Co-Creation and Co-Production of Health Promoting Activities Addressing Older People-A Scoping Review.

The global population is aging and the promotion of health and well-being for this generation is essential. Co-creative and co-productive practices can be solutions to welfare challenges in local policies. Therefore, this scoping review aimed to understand the extent and type of evidence in relation to the co-creation and co-production of health-promoting activities addressing older people aged 60+ years and to examine the influence of co-creative and co-productive activities on health and well-being, including influential factors for co-creation and co-production. We searched for peer-reviewed and grey literature in ten scientific and five non-scientific databases. From the 2648 studies retrieved, 18 articles were included in this review. Then, an inductive thematic content analysis was applied to the analysis. Three categories related to co-creative and co-productive activities emerged: "Social and physical activities", "Development of age-friendly environments", and "Discussions of healthy and active aging". Facilitating factors for co-creation and co-production were related to the planning and structure of the process and recognition of participants' time and resources, while the recruitment of participants and their time and resources were the main barriers. Future studies should target co-creative and co-productive interventions to concrete areas and specific sub-groups and be aware of factors influencing a co-creative or co-productive relationship with older people.

Fibrin clot structure - pro-fibrinolytic effect of oral contraceptives in apparently healthy women.

Fibrin metabolism is influenced by many factors. The velocity of fibrin formation, genetic polymorphisms, fibrinolytic features and the structure of the fibrin clot are determinants of fibrin turnover. Oral contraceptives (OCs) have significant impact on the haemostatic system, by increasing the concentration of coagulation factors, plasminogen and tissue plasminogen activator activity, and decreasing the concentration of haemostatic inhibitors. The present study addresses the influence of OCs on fibrin structure and fibrin metabolism. The study included 70 women treated with seven different OC-formulations. Blood was collected at baseline and after six months of OCs. The plasma concentration of fibrinogen, thrombin-antithrombin complex (TAT), plasminogen, plasmin-antiplasmin complex (PAP), D-Dimer and thrombin generation measures were determined. Fibrin structure measures and fibrin clot lysis not affected by the plasma concentration of plasminogen activators and inhibitors were determined. OCs increased the concentration of fibrinogen, TAT, plasminogen, PAP and D-dimer significantly and affected measures of thrombin generation (p<0.001). The maximal optical density of fibrin (p<0.001), the fibrin fibre density (p=0.03), fibrin fibre diameter (p=0.003), fibrin mass-length ratio (p<0.001) and lysis per hour (p<0.001) increased significantly upon OC-treatment. Lysis per hour was not correlated to the concentration of plasminogen. We conclude that the effect of OCs on the coagulation system is balanced by alterations in fibrin structure, facilitating clot lysis and contributing to the fibrinolytic susceptibility already present in women treated with OC. These alterations may counterbalance the OC-induced increased thrombin generation and reduced coagulation inhibitory potential, contributing to maintenance of the haemostatic balance in women receiving OCs.

Oral anticoagulants in coronary heart disease (Section IV). Position paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease.

Until recently, vitamin K antagonists (VKAs) were the only available oral anticoagulants evaluated for long-term treatment of patients with coronary heart disease (CHD), particularly after an acute coronary syndrome (ACS). Despite efficacy in this setting, VKAs are rarely used because they are cumbersome to administer. Instead, the more readily manageable antiplatelet agents are the mainstay of prevention in ACS patients. This situation has the potential to change with the introduction of non-VKA oral anticoagulants (NOACs), which are easier to administer than VKAs because they can be given in fixed doses without routine coagulation monitoring. The NOACs include dabigatran, which inhibits thrombin, and apixaban, rivaroxaban and edoxaban, which inhibit factor Xa. Apixaban and rivaroxaban were evaluated in phase III trials for prevention of recurrent ischaemia in ACS patients, most of whom were also receiving dual antiplatelet therapy with aspirin and clopidogrel. Although at the doses tested rivaroxaban was effective and apixaban was not, both agents increased major bleeding. The role for the NOACs in ACS management, although promising, is therefore complicated, because it is uncertain how they compare with newer antiplatelet agents, such as prasugrel, ticagrelor or vorapaxar, and because their safety in combination with these other drugs is unknown. Ongoing studies are also now evaluating the use of NOACs in non-valvular atrial fibrillation patients, where their role is established, with coexistent ACS or coronary stenting. Focusing on CHD, we review the results of clinical trials with the NOACs and provide a perspective on their future incorporation into clinical practice.

Gender Differences in Fibrin Polymerization and Lysability of Fibrin in Patients with Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia for both men and women. The embolic cardiovascular events represent serious complications of AF, and apparently women are affected more seriously than men. Little is known about prothrombotic factors and possible gender differences. The present study aimed to characterize fibrin polymerization, fibrinolysis, and fibrin fiber properties in men and in women with AF. MATERIALS AND METHODS: Forty-six female and 101 male patients with AF and without previous stroke were included. Polymerization kinetics, lysis of preformed clot, and fibrin fiber properties were determined by turbidimetric methods. RESULTS: Women were slightly older than men (P < .01), and the male group had a higher systolic blood pressure (P < .01) and a higher incidence of peripheral arterial disease (P < .01) than the female group. Compared with men, women had a higher Vmax during fibrin polymerization (P < .04) and a lower lysability of fibrin, when recombinant tissue plasminogen activator (rt-PA) was added during clot formation (P < .01), while external lysis (rt-PA added after clot formation), plasma fibrinolytic activity, d-dimer, and fibrin fiber properties did not differ between men and women. A significantly higher number of men received acetylsalicylic acid (ASA) compared with women (P < .004). Subgroup analyses on subjects not receiving ASA demonstrated that women still had higher Vmax (P < .04) and a lower rt-PA-induced fibrinolysis (P < .03). CONCLUSION: Women with AF have a higher velocity of lateral aggregation of fibrin fiber protofibrils and a lower lysis of fibrin clots than men.

Lysability of fibrin clots is a potential new determinant of stroke risk in atrial fibrillation.

INTRODUCTION: Atrial fibrillation increases the risk of ischemic stroke, but the risk depends on other factors as well. Present risk stratification schemes use age and co-morbidities, but not biochemical markers. We investigated the hypothesis that the formation, structure and lysability of fibrin clots are potential determinants of stroke risk in patients with atrial fibrillation. MATERIALS AND METHODS: A total of 179 patients with atrial fibrillation in stable anticoagulant treatment were included. Thirty-two had a previous ischemic stroke. We measured thrombin generation, plasma concentrations of fibrinogen and C-reactive protein and analysed fibrin structure and lysability by turbidity. Fibrinolytic capacity was measured using the euglobulin fraction of plasma expressed in terms of t-PA equivalents (IU/ml). RESULTS: The patients with previous stroke had a slightly higher burden of co-morbidities compared with the remaining patients as indicated by the CHA2DS2-VASc score, but no significant differences were found regarding age, fibrinogen concentration, C-reactive protein, thrombin generation or fibrinolytic capacity. Furthermore, the patients with previous stroke had a higher mass/length ratio of fibrin fibers (5.5 vs. 5.1 x10(12) Da/cm, p=0.044) and an increased lysability (79.3 vs. 55.3%, p<0.01). CONCLUSION: The higher lysability of fibrin clots in atrial fibrillation patients with previous stroke is most likely a result of a difference in fibrin fiber properties. An increased lysability may increase the risk of embolization of clots formed in the atria, and therefore fibrin clot structure seems to be a determinant of stroke risk in atrial fibrillation.

Difference in fibrinolytic capacity in young patients with venous thrombosis or ischaemic stroke.

Many recent studies focus on the common pathophysiological mechanisms and risk factors for arterial and venous thrombosis. We investigated the hypothesis that fibrinolytic capacity is similar in patients with ischaemic stroke and venous thromboembolism. Retrospective study of 604 consecutive patients (age <50 years) referred to systematic thrombophilia testing at a single regional centre. The thrombophilia test included clinical variables, genetic polymorphisms, biomarkers of coagulation and a global assay of fibrinolysis that tested the patient's blood fibrinolytic capacity by application of the euglobulin fraction of plasma to a preformed clot of plasminogen-rich bovine fibrin. The patients with venous thromboembolism (n = 284) were slightly younger (32.3 vs. 33.9 years; <0.01) than those with ischaemic stroke (n = 320), had a significantly higher prevalence of obesity (28 vs. 18%; P < 0.01), higher plasminogen activator inhibitor 1 (PAI-1) activity (12.3 vs. 11.1 IU/ml; P = 0.049) and a significantly lower fibrinolytic capacity (3.4 vs. 3.9 IU/ml; P < 0.01). The lower fibrinolytic capacity in patients with venous thromboembolism was also observed in the subgroup of patients with PAI-1 activity within the normal range (n = 430, 3.7 vs. 4.1IU/ml; P < 0.01). After adjustment for age, BMI, fibrinogen concentration, PAI-1 activity and tissue plasminogen activator activity, fibrinolytic capacity still differed significantly between the two groups. Our results indicate that the capacity for fibrinolysis is lower in young patients with venous thromboembolism than ischaemic stroke, suggesting a different mechanistic role of fibrinolysis in arterial and venous thromboembolism.

Postprandial coagulation activation in overweight individuals after weight loss: acute and long-term effects of a high-monounsaturated fat diet and a low-fat diet.

Diet is important in the prevention of cardiovascular disease, and it has been suggested that a high-MUFA diet is more cardioprotective than a low-fat diet. We hypothesised that the postprandial thrombotic risk profile is improved most favourably by a high-MUFA diet compared with a low-fat diet. This was tested in a parallel intervention trial on overweight individuals (aged 28.4 (SD 4.7) years) randomly assigned to a MUFA-diet (35-45% of energy as fat; >20% as MUFA, n = 21) or a low-fat (LF) diet (20-30% of energy as fat, n = 22) for 6 months after a weight loss of ~10%. All foods were provided free of charge from a purpose-built supermarket. Meal tests designed after the same principles were performed before and after the dietary intervention, and blood samples were collected at 8.00 h (fasting), 12.00 h, and 18.00 h and analysed for factor VII coagulant activity (FVII:C), activated FVII, fibrinogen, prothrombin fragment 1 + 2 (F1 + 2), D-dimer, plasminogen activator inhibitor (PAI:Ag), and thrombin activatable fibrinolysis inhibitor. There were significant postprandial increases in F1 + 2 and D-dimer before and after dietary intervention, with significantly lower values after 6 months. No significant differences were observed between the postprandial changes induced by the two diets. The postprandial decrease in FVII:C and PAI:Ag did not differ before and after intervention, irrespective of the diets. Our findings suggest postprandial coagulation activation in overweight subjects with more pronounced acute than long-term effects. We observed similar effects of the MUFA diet and the LF diet on the postprandial prothrombotic risk profile.

Vitamin K antagonists in heart disease: current status and perspectives (Section III). Position paper of the ESC Working Group on Thrombosis--Task Force on Anticoagulants in Heart Disease.

Oral anticoagulants are a mainstay of cardiovascular therapy, and for over 60 years vitamin K antagonists (VKAs) were the only available agents for long-term use. VKAs interfere with the cyclic inter-conversion of vitamin K and its 2,3 epoxide, thus inhibiting γ-carboxylation of glutamate residues at the amino-termini of vitamin K-dependent proteins, including the coagulation factors (F) II (prothrombin), VII, IX and X, as well as of the anticoagulant proteins C, S and Z. The overall effect of such interference is a dose-dependent anticoagulant effect, which has been therapeutically exploited in heart disease since the early 1950s. In this position paper, we review the mechanisms of action, pharmacological properties and side effects of VKAs, which are used in the management of cardiovascular diseases, including coronary heart disease (where their use is limited), stroke prevention in atrial fibrillation, heart valves and/or chronic heart failure. Using an evidence-based approach, we describe the results of completed clinical trials, highlight areas of uncertainty, and recommend therapeutic options for specific disorders. Although VKAs are being increasingly replaced in most patients with non-valvular atrial fibrillation by the new oral anticoagulants, which target either thrombin or FXa, the VKAs remain the agents of choice for patients with atrial fibrillation in the setting of rheumatic valvular disease and for those with mechanical heart valves.

General mechanisms of coagulation and targets of anticoagulants (Section I). Position Paper of the ESC Working Group on Thrombosis--Task Force on Anticoagulants in Heart Disease.

Contrary to previous models based on plasma, coagulation processes are currently believed to be mostly cell surface-based, including three overlapping phases: initiation, when tissue factor-expressing cells and microparticles are exposed to plasma; amplification, whereby small amounts of thrombin induce platelet activation and aggregation, and promote activation of factors (F)V, FVIII and FXI on platelet surfaces; and propagation, in which the Xase (tenase) and prothrombinase complexes are formed, producing a burst of thrombin and the cleavage of fibrinogen to fibrin. Thrombin exerts a number of additional biological actions, including platelet activation, amplification and self-inhibition of coagulation, clot stabilisation and anti-fibrinolysis, in processes occurring in the proximity of vessel injury, tightly regulated by a series of inhibitory mechanisms. "Classical" anticoagulants, including heparin and vitamin K antagonists, typically target multiple coagulation steps. A number of new anticoagulants, already developed or under development, target specific steps in the process, inhibiting a single coagulation factor or mimicking natural coagulation inhibitors.

The influence of VKORC1 and CYP2C9 gene sequence variants on the stability of maintenance phase warfarin treatment.

INTRODUCTION: A substantial part of the inter-individual variation in vitamin K-antagonist dose can be explained by certain sequence variants in the genes CYP2C9 (NG_008385.1:g.8633C>T or *1/*2, NG_008385.1:g.47639A>C or *1/*3) and VKORC1 (NG_011564.1:g.6399C>T). Patients possessing these variant alleles require lower doses and have increased risk of overanticoagulation. METHODS: We investigated the influence of the above sequence variants on stability of maintenance phase warfarin therapy in a prospective study of 300 consecutive patients followed for one year at an anticoagulant clinic. RESULTS: Patients having one VKORC1 variant allele (n=144) had a time in therapeutic range of INR (TTR) of 71.4%, significantly lower (p=0.02) than the 76.7% TTR of patients with none (n=96) or two (n=46) variant alleles. Patients carrying the CYP2C9 *3 allele (n=40) trended towards lower TTR than patients without this variant allele (69.8% vs. 74.7%, p=0.09). Six patients possessed two variant alleles of CYP2C9 (*2/*3 or *3/*3) and had significantly lower TTR (60.5% vs. 74.3%, p=0.012) and higher risk of an INR>4.5 (67% vs. 23%, p=0.03) compared with the remaining patients. CONCLUSIONS: We observed modest effects of common gene sequence variants in CYP2C9 and VKORC1 on stability of maintenance phase warfarin therapy. Patients attending an anticoagulant clinic using computer-assisted dosage were safely monitored regardless of these sequence variants, but for the small subgroup of patients with the CYP2C9 genotype *2/*3 or *3/*3, treatment stability was reduced.

Randomized controlled trial of cholecalciferol supplementation in chronic kidney disease patients with hypovitaminosis D.

BACKGROUND: Hypovitaminosis D is common in chronic kidney disease (CKD). Effects of 25-hydroxyvitamin D replenishment in CKD are not well described. METHODS: An 8-week randomized, placebo-controlled, double-blind parallel intervention study was conducted in haemodialysis (HD) and non-HD CKD patients. Treatment consisted of 40,000 IU of cholecalciferol orally per week. Plasma 25-hydroxyvitamin D (25-OHD), plasma 1,25-dihydroxyvitamin D (1,25-diOHD), plasma parathyroid hormone (PTH), serum phosphate, ionized serum calcium and serum fibroblast growth factor 23 (FGF-23) were analysed. We also investigated biomarkers related to cardiovascular disease (plasma D-dimer, plasma fibrinogen, plasma von Willebrand factor antigen and activity, plasma interleukin 6, plasma C-reactive protein, blood pressure, aortic augmentation index, aortic pulse wave velocity and 24-h urinary protein loss). Objective and subjective health variables were assessed (muscle function tests, visual analogue scores and Health Assessment Questionnaire). RESULTS: Fifty-two CKD patients with 25-OHD <50 nmol/L at screening were included. Cholecalciferol supplementation led to a significant increase to a median of 155 nmol/L 25-OHD (interquartile range 137-173 nmol/L) in treated patients (n = 25, P < 0.001). In non-HD patients, we saw a significant increase in 1,25-diOHD (n = 13, P < 0.01) and a lowering of PTH (n = 13, P < 0.001). This was not observed in HD patients. Cholecalciferol supplementation caused a significant increase in serum calcium and FGF-23. CONCLUSIONS: 25-OHD replenishment was effectively obtained with the employed cholecalciferol dosing. In non-HD patients, it had favourable effects on 1,25-diOHD and PTH. Vitamin D-supplemented patients must be monitored for hypercalcaemia. The present study could not identify significant pleiotropic effects of 25-OHD replenishment.

New oral anticoagulants in atrial fibrillation and acute coronary syndromes: ESC Working Group on Thrombosis-Task Force on Anticoagulants in Heart Disease position paper.

Until recently, vitamin K antagonists were the only available oral anticoagulants, but with numerous limitations that prompted the introduction of new oral anticoagulants targeting the single coagulation enzymes thrombin (dabigatran) or factor Xa (apixaban, rivaroxaban, and edoxaban) and given in fixed doses without coagulation monitoring. Here we review the pharmacology and the results of clinical trials with these new agents in stroke prevention in atrial fibrillation and secondary prevention after acute coronary syndromes, providing perspectives on their future incorporation into clinical practice. In phase III trials in atrial fibrillation, compared with warfarin, dabigatran etexilate 150 mg B.I.D. reduced the rates of stroke/systemic embolism without any difference in major bleeding; dabigatran etexilate 110 mg B.I.D. had similar efficacy with decreased bleeding; apixaban 5 mg B.I.D. reduced stroke, systemic embolism, and mortality as well as major bleeding; and rivaroxaban 20 mg Q.D. was noninferior to warfarin for stroke and systemic embolism without a difference in major bleeding. All these agents reduced intracranial hemorrhage. Edoxaban is currently being evaluated in a further large phase III trial. Apixaban and rivaroxaban were evaluated in phase III trials for prevention of recurrent ischemia in patients with acute coronary syndromes who were mostly receiving dual antiplatelet therapy, with conflicting results on efficacy but consistent results for increased major bleeding. Overall, the new oral anticoagulants are poised to replace vitamin K antagonists for many patients with atrial fibrillation and may have a role after acute coronary syndromes. Although convenient to administer and manage, they present challenges that need to be addressed.

Application of the UK NHS Improvement Anticoagulation Commissioning Support Document for 'safety indicators' in atrial fibrillation. Results of the European Action on Anticoagulation study.

INTRODUCTION: 'Safety indicators' in the anticoagulant management of atrial fibrillation (AF) are listed in the UK NHS Improvement Document, 'Anticoagulation for AF', aiming to promote quality services. Acceptable clinical event rates are not quantified in the document. OBJECTIVE: To provide clinical evaluation of the relevant safety indicators using data from a recent large European Action on Anticoagulation (EAA) study. RESULTS: 469 clinical events were recorded in 5839 outpatients in the EAA study. The safety indicators listed in the NHS Improvement Document were related to these patients with AF. The relevance of the 'safety indicators' is confirmed by the EAA study for patients starting oral anticoagulation and for those already receiving oral anticoagulation, and quantified. CONCLUSION: The EAA clinical study provides a quantitative basis for the safety indicators' in AF listed in the NHS Commissioning Support Document and emphasises the importance of the document.

Multivariate analysis of the relation between diet and warfarin dose.

PURPOSE: The vitamin K antagonist (VKA) warfarin is effective for the prevention of thromboembolisms. Maintenance doses differ greatly among patients and are known to be primarily determined by genetic polymorphisms. The relative impact of dietary vitamin K intake is still a matter of debate. We hypothesize that a multivariate model is more suitable for exploring the relation between dietary intake of vitamin K and warfarin dose than conventional uni- or bivariate analyses. METHODS: In a cross-sectional study, we interviewed 244 patients in the maintenance phase of warfarin therapy and detected polymorphisms in the VKORC1 and CYP2C9 genes. Dietary vitamin K intake was estimated from food frequency questionnaires. RESULTS: A univariate correlation analysis and the regression coefficient from the multivariate model showed a small but significant negative relation between vitamin K intake and warfarin dose. A loading plot of the partial least squares regression model illustrated this counter-intuitive observation, which might be explained by the latent structure between variables. The variation in warfarin dose could be divided into two significant latent variables, the so-called components. In component one, pharmacogenetics explained 52% of dose variation. Component two described health-related behavior (diet, physical activity and body weight) and explained 8% of dose variation. Here, vitamin K intake positively correlated with warfarin dose. DISCUSSION: This study highlights the importance of choosing a statistical method that reflects the complexity of data for interpretation of results from observational studies. The multivariate model appears to be well suited to describe the complex relationship between vitamin K intake and VKA dose.

Genetic, clinical and behavioural determinants of vitamin K-antagonist dose--explored through multivariable modelling and visualization.

Vitamin K antagonists (VKA) are highly effective anticoagulants but their use is hampered by multiple interactions with food and medicine and a narrow therapeutic range. The large variation in dose requirements has led to the development of several dosing algorithms based on pharmacogenetic and clinical variables. In contrast, evidence about the influence of behavioural (i.e. diet and exercise) and socio-psychological factors is sparse. To investigate the impact of pharmacogenetic, clinical, behavioural and socio-psychological factors on maintenance dose of VKA. In a cross-sectional study, we interviewed 250 consecutive patients from an anticoagulant clinic and subsequently measured pharmacogenetic and anthropometric variables. Statistical analyses were carried out using linear regression and multivariable models with visualization features. In both types of analyses, the strongest determinants of VKA dose were polymorphisms in the VKORC1 and CYP2C9 genes and age. Half of the variation in VKA dose could be explained by a linear regression model including four variables, while a multivariable model with 20 pharmacogenetic and clinical variables explained 60%. A multivariable model including 94 predictor variables was not notably better regarding predictive performance, but visualization of this model offered information about the correlation structure between predictor variables. The strongest determinants of VKA dose are well-known pharmacogenetic variables and age. The variables describing health-related behaviour and socio-psychological factors are strongly inter-correlated and not useful in dosing algorithms.

Plasma factor VII-activating protease is increased by oral contraceptives and induces factor VII activation in-vivo.

UNLABELLED: Oral contraceptive (OC) use influences the hemostatic system significantly and is a risk factor for development of cardiovascular disease. Factor VII-activating protease (FSAP) has potential effects on hemostasis. The 1601GA genotype of the 1601G/A polymorphism in the FSAP gene expresses a FSAP alloenzyme with reduced pro-fibrinolytic activity. Presently, we address whether OC use and OC formulation affect FSAP measures in human blood. Healthy women (n=588) were allocated to six cycles of OCs with estrogen contents of 20 µg (n=158), 30 µg (n=284), 35 µg (n=79) or 50 µg (n=67) combined with various progestins. FSAP genotypes, FSAP and factor VII (FVII) plasma measures were assessed at baseline and after 6 cycles of OC. The 1601GA genotype was present in 49 (8.3%) of the women and was associated with significantly reduced levels of FSAP (P≤0.001). OC use increased FSAP antigen by 25% and FSAP activity by 59% (P<0.001). The FSAP increase was comparable in the seven different OC treatment groups (P>0.05). The relative increase in FSAP activity was significantly higher in women carrying the 1601GG genotype (63%) than in women carrying 1601GA genotype (50%) (P=0.01) and was associated with an increased activation of FVII. IN CONCLUSION: OC use increases the plasma measures of FSAP. The increase in FSAP is comparable in the seven OC-groups studied but is more significant in women carrying the 1601GG genotype than in women with the 1601GA genotype and results in increased activation of FVII suggesting that FSAP-induced activation of FVII takes place in-vivo and not only in-vitro as hitherto described.

Plenty of pills: polypharmacy prevails in patients of a Danish anticoagulant clinic.

PURPOSE: Vitamin K antagonist (VKA) treatment can successfully prevent thromboembolic complications, but the modality has a narrow therapeutic window and numerous interactions with other pharmaceuticals. The aim of the study reported here was to describe the use of co-medications and the prevalence of polypharmacy among patients treated with VKA. METHODS: In a cross-sectional study, 250 consecutive patients (65% male, median age 68 years, most common indication for VKA treatment: atrial fibrillation) in the maintenance phase of VKA treatment were interviewed about their use of prescription medications, over-the-counter drugs and alternative medicines during the last 7 days. RESULTS: The interviewed patients used a median of five medications (range 1-13), including VKA. Approximately 50% of the patients also took alternative medicines. A wide range of conventional and alternative medicines were used, several of which harbour possible interactions with VKA. Polypharmacy was defined as the use of five or more medications, excluding alternative medicines. The group of polypharmacy patients included 53% of the study population. The use of amiodarone, age >50 years, the indication for VKA treatment being atrial fibrillation or mechanical heart valves and diabetes were independent predictors of polypharmacy. CONCLUSIONS: The results of this study highlight that polypharmacy is a common phenomenon among patients on anticoagulant medication, particularly among elderly patients or those suffering from cardiovascular disease or diabetes.