Role of a National Health Service Electronic Prescriptions Database in the Detection of Prescribing and Dispensing Issues and Adherence Evaluation of Direct Oral Anticoagulants.

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.

Quantitative Adherence Level Evaluation Among Long-Term Antiretroviral Therapy Patients in Latvia.

Introduction: The global prevalence of human immunodeficiency virus (HIV) remains substantial, particularly in regions with limited resources, despite the progress in scientific knowledge and the accessibility of antiretroviral therapy (ART). ART is the cornerstone of HIV treatment. Ensuring proper adherence to medication therapy is essential for effective HIV infection control. Meanwhile, Latvia reported one of the highest rates of HIV infections among EU countries. Purpose: This study aimed to assess adherence levels to ART among long-term users by utilizing the National Health Service prescription electronic database records. It is essential to determine whether non-adherence is a problem at the state level. Patients and Methods: This retrospective study was conducted utilizing the Latvian National Health Service's reimbursed prescription database, covering the period from January 2017 to December 2018. The analysis included ART prescriptions. Medication adherence was assessed using a Proportion of Days Covered (PDC) calculation. The adherence rates were categorized into three groups: (1) < 80% (non-adherence), (2) 80% to 90% (suboptimal adherence), and (3) > 90% (optimal adherence) groups. Results: A total of 25,892 ARV medicines prescription records for 1471 patients were analysed. The adherence level of long-term ART was 38.3%. Of all patients, only 37 (2.5%) had achieved an optimal and 25 (1.7%) suboptimal adherence level. Meanwhile, the remaining patients (95.8%) were identified as non-adherent to therapy. It has been determined that 96.1% (n=1414) of patients experienced a time gap of more than 90 days between their prescriptions at least once. On average, each patient had 3.5 of these gaps, with a maximum of 7 times. Conclusion: Medication adherence level to ART is low in Latvia. Less than 3% of patients achieved optimal adherence levels with a PDC higher than 90%. These results are concerning. Further studies and interventions must be conducted to enhance adherence levels.

National Trends in the Use of State-Reimbursed Lipid-Lowering Medications in Latvia (2012-2021).

BACKGROUND: We aimed to estimate the trends in dispensing rate and the spectrum of all state-funded lipid-lowering medications (LLMs) in Latvia over a decade. METHODS: Using data from the National Health Service of the Republic of Latvia, we retrospectively analyzed all dispensed LLM-containing drug units in a ten-year period from 2012 to 2021. RESULTS: In Latvia, 318.2 million oral and 994 subcutaneous units of LLMs were dispensed over a decade. Statins were the most dispensed LLMs (94.5%), and their use doubled from 19.7 to 43.5 million units. The proportion of high-intensity statins increased from 31.3% to 45.2%. The dispensing rate of ezetimibe increased from 184.7 thousand to 4.8 million. The share of fixed-dose statin combinations with ezetimibe grew from 0.2% to 10.0% among all statins and from 22.2% to 90.9% among all ezetimibe units. Statin use for primary and secondary prevention increased from 7.0 to 19.9 million and from 12.8 to 23.6 million units, respectively. CONCLUSION: The dispensing rate of statins doubled, and the use of ezetimibe increased more than 25 times in Latvia over a decade. The proportion of high-intensity statins increased from one third to almost half of all statins. Fixed-dose statin combinations with ezetimibe became frequently used.

Stability of Direct Oral Anticoagulants Concentrations in Blood Samples for Accessibility Expansion of Chromogenic Assays.

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.

Opportunities of Amlodipine as a Potential Candidate in the Evaluation of Drug Compliance during Antihypertensive Therapy.

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 (<65 years). Assessment of adherence rate to antihypertensive medications was performed using a measurement of systolic blood pressure and comparing this to ESC hypertension guideline data. A simple liquid chromatography-tandem mass spectrometer (LC-MS/MS) method for determination of amlodipine and dehydroamlodipine was developed and validated according to the European Medicines Agency guideline on bioanalytical method validation at the Latvian Institute of Organic Synthesis. Results: A total of 81 patients with arterial hypertension were enrolled in this study. A significant number of patients were overweight (N = 33, 40.7%) and obese (N = 36, 44.4%). To control arterial hypertension, 70 (86.4%) patients used fixed-dose combinations, where one of the components was amlodipine. Practically, 36 (44.4%) hypertensive subjects were not able to comply with target blood pressure. Nonetheless, 38 (46.9%) patients who received fixed-dose combinations were able to comply with target blood pressure. Conclusions: Adherence to ESC hypertension guideline proposed target blood pressure was relatively low among hypertensive subjects even though a significant number of patients were taking fixed-dose combinations. Therefore, optimizing prevention, recognition, and care of hypertensive young adults require intensive educational interventions. Moreover, survey data suggest that therapeutic drug monitoring using the validated simple, sensitive LC-MS/MS method is pivotal for further understanding factors influencing adherence.

The Impact of International Nonproprietary Names Integration on Prescribing Reimbursement Medicines for Arterial Hypertension and Analysis of Medication Errors in Latvia.

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.

Adherence Level to Arterial Hypertension Treatment: A Cross-Sectional Patient Survey and Retrospective Analysis of the NHS Prescription Database.

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.

Factors related to poor adherence in Latvian asthma patients.

BACKGROUND: The problem of nonadherence to therapy is a key reason of insufficient asthma control. Evaluating the beliefs about asthma medication, cognitive and emotional perceptions may help to identify patients with poor adherence to treatment in clinical practice which need additional attention in order to increase the likelihood of them taking their asthma medication according to the prescribed treatment protocol. The purpose of this study is to assess whether beliefs about asthma medication, cognitive and emotional factors are related to poor treatment adherence of asthma medication in a sample of asthma patients in Latvia. METHODS: Study subjects were asthma patients attending outpatient pulmonologist consultations in Latvia during September 2013 to December 2015. Beliefs about asthma medicine, cognitive and emotional factors related to asthma were determined in a cross-sectional, self-administered survey. The validated Beliefs about Medicines Questionnaire (BMQ) and the Brief Illness Perception Questionnaire (brief IPQ) were used. Treatment adherence was assessed using 5-item version of the Medication Adherence Reporting Scale (MARS). The total sample size was 352 patients. Logistic regression models were used to predict poor adherence to asthma treatment. The validity of each logistic regression model was assessed by the Hosmer/Lemeshow test. The main outcome measure was self-reported adherence to treatment. RESULTS: The more the patients agreed with the statement "My future health depends on my asthma medication" the lower the possibility of poor adherence to asthma treatment (OR 0.42; 95% CI 0.24-0.74). The more concerned the patients were in regard to long-term effects of their medication (OR 2; 95% CI 1.22-3.27), the higher the probability of poor treatment adherence. CONCLUSIONS: Screening asthma patients using the BMQ may help to identify those to benefit from interventions targeting their concerns and medication beliefs in order to improve adherence to asthma medication.

Role of genetic factors on the effect of additional loading doses and two maintenance doses used to overcome clopidogrel hyporesponsiveness.

BACKGROUND AND OBJECTIVE: Additional loading doses and higher maintenance doses (MDs) have been used to overcome hyporesponsiveness of clopidogrel. We aimed to investigate whether genetic polymorphisms of two cytochromes (CYP2C19 and CYP2C9) and ABCB1 modify effect of such dose-adjustment strategy. MATERIALS AND METHODS: We enrolled 118 patients undergoing elective or acute percutaneous coronary intervention (PCI) with drug eluting stent (DES). Platelet reactivity index (PRI) was measured using the vasodilator-stimulated phosphoprotein (VASP) index and a cut-off value of ≥ 60% was defined as hyporesponsiveness. Polymorphism of two cytochromes (CYP2C19, CYP2C9) and gene ABCB1 were determined. In patients hyporesponsive to the initial LD the dose-adjustment 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. 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 subsequent additional LDs. Both MDs were less effective in presence of CYP2C19*2. Target PRI was, however, more frequently achieved with higher MD even in presence of CYP2C19*2 (in 70.6% vs. 23.5% of hyporesponders, P=0.008). No such differences were observed for other polymorphisms. CONCLUSIONS: In patients hyporesponsive to a routine clopidogrel doses the potency of additional LD and higher MD of clopidogrel is compromised by presence of CYP2C19*2 allele. The dose-adjustment strategy is not affected by ABCB1 C3435T or CYP2C9 genotypes.

Clopidogrel and the possibility of drug-drug interaction in primary health care.

INTRODUCTION: Clopidogrel ineffectiveness is a serious problem in antiplatelet therapy. Many factors may contribute to this phenomenon. One of them is clopidogrel drug-drug interaction with CYP2C19 and CYP3A4 enzyme inhibitors. The main goal of this descriptive study was to assess the prevalence of cases of clopidogrel-drug interactions in the primary health care physicians' practices. MATERIALS AND METHODS: During 2010-2011, 80 patients receiving clopidogrel antiplatelet therapy from primary care physicians' clinical practices were involved in this study. By using questionnaires and case histories, the following information was collected: Age, gender, clinical diagnoses, and medications used. RESULTS: IN THE CURRENT STUDY, DRUGS WERE USED THAT COULD POTENTIALLY INFLUENCE THE EFFECT OF CLOPIDOGREL: Omeprazole, lipophilic statins, calcium channel blockers (CCB). There was a different use of the above-mentioned drugs before and after the initiation of the clopidogrel therapy, e.g., 12 (15.0%) and 44 (55.0%) patients used proton pump inhibitors (PPI) before and after the clopidogrel therapy accordingly (P = 0.16; χ (2) = 1.91). However, pantoprazole was recommended more often than other PPI. The use of the potential CYP3A4 inhibitors - lipophilic statins and CCB - was increased after the prescription of clopidogrel too. Concomitant use of statins (mainly atorvastatin) with clopidogrel was observed in 75 (93.8%) patients and the use of CCB (mainly amlodipine) - in 33 (41.3%) patients. CONCLUSION: In the primary health care practices, it is revealed that there is co-medication of clopidogrel with weak CYP3A4 inhibitors, such as lipophilic statins and amlodipine, and with the moderate CYP2C19 inhibitor - omeprazole. The latter co-medication is potentially harmful and it is very important to inform the first care professionals about the opportunity to change omeprazole to pantoprazole, which does not influence clopidogrel biotransformation.