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

Publisher Copyright: © 2023 by the authors.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.Peer reviewe

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

Publisher Copyright: © 2022 by the authors.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.publishersversionPeer reviewe

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

Publisher Copyright: © 2023 by the authors.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.Peer reviewe

Current state of angina treatment in the outpatient population and heart rate monitoring survey in Latvia (relity latvia)

The aim of the REALITY Latvia survey was to accumulate information about treated stable angina outpatients regarding their characteristics, heart rate (HR), treatment, and quality of life. Thirty cardiologists were involved with 1-15 patients each. In total, data about 300 patients were obtained. Patients were examined and questioned during one visit. A high HR was defined above 70 beats per minute (bpm), in accordance to recent evidence. Mean HR was 70.3 ± 11.3 bpm and 45% of patients had HR above 70 bpm. The opinion of practitioners regarding HR differed. For example, a HR level within the range 70-80 bpm was perceived by cardiologists as “normal”, “borderline high” and “high”. The mean target HR that physicians wanted to achieve was 60.1 ± 4.7 bpm. Beta blockers were used in 91% of cases. The more widely used beta blockers were metoprolol (47%) and bisoprolol (35%) in mean daily doses 69.7 ± 30.1 mg and 5.3 ± 2.0 mg, respectively. REALITY Latvia data suggest that, despite wide use of beta blockers, HR control in stable angina patients is insufficient. This is caused by insufficient understanding of HR as a treatment target by physicians and use of beta blockers in suboptimal dosages.publishersversionPeer reviewe

Heart rate and other risk factors in outpatients with stable coronary artery disease in Latvia

Funding Information: This survey was supported by Servier Latvia.The aim of the study was to characterise coronary artery disease (CAD) outpatients in Latvia by risk factors (RF) including heart rate (HR), physical examination data, clinical data and treatment. Twelve practitioners had each examined and questioned 6 to 12 patients with established CAD (n = 120). The most frequent cardiovascular (CV) RF and co-morbidity were dyslipidemia (94.2%) and hypertension (78.3%), respectively. Prevalence of increased resting HR (≥70 bpm) was 35.9% and 33.6%, when measured by pulse palpation and electrocardiography, respectively. Regarding other RFs, prevalence of treated but insufficiently controlled blood pressure 140/90 mmHg, total cholesterol 1 > 5 mmol/l and triglycerides > 1.7 mmol/l was 25.8%, 30.1% and 33.3%, respectively. Aspirin, statins and angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers were used in 96.7%, 94.2% and 85.0% of cases, respectively. Beta blockers were used in 81.7% of cases. Average daily doses of most frequently used β blockers (metoprolol and bisoprolol) were 32% and 53% from target doses, respectively. In three cases β blockers were combined with ivabradin. Our results suggest that practitioners follow guidelines and consider CV prevention by treating CAD patients. Our data identified, however, unused potential for better control of increased HR by higher doses and combinations of HR-reducing agents.publishersversionPeer reviewe

Nitric oxide production and arachidonic acid metabolism in platelet membranes of coronary heart disease patients with and without diabetes

Aim: To evaluate the levels of nitrite (NO2-) and nitrate (NO3-) ions and the incorporation of [3H]arachidonic acid (AA) into phospholipids of platelet membranes from coronary artery disease (CAD) patients with and without diabetes (NIDDM). Subjects and Methods: Eighteen CAD patients (group A), 18 CAD patients with NIDDM (group B), and 20 healthy controls (group C) without dyslipidemia, peripheral vascular disease and hypertension were included in the study. The groups were matched for age, sex and body mass index. The diagnosis of CAD was confirmed by coronary angiography. The nitric oxide end products (NOx), NO2- plus NO3- ions in platelet membranes, were determined using a spectrophotometric method based on the Griess reaction. The turnover of phospholipids was evaluated by incorporation of [3H]AA into platelet membrane phospholipids. Results: A significantly smaller amount of NOx ions was in the platelet membrane of groups A (40 ± 8 μmol/l) and B (29 ± 10 μmol/l) than C (57 ± 6 μmol/l), p < 0.001. Conversely a significantly greater amount of [3H]AA was incorporated into platelet phospholipids of group B patients (5,123 ± 1,637 dpm/mg) than groups A (3,159 ± 1,253 dpm/mg; p < 0.002) and C (1,621 ± 417 dpm/mg). An inverse correlation between [3H]AA incorporation and NOx levels was established: r = -0.76 (p < 0.05, n = 36) in CAD patients. Conclusions: Diabetes in CAD patients decreased the ability to produce platelet-derived NO and affects AA metabolism. This may result in higher platelet sensitivity to aggregating stimuli.publishersversionPeer reviewe

Analysis of polymorphisms at the adiponectin gene locus in association with type 2 diabetes, body mass index and cardiovascular traits in Latvian population

Funding Information: The work was supported by the National Research Programme in Medicine 2006–2009 project No. 14, “Creation of the unified and generally accessible data base on the main life expectancy and life quality threatening pathologies and epidemiology of their risk factors in Latvian population”, Latvian Council of Science Grant 01.0023.01. We acknowledge Genome Database of Latvian Population, Latvian Biomedical Research and Study Centre for providing data and DNA samples. Copyright: Copyright 2010 Elsevier B.V., All rights reserved.Despite the number of recently conducted studies seeking to determine the association between genetic variants of adiponectin gene and susceptibility to type 2 diabetes (T2D) and increased body mass index (BMI), the results obtained are often inconsistent. To determine the impact of common polymorphisms in promoter and coding regions of adiponectin gene on these conditions in Latvian population, we selected ten SNPs (rs2241767, rs1501299, rs3777261, rs16861210, rs2241766, rs822396, rs182052, rs17300539, rs16861194, rs266729) based on haploblock structure and previously reported association studies. The selected SNPs were screened in a study group of 835 participants from the Genome Data Base of Latvian Population and mainly consisted of patients with T2D and coronary heart disease. None of the individual polymorphisms were significantly associated with T2D status or BMI when analysed using logistic or linear regression and adjusted for gender, age and other significant covariates. Frequency of rs2241766 T allele homozygotes however was significantly increased in T2D patients compared to controls (uncorrected P = 0.007). When analysed with other traits, the rs182052 G allele was found to be less frequent in patients suffering from myocardial infarction (P = 0.02; OR = 0.76, CI95% [0.61-0.92]) compared to others. Haplotype analysis revealed significant association of one haplotype with atrial fibrillation (uncorrected P = 0.01). In summary, we conclude that SNPs in adiponectin gene are unlikely to represent the risk for T2D, but may be involved in pathogenesis of CHD in the Latvian population.publishersversionPeer reviewe

Bempedoic acid in the management of lipid disorders and cardiovascular risk. 2023 position paper of the International Lipid Expert Panel (ILEP)

Cardiovascular disease (CVD) is a chronic non-communicable disease (NCD) and the predominant cause of morbidity and mortality worldwide. Substantial reductions in the CVD prevalence have been achieved in recent years by the attenuation of risk factors (particularly hypertension and dyslipidaemias) in primary and secondary prevention. Despite the remarkable success of lipid lowering treatments, and of statins in particular, in reducing the risk of CVD, there is still an unmet clinical need for the attainment of guideline lipid-targets in even 2/3 of patients. Bempedoic acid, the first in-class inhibitor of ATP-citrate lyase presents a new approach to lipid-lowering therapy. By reducing the endogenous production of cholesterol, upstream of the rate-limiting enzyme HMG-CoA-reductase, i.e., the target of statins, bempedoic acid reduces circulating plasma concentrations of low-density lipoprotein cholesterol (LDL-C), and major adverse CVD events (MACE). Bempedoic acid has the potential to contribute to the reduction of CVD risk not only as monotherapy, but even further as part of a lipid-lowering combination therapy with ezetimibe, reducing LDL-C cholesterol up to 40%. This position paper of the International Lipid Expert Panel (ILEP) summarises the recent evidence around the efficacy and safety of bempedoic acid and presents practical recommendations for its use, which complement the 'lower-is-better-for-longer' approach to lipid management, which is applied across international guidelines for the management of CVD risk. Practical evidence-based guidance is provided relating to the use of bempedoic acid in atherosclerotic CVD, familial hypercholesterolaemia, and statin intolerance. Although there are still no sufficient data avilable for the role of bempedoic acid in the primary prevention of CVD, its favourable effects on plasma glucose and inflammatory markers makes this drug a rational choice in the patient-centred care of specific groups of primary prevention

Genetic Characteristics of Latvian Patients with Familial Hypercholesterolemia: The First Analysis from Genome-Wide Sequencing

This article belongs to the Special Issue New Possibilities for the Treatment of DyslipidemiasBackground: There is limited data on the genetic characteristics of patients with familial hypercholesterolemia (FH) in Latvia. We aim to describe monogenic variants in patients from the Latvian Registry of FH (LRFH). Methods: Whole genome sequencing with 30 coverage was performed in unrelated index cases from the LRFH and the Genome Database of Latvian Population. LDLR, APOB, PCSK9, LDLRAP1, ABCG5, ABCG8, LIPA, LPA, CYP27A1, and APOE genes were analyzed. Only variants annotated as pathogenic (P) or likely pathogenic (LP) using the FH Variant Curation Expert Panel guidelines for LDLR and adaptations for APOB and PCSK9 were reported. Results: Among 163 patients, the mean highest documented LDL-cholesterol level was 7.47 1.60 mmol/L, and 79.1% of patients had LDL-cholesterol 6.50 mmol/L. A total of 15 P/LP variants were found in 34 patients (diagnostic yield: 20.9%): 14 in the LDLR gene and 1 in the APOB gene. Additionally, 24, 54, and 13 VUS were detected in LDLR, APOB, and PCSK9, respectively. No P/LP variants were identified in the other tested genes. Conclusions: Despite the high clinical likelihood of FH, confirmed P/LP variants were detected in only 20.9% of patients in the Latvian cohort when assessed with genome-wide next generation sequencing.This research is funded by the Latvian Council of Science, project “Low-coverage whole-genome sequencing analysis of polygenic mechanisms of high cholesterol levels in patients with clinically diagnosed or possible familial hypercholesterolemia”, project No. lzp-2020/1-0151.info:eu-repo/semantics/publishedVersio