Browsing by Author "Urtāne, Inga"

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    Adherence Level to Arterial Hypertension Treatment: A Cross-Sectional Patient Survey and Retrospective Analysis of the NHS Prescription Database
    (2021-08-23) Gavrilova, Anna; Bandere, Dace; Logviss, Konstantīns; Šmits, Dins; Urtāne, Inga; Department of Pharmaceutical Chemistry; Red Cross Medical College of Rīga Stradiņš University; Department of Applied Pharmacy; Department of Public Health and Epidemiology
    One of the major problems in cardiology practice is poor adherence to antihypertensive medication. This study aimed to evaluate medication adherence; we also aim to investigate the predictors of intentional and unintentional non-adherence. We issued a survey containing questions about patient demographics, blood pressure control, pharmaceutical care, and adherence level to medication. Retrospective analysis of the prescription database of the National Health Service of the Republic of Latvia was performed. The prevalence of non-adherence was 45.9%. The lowest adherence rate (38.2%) was found among patients taking medication for 2–4.9 years. Even though 84.7% of respondents had a blood pressure monitor at home, only 25.3% of them reported measuring blood pressure regularly. There were differences between the groups of adherent patients in terms of the patients’ net income (p = 0.004), medication co-payments (p = 0.007), and whether the pharmacist offered to reduce the costs of drug therapy (p = 0.002). Roughly half of the prescriptions (50.4%) containing perindopril were purchased by patients from pharmacies. The medication adherence level and blood pressure control at home were assessed as low. Intentionally non-adherent respondents discontinued their medication because of fear of getting used to medicines. The pharmacists’ behaviour in terms of offering to reduce the costs of medications used was influenced by socio-economic factors.
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    Ģenētisko faktoru ietekme uz papildu klopidogrela devu efektivitāti personalizētās terapijas nodrošināšanai pacientiem ar hiporesponsivitāti. Promocijas darba kopsavilkums
    (Rīgas Stradiņa universitāte, 2014) Urtāne, Inga; Latkovskis, Gustavs; Štokmane, Aina Silvija
    Ievads. Samazināta reakcija uz klopidogrelu (hiporesponsivitāte) saistīta ar kardiovaskulāro (KV) notikumu risku pacientiem pēc perkutānas koronāras intervences (PCI). Lai gan klopidogrela hiporesponsivitāti ir mēģināts pārvarēt ar papildu piesātinošām devām (PD) un lielākām uzturošām devām (UD), vēl joprojām nav skaidra ģenētisko faktoru ietekme uz individuāli pielāgotu klopidogrela devu terapijas efektivitāti. Mērķis. Analizēt CYP2C19, CYP2C9 un ABCB1 ģenētisko polimorfismu ietekmi uz klopidogrela papildu PD (600 mg) un palielinātu UD (150 mg) efektu hiporesponsivitātes pārvarēšanai, kā arī noskaidrot augstāka PRI mērķa (<60%) drošumu ilgtermiņā 1 gada laikā. Metodes. Prospektīvā pētījumā tika iekļauti 118 pacienti ar zālēm pārklāta stenta (DES) implantāciju. Pacientiem tika noteikts trombocītu reaktivitātes indekss (PRI), izmantojot plūsmas citometriju ar vazodilatatorstimulējošā fosfoproteīna (VASP) metodi. Visiem pacientiem noteikti sekojoši ģenētiskie polimorfismi: CYP2C19, CYP2C9 un ABCB1. Samazinātas klopidogrela darbības gadījumā (PRI <60%) pacienti saņēma līdz 3 papildu 600 mg PD, atkārtoti pārbaudot PRI. Apsekošanas vizītes pēc 40 dienām tika veiktas visiem pacientiem, lietojot 75 mg UD un papildus pēc 10 dienām tiem, kuri lietoja 150 mg UD. Ilgtermiņa klīniskā apsekošana veikta visiem pacientiem. Rezultāti. Samazinātu klopidogrela darbību pirmajā VASP analīzē novēroja 68 pacientiem (72,3%). PRI bija augstāks pacientiem ar CYP2C19*2 polimorfismu, salīdzinot ar biežāk sastopamo (wild-type) genotipu, attiecīgi 78,2±13,1 un 65,3±19,5; p=0,005. Pēc pirmās papildu 600 mg PD mazāks PRI samazinājums bija pacientiem ar CYP2C19*2 polimorfismu (25,5±15,6 un 35,5±16,8; p=0,025). Pacientiem ar CYP2C19*2 bija augstāks PRI pie abām klopidogrela UD: 10. dienā ar 150 mg (attiecīgi 53,3±12,1 un 40,3±13,5; p=0,001) un 40. dienā ar 75 mg (65,5±10,4 un 56,3±14,5; p=0,020). Pārējiem polimorfismiem nozīmīgu saistību ar PRI neatrada. Pacientiem ar hiporesponsivitāti bija augstāks ĶMI (32,8±3,9 vs 29,6±4,9; p=0,007), kā arī biežāk sastopama vienlaicīga PSI terapija (16 vs 7; p=0,381). Secinājumi. Pacientiem ar vismaz vienu CYP2C19*2 alēli klopidogrela standarta PD un papildu PD efektivitāte ir pazemināta. Šīs alēles nēsātājiem augstāka 150 mg klopidogrela UD ir efektīvāka, bet joprojām nav pietiekama 29% gadījumu. Augstāks ķermeņa masas indekss (ĶMI) un protonu sūkņa inhibitoru (PSI) lietošana asociējas ar tendenci uz samazinātu klopidogrela efektivitāti.
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    Ģenētisko faktoru ietekme uz papildu klopidogrela devu efektivitāti personalizētās terapijas nodrošināšanai pacientiem ar hiporesponsivitāti. Promocijas darbs
    (Rīgas Stradiņa universitāte, 2014) Urtāne, Inga; Latkovskis, Gustavs; Štokmane, Aina Silvija
    Ievads. Samazināta reakcija uz klopidogrelu (hiporesponsivitāte) saistīta ar kardiovaskulāro (KV) notikumu risku pacientiem pēc perkutānas koronāras intervences (PCI). Lai gan klopidogrela hiporesponsivitāti ir mēģināts pārvarēt ar papildu piesātinošām devām (PD) un lielākām uzturošām devām (UD), vēl joprojām nav skaidra ģenētisko faktoru ietekme uz individuāli pielāgotu klopidogrela devu terapijas efektivitāti. Mērķis. Analizēt CYP2C19, CYP2C9 un ABCB1 ģenētisko polimorfismu ietekmi uz klopidogrela papildu PD (600 mg) un palielinātu UD (150 mg) efektu hiporesponsivitātes pārvarēšanai, kā arī noskaidrot augstāka PRI mērķa (<60%) drošumu ilgtermiņā 1 gada laikā. Metodes. Prospektīvā pētījumā tika iekļauti 118 pacienti ar zālēm pārklāta stenta (DES) implantāciju. Pacientiem tika noteikts trombocītu reaktivitātes indekss (PRI), izmantojot plūsmas citometriju ar vazodilatatorstimulējošā fosfoproteīna (VASP) metodi. Visiem pacientiem noteikti sekojoši ģenētiskie polimorfismi: CYP2C19, CYP2C9 un ABCB1. Samazinātas klopidogrela darbības gadījumā (PRI <60%) pacienti saņēma līdz 3 papildu 600 mg PD, atkārtoti pārbaudot PRI. Apsekošanas vizītes pēc 40 dienām tika veiktas visiem pacientiem, lietojot 75 mg UD un papildus pēc 10 dienām tiem, kuri lietoja 150 mg UD. Ilgtermiņa klīniskā apsekošana veikta visiem pacientiem. Rezultāti. Samazinātu klopidogrela darbību pirmajā VASP analīzē novēroja 68 pacientiem (72,3%). PRI bija augstāks pacientiem ar CYP2C19*2 polimorfismu, salīdzinot ar biežāk sastopamo (wild-type) genotipu, attiecīgi 78,2±13,1 un 65,3±19,5; p=0,005. Pēc pirmās papildu 600 mg PD mazāks PRI samazinājums bija pacientiem ar CYP2C19*2 polimorfismu (25,5±15,6 un 35,5±16,8; p=0,025). Pacientiem ar CYP2C19*2 bija augstāks PRI pie abām klopidogrela UD: 10. dienā ar 150 mg (attiecīgi 53,3±12,1 un 40,3±13,5; p=0,001) un 40. dienā ar 75 mg (65,5±10,4 un 56,3±14,5; p=0,020). Pārējiem polimorfismiem nozīmīgu saistību ar PRI neatrada. Pacientiem ar hiporesponsivitāti bija augstāks ĶMI (32,8±3,9 vs 29,6±4,9; p=0,007), kā arī biežāk sastopama vienlaicīga PSI terapija (16 vs 7; p=0,381). Secinājumi. Pacientiem ar vismaz vienu CYP2C19*2 alēli klopidogrela standarta PD un papildu PD efektivitāte ir pazemināta. Šīs alēles nēsātājiem augstāka 150 mg klopidogrela UD ir efektīvāka, bet joprojām nav pietiekama 29% gadījumu. Augstāks ķermeņa masas indekss (ĶMI) un protonu sūkņa inhibitoru (PSI) lietošana asociējas ar tendenci uz samazinātu klopidogrela efektivitāti.
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    The Impact of International Nonproprietary Names Integration on Prescribing Reimbursement Medicines for Arterial Hypertension and Analysis of Medication Errors in Latvia
    (2022-08-16) Gavrilova, Anna; Zolovs, Maksims; Latkovskis, Gustavs; Urtāne, Inga; Department of Pharmaceutical Chemistry; Red Cross Medical College of Rīga Stradiņš University; Statistics Unit
    The use of international nonproprietary names (INNs) has been mandatory for prescriptions of state-reimbursed drugs in Latvia since 1 April 2020. In a retrospective analysis, we aimed to examine the impact of the new regulation on changes in the prescribing and dispensing practice of antihypertensive agents with an example of bisoprolol or/and perindopril and their combinations. All state-reimbursed bisoprolol and/or perindopril prescriptions for arterial hypertension were evaluated in two time periods: 1 April 2018 to 31 March 2019 and 1 April 2020 to 31 March 2021. The proportion of INN prescriptions increased from 2.1% to 92.3% ( p < 0.001, φ = 0.903). The rate of fixed-dose combinations (FDCs) increased from 60.8% to 66.5% ( p < 0.001, φ = 0.059). The rate of medication errors was 0.6%. The most common (80.6%) error was that the dispensed medicine dose was larger or smaller than indicated on the prescription. In addition, prescribing an FDC medicine increased the chance of making an error by 2.5 times on average. Regulatory changes dramatically affected the medicine-prescribing habits of INNs. The increase in FDC prescription rates may align with the recommendations of the 2018 ESC/ESH guidelines. The proportion of total errors is estimated as low, but control mechanisms are needed to prevent them.
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    Knowledge about Disease, Medication Therapy, and Related Medication Adherence Levels among Patients with Hypertension
    (2019-10-28) Gavrilova, Anna; Bandere, Dace; Rutkovska, Ieva; Šmits, Dins; Mauriņa, Baiba; Poplavska, Elita; Urtāne, Inga; Department of Pharmaceutical Chemistry; Department of Applied Pharmacy; Department of Public Health and Epidemiology; Institute of Public Health
    Background and Objectives: A particular problem in cardiology is poor adherence to pharmacological treatment among patients with hypertension. It is known that approximately half of these patients do not use their medications as prescribed by their doctor. Patients may choose not to follow the doctor's recommendations and regularly do not control their blood pressure, owing to many factors. A convenient method for measuring the level of adherence is the Morisky Medication Adherence Scale, which also provides insight into possible remedies for low adherence. We investigated their therapy, knowledge about the disease and its control, and demographic differences to assess the adherence of patients with hypertension. Materials and Methods: This was a cross-sectional observational study. Data were collected through a survey of 12 pharmacies in Latvia. The study involved 187 participants with hypertension. Results: The prevalence of non-adherence was 46.20% in Latvia. The oldest patients were the most adherent (p = 0.001, β = 0.27). The higher the self-rated extent from 0 to 10, to which the patient takes their antihypertensives exactly as instructed by their physician, the higher the level of adherence (p < 0.0001, β = 0.38), where at "0", the patient does not follow physician instructions at all, and at "10", the patient completely follows the physician's instructions. Non-adherent patients tend to assess their medication-taking behavior more critically than adherent patients. The longer the patient is known to suffer from hypertension, the more adherent he or she is (p = 0.014, β = 0.19). Conclusions: Medication non-adherence among patients with hypertension is high in Latvia. Further investigations are needed to better understand the reasons for this and to establish interventions for improving patient outcomes.
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    Opportunities of Amlodipine as a Potential Candidate in the Evaluation of Drug Compliance during Antihypertensive Therapy
    (2023-02-10) Kustovs, Dmitrijs; Urtāne, Inga; Sevostjanovs, Eduards; Moreino, Eva; Trušinskis, Kārlis; Department of Pharmaceutical Chemistry; Department of Internal Diseases
    Background and Objectives: Blood pressure measurement is essential evidence to establish that the chosen medicine and dosage are appropriate, and also indirectly indicates whether the medicine is being used at all. Therefore, current research compares adherence to the target blood pressure at home and in the hospital between different age groups, using similar combinations of the drugs prescribed by the doctor within ongoing antihypertensive therapy. Moreover, it is very important to develop a method for the determination of amlodipine and its metabolite, which would suitable for clinical applications, when the result is needed as quick as possible. Materials and Methods: This prospective study included patients aged ≥18 years who were diagnosed with hypertension. Subjects were divided into two age groups according to European Society of Cardiology (ESC) hypertension guidelines; older patients (≥65 years) and adult patients (
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    Role of a National Health Service Electronic Prescriptions Database in the Detection of Prescribing and Dispensing Issues and Adherence Evaluation of Direct Oral Anticoagulants
    (2024-05-09) Gavrilova, Anna; Zolovs, Maksims; Šmits, Dins; Ņikitina, Anastasija; Latkovskis, Gustavs; Urtāne, Inga; Department of Pharmaceutical Chemistry; Statistics Unit; Department of Public Health and Epidemiology
    Background: Anticoagulation therapy plays a crucial role in the management of atrial fibrillation (AF) by significantly reducing the risk of stroke. Direct oral anticoagulants (DOAC) became preferred over warfarin due to their superior safety and efficacy profile. Assessing adherence to anticoagulation therapy is necessary in clinical practice for optimising patient outcomes and treatment efficacy, thus emphasising its significance. Methods: A retrospective study utilised the Latvian National Health Service reimbursement prescriptions database, covering prescriptions for AF and flutter from January 2012 to December 2022. The proportion of days covered method was selected for adherence assessment, categorising it into three groups: (1) below 80%, (2) between 80% and 90%, and (3) above 90%. Results: A total of 1,646,648 prescriptions were analysed. Dabigatran prescriptions started declining after 2020, coinciding with a decrease in warfarin prescriptions since 2018. The total adherence levels to DOAC therapy were 69.4%. Only 44.2% of users achieved an adherence level exceeding 80%. The rate of paper prescriptions decreased from 98.5% in 2017 to 1.3% in 2022. Additionally, the utilisation of international non-proprietary names reached 79.7% in 2022. Specifically, 16.7% of patients selected a single pharmacy, whereas 27.7% visited one or two pharmacies. Meanwhile, other patients obtained medicines from multiple pharmacies. Conclusions: The total adherence level to DOAC therapy is evaluated as low and there was no significant difference in age, gender, or “switcher” status among adherence groups. Physicians’ prescribing habits have changed over a decade.
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    The Role of Genetic Factors on the Effect of Additional Doses of Clopidogrel to Improve Personalized Effectiveness in Patients. Summary of the Doctoral Thesis
    (Rīga Stradiņš University, 2014) Urtāne, Inga; Latkovskis, Gustavs; Štokmane, Aina Silvija
    Introduction. Hyporesponsiveness to clopidogrel has been associated with increased risk of cardiovascular events for patients undergoing percutaneous coronary intervention (PCI). Low response to clopidogrel (hyporesponsivevess) may be overcome by additional loading doses (LD) and higher maintenance doses (MD). The influence of genetic polymorphisms on efficacy of personalized clopidogrel dosing remains unclear. The aim of this study was to investigate whether genetic polymorphisms of two cytochromes (CYP2C19, CYP2C9) and ABCB1 modify effect of additional LDs (600 mg) and higher MD (150 mg) used to overcome hyporesponsiveness of clopidogrel and to evaluate long-term safety of higher platelet reactivity index (PRI) cutoff value of <60% during one year period after PCI. Methods. In a prospective single-center study we enrolled 118 patients undergoing PCI with drugeluting stent (DES). PRI was measured using the Vasodilator-Stimulated Phosphoprotein index (VASP). Genetic polymorphisms of CYP2C19, CYP2C9 and ABCB1 were determined. In patients hyporesponsive to the initial LD the doseadjustment was performed using up to 3 additional 600 mg LDs in order to achieve PRI <60%, and both 150 mg and 75 mg MD were tested at the follow-up. Long-term clinical follow up was obtained in all patients. Results. Patients with at least one CYP2C19*2 allele had higher baseline PRI after the initial LD (78.2±13.1 vs 65.3±19.5, p=0.005). The PRI reduction with additional LD was significantly smaller in carriers of the CYP2C19*2 (25.2±15.6 vs 35.5±16.8, p=0.025) and similar trend was observed with additional LDs. Both MDs were less effective in presence of CYP2C19*2: 53.3±12.1 vs 40.3±13.5, respectively; p=0.001 on day 10 while on MD of 150 mg, and 65.5±10.4 vs 56.3±14.5, respectively; p=0.020 on day 40 on MD of 75 mg. No such differences were observed for other polymorphisms. Low responders to clopidogrel had higher body mass index (BMI) (32.8±3.9 vs 29.6±4.9; p=0.007). More patients in hyporesponders group had concomitantly proton pump inhibitor (PPI) therapy compared to responders (16 vs 7; p=0.381). Conclusions. The patients carrying at least one loss-of-function CYP2C19*2 allele have significantly higher PRI following an initial LD and additional LDs. In the presence of CYP2C19*2 higher MD of clopidogrel (150 mg) was more effective but still remains insufficient in 29% of cases. Higher BMI and use of PPIs were associated with a trend to decreased efficiency of clopidogrel.
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    Stability of Direct Oral Anticoagulants Concentrations in Blood Samples for Accessibility Expansion of Chromogenic Assays
    (2023-07-21) Gavrilova, Anna; Meisters, Jānis; Latkovskis, Gustavs; Urtāne, Inga; Department of Pharmaceutical Chemistry; Red Cross Medical College of Rīga Stradiņš University
    Background and Objectives: Direct oral anticoagulants (DOACs) are used for minimising the risk of thromboembolic events. In clinical practice, there is no need to measure DOAC concentration in the routine. Nevertheless, there are cases where such measurements are necessary, as the European Society of Cardiology's guideline recommends. However, determining DOAC levels is not available for everyone due to chromogenic assay availability limitations from sample storage problems, as tests are performed only in a few healthcare settings. This study aimed to assess whether more applicable storage conditions could be used for transportation to provide chromogenic assays for outpatient healthcare and other hospitals' practices. Materials and Methods: Chromogenic assays measuring anti-FXa (for rivaroxaban and edoxaban) and anti-FIIa (for dabigatran) were used. Concentrations were determined immediately after blood collection as baseline value: (1) after the storage of citrated whole blood in refrigerator (+2-8 °C); (2) of citrated plasma in refrigerator (+2-8 °C); and (3) of citrated frozen plasma (-20 °C) on the third and seventh days of storage. Acceptable change limits were considered stable if the deviation did not exceed ±20% of the baseline value. Results: The median (Cl 95%) baseline value of rivaroxaban was 168 (147-236) ng/mL; of dabigatran 139 (99-178) ng/mL; and of edoxaban-174 (135-259) ng/mL. The median deviation from a baseline value stored as citrate whole blood samples (+2-8 °C) was 5.4% and 3.4%; as citrated plasma (+2-8 °C) was 0.4% and -0.6%; and as citrated frozen plasma (-20 °C) was -0.2% and 0.2% on the third and seventh days of storage, respectively. Conclusions: Our data suggest that whole blood samples stored in a refrigerator, as well as citrated plasma samples stored in both the refrigerator and freezer, preserve DOAC concentration stable at +2-8 °C or -20 °C for up to 7 days, and are suitable for transportation, except for low-concentration samples.