| 1. |
- Pirmohamed, Munir, et al.
(author)
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A Randomized Trial of Genotype-Guided Dosing of Warfarin
- 2013
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In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 369:24, s. 2294-2303
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Journal article (peer-reviewed)abstract
- Background: The level of anticoagulation in response to a fixed-dose regimen of warfarin is difficult to predict during the initiation of therapy. We prospectively compared the effect of genotype-guided dosing with that of standard dosing on anticoagulation control in patients starting warfarin therapy.Methods: We conducted a multicenter, randomized, controlled trial involving patients with atrial fibrillation or venous thromboembolism. Genotyping for CYP2C9*2, CYP2C9*3, and VKORC1 (-1639GA) was performed with the use of a point-of-care test. For patients assigned to the genotype-guided group, warfarin doses were prescribed according to pharmacogenetic-based algorithms for the first 5 days. Patients in the control (standard dosing) group received a 3-day loading-dose regimen. After the initiation period, the treatment of all patients was managed according to routine clinical practice. The primary outcome measure was the percentage of time in the therapeutic range of 2.0 to 3.0 for the international normalized ratio (INR) during the first 12 weeks after warfarin initiation.Results: A total of 455 patients were recruited, with 227 randomly assigned to the genotype-guided group and 228 assigned to the control group. The mean percentage of time in the therapeutic range was 67.4% in the genotype-guided group as compared with 60.3% in the control group (adjusted difference, 7.0 percentage points; 95% confidence interval, 3.3 to 10.6; P<0.001). There were significantly fewer incidences of excessive anticoagulation (INR 4.0) in the genotype-guided group. The median time to reach a therapeutic INR was 21 days in the genotype-guided group as compared with 29 days in the control group (P<0.001).Conclusions: Pharmacogenetic-based dosing was associated with a higher percentage of time in the therapeutic INR range than was standard dosing during the initiation of warfarin therapy.
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| 2. |
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| 3. |
- Arvidsson, Anna, 1973, et al.
(author)
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Characterisation of structures in salivary secretion film formation. An experimental study with atomic force microscopy
- 2004
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In: Biofouling. - : Informa UK Limited. - 0892-7014 .- 1029-2454. ; 20:3, s. 181-8
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Journal article (peer-reviewed)abstract
- The purpose of the present study was to characterise the structure dynamics of pure salivary secretions retained on controlled surfaces with different surface energies in the early stage of salivary film formation. Germanium prisms prepared to have either low surface energy or medium surface energy were incubated in fresh secretions of either human parotid saliva (HPS) or human submandibular/sublingual saliva (HSMSLS) for 15, 90, and 180 min. After controlled rinsing with distilled water, the surfaces were air dried and thereafter imaged with atomic force microscopy (AFM). The amount of adsorbed material and the size of the structures detected increased with increased saliva exposure time. The film thicknesses varied from 10 to 150 nm, and both HPS and HSMSLS films contained structures with diameters varying from 40 nm to 2 microm. Some of these were clustered into special formations. The HPS films exhibited a more granular morphology than the HSMSLS films. Furthermore, branched lines were detected on the low surface energy germanium prisms incubated in saliva. The results indicate that exposure time, surface energy, and type of salivary secretion all are factors affecting the adsorption characteristics of salivary films.
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| 4. |
- Baron, Tomasz, et al.
(author)
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Changes in global longitudinal strain and left ventricular ejection fraction during the first year after myocardial infarction : results from a large consecutive cohort
- 2018
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In: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 19:10, s. 1165-1173
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Journal article (peer-reviewed)abstract
- Aims: To determine changes of global longitudinal strain (GLS) and their predictors in relation to classical echocardiographic parameters of left ventricular (LV) function, over 1 year, in consecutive patients with myocardial infarction (MI) and initially normal or impaired LV ejection fraction (EF).Methods and results: A total of 285 patients with MI prospectively included in the REBUS (RElevance of Biomarkers for future risk of thromb-oembolic events in UnSelected post-myocardial infarction patients) study underwent echocardiography within 72 h from admission and after 1 year. At baseline, 213 (74.7%) of MI patients had a normal EF (≥52% in men or ≥54% in women), but in 70.4% of them, an impaired GLS ( ≥ -18.0%) was observed. During 1-year follow-up, in patients with normal EF at baseline, GLS improved from -15.8% to - 17.4% (10.1% relative change); EF decreased from 62.5% to 59.9% (4.0% relative change); indexed end-diastolic volume, indexed end-systolic volume, and indexed stroke volume increased with 15.6%, 24.8%, and 10.0% of relative change, respectively (P < 0.001 for all the comparisons). In the whole cohort, initial impairment of LV function [by EF, wall motion score index (WMSI), or GLS], male gender, non-smoking, and treatment with beta-blockers were the independent predictors of GLS improvement. In the group with initially impaired EF, over 1 year GLS improved from -11.9% to - 14.8% (24.4% relative change) and EF from 44.6% to 52.6% (18.2% relative change) (P < 0.001 for both). Improvement in GLS significantly correlated with EF increase in the group with impaired EF (r = -0.41, P = 0.001) but not in the patients with normal EF (r = -0.14, P = ns).Conclusions: Despite diveregent evolution of GLS compared with EF and ventricular volumes, one year after MI GLS significantly improved in patients with initially both normal and impaired EF. Initial impairment of LV function (by EF, WMSI, or GLS), male gender, non-smoking, and treatment with beta-blockers were independent predictors of GLS improvement. LV remodelling was present even in patients with normal EF at baseline and during follow-up, confirming limited functional assessment by EF alone.
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| 5. |
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| 6. |
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| 7. |
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| 8. |
- Baron, Tomasz, et al.
(author)
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Usefulness of traditional echocardiographic parameters in assessment of left ventricular function in patients with normal ejection fraction early after acute myocardial infarction : results from a large consecutive cohort
- 2016
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In: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 17:4, s. 413-420
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Journal article (peer-reviewed)abstract
- AIMS: The aim of this study was to assess the frequency of left ventricular (LV) systolic function impairment using classical echocardiographic parameters and their relation to myocardial damage in patients hospitalized for acute myocardial infarction (MI) with normal LV ejection fraction (LVEF ≥52% in males or ≥54% in females).METHODS AND RESULTS: All 421 consecutive patients with MI included in the REBUS (RElevance of Biomarkers for future risk of thromboembolic events in UnSelected post-myocardial infarction patients) study underwent two-dimensional and Doppler echocardiography within 72 h after admission. A normal LVEF was present in 262 (73.8%) of the 355 patients ultimately enrolled in the study. Patients with normal LVEF more often presented with non-ST-elevation myocardial infarction and had less comorbidities when compared with those with impaired LVEF. No differences in demographic factors or relevant medications were observed. Higher value of mean annular plane systolic excursion (MAPSE), lower wall motion score index (WMSI), lower LV as well as left atrial volumes characterized patients with normal LVEF. Impaired MAPSE was present in 64.4%, WMSI >1 in 72.1%, and dilated left atrium in 33.6% of those patients. Maximal cardiac troponin concentration reflecting infarct size showed the strongest association with WMSI (β = 0.35), followed by LVEF (β = -0.29), MAPSE (β = -0.25), and indexed LV end-systolic volume (β = 0.19; P < 0.001 for all the models).CONCLUSION: In two-third of patients with MI and normal LVEF, at least one of the other markers of systolic function was outside of the normal range. WMSI reflected the size of MI better than global LV function parameters as LVEF or MAPSE.
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| 9. |
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| 10. |
- Batra, Gorav, et al.
(author)
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Oral anticoagulants, time in therapeutic range and renal function over time in real-life patients with atrial fibrillation and chronic kidney disease
- 2022
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In: Open heart. - : BMJ Publishing Group Ltd. - 2053-3624. ; 9:2
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Journal article (peer-reviewed)abstract
- AIMS: To describe the use of warfarin and direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and chronic kidney disease (CKD), to evaluate changes in renal function over time and predictors of rapid decline, and to describe time in therapeutic range (TTR) and predictors of poor TTR among patients on warfarin.METHODS AND RESULTS: Using data from AuriculA, the Swedish oral anticoagulation registry, patients with AF on warfarin or DOAC were identified between 2013 and 2018 (N=6567). Estimated glomerular filtration rate (eGFR) was calculated and categorised into normal (≥90 mL/min/1.73 m2), mild CKD (60-89 mL/min/1.73 m2), moderate CKD (30-59 mL/min/1.73 m2), severe CKD (15-29 mL/min/1.73 m2) and end-stage CKD (<15 mL/min/1.73 m2)/dialysis. TTR was estimated using international normalised ratio (INR) measurements. Predictors of eGFR decline over time and of poor TTR were estimated using regression analysis. Between 2013 and 2018, use of DOAC increased from 9.2% to 89.3%, with a corresponding decline in warfarin. A similar trend was observed in patients with mild to moderate CKD, while DOAC over warfarin increased slower among patients with severe to end-stage CKD/dialysis. In patients treated with warfarin, the median TTR was 77.1%. Worse TTR was observed among patients with severe CKD (70.0%) and end-stage CKD/dialysis (67.5%). A gradual annual decline in eGFR was observed (-1.1 mL/min/1.73 m2), with a more rapid decline among patients with older age, female sex, diabetes mellitus and/or heart failure.CONCLUSION: In patients with AF, use of DOAC has steadily increased across different CKD stages, but not in patients with severe to end-stage CKD/dialysis despite these patients having poor INR control. Patients with AF have a gradual decline in renal function, with a more rapid decline among a subgroup of patients.
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| 11. |
- Bay, Annika, 1970-, et al.
(author)
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Symptoms during pregnancy in primiparous women with congenital heart disease.
- 2024
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In: Scandinavian Cardiovascular Journal. - : Taylor & Francis. - 1401-7431 .- 1651-2006. ; 58:1
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Journal article (peer-reviewed)abstract
- Background: As more women with congenital heart disease (CHD) are reaching childbearing age, it becomes more common for their symptoms to be evaluated during pregnancy. However, pregnancy-related symptoms are similar to those caused by heart disease. This study investigated the prevalence of factors associated with symptoms during pregnancy in women with CHD.Methods: The national birth register was searched for primiparous women with CHD who were registered in the national quality register for patients with CHD.Results: Symptoms during the third trimester were reported in 104 of 465 evaluated women. The most common symptom was palpitations followed by dyspnea. Factors associated with symptoms were tested in a univariable model; higher NYHA classification (>1) (OR 11.3, 95%CI 5.5-23.2), low physical activity (≤3 h/week) (OR 2.1 95%CI 1.3-3.6) and educational level ≤ 12 years (OR 1.9 95%CI 1.2-3.0) were associated with having symptoms. In multivariable analysis, low physical activity level (OR 2.4 95%CI 1.2-5.0) and higher NYHA class (OR 11.3 95%CI 5.0-25.6) remained associated with symptoms during pregnancy. There were no cases with new onset of impaired systemic ventricular function during pregnancy.Conclusion: Symptoms during pregnancy are common in women with CHD but are often already present before pregnancy. Because ordinary symptoms during pregnancy often overlap with symptoms of heart disease, it is important to know if symptoms were present before pregnancy and if they became worse during pregnancy. These results should be included in pre-pregnancy counselling and considered in the monitoring during pregnancy.
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| 12. |
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| 13. |
- Berglund, Elisabeth, et al.
(author)
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High incidence of infective endocarditis in adults with congenital ventricular septal defect
- 2016
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In: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 102:22, s. 1835-1839
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Ventricular septal defects (VSDs), if haemodynamically important, are closed whereas small shunts are left without intervention. The long-term prognosis in congenital VSD is good but patients are still at risk for long-term complications. The aim of this study was to clarify the incidence of infective endocarditis (IE) in adults with VSD. METHODS: The Swedish registry for congenital heart disease (SWEDCON) was searched for adults with VSD. 779 patients were identified, 531 with small shunts and 248 who had the VSD previously closed. The National Patient Register was then searched for hospitalisations due to IE in adults during a 10-year period. RESULTS: Sixteen (2%) patients were treated for IE, 6 men and 10 women, with a mean age of 46.3+/-12.2 years. The incidence of IE was 1.7-2.7/1000 years in patients without previous intervention, 20-30 times the risk in the general population. Thirteen had small shunts without previous intervention. There was no mortality in these 13 cases. Two patients had undergone repair of their VSD and also aortic valve replacement before the episode of endocarditis and a third patient with repaired VSD had a bicuspid aortic valve, all of these three patients needed reoperation because of their IE and one patient died. No patient with isolated and operated VSD was diagnosed with IE. CONCLUSIONS: A small unoperated VSD in adults carries a substantially increased risk of IE but is associated with a low risk of mortality.
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| 14. |
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| 15. |
- Cederlöf, Elin, et al.
(author)
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Pregnancy Complications and Risk of Cardiovascular Disease Later in Life : A Nationwide Cohort Study
- 2022
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In: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 11:2
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Journal article (peer-reviewed)abstract
- Background: The aim of this study was to investigate the associations between pregnancy complications and cardiovascular mortality and hospitalizations of cardiovascular disease (CVD) after adjustment for major confounding.Methods and Results: In a nationwide register‐based cohort study, women with singleton births between 1973 and 2014 were included from the Swedish Medical Birth Register. Outcomes of mortality and hospitalizations of CVD were collected from the Cause of Death Register and the National Inpatient Register. The cohort was followed from the date of the first delivery until death or end of follow‐up, whichever occurred first. The pregnancy complications studied were preeclampsia or eclampsia, gestational hypertension, gestational diabetes, preterm birth, small for gestational age, and stillbirth. Among the 2 134 239 women (mean age at first pregnancy, 27.0 [SD, 5.1] and mean parity 1.96 [SD, 0.9]), 19.1% (N=407 597) had 1 of the studied pregnancy complications. All pregnancy complications were associated with all‐cause and cardiovascular mortality and hospitalization for CVD (ischemic heart disease, ischemic stroke, and peripheral artery disease) after adjustment for major confounding in a Cox proportional hazard regression model. The adjusted hazard ratio for cardiovascular mortality was 1.84 (95% CI, 1.38–2.44) for preterm birth and 3.14 (95% CI, 1.81–5.44) for stillbirth.Conclusions: In this large cohort study, pregnancy complications were associated with all‐cause mortality, cardiovascular mortality, and hospitalizations for CVD, also after adjusting for confounding, including overweight, smoking, and comorbidities. The study highlights that less established pregnancy complications such as preterm birth and stillbirth are also associated with cardiovascular mortality and CVD.
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| 16. |
- Cederlöf, Elin Täufer, et al.
(author)
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Biomarkers associated with cardiovascular disease in women with spontaneous preterm birth : A case-control study.
- 2024
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In: Acta Obstetricia et Gynecologica Scandinavica. - 0001-6349 .- 1600-0412.
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Women with spontaneous preterm birth have an increased risk of cardiovascular disease later in life. Studies suggest potential pathophysiological mechanisms in common, but whether these could be identified by measurement of soluble circulating protein biomarkers in women with spontaneous preterm birth is unknown. The aim of this study was to determine if protein biomarkers associated with cardiovascular disease distinguish women with spontaneous preterm birth from healthy controls, both at pregnancy and at follow up.MATERIAL AND METHODS: Study participants were identified in the population-based Uppsala biobank of pregnant women in Sweden, where plasma samples were collected in mid-pregnancy. In a first screening phase, we identified participants who subsequently experienced spontaneous preterm birth (<37 weeks) in the index pregnancy (N = 13) and controls (N = 6). In these samples, differences in protein expression were examined by comparative mass spectrometry. In a second validation phase, we invited 100 cases with previous spontaneous preterm birth in the index pregnancy and 100 controls (matched for age, body mass index, and year of delivery) from the same source population, to a follow-up visit 4-15 years after pregnancy. At follow up, we collected plasma samples and data on cardiovascular risk factors. We measured concentrations of selected biomarkers identified in the screening phase, as well as lipid profiles in samples both from pregnancy (biobank) and follow up.CLINICALTRIALS: gov registration NCT05693285.RESULTS: In the screening phase, fibrinogen, cadherin-5, complement C5, factor XII, plasma kallikrein, apolipoprotein M, and vitamin D-binding protein differed significantly at pregnancy. In the validation phase, 65 women agreed to participate (35 cases and 30 controls), with a median follow-up time of 11.8 years since pregnancy. The concentration of fibrinogen (p = 0.02) and triglycerides (p = 0.03) were slightly higher in cases compared with matched controls at follow up.CONCLUSIONS: Compared with women without preterm birth, those with spontaneous preterm birth had slightly higher concentrations of fibrinogen, both at mid-pregnancy and a decade after pregnancy. Additionally, we found slightly higher concentration of triglycerides at follow up in women with previous spontaneous preterm birth. The relevance of this finding is uncertain but might indicate potential pathophysiological mechanisms in common between spontaneous preterm birth and cardiovascular disease.
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| 17. |
- Christersson, Cecilia, et al.
(author)
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A predictive model for alternative admission to dental education.
- 2015
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In: European Journal of Dental Education. - : Wiley. - 1396-5883 .- 1600-0579. ; 19:4, s. 251-258
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Journal article (peer-reviewed)abstract
- To compare academic progress and performance of students admitted through two admission systems and to analyse the predictive power of different components in an alternative admission.
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| 18. |
- Christersson, Christina, et al.
(author)
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Comparison of warfarin versus antiplatelet therapy after surgical bioprosthetic aortic valve replacement
- 2020
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In: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 106:11, s. 838-844
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To compare effectiveness of warfarin and antiplatelet exposure regarding both thrombotic and bleeding events, following surgical aortic valve replacement with a biological prosthesis(bioSAVR).METHODS: The study included all patients in Sweden undergoing a bioSAVR during 2008-2014 who were alive at discharge from the index hospital stay. Exposure was analysed and defined as postdischarge dispension of any antithrombotic pharmaceutical, updated at each following dispensions and categorised as single antiplatelet (SAPT), warfarin, warfarin combined with SAPT, dual antiplatelet (DAPT) or no antithrombotic treatment. Exposure to SAPT was used as comparator. Outcome events were all-cause mortality, ischaemic stroke, haemorrhagic stroke, any thromboembolism and major bleedings. We continuously updated adjustments for comorbidities with any indication for antithrombotic treatment by Cox regression analysis.RESULTS: We identified 9539 patients with bioSAVR (36.8% women) at median age of 73 years with a mean follow-up of 3.13 years. As compared with SAPT, warfarin alone was associated with a lower incidence of ischaemic stroke (HR 0.49, 95% CI 0.35 to 0.70) and any thromboembolism (HR 0.75, 95% CI 0.60 to 0.94) but with no difference in mortality (HR 0.94, 95% CI 0.78 to 1.13). The incidence of haemorrhagic stroke (HR 1.94, 95% CI 1.07 to 3.51) and major bleeding (HR 1.67, 95% CI 1.30 to 2.15) was higher during warfarin exposure. As compared with SAPT, DAPT was not associated with any difference in ischaemic stroke or any thromboembolism. Risk-benefit analyses demonstrated that 2.7 (95% CI 1.0 to 11.9) of the ischaemic stroke cases could potentially be avoided per every haemorrhagic stroke caused by warfarin exposure instead of SAPT during the first year.CONCLUSION: In patients discharged after bioSAVR, warfarin exposure as compared with SAPT exposure was associated with lower long-term risk of ischaemic stroke and thromboembolic events, and with a higher incidence of bleeding events but with similar mortality.
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| 19. |
- Christersson, Christina, et al.
(author)
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D-dimer and risk of thromboembolic and bleeding events in patients with atrial fibrillation : observations from the ARISTOTLE trial
- 2014
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In: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 12:9, s. 1401-1412
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Journal article (peer-reviewed)abstract
- BackgroundD-dimer is related to adverse outcomes in arterial and venous thromboembolic diseases. ObjectivesTo evaluate the predictive value of D-dimer level for stroke, other cardiovascular events, and bleeds, in patients with atrial fibrillation (AF) treated with oral anticoagulation with apixaban or warfarin; and to evaluate the relationship between the D-dimer levels at baseline and the treatment effect of apixaban vs. warfarin. MethodsIn the ARISTOTLE trial, 18201 patients with AF were randomized to apixaban or warfarin. D-dimer was analyzed in 14878 patients at randomization. The cohort was separated into two groups; not receiving vitaminK antagonist (VKA) treatment and receiving VKA treatment at randomization. ResultsHigher D-dimer levels were associated with increased frequencies of stroke or systemic embolism (hazard ratio [HR][Q4 vs. Q1]1.72, 95% confidence interval [CI]1.14-2.59, P=0.003), death (HR[Q4 vs. Q1]4.04, 95%CI3.06-5.33) and major bleeding (HR[Q4 vs. Q1]2.47, 95%CI1.77-3.45, P<0.0001) in the no-VKA group. Similar results were obtained in the on-VKA group. Adding D-dimer level to the CHADS(2) score improved the C-index from 0.646 to 0.655 for stroke or systemic embolism, and from 0.598 to 0.662 for death, in the no-VKA group. D-dimer level improved the HAS-BLED score for prediction of major bleeds, with an increase in the C-index from 0.610 to 0.641. There were no significant interactions between efficacy and safety of study treatment and D-dimer level. ConclusionIn anticoagulated patients with AF, the level of D-dimer is related to the risk of stroke, death, and bleeding, and adds to the predictive value of clinical risk scores. The benefits of apixaban were consistent, regardless of the baseline D-dimer level.
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| 20. |
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| 21. |
- Christersson, Christina, et al.
(author)
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Early decrease in coagulation activity after myocardial infarction is associated with lower risk of new ischemic events : Observations from the ESTEEM trial
- 2007
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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 28:6, s. 692-698
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Journal article (peer-reviewed)abstract
- AIM: Patients with a recent myocardial infarction have an increased risk of recurrent ischaemic events. In the ESTEEM trial, the oral direct thrombin inhibitor ximelagatran reduced the risk of new ischaemic events when compared with placebo in aspirin treated post myocardial infarction patients. Ximelagatran persistently reduced markers of coagulation activity, i.e. prothrombin fragment 1 + 2 (F1 + 2) and D-dimer levels. The aim of this substudy was to evaluate the levels of these markers and activated thromboplastin time (APTT) in relation to new ischaemic events or bleeding. METHODS AND RESULTS: In the substudy, 518 out of 1883 patients were included and within 14 days after a myocardial infarction randomized to ximelagatran or placebo for 6 months. The clinical endpoints death, myocardial infarction, severe recurrent ischaemia, ischaemic stroke, and bleeding were evaluated. The levels of F1 + 2, D-dimer, and APTT were analysed at randomization and in serial samples during the study. Ximelagatran treatment appeared to have a larger treatment effect in patients with F1 + 2 and D-dimer levels above the median at randomization with a reduction of ischaemic events from 18 to 9% (P = 0.03) for F1 + 2 and from 20 to 9% for D-dimer (P = 0.009). A reduction of D-dimer levels was found in 60% of the patients 1 week after randomization and these patients had less ischaemic events when compared with patients with unchanged or increased levels (P = 0.03) regardless of treatment. F1 + 2 and D-dimer levels were unrelated to bleeding risk. In the ximelagatran group, increased APTT was not related to ischaemic events but associated with a raised risk of bleeding. CONCLUSION: A reduction of initially high coagulation activity, as measured by the D-dimer level, in patients with recent myocardial infarction identifies patients with a decreased risk of new ischaemic events, regardless whether the reduction occurs spontaneously or is induced by pharmacological means. Patients with higher initial coagulation activity seemed to benefit most from long-term treatment with ximelagatran.
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| 22. |
- Christersson, Christina, et al.
(author)
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Effect of apixaban compared with warfarin on coagulation markers in atrial fibrillation.
- 2019
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In: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 105:3, s. 235-242
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Compare the effect of apixaban and warfarin on coagulation and primary haemostasis biomarkers in atrial fibrillation (AF).METHODS: The biomarker substudy from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial included 4850 patients with AF randomised to treatment with apixaban or warfarin. Sixty per cent of patients used vitamin K antagonist (VKA) within 7 days before randomisation. Prothrombin fragment 1+2 (F1+2), D-dimer, soluble CD40 ligand (sCD40L) and von Willebrand factor (vWF) antigen were analysed at randomisation and after 2 months of study treatment.RESULTS: In patients not on VKA treatment at randomisation, F1+2 and D-dimer levels were decreased by 25% and 23%, respectively, with apixaban, and by 59% and 38%, respectively, with warfarin (p<0.0001 for treatment differences for both). In patients on VKA at randomisation, F1+2 and D-dimer levels increased by 41% and 10%, respectively, with apixaban and decreased by 37% and 11%, respectively, with warfarin (p<0.0001 for treatment differences for both). sCD40L levels were slightly increased at 2 months, regardless of VKA or randomised treatment. Apixaban and warfarin also both reduced vWF antigen regardless of VKA treatment. The efficacy (stroke) and safety (bleeding) of apixaban compared with warfarin was similar irrespectively of biomarker levels at 2 months.CONCLUSIONS: Treatment with apixaban compared with warfarin for stroke prevention in patients with AF was associated with less reduction in thrombin generation and fibrin turnover. This effect of apixaban could contribute to the clinical results where apixaban was superior to warfarin both in stroke prevention and in reducing bleeding risk.TRIAL REGISTRATION NUMBER: NCT00412984.
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| 23. |
- Christersson, Christina, et al.
(author)
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Evaluation of microparticles in whole blood by multicolour flow cytometry assay
- 2013
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In: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 73:3, s. 229-239
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Journal article (peer-reviewed)abstract
- ObjectiveTo develop and evaluate a multicolour flow cytometry method for analysis of microparticles (MPs) in fresh whole blood without any centrifugation steps or freezing/thawing procedure. Materials and methodsFlow cytometry was performed using a FC500 MPL cytometer. The compensation in the protocol was performed based on the platelet population. Polystyrene microspheres 0.50–1.27 μm were used for size position, and the MP gate was set as particles 0.5–1.0 μm. Whole blood was incubated with annexin V and antibodies to tissue factor (TF), platelets (CD41 and CD62P), monocyte (CD14) and endothelial cells (CD144). For comparison, MPs from platelet free supernatant was used. The TF activity was evaluated by Calibrated Automated Thrombogram. ResultsAnnexin V was used to distinguish true events from background noise. For standardization, each analysis included 10,000 events in the gate of platelets. There were 622(462–1001) MPannV+/10,000 platelets and of these, 66 (49–82)/10,000 platelets expressed TF. After correction for the individual platelet counts, the amount of circulating MPannV+ was 17.1 (12.1–24.9) × 109/L in whole blood, and of these, 10% (6–12%) expressed TF. The majority of the MPs expressed CD41, and 5.6% (2.2–6.9%) of these co-expressed TF. The amount of CD41 + MPannV+ tended to correlate to the TF activity in whole blood. There was no correlation between the MPannV+ in whole blood and MPs derived from platelet free supernatant. Patients with pulmonary arterial hypertension and stable coronary artery disease had increased concentrations of CD41 + MPannV+ in whole blood.ConclusionThis multicolour flow cytometry assay in whole blood mimics the in vivo situation by avoiding several procedure steps interfering with the MP count. By standardized quantification of MPs a reference interval of MPs can be created.
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| 24. |
- Christersson, Christina, et al.
(author)
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Haemorrhagic stroke and major bleeding after intervention with biological aortic valve prosthesis : risk factors and antithrombotic treatment
- 2020
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In: European Heart Journal, Supplement. - : OXFORD UNIV PRESS. - 1520-765X .- 1554-2815. ; 22:C, s. C26-C33
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Journal article (peer-reviewed)abstract
- The majority of patients with severe aortic stenosis are recommended intervention with a surgical biological prosthesis (bioSAVR) or a transcatheter aortic valve intervention (TAVI). The antithrombotic strategies after aortic valve intervention vary and include drugs targeting both platelets and the coagulation cascade. Long-term exposure and changes of antithrombotic treatment influence the risk of both bleeding and thromboembolic events. The aim was to describe an unselected sample of patients who have experienced haemorrhagic stroke and other major bleeding events after biological aortic prosthesis, their antithrombotic treatment and changes of treatments in relation to the bleeding event. All patients performing an bioSAVR or a TAVI 2008-2014 were identified in the SWEDEHEART registry and included in the study (n =10 711). The outcome events were haemorrhagic stroke and other major bleeding event. Information of drug exposure was collected from the dispensed drug registry. The incidence rate of any bleeding event was 2.85/100 patient-years the first year after aortic valve intervention. Heart failure and atrial fibrillation were present more often in patients with a first haemorrhagic stroke or other major bleeding event compared to without. The proportion of exposure to warfarin was 28.7% vs. 21.3% in patients with and without a haemorrhagic stroke. Comparable figures were 31.2% vs. 19.0% in patients with and without other major bleeding event. During 1 month prior a haemorrhagic stroke or other major bleeding event 39.4% and 38.0%, respectively, of the patients not previously exposed to antithrombotic treatment started warfarin or single antiplatelet therapy. Major bleeding events are not uncommon after aortic valve intervention with a biological prosthesis. Evaluation of comorbidities and previous bleeding might improve risk stratification for bleeding in these elderly patients. The pattern of change of antithrombotic treatment was similar in the groups with and without a bleeding event and in most patients the antithrombotic regime was unchanged the month before an event.
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