Polypharmacy and potentially inappropriate prescribing of benzodiazepines in older nursing home residents.

INTRODUCTION: Previous research has raised concerns about high prevalence of drug-related problems, polypharmacy and inappropriate benzodiazepine prescribing in nursing homes (NHs) and confirmed lack of studies from Central and South-Eastern Europe. The aim of our study was to determine the prevalence and characteristics of polypharmacy, hyperpolypharmacy and inappropriate benzodiazepine prescribing in NH residents in Croatia. METHODS: Data from 226 older NH residents from five Croatian NHs were collected using the InterRAI Long-Term Care Facilities assessment form. The prevalence and determinants of polypharmacy/hyperpolypharmacy and patterns of inappropriate benzodiazepine prescribing were documented. RESULTS: The prevalence of polypharmacy (49.6%) and hyperpolypharmacy (25.7%) among NH residents was high. In our study, 72.1% of NH residents were prescribed at least one psychotropic agent, 36.7% used 2-3 psychotropics and 6.6% used 4+ psychotropics. Among benzodiazepine users (55.8%), 28% of residents were prescribed benzodiazepines in higher than recommended geriatric doses, 75% used them for the long term and 48% were prescribed concomitant interacting medications. The odds of being prescribed polypharmacy/hyperpolypharmacy were significantly higher for older patients with polymorbidity (6+ disorders, proportional odds ratio (POR) = 19.8), type II diabetes (POR = 5.2), ischemic heart disease (POR = 4.6), higher frailty (Clinical Frailty Scale (CFS ≥5); POR = 4.3) and gastrointestinal problems (POR = 4.8). CONCLUSIONS: Our research underscores the persistent challenge of inappropriate medication use and drug-related harms among older NH residents, despite existing evidence and professional campaigns. Effective regulatory and policy interventions, including the implementation of geriatrician and clinical pharmacy services, are essential to address this critical issue and ensure optimal medication management for vulnerable NH populations.

Prevalence, country-specific prescribing patterns and determinants of benzodiazepine use in community-residing older adults in 7 European countries.

BACKGROUND: The use of benzodiazepines (BZDs) in older population is often accompanied by drug-related complications. Inappropriate BZD use significantly alters older adults' clinical and functional status. This study compares the prevalence, prescribing patterns and factors associated with BZD use in community-dwelling older patients in 7 European countries. METHODS: International, cross-sectional study was conducted in community-dwelling older adults (65 +) in the Czech Republic, Serbia, Estonia, Bulgaria, Croatia, Turkey, and Spain between Feb2019 and Mar2020. Structured and standardized questionnaire based on interRAI assessment scales was applied. Logistic regression was used to evaluate factors associated with BZD use. RESULTS: Out of 2,865 older patients (mean age 73.2 years ± 6.8, 61.2% women) 14.9% were BZD users. The highest prevalence of BZD use was identified in Croatia (35.5%), Spain (33.5%) and Serbia (31.3%). The most frequently prescribed BZDs were diazepam (27.9% of 426 BZD users), alprazolam (23.7%), bromazepam (22.8%) and lorazepam (16.7%). Independent factors associated with BZD use were female gender (OR 1.58, 95%CI 1.19-2.10), hyperpolypharmacy (OR 1.97, 95%CI 1.22-3.16), anxiety (OR 4.26, 95%CI 2.86-6.38), sleeping problems (OR 4.47, 95%CI 3.38-5.92), depression (OR 1.95, 95%CI 1.29-2.95), repetitive anxious complaints (OR 1.77, 95%CI 1.29-2.42), problems with syncope (OR 1.78, 95%CI 1.03-3.06), and loss of appetite (OR 0.60, 95%CI 0.38-0.94). In comparison to Croatia, residing in other countries was associated with lower odds of BZD use (ORs varied from 0.49 (95%CI 0.32-0.75) in Spain to 0.01 (95%CI 0.00-0.03) in Turkey), excluding Serbia (OR 1.11, 95%CI 0.79-1.56). CONCLUSIONS: Despite well-known negative effects, BZDs are still frequently prescribed in older outpatient population in European countries. Principles of safer geriatric prescribing and effective deprescribing strategies should be individually applied in older BZD users.

Deprescribing potential of commonly used medications among community-dwelling older adults: insights from a pharmacist's geriatric assessment.

Pharmacist's geriatric assessment can provide valuable insights into potential deprescribing targets, while including important information on various health-related domains. Data collected from a geriatric assessment questionnaire, for 388 patients, from the Croatian cohort of the EuroAgeism H2020 ESR 7 international project, along with guideline-based deprescribing criteria, were used to analyse potentially inappropriate prescribing of four medication groups (benzodiazepines (BZN), proton pump inhibitors (PPI), opioids, and non-steroidal anti-inflammatory drugs (NSAID)), and to assess the deprescribing potential. Binary logistic regression was used to explore the effects of age, gender, number of medicines and diagnoses, self-reported health, frailty score, and healthcare utilization on the likelihood of needing deprescribing. More than half of participants (n = 216, 55.2%) are candidates for deprescribing, with 31.1% of PPI, 74.8% of NSAID, 75% of opioid, and 96.1% of BZN users meeting at least one criterion. Most common criteria for deprescribing were inappropriately long use and safety concerns. Women (aOR = 2.58; p < 0.001), those reporting poor self-reported health (aOR = 5.14; p < 0.001), and those exposed to polypharmacy (aOR = 1.29; p < 0.001) had higher odds of needing to have medicines deprescribed. The high rate of deprescribing potential warrants prompt action to increase patient safety and decrease polypharmacy. Pharmacist's geriatric assessment and deprescribing-focused medication review could be used to lead a personalised approach.

Specific adverse outcomes associated with selective serotonin reuptake inhibitors use in COVID-19 patients might be potentiated by remdesivir use.

BACKGROUND: Due to non-consistent reports in the literature, there are uncertainties about the potential benefits and harms of selective serotonin reuptake inhibitors (SSRIs) in patients with Coronavirus disease 2019 (COVID-19). AIM: To investigate associations of SSRIs with clinical characteristics and unwanted outcomes among real-life severe and critical COVID-19 patients and their relationship with remdesivir (RDV) use. METHODS: This retrospective cohort study evaluated a total of 1558 COVID-19 patients of the white race treated in a tertiary center institution, among them 779 patients treated with RDV and 779 1:1 case-matched patients. RESULTS: A total of 78 (5%) patients were exposed to SSRIs during hospitalization, similarly distributed among patients treated with RDV and matched patients (5.1 and 4.9%). No significant associations of SSRI use with age, sex, comorbidity burden, and COVID-19 severity were present in either of the two cohorts (p > 0.05 for all analyses). In multivariate analyses adjusted for clinically meaningful variables, SSRI use was significantly associated with higher mortality among RDV (adjusted odds ratio (aOR) 2.0, p = 0.049) and matched patients (aOR 2.22, p = 0.044) and with higher risk for mechanical-ventilation (aOR 2.57, p = 0.006), venous-thromboembolism (aOR 3.69, p = 0.007), and bacteremia (aOR 2.22, p = 0.049) among RDV treated patients. CONCLUSIONS: Adverse outcomes associated with SSRI use in COVID-19 patients might be potentiated by RDV use, and clinically significant interactions between these two drug classes might exist. Although our findings raise important considerations for clinical practice, they are limited by retrospective nature of the study, lack of ethnic diversity, and the potential for unmeasured confounding factors. Future studies exploring underlying biological mechanisms are needed.

Patterns of corticosteroid use among remdesivir and matched patients and associated clinical outcomes in hospitalized COVID-19 patients.

INTRODUCTION: We aimed to investigate patterns of corticosteroid use and their relationship with remdesivir use and clinical outcomes in a large real-life cohort of COVID-19 patients treated in a tertiary-level institution. METHODS: We retrospectively analyzed a total of 1558 severe and critical COVID-19 patients, including 779 patients treated with remdesivir and 779 matched control patients. RESULTS: A total of 167 (10.7%) patients received none, 710 (45.6%) low, 539 (34.6%) high, and 142 (9.1%) very high corticosteroid doses. Patients treated with remdesivir had significantly longer exposure to corticosteroids, received higher average and maximal daily doses, and cumulative corticosteroid doses. In the multivariate analysis remdesivir use, lower cumulative comorbidity burden, higher severity of COVID-19 symptoms, and mechanical ventilation were recognized as mutually independent predictors of the use of higher corticosteroid doses. Higher corticosteroid doses were associated with significantly increased mortality.Among non-remdesivir treated patients, there was a U-shaped relationship between maximal daily corticosteroid dose and mortality. Among remdesivir treated patients gradual increase in mortality with increasing corticosteroid doses was observed. CONCLUSION: Patterns of corticosteroid use differ regarding the use of remdesivir and may moderate its association with survival among severe and critical COVID-19 patients.

Corticosteroid Dosing Level, Incidence and Profile of Bacterial Blood Stream Infections in Hospitalized COVID-19 Patients.

COVID-19 patients with severe or critical symptoms are often treated with corticosteroids, per contemporary guidelines. Due to their immunosuppressive and immunomodulatory properties, corticosteroids are associated with the development of superinfections. We aimed to retrospectively assess patterns of corticosteroid use and the profiles of bacterial blood stream infections associated with exposure to different dosing levels, in a cohort of 1558 real-life adult COVID-19 patients. A total of 1391 (89.3%) patients were treated with corticosteroids, with 710 (45.6%) patients receiving low, 539 (34.6%) high and 142 (9.1%) very high corticosteroid doses. Bacteremia developed in a total of 178 (11.4%) patients. The risk of bacteremia was of similar magnitude between the no and low-dose corticosteroid treatments (p = 0.352), whereas it progressively increased with high (OR 6.18, 95% CI (2.66-14.38), p < 0.001) and very high corticosteroid doses (OR 8.12, 95% CI (3.29-20.05), p < 0.001), compared to no corticosteroid treatment. These associations persisted after multivariate adjustments and were present independently of sex, comorbidity burden, and mechanical ventilation. The profiles of individual bacterial pathogens differed depending on the used corticosteroid doses. High and very high corticosteroid doses are frequently used for real-life COVID-19 patients with severe and critical clinical presentations and are associated with a higher risk of bacteremia independently of sex, comorbidity burden, and mechanical ventilation use.

Clinical decision-making in benzodiazepine deprescribing by healthcare providers vs. AI-assisted approach.

AIMS: The aim of this study was to compare the clinical decision-making for benzodiazepine deprescribing between a healthcare provider (HCP) and an artificial intelligence (AI) chatbot GPT4 (ChatGPT-4). METHODS: We analysed real-world data from a Croatian cohort of community-dwelling benzodiazepine patients (n = 154) within the EuroAgeism H2020 ESR 7 project. HCPs evaluated the data using pre-established deprescribing criteria to assess benzodiazepine discontinuation potential. The research team devised and tested AI prompts to ensure consistency with HCP judgements. An independent researcher employed ChatGPT-4 with predetermined prompts to simulate clinical decisions for each patient case. Data derived from human-HCP and ChatGPT-4 decisions were compared for agreement rates and Cohen's kappa. RESULTS: Both HPC and ChatGPT identified patients for benzodiazepine deprescribing (96.1% and 89.6%, respectively), showing an agreement rate of 95% (κ = .200, P = .012). Agreement on four deprescribing criteria ranged from 74.7% to 91.3% (lack of indication κ = .352, P < .001; prolonged use κ = .088, P = .280; safety concerns κ = .123, P = .006; incorrect dosage κ = .264, P = .001). Important limitations of GPT-4 responses were identified, including 22.1% ambiguous outputs, generic answers and inaccuracies, posing inappropriate decision-making risks. CONCLUSIONS: While AI-HCP agreement is substantial, sole AI reliance poses a risk for unsuitable clinical decision-making. This study's findings reveal both strengths and areas for enhancement of ChatGPT-4 in the deprescribing recommendations within a real-world sample. Our study underscores the need for additional research on chatbot functionality in patient therapy decision-making, further fostering the advancement of AI for optimal performance.

Deprescribing in a multimorbid older adult: A case vignette study among community pharmacists and primary care physicians.

Collaborative deprescribing can include pharmacists' medication review with identification and suggestion of potential deprescribing targets to physicians. Case vignettes can be a valuable method for researching variations in clinical decision making, especially in settings unaccustomed to newer clinical approaches such as deprescribing. This study aimed to explore if pharmacists can identify deprescribing targets and if physicians would accept pharmacist's deprescribing rationales. A cross-sectional study was performed using an online case vignette based on a real-life elderly patient. Pharmacists were asked to indicate which medicines they would recommend deprescribing, alongside a rationale. Physicians were asked to state their acceptance of the proposed pharmacist's deprescribing suggestion. Pharmacists gave 1275 deprescribing rationales, and most were given for deprescribing opioids, NSAID and diuretics. Physicians would accept rationales to deprescribe a median of 10 medicines, while pharmacist would recommend deprescribing a median of six medicines. Most difference lays in deprescribing of preventative medicines. Healthcare providers share agreement on deprescribing targets, but pharmacists show hesitancies in making recommendations that could hamper potential collaboration. Action is needed to improve pharmacists' skills in recognizing deprescribing targets and confidence in making suggestions, which could lead to opening of possibilities for joint patient care.

Differences in Factors Influencing Deprescribing between Primary Care Providers: Cross-Sectional Study.

Deprescribing is a notable approach to improve medication management, but few healthcare systems recognize it. To introduce a new practice, it is important to examine the factors influencing the provision of a new or elaborate cognitive service within the desired setting. This study explores the perceived barriers and facilitators of deprescribing by primary healthcare providers, and identifies the factors associated with a willingness to suggest deprescribing. A cross-sectional survey was conducted (in Croatia, between October 2021 and January 2022) using a validated comprehensive healthcare providers' opinions, preferences, and attitudes towards deprescribing (CHOPPED) questionnaire. A total of 419 pharmacists and 124 physicians participated. Participants showed a high willingness to deprescribe, with significantly higher scores in physicians than in pharmacists (5.00 (interquartile range-IQR 5-5) vs. 4.00 (IQR 4-5), p < 0.001). Pharmacists had significantly higher scores in seven out of ten factors (knowledge, awareness, collaboration facilitators, competencies facilitators, healthcare system facilitators, collaboration barriers, competencies barriers) while in the remaining three factors (patient facilitators, patient and healthcare system barriers) there was no difference in scores. The strongest positive correlation with willingness to suggest deprescribing was found with the collaboration and healthcare system facilitators factors for pharmacists (G = 0.331, p < 0.001, and G = 0.309, p < 0.001, respectively), and with knowledge, awareness, and patient facilitators factors for physicians (G = 0.446, p = 0.001; G = 0.771, p < 0.001; and G = 0.259, p = 0.043, respectively). Primary healthcare providers are willing to suggest deprescribing but face different barriers and facilitators. For pharmacists, the most important facilitators were extrinsic, while for physicians they were more intrinsic and patient related. The stated results provide target areas which one could focus upon to help to engage healthcare providers in deprescribing.

Development and Validation of Comprehensive Healthcare Providers' Opinions, Preferences, and Attitudes towards Deprescribing (CHOPPED Questionnaire).

Successful implementation of deprescribing requires exploring healthcare professionals' opinions, preferences, and attitudes towards deprescribing. The aim of this study was to develop and validate the questionnaire exploring healthcare providers' opinions preferences and attitudes towards deprescribing (CHOPPED questionnaire). This was a cross-sectional on-line survey. A comprehensive 58-item questionnaire, in two versions (for pharmacists and physicians), was developed through an extensive literature review and interviews with experts. The questionnaire was validated, and its reliability was assessed through data collected from 356 pharmacists and 109 physicians. Exploratory factor analysis was performed, and 37- and 35-item questionnaires were developed. Ten factors were identified: knowledge, awareness, patient barriers and facilitators, competencies barriers and facilitators, collaboration barriers and facilitators, and healthcare system barriers and facilitators. The CHOPPED tool has satisfactory face, content (CVR > 0.62) (content validity ratio), construct, and criterion validity. The reliability statistics of all factors in both versions was acceptable with Cronbach's alpha > 0.6. Test−retest reliability analysis showed that gamma rank correlations of total factor scores were strong and very strong (between 0.519 and 0.938). The CHOPPED tool can be used as a valid and reliable tool to explore healthcare providers' opinions and attitudes toward discontinuing medications in the primary care setting in Croatia.

Community-based pharmacists' role in deprescribing: A systematic review.

AIMS: Community-based pharmacists are an important stakeholder in providing continuing care for chronic multi-morbid patients, and their role is steadily expanding. The aim of this study is to examine the literature exploring community-based pharmacist-initiated and/or -led deprescribing and to evaluate the impact on the success of deprescribing and clinical outcomes. METHODS: Library and clinical trials databases were searched from inception to March 2020. Studies were included if they explored deprescribing in adults, by community-based pharmacists and were available in English. Two reviewers extracted data independently using a pre-agreed data extraction template. Meta-analysis was not performed due to heterogeneity of study designs, types of intervention and outcomes. RESULTS: A total of 24 studies were included in the review. Results were grouped based on intervention method into four categories: educational interventions; interventions involving medication review, consultation or therapy management; pre-defined pharmacist-led deprescribing interventions; and pharmacist-led collaborative interventions. All types of interventions resulted in greater discontinuation of medications in comparison to usual care. Educational interventions reported financial benefits as well. Medication review by community-based pharmacist can lead to successful deprescribing of high-risk medication, but do not affect the risk or rate of falls, rate of hospitalisations, mortality or quality of life. Pharmacist-led medication review, in patients with mental illness, resulting in deprescribing improves anticholinergic side effects, memory and quality of life. Pre-defined pharmacist-led deprescribing did not reduce healthcare resource consumptions but can contribute to financial savings. Short follow-up periods prevent evaluation of long-term sustainability of deprescribing interventions. CONCLUSION: This systematic review suggests community-based pharmacists can lead deprescribing interventions and that they are valuable partners in deprescribing collaborations, providing necessary monitoring throughout tapering and post-follow-up to ensure the success of an intervention.

Real-life experience with remdesivir for treatment of hospitalized coronavirus disease 2019 patients: matched case-control study from a large tertiary hospital registry.

AIM: To evaluate the association of remdesivir use and the survival of hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS: We retrospectively reviewed the medical records of 5959 COVID-19 patients admitted to our tertiary-level hospital from March 2020 to June 2021. A total of 876 remdesivir-treated patients were matched with 876 control patients in terms of age, sex, Charlson comorbidity index (CCI), WHO-defined COVID-19 severity on admission, and oxygen requirement at the time of remdesivir use. RESULTS: Among 1752 COVID-19 patients (median age 66 years, 61.8% men), 1405 (80.2%) had severe and 311 (17.8%) had critically severe COVID-19 on admission. Remdesivir was given at a median of one day after hospital admission and at a median of eight days from the onset of symptoms. Overall, 645 (73.6%) patients received remdesivir before high-flow oxygen therapy (HFOT) or mechanical ventilation (MV), 198 (22.6%) after HFOT institution, and 83 (9.5%) after MV institution. Remdesivir use was associated with improved survival in the entire cohort (hazard ratio 0.79, P=0.006). Survival benefit was evident among patients receiving remdesivir during low-flow oxygen requirement (hazard ratio 0.61, P<0.001) but not among patients who received it after starting HFOT (P=0.499) or MV (P=0.380). CONCLUSION: Remdesivir, if given during low-flow oxygen therapy, might be associated with survival benefit in hospitalized COVID-19 patients.

Pharmacists' interventions improve health-related quality of life of rural older person on warfarin: a randomized controlled trial.

Warfarin therapy can significantly affect patients' quality of life and cause therapy discontinuation. This study aimed to investigate the effect of the pharmacists' interventions on the health-related quality of life (HRQoL) in older rural patients on warfarin therapy. Eligible older patients from rural area of Croatian province Slavonia were randomized into the intervention and control groups and followed for six months. Repeated education and a follow-up plan were provided to the participants in the intervention group, and if needed, the pharmacist intervened to optimize warfarin therapy. Secondary analysis on HRQoL data are presented here. Main outcome measure was Duke anticoagulation satisfactions scale questionnaire score. In total, 131 participants finished the study (median age 73 years; 51.1% male). Participants in the intervention group scored significantly lower (median being 86.5 and 66.0 in the control and intervention groups, respectively; p < 0,001), indicating higher HRQoL. Adverse drug reactions and pharmacist's intervention were identified as predictive factors for patients' HRQoL (r2 = 65.5%, P < 0.001). The study demonstrated that community pharmacist's interventions can improve HRQoL of older patients taking warfarin what is of particular significance for patients living in rural areas with less accessible healthcare and lower socio-economic status.Clinicaltrials.gov (ID: NCT03212898), 11/07/2017, retrospectively registered.

Exploring Patients' Attitudes Toward Deprescribing and Their Perception of Pharmacist Involvement in a European Country: A Cross-Sectional Study.

PURPOSE: To explore how adult patients perceive deprescribing in a country with developing pharmaceutical care. PATIENTS AND METHODS: This was a multicenter cross-sectional study conducted in ten community pharmacies across Croatia. Community-dwelling adults 40 years and older, taking at least one prescription medication long term, were invited to participate. The revised and validated Patients' Attitude Towards Deprescribing Questionnaire was used to investigate community-dwelling adults' opinions on potential medication discontinuation. Questions regarding the patients' perception of pharmacist competences and involvement as well as patients' preferences in deprescribing were added. Collected data were analyzed using IBM SPSS Statistics using descriptive and inferential statistical analysis. Binary logistic regression was used to explore potential predictive factors of willingness to have medication deprescribed. All tests were performed as two-tailed and a p < 0.05 was considered statistically significant. RESULTS: A total of 315 adults aged 40 years and older completed the questionnaire. Majority of participants, 83.81% (95% CI, 79.72% to 87.90%) stated that they were satisfied with their medications, and 83.81% (95% CI, 79.72% to 87.90%) would be willing to deprescribe one or more medications. Participants expressed a positive attitude toward pharmacists' competences (68.89%, 95% CI, 63.75% to 74.03%) and involvement in deprescribing (71.11%, 95% CI, 66.08% to 76.14%). Participants who stated specific medication as deprescribing preference were more likely show dissatisfaction with current medication and show greater willingness to have medication deprescribed. Three factors were found to be associated with a positive attitude towards deprescribing: low concerns about stopping factor score (aOR 0.54, 95% CU=0.35-0.84; p=0.006), low appropriateness factor score (aOR 0.62, 95% CI=0.39-0.98; p=0.039), and a positive opinion on pharmacist involvement (aOR 2.35, 95% CI=1.18-4.70; p= 0.016). CONCLUSION: This study showed the patient's willingness for deprescription as well as their positive attitude towards pharmacists being involved in the process. Results favour transition to a patient-centred care and shared-decision making model.

Pharmacists' role, work practices, and safety measures against COVID-19: A comparative study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic poses a great challenge to health systems and their most accessible assets-community pharmacies. Pharmacists faced many challenges such as incorporating safety measures, changes in working schedule and workload, and meeting specific patients' needs. OBJECTIVES: This study aimed to explore and compare the community pharmacists' roles, practices, implemented safety measures, and psychological toll in Croatia and Serbia during the COVID-19 pandemic. METHODS: A cross-sectional study employing an online survey was conducted in 2 countries over a period of 6 weeks during 2020. The survey consisted of 65 items that explored sociodemographic characteristics of participants and their workplaces, including safety measures, pharmaceutical care, and their psychology while working during the COVID-19 pandemic. RESULTS: In total, 574 pharmacists participated in the study, of which, 90% were female, with a mean age of 38 years (interquartile range 30.5-47). The study identified new pharmacists' roles that evolved during the COVID-19 pandemic: manufacturing hand sanitizers in community pharmacies, online patient counseling, and home delivery of medicines. Croatian and Serbian pharmacists exhibited disparities in their incorporated safety measures (higher for Croatia; P ≤ 0.001) and satisfaction with work organization and counseling activities (higher for Serbia; P < 0.001). Serbian participants were less satisfied with the public perception of their role during the pandemic, and overall satisfaction was low, with a negative impact on mood and productivity. CONCLUSIONS: The study revealed the implications for community pharmacists during the pandemic in both countries. The extent of systematic and logistical support provided to them during the pandemic could be an explanation for the highlighted differences. It is imperative to develop a more effective strategy to counter potential health crises to ensure a better response from primary care pharmacists in the future.

Pharmacists' influence on adverse reactions to warfarin: a randomised controlled trial in elderly rural patients.

Background Adverse reactions to warfarin may be serious and can lead to hospitalisation or death. Minimising the risk of adverse drug reactions through the intervention of community pharmacists is important for patients receiving warfarin, especially for elderly (≥ 65 years) patients living in rural areas. Objective To evaluate the impact of an intervention by community pharmacists on the risk of adverse drug reactions in elderly rural patients receiving warfarin. Setting: A community pharmacy in a rural area of Croatia. Method We conducted a prospective randomised trial. Eligible patients were recruited at the pharmacy and randomised into one of two groups. The participants were followed up every month for 6 months. Main outcome measure: The incidence and type of adverse drug reactions caused by warfarin and the time-to-event. Results In total, 140 patients were randomized and 131 patients completed the study; 65 patients were in the intervention group. The median age of patients was 73 years of age. The cumulative incidence of adverse drug reactions was significantly lower in the intervention group (6-months rate 29% vs. 85% for intervention and control, respectively; hazard ratio = 0.17, p < 0.001) than in the control group. Factors multivariately associated with the development of adverse drug reactions related to warfarin (p < 0.05) were the absence of pharmaceutical intervention, higher time in therapeutic range, change of warfarin dose, changes in dietary vitamin K intake, and marital status other than married. Conclusion Overall, the pharmacist's intervention significantly prolonged the time to occurrence of adverse drug reactions and reduced their incidence.