Factors Facilitating and Hindering Development of a Medication Use Review Service in Eastern Europe and Iran-Cross-Sectional Exploratory Study.

Polypharmacy is a common issue in patients with chronic diseases. Eastern-European countries and Iran are exploring possibilities for implementing the Medication Use Review (MUR) as a measure for optimizing medication use and ensuring medication safety in polypharmacy patients. The aim of this study was to gain insights into the development of the community pharmacy sector and map facilitators and barriers of MUR in Eastern Europe and Iran. The representatives of the framework countries received a questionnaire on community pharmacy sector indicators, current and future developments of pharmacies, and factors encouraging and hindering MUR. To answer the questionnaire, all representatives performed document analysis, literature review, and qualitative interviews with key stakeholders. The socio-ecological model was used for inductive thematic analysis of the identified factors. Current community pharmacist competencies in framework countries were more related to traditional pharmacy services. Main facilitators of MUR were increase in polypharmacy and pharmaceutical waste, and access to patients' electronic list of medications by pharmacists. Main barriers included the service being unfamiliar, lack of funding and private consultation areas. Pharmacists in the framework countries are well-placed to provide MUR, however, the service needs more introduction and barriers mostly on organizational and public policy levels must be addressed.

Medication-related factors associated with proton pump inhibitor prescription beyond official guidelines in older adults.

PURPOSE: To investigate the relationship between medications with a known risk of gastrointestinal bleeding and proton pump inhibitor (PPI) prescription not according to guidelines. METHODS: An analysis of the records of 592 hospitalised patients aged 65 years or older was undertaken. The number of all medicines, potentially inappropriate medicines according to the EU(7)-PIM list and the Beers Criteria 2019 and medicines with a known risk of gastrointestinal bleeding, was compared in patients with PPI prescription not given based on guidelines and in patients with no PPI prescription. RESULTS: Patients prescribed PPI not based on guidelines used more medications on average (9.6 vs. 6.4, p < 0.001), more PIMs according to the EU(7)-PIM list (2.4 vs. 1.1, p < 0.001) and the Beers criteria (2.0 vs. 0.6, p < 0.001) at hospital admission and at discharge (8.9 vs. 7.5, p < 0.001, mean number of medications), (2.0 vs. 1.2, p < 0.001, EU(7)-PIM list), (1.9 vs. 0.8, p < 0.001, Beers criteria) than patients with no PPI prescription. Patients prescribed PPI not according to guidelines were more frequently using direct oral anticoagulants (28% vs. 12.8%, p < 0.001), corticosteroids (5.3% vs. 0.7%, p = 0.025) at hospital admission and at discharge (25.9% vs. 16.5%, p = 0.018, oral anticoagulants), (6.6% vs. 1%, p = 0.006, corticosteroids), (13.3% vs. 5.4%, p = 0.004, warfarin) than patients with no PPI prescription. CONCLUSION: The number of medications, potentially inappropriate medications according to the EU(7)-PIM list and Beers criteria, and the use of direct oral anticoagulants, warfarin and corticosteroid prescriptions were the medication-related factors associated with PPI prescription not according to guidelines in elderly patients.

Relationship between adolescents' and their parents' attitudes toward medicines and awareness of the risk of medicines.

Background When they reach adolescence, children begin to independently use medicine without their parents' supervision, but parents usually still want to be involved in their drug therapy. Objective The aim of this study was to investigate how parental attitudes and awareness toward medicine relate to adolescents' attitudes and awareness. Setting Twelve secondary schools in different regions of the Slovak Republic. Method Adolescents and parents responded to a questionnaire, and the answers were paired and analysed. Parental and adolescents' attitudes toward medicines and awareness of the risk of medicines were measured using a five-point Likert scale. Main outcome measure The strength of the relationship between parents' and their adolescent children's level of agreement with statements about medicines. Results There were significant differences between parentsá¾½ and adolescents' mean Likert scores for statements about their attitudes toward medicines and their awareness of the risk of medicines (p < 0.05). Parents and adolescents were not fully aware of the risks of cough medicine (73.5% and 76.1%), antihistamines (32.7% and 52.1%), painkillers (33.6% and 47%) and combining medicines (25.2% and 40.4%). More than half of the parents and adolescents had a positive perception of the effectiveness of medication and believed that taking medicine would not hurt adolescents. Parents' and adolescents' responses to the statements were directly proportional (r = 0.94, p < 0.001). Conclusion The analysis revealed a relationship between Slovakian adolescents' and their parents' attitudes and awareness toward medicine; it highlighted areas of adolescents' and parents' education about the proper use of medications.

Adolescents' knowledge and perception of medicine risk.

BACKGROUND: Adolescents often start to use medicines independently without having sufficient knowledge or previous experience, which can lead to the inappropriate use of medicines. METHODS: Adolescents' knowledge of medicines, perception of their effectiveness, risk of the medicines and a possible association between these terms and health status, age and gender were studied. A questionnaire-based survey was conducted in 13-18-year-old adolescents in secondary school. RESULTS: There were differences in adolescents' knowledge, attitude and perception of risk of medicines related to their age, gender and, to a lesser extent, health status. Chronically ill adolescents had better knowledge about allergy medicines according to the mean score of a 5-point Likert scale (1, strongly agree; 5, strongly disagree; 2.30 vs 2.51, P = 0.005) and they agreed to a lesser extent than healthy adolescents that rescription medicines improve their health (2.21 vs 2.05, P = 0.034). Medicine knowledge differed significantly with age (P < 0.001). Older adolescents (16-18 years old) were more knowledgeable about medicines (1.33-3.04 vs 1.64-3.71, P < 0.05) and they agreed to a lesser extent than younger adolescents (2.11-4.03 vs 1.86-3.56, P < 0.05) with statements that prescription medicines are effective and safe. Girls were more knowledgeable than boys (1.43-3.04 vs 1.64-3.14, P < 0.05) and preferred to discuss medicines with their parents. CONCLUSION: The level of knowledge and the perception of medicine risk are associated with the health status, age and gender of adolescents, and health-care professionals need to be aware of this when educating adolescents.

Caustic Ingestion in the Elderly: Influence of Age on Clinical Outcome.

Caustic poisonings are still associated with many fatalities. Studies focusing on the elderly are rare. The purpose of the present study was to compare the clinical outcomes of caustic ingestion injury in elderly and non-elderly adults with regard to gender, intent of exposure, substance ingested, severity of mucosal injury, complications, and mortality. Caustic substance exposures reported to the National Toxicological Information Centre in Slovakia during 1998-2015 were reviewed retrospectively. The patients were divided into two groups: the non-elderly (<60 years) and elderly adults (≥60 years). The mortality rate in the elderly was significantly higher (elderly 23.0% vs. non-elderly 11.3%; p = 0.041). The risk of fatal outcome in the elderly was increased by acid ingestion (OR = 7.822; p = 0.002), particularly hydrochloric acid (OR = 5.714, p = 0.006). The incidence of respiratory complications was almost two times higher in the elderly was 31.1% vs. 17.4% for the non-elderly (p = 0.037). Respiratory complications significantly correlated with an increased mortality rate (p = 0.001) in the elderly whereas there was no association between GI complications and mortality in the elderly (p = 0.480). Elderly patients with respiratory complications had the poorest clinical outcomes. The highest risk of complications and fatalities was observed in patients after hydrochloric acid ingestion.

Identifying the interprofessional agreement between community pharmacists and general practitioners views on collaborative practice in Slovakia.

BACKGROUND: The collaboration of community pharmacists (CPs) and general practitioners (GPs) has a positive effect on healthcare outcomes. There are still many countries, where no efforts have been made to enhance this type of teamwork. There is no evidence of how GPs and CPs collaborate in Slovakia. The objective of this study is to identify the current level of GPs and CPs teamwork in Slovakia and to identify the key factors, where these professions agree. METHODS: Two parallel electronic surveys were prepared and sent out by e-mail to CPs and GPs in Slovakia. The questions in the multi-choice questionnaires were divided into 6 sections: teamwork experience, attitudes to collaborative practice, preferred method of communication, preferred tasks done by CPs, anticipated areas of future collaboration and perceived barriers to collaborative practice. The results were analyzed separately by the proportion of agreements within each group. RESULTS: From the total of 670 questionnaires, which were sent out (434 to GPs and 236 to CPs) 347 were completed and returned by GPs (79.95%) and 181 by CPs (76.7%). The overall response rate was 78.33%. The perfect match of agreements between the CPs and the GPs answers was identified in: their preference to collaborate face-to-face (p = 0.0001) perception of the role of the community pharmacist (p < 0.0001) barriers to collaboration (p < 0.0001) areas for future collaboration (p = 0.0468) The majority of respondents confirmed (without proportional agreement) that their collaboration improves patient outcomes (71.3% of CPs, 60.5% of GPs), however, only 15.5% CPs and 17.6% GPs indicated, that they would consider team-working in the future. CONCLUSION: The responding health professionals agreed about the current role of CPs in Slovakia. Both professions reported their willingness to collaborate in the following areas: 1. patient counselling and 2. patient adherence improvement. Face-to-face communication was preferred by both groups of respondents, as a potential key factor to improve their relationships (general trust). However, in order to create a sustainable collaborative environment, the identified barriers need to be taken into account.Key words: agreement barriers collaboration community pharmacist general practitioner.

The effectiveness of daily SMS reminders in pharmaceutical care of older adults on improving patients' adherence to antihypertensive medication (SPPA): study protocol for a randomized controlled trial.

BACKGROUND: Despite a variety of efficient and cost-effective antihypertensive medication, hypertension remains a serious health and economic burden. High consumption of cardiovascular drugs in the Slovak Republic does result neither in better hypertension control nor in significant decrease in cardiovascular mortality. At the same time, Slovakia has alarmingly low patients' adherence to medication intake. Studies have shown the efficiency of short messaging service (SMS) reminders to improve patients' adherence and health outcomes at low costs. Since SMS is popular among Slovaks, this approach may be feasible also in Slovakia. The primary objective is to assess if daily SMS reminders of antihypertensive medication intake provided by pharmacists in addition to the standard pharmaceutical care increase the proportion of adherent older hypertensive ambulatory patients. METHODS: The SPPA trial is a pragmatic randomized parallel group (1:1) trial in 300 older hypertensive patients carried out in community pharmacies in Slovakia. Trial pharmacies will be selected from all main regions of Slovakia. Trial intervention comprises daily personalized SMS reminders of medication intake embedded into usual pharmaceutical practice. The primary outcome is a combined adherence endpoint consisting of subjective self-reported medication adherence via the eight-item Morisky Medication Adherence Scale (MMAS-8) and objective pill count rate. Secondary outcomes include: change in the MMAS-8; comparison of adherence rates using pill count; change in systolic blood pressure; and patient satisfaction. Also, direct treatment costs will be evaluated and a cost-effectiveness analysis will be carried out. DISCUSSION: The SPPA trial engages community pharmacists and mobile health (mHealth) technologies via evidence-based pharmaceutical care to efficiently and cost-effectively addresses current main healthcare challenges: high prevalence of hypertension; overconsumption of cardiovascular medicines; low adherence to medication treatment; and resulting uncontrolled blood pressure. The results may identify new possibilities and capacities in healthcare with low additional costs and high value to patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03105687 . Registered on 07 March 2017.

Off-label and unlicensed use of medicinal products in the neonatal setting in the Slovak Republic.

BACKGROUND: Frequent prescription of medication in an unapproved manner (off-label or unlicensed) in the neonatal setting is a result of the limited availability of adequately studied drugs in the pediatric population. Given that little information is available on this issue from eastern European countries, the purpose of this study was to describe for the first time the extent and pattern of off-label or unlicensed use of medicines in newborns in the Slovak Republic. METHODS: Cross-sectional study was performed at the Department of Pathological Newborns of Children's University Hospital, Bratislava, and Unit of Pathological Newborns of Teaching Hospital Nitra. Data were collected on hospitalized neonates admitted between 1 April and 30 September 2012 who received pharmacotherapy. Label status of the administered drugs was determined according to the Slovak Summaries of Product Characteristics. RESULTS: A total of 962 prescriptions referring to 97 different medications was administered to 202 hospitalized newborns (46% premature). Anti-infectives and alimentary drugs were the most commonly prescribed. Of all prescriptions, 43% were identified as off-label and 4.8% as unlicensed. At least one off-label or unlicensed drug was given to 88.6% of patients. Ketoconazole was the most frequent drug used in an unapproved manner. A total of 13.8% of all prescriptions was administered despite contraindication. CONCLUSIONS: Administration of drugs to newborns in an unapproved manner was common in the participating Slovak neonatal wards, reflecting the lack of appropriate pediatric drug labeling.

Influence of hospitalisation on the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in elderly hypertensive patients.

BACKGROUND AND AIMS: The underutilization of beneficial cardiovascular medications such as angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) in the elderly patients continues to be a matter of concern. The aim of the presented study was to compare the prescription of ACEI and ARB in elderly hypertensive patients at the time of hospital admission and discharge and to identify patient-related factors which determine the prescription of ACEI/ARB. METHODS: The study sample (n = 1111) was selected from 2,157 patients hospitalised at long-term care departments of three municipal hospitals during the period between January 1, 2008 and December 31, 2009 and included hypertensive patients aged ≥65 years suffering from myocardial infarction, heart failure, atrial fibrillation, diabetes mellitus or nephropathy. RESULTS: In hypertensive patients with myocardial infarction, diabetes mellitus and nephropathy, a significant increase was found in the use of ACEI/ARB during hospitalisation. However, there was no similar change in the use of such medications during hospitalisation in patients with heart failure and atrial fibrillation. Age ≥85 years (OR = 0.59 and OR = 0.50 at hospital admission and discharge, respectively), depression (OR = 0.63 at hospital discharge) and the systolic blood pressure ≤115 mmHg (OR = 0.45 at hospital discharge) decreased the probability of ACEI/ARB prescription. On the other hand, increasing the number of evaluated co-morbid conditions increased the patient's likelihood of being an "ACEI/ARB user" (OR = 1.20 at hospital discharge). CONCLUSIONS: Our study has identified a subset of elderly hypertensive patients (with heart failure, atrial fibrillation) in whom the use of ACEI/ARB could be improved.

Characteristics of elderly patients who consider over-the-counter medications as safe.

BACKGROUND: There is a lack of studies evaluating the factors which influence the perception of safety of over-the-counter (OTC) medications by elderly patients. OBJECTIVE: The aim of our questionnaire survey was to evaluate the perception of the risk of OTC medications by elderly patients and to identify patient-associated characteristics which determine elderly persons who consider OTC medications as safe. SETTING: 25 community pharmacies in different regions of the Slovak Republic. METHODS: A 54-items questionnaire was provided to patients aged ≥65 years who were purchasing at least one OTC medication during the period from May 2010 to November 2010. The questions elicited information on (a) self-assessment of health status; (b) basic characteristics of OTC medications use (e.g. frequency, duration); (c) patients' knowledge on OTC medications; (d) participants' perception of the risk of OTC medications; (e) the list of OTC and prescription-only medications taken; and (f) sociodemographic characteristics of respondents. RESULTS: Of the 793 questionnaires distributed, 519 were finally included in the statistical analysis (response rate of 65.4 %). Women were prevailing in the analysed group (n = 361; 69.6 %). The average age of participants was 72.2 ± 5.6 years. Majority (n = 392, 75.5 %) of the respondents considered OTC medications as safe. Multivariate analysis (binary logistic regression) revealed that elderly patients who considered OTC medications as safe were characterised by use of OTC medications every day (OR = 2.09), preferring a wide range of such drugs in pharmacies (OR = 2.86), considering such medications as effective (OR = 10.33), obtaining information on OTC drugs from pharmacists (OR = 1.91) and willingness to possibly purchase OTC medications outside pharmacies (OR = 3.35). On the other hand, allergic conditions as a reason for purchasing OTC medications (OR = 0.23), recommendation of a physician regarding the choice of OTC medications (OR = 0.51) and considering concurrent use of several medications as a factor increasing the risk of adverse drug reactions (OR = 0.62) emerged as important factors that decreased the probability of elderly patients considering OTC medications as safe. CONCLUSIONS: The survey identified various factors that influenced the perceptions of the safety of OTC medications by the elderly and indicated that pharmacists represent the most trusted source of information about OTC medications.

The use of medications with anticholinergic properties and risk factors for their use in hospitalised elderly patients.

PURPOSE: The aims of the present study were to evaluate the use of drugs with anticholinergic properties in elderly patients and to identify risk factors that increase the patient's chance of being given such medications. METHODS: The study was performed on a sample of 1636 patients aged ≥65 years hospitalised during the period between 1 January 2008 and 31 December 2009 in three municipal hospitals. To evaluate the factors influencing the use of anticholinergic medications, we compared two groups-users and non-users of such drugs-in terms of sociodemographic and clinical characteristics as well as comorbid conditions. The most important risk factors were identified using the binary logistic regression model. RESULTS: Hospitalisation led to a significant increase in the prevalence of anticholinergic medication users, when comparing their occurrence at the time of hospital admission and discharge (10.5% and 14.2%, respectively; p < 0.001). A significantly higher total number of prescribed drugs were found in the group of users compared with non-users, at both hospital admission (7.2 ± 3.5 vs 5.7 ± 3.1; p < 0.001) and discharge (8.7 ± 3.1 vs 7.5 ± 2.9; p < 0.001). Immobilisation, urinary incontinence and retention, constipation, gastroduodenal ulcer disease as well as neurologic and psychiatric comorbidities (depression, Parkinson's disease, epilepsy) appeared as the most important risk factors of using anticholinergic medications. CONCLUSIONS: Physicians should be aware of the greater risk of adverse anticholinergic effects of drugs in certain therapeutic classes in the elderly. In patients with risk factors mentioned previously, special attention should be paid to active identification of anticholinergic effects of medications.

The effect of selected patient's characteristics on the choice of antihypertensive medication in the elderly in Slovakia.

PURPOSE: The aim of the present study was to determine which patient-related characteristics influence the selection of the antihypertensive drug class in elderly patients in Slovakia. METHODS: The sample for our study (n = 401) was selected from 1045 patients admitted to the Department of Internal Medicine of a general hospital during the period of 1 December 2003-31 March 2005. Patients aged 65 or more with documented arterial hypertension and treated with at least one antihypertensive drug were enrolled in our retrospective study. Specific socio-demographic and clinical characteristics as well as cardiovascular comorbid conditions were evaluated as potential factors that could have influenced the choice of antihypertensive drug class. RESULTS: The most frequently prescribed antihypertensive drugs were angiotensin-converting enzyme (ACE) inhibitors and diuretics (61.8% and 60.1% of patients, respectively). Patients aged >/= 85 years had lower probability of ACE inhibitors prescription (OR = 0.49). Females had higher chance of calcium channel blockers use (OR = 3.84) and lower odds of diuretics administration (OR = 0.50). In patients living alone, ACE inhibitors were preferred (OR = 2.16). The use of diuretics was more frequent in polymorbid patients (OR = 1.95). Immobile patients had lower chance of being prescribed beta-blockers and calcium channel blockers (OR = 0.25 and OR = 0.39, respectively). CONCLUSION: The present study revealed that the selection of the antihypertensive drug class in elderly patients is influenced not only by comorbid conditions present but also by socio-demographic and clinical characteristics, such as age, sex, living alone, polymorbidity and immobilization. These characteristics reflect the doctor's perception of risk from pharmacotherapy of hypertension in elderly patients.

Alcohol intoxication requiring hospital admission in children and adolescents: retrospective analysis at the University Children's Hospital in the Slovak Republic.

BACKGROUND: Few epidemiological studies have investigated the problem of children and adolescents taken to hospital with acute alcohol intoxication. METHODS: We reviewed the medical records of children and adolescents aged

Adverse drug reactions related to hospital admission in Slovak elderly patients.

The aims of the present study were: to evaluate the prevalence of adverse drug reactions (ADRs) leading to hospitalization in elderly patients; to analyze the drugs which have been identified as having causal relationship with ADRs and to identify risk factors which predispose the patient to such ADRs. The study has been performed in 600 patients aged> or =65 years, hospitalized in a general hospital between 1 December 2003 and 31 March 2005. The ADRs recorded in patient's documentation as one of the reasons for hospital admission were evaluated. ADRs leading to hospital admission were recorded in 47 (7.8%) patients. ADRs in 43 patients represented A-type ADRs which are preventable. The most frequent ADRs were cardiovascular disorders. According to the results of multivariate analysis ischemic heart disease (odds ratio (OR)=4.50; 95% confidence interval (CI)=1.36-14.88), depression (OR, 2.49; 95% CI, 1.08-5.77) and heart failure (OR, 2.08; 95% CI, 1.13-3.81) were the most important patient-related characteristics predicting ADRs leading to hospitalization. The majority of ADRs in elderly patients could be avoided. Regular re-evaluation of the medication as well as taking into account the specific features of elderly patients represent the most important tools for ADR prevention.

The effect of simvastatin on coenzyme Q and antioxidant/oxidant balance in diabetic-hypercholesterolaemic rats.

The effect of simvastatin administered for 10 days on coenzyme Q and antioxidant/oxidant balance in a rat model of diabetes mellitus and hypercholesterolaemia was studied. In the diabetic-hypercholesterolaemic rats the signs of oxidative stress-decreased alpha-tocopherol/cholesterol in the plasma (p < 0.01) and alpha-tocopherol in liver (p < 0.001) together with increased lipid peroxidation in the liver (TBARS, p < 0.05) were found. Increased coenzyme Q9 concentrations in the plasma (p < 0.05) and liver (p < 0.01), coenzyme Q10 in the myocardium (p < 0.05) and in the liver (p < 0.01) may indicate adaptation to oxidative stress. Administration of simvastatin (10 mg/kg) to the diabetic-hypercholesterolaemic rats counteracted increased myocardial (coenzyme Q10, p < 0.05) and liver (total coenzyme Q9, p < 0.05) coenzyme Q concentrations but did not improve alpha-tocopherol depletion and increased formation of TBARS in the liver. Even though simvastatin treatment did not induce coenzyme Q deficiency in plasma, heart and liver of the diabetic-hypercholesterolaemic rats as compared to the control levels, it was not able to prevent completely the changes in antioxidant/oxidant balance induced by diabetes and hypercholesterolaemia. The results highlight the importance of studying the effect of statins on the coenzyme Q levels in the animal models of pathological conditions known to change the initial antioxidant defence system.

Polypharmacy in elderly hospitalised patients in Slovakia.

OBJECTIVE: The aims of the present study were to: analyse the prevalence of polypharmacy in a group of older patients; evaluate the influence of hospital stay on the number of drugs taken; assess the most frequently prescribed pharmacological classes; identify risk factors that predisposed the patient to polypharmacy. Setting The study was carried out in the Department of Internal Medicine of a non-university general hospital. METHOD: In the retrospective study, 600 patients aged 65 years or more were enrolled. They were hospitalised in the period from 1st December 2003 to 31st March 2005. Each person taking six or more medications per day was considered to be a patient with polypharmacy. Particular sociodemographic and clinical characteristics, as well as comorbid conditions, were evaluated as factors potentially influencing the prevalence of polypharmacy. MAIN OUTCOME MEASURE: The number and type of medications taken at the time of hospital admission and discharge were recorded and compared for each patient. RESULTS: Polypharmacy on admission and at discharge was observed in 362 (60.3%) and 374 (62.3%) patients, respectively. Hospitalisation led to a significant increase in the number of medications. The spectrum of medications used corresponded to the proportions of diagnoses in the evaluated group, in which cardiovascular diseases were most prevalent. According to the multivariate analysis using a logistic regression model, diabetes mellitus (odds ratio (OR) 2.40; 95% confidence interval (CI): 1.64-3.50), heart failure (OR 2.14; 95% CI: 1.46-3.14), dementia (OR 2.12; 95% CI: 1.26-3.57), living alone (OR 2.00; 95% CI: 1.28-3.10), arterial hypertension (OR 1.63; 95% CI: 1.08-2.44) and cerebrovascular disease (OR 1.58; 95% CI: 1.03-2.44) significantly increased the risk of the presence of polypharmacy. CONCLUSION: Our study confirmed a relatively high prevalence of polypharmacy in Slovak elderly patients. Polypharmacy risk rose especially with the increased prevalence of diseases of advancing age (diabetes mellitus, heart failure, arterial hypertension, dementia and cerebrovascular diseases). The increasing numbers of medications in inpatients indicate the need for the careful re-evaluation of pharmacotherapy during the stay in hospital.

The myocardial infarct size-limiting and antiarrhythmic effects of acyl-CoA:cholesterol acyltransferase inhibitor VULM 1457 protect the hearts of diabetic-hypercholesterolaemic rats against ischaemia/reperfusion injury both in vitro and in vivo.

The study was designed to characterise the influence of a novel acyl-CoA:cholesterol acyltransferase inhibitor, VULM 1457, on the severity of myocardial ischaemia-reperfusion injury in a model of diabetes mellitus and hypercholesterolaemia induced by co-administration of streptozotocin and a high fat-cholesterol diet. We used Langendorff-perfused rat hearts to measure the size of myocardial infarction after 30 min of regional ischaemia, followed by a 2-h reperfusion period, and open-chest rats were exposed to 6 min of ischaemia and 10 min of reperfusion to analyse ventricular arrhythmias. In addition to the high fat-cholesterol diet, VULM 1457 was administered to the diabetic-hypercholesterolaemic rats for 5 days. Decreased plasma and liver cholesterol levels and a significantly reduced occurrence of ventricular fibrillation (29% vs. 100%, P<0.01), determined via the mean number and duration of episodes (0.6+/-0.4 and 2.1+/-1.4 s vs. 2.8+/-0.8 and 53.5+/-14.4 s in diabetic-hypercholesterolaemic rats, both P<0.01), were observed in these animals. Lethal ventricular fibrillation was suppressed, and arrhythmia severity was also significantly decreased in these animals as compared to the non-treated animals (2.9+/-0.6 vs. 4.9+/-0.2; P<0.05). A smaller infarct size, normalised to the size of area at risk, was observed in the treated diabetic-hypercholesterolaemic group as compared to the non-treated group (16.3+/-1.9% vs. 37.3+/-3.1%; P<0.01). Aside from remarkable hypolipidaemic activity, VULM 1457 improved the overall myocardial ischaemia-reperfusion injury outcomes in the diabetic-hypercholesterolaemic rats by suppressing arrhythmogenesis as well as by reducing myocardial necrosis.