studies, we have noted that risk factors for VTE, such as alcohol consumption and physical activity, can differ between sexes. The aim of the present study was to estimate the incidence of first-ever VTE and the association of traditional cardiovascular risk factors with VTE risk in men and women separately. MATERIALS AND METHODS: Inhabitants of Västerbotten County in northern Sweden, who had participated in a health examination between 1985 and 2014 were included. The mean age at inclusion was 46.3 years (range 26-65 years). All first-ever VTE events experienced by the participants from the health examination to September 5, 2014 were identified and validated. RESULTS: A total of 1110 men and 944 women had an objectively verified first-ever VTE event. The incidence of VTE was 1.54 (95% CI 1.45-1.63) per 1000 years of follow-up for men and 1.22 (95% CI 1.14-1.30) for women. Higher age, weight and body mass index were associated with increased risk of VTE in both sexes. Men with hypertension had a lower risk of VTE, HR 0.75 (95% CI 0.65-0.87) and men with more than secondary school education had a higher risk of VTE. Taller women had an increased risk of VTE. CONCLUSIONS: In the studied age group, we found that men had a higher incidence of first-ever VTE than women. Notably, we also found that hypertension was associated with lower risk of VTE in men but not in women.

Adverse outcomes in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: Follow-up of patients diagnosed 2002-2017 in a complete coverage and nationwide agnostic register study.

Tyrosine kinase inhibitors (TKIs) have profoundly improved the clinical outcome for patients with chronic myeloid leukemia (CML), but their overall survival is still subnormal and the treatment is associated with adverse events. In a large cohort-study, we assessed the morbidity in 1328 Swedish CML chronic phase patients diagnosed 2002-2017 and treated with TKIs, as compared to that in carefully matched control individuals. Several Swedish patient registers with near-complete nationwide coverage were utilized for data acquisition. Median follow-up was 6 (IQR, 3-10) years with a total follow-up of 8510 person-years for the full cohort. Among 670 analyzed disease categories, the patient cohort showed a significantly increased risk in 142 while, strikingly, no category was more common in controls. Increased incidence rate ratios/IRR (95% CI) for more severe events among patients included acute myocardial infarction (AMI) 2.0 (1.5-2.6), heart failure 2.6 (2.2-3.2), pneumonia 2.8 (2.3-3.5), and unspecified sepsis 3.5 (2.6-4.7). When comparing patients on 2nd generation TKIs vs. imatinib in a within-cohort analysis, nilotinib generated elevated IRRs for AMI (2.9; 1.5-5.6) and chronic ischemic heart disease (2.2; 1.2-3.9), dasatinib for pleural effusion (11.6; 7.6-17.7) and infectious complications, for example, acute upper respiratory infections (3.0; 1.4-6.0). Our extensive real-world data reveal significant risk increases of severe morbidity in TKI-treated CML patients, as compared to matched controls, particularly for 2nd generation TKIs. Whether this increased morbidity may also translate into increased mortality, thus preventing CML patients to achieve a normalized overall survival, needs to be further explored.

Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population.

BACKGROUND: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population. METHODS: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data. RESULTS: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population. CONCLUSIONS: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.

Prophylactic anticoagulants to prevent venous thromboembolism in patients with nephrotic syndrome-A retrospective observational study.

BACKGROUND: Nephrotic syndrome (NS) is associated with increased risk of venous thromboembolism (VTE). Guidelines suggest prophylactic anticoagulants to patients with high risk of thrombosis and low risk of bleeding, but the evidence behind this is poor. This study aims to investigate the effectiveness and risks of prophylactic anticoagulants (PAC) and investigate risk factors for VTE and bleeding in NS. METHODS: A retrospective medical records study including adults with NS, biopsy proven glomerular disease in the county of Västernorrland, Sweden. Outcomes were VTE, bleeding and death. Patients divided into PAC- and no PAC group were compared using Fisher's exact test. Patient time was divided into serum/plasma(S/P)-albumin intervals (<20g/L and ≥20g/L) and VTE- and bleeding rates were calculated. RESULTS: In 95 included NS patients (PAC = 40, no PAC = 55), 7 VTE (7.4%) and 17 bleedings (18%) were found. Outcomes didn't differ significantly between the PAC and no PAC group. Time with S/P-albumin <20g/L conferred higher rates/100 years of VTE (IRR 21.7 (95%CI 4.5-116.5)) and bleeding (IRR 5.0 (1.4-14.7)), compared to time with S/P-albumin>20g/L. CONCLUSION: Duration of severe hypoalbuminemia (S/P-albumin <20g/L) in NS is a risk factor for both VTE and bleeding. There is a need for randomized controlled studies regarding the benefit of PAC in NS as well as risk factors of thrombosis and bleeding in NS.

Successful tyrosine kinase inhibitor discontinuation outside clinical trials - data from the population-based Swedish chronic myeloid leukaemia registry.

Clinical trials show that tyrosine kinase inhibitor (TKI) treatment can be discontinued in selected patients with chronic myeloid leukaemia (CML). Although updated CML guidelines support such procedure in clinical routine, data on TKI stopping outside clinical trials are limited. In this retrospective study utilising the Swedish CML registry, we examined TKI discontinuation in a population-based setting. Out of 584 patients diagnosed with chronic-phase CML (CML-CP) in 2007-2012, 548 had evaluable information on TKI discontinuation. With a median follow-up of nine years from diagnosis, 128 (23%) discontinued TKI therapy (≥1 month) due to achieving a DMR (deep molecular response) and 107 (20%) due to other causes (adverse events, allogeneic stem cell transplant, pregnancy, etc). Among those stopping in DMR, 49% re-initiated TKI treatment (median time to restart 4·8 months). In all, 38 patients stopped TKI within a clinical study and 90 outside a study. After 24 months 41·1% of patients discontinuing outside a study had re-initiated TKI treatment. TKI treatment duration pre-stop was longer and proportion treated with second-generation TKI slightly higher outside studies, conceivably affecting the clinical outcome. In summary we show that TKI discontinuation in CML in clinical practice is common and feasible and may be just as successful as when performed within a clinical trial.

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.