Rationale, design, and methodology of the EPIC (Epidemiology of Polypharmacy and Potential Drug-Drug Interactions in Elderly Cardiac Outpatients) study.

OBJECTIVE: The aim of this study is to assess the prevalence of polypharmacy, inappropriate drug use, and drug-drug interactions (DDIs) in elderly patients presenting at outpatient cardiology clinics in Turkey. METHODS: The EPIC (Epidemiology of Polypharmacy and Potential Drug-Drug Interactions in Elderly Cardiac Outpatients) study will be an observational, real-world, multicenter study conducted to evaluate DDIs and polypharmacy in elderly cardiac outpatients. All consecutive patients (aged ≥65 years) admitted to outpatient cardiology clinics between July 30, 2018 and July 30, 2019 who provide written, informed consent will be enrolled. A total of approximately 5000 patients are to be enrolled in this non-interventional study. All of the data will be collected at one point in time and current clinical practice will be evaluated (ClinicalTrials.gov NCT03370523). RESULTS: Patient demographics, comorbid disease characteristics, laboratory test results, and details of medication use will be collected using self-reports and medical records. The severity of comorbid disease will be recorded and scored according to Charlson Comorbidity Index (CCI) and patients will be divided into 3 groups: mild, those with a CCI score of 1-2; moderate, those with a CCI score of 3-4; and severe, those with a CCI score of ≥5. Polypharmacy will be defined as the use of 5 or more medications at one time. DDIs will be determined using the Lexicomp Online drug interaction screening tool and potentially inappropriate medications will be defined based on the 2015 update of the Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. Severe drug interactions will be defined as those in category D or X. CONCLUSION: EPIC will be the first large-scale study in Turkey to evaluate polypharmacy, potentially inappropriate medications, and DDIs in elderly cardiac outpatients in a real-world clinical setting.

Geographical Variations in Patients with Heart Failure and Preserved Ejection Fraction: A Sub-Group Analysis of the APOLLON Registry

Background: Clinical characteristics of patients with heart failure may vary geographically. However, limited data are available regarding the geographical differences of patients with heart failure and preserved ejection fraction. Aims: The present subgroup analysis aims to investigate the geographical differences in clinical characteristics, management, and primary etiology of patients with heart failure and preserved ejection fraction in Turkey. Study Design: A cross-sectional study. Methods: A comPrehensive, ObservationaL registry of heart faiLure with mid-range and preserved ejection fractiON (APOLLON) is a multicenter and observational study conducted in seven regions of Turkey (NCT03026114). The present study is a post-hoc analysis of the APOLLON registry. In this substudy, we compared the clinical characteristics of 819 consecutive patients with heart failure and preserved ejection fraction (mean age, 67 years; 57.8% women) admitted to cardiology outpatient units in different geographical regions. Results: Based on the geographical distribution of the entire Turkish population, the highest number of patients enrolled were from Marmara (271 patients, 33.1%). All demographical characteristics, clinical and laboratory findings, comorbidities, primary etiology, and medications prescribed were significantly different between the regions. Furthermore, inter-regional gender differences were identified. Comparatively, the Aegean and Mediterranean regions had older patients with heart failure and preserved ejection fraction (p<0.001), and the Black Sea, Southeast, and East Anatolia regions had predominantly male patients (51.2, 54.5, and 56.9%, respectively; p=0.002). Notably, the Mediterranean and Southeast Anatolia had more symptomatic patients, and history of hospitalization for heart failure was more prevalent in Southeast Anatolia (33.3%, p<0.001). Prevalence of atrial fibrillation was higher in the Mediterranean and Southeast Anatolia regions (51 and 48.5%, p<0.001), and patients with heart failure and preserved ejection fraction had a higher prevalence of hypertension in the Mediterranean, Southeast Anatolia, and Black Sea regions (p=0.002). Angiotensin-converting enzyme inhibitors were more frequently prescribed in East Anatolia (52.3%, p=0.001), and the prevalence of patients with heart failure and preserved ejection fraction using loop diuretics (48.8%, p=0.003) was higher in the Black Sea region. Conclusion: This study was the first to show geographical differences in clinical characteristics of patients with heart failure and preserved ejection fraction in Turkey. Determination of the clinical characteristics of the heart failure and preserved ejection fraction population based on the geographical region may enables physicians to adopt a region-specific clinical approach toward heart failure and preserved ejection fraction.

Design and rationale for the ASSOS study: Appropriateness of aspirin use in medical outpatients a multicenter and observational study.

OBJECTIVE: The aim of this study was to describe the current status of aspirin use and the demographic characteristics of patients on aspirin for primary and secondary prevention of cardiovascular diseases. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study (ASSOS) trial was a multicenter, cross-sectional, and observational study conducted in Turkey. The study was planned to include 5000 patients from 14 cities in Turkey. The data were collected at one visit, and the current clinical practice regarding aspirin use was evaluated (ClinicalTrials.gov number NCT03387384). RESULTS: The study enrolled all consecutive patients who were admitted to the outpatient cardiology clinics from March 2018 until June 2018. Patients should be at least 18 years old, have signed written informed consent, and on aspirin (80-325 mg) therapy within the last 30 days. Cardiologists from the hospital participates in the study. Patients were divided into 2 categories according to presence or absence of atherosclerotic cardiovascular disease, namely secondary prevention group and primary prevention group, respectively. The appropriate use of aspirin in the primary and secondary prevention groups was assessed according to the European Society of Cardiology guidelines and US Preventive Services Task Force. The patients' gastrointestinal bleeding risk factors and colorectal cancer risk were evaluated. CONCLUSION: The ASSOS registry will be the most comprehensive and largest study in Turkey evaluating the appropriateness of aspirin use. The results of this study help understand the potential misuse of aspirin in a real-world setting.

The association of paraoxonase 1 gene L55M polymorphism with the extent and severity of coronary artery disease in the Turkish population and its dependence on gender.

OBJECTIVE: Coronary artery disease (CAD) is a common, complex, and progressive disorder characterized by the accumulation of lipids and fibrous elements in the arteries. It is one of the leading causes of death in industrialized nations. Oxidative modification of low-density lipoprotein (LDL) in the arterial wall plays an important role in the initiation and progression of atherosclerosis. Paraoxonase1 (PON1) is involved in lipid metabolism and is believed to protect LDL oxidation. In our study, we aimed to clarify the relationship between PON1 gene L55M polymorphism and the extent and severity of CAD. METHODS: In total, 114 patients (54 males, mean age: 56.7 ± 12.0 years; 60 females, mean age: 55.7 ± 13.2 years) with stable angina or angina equivalent symptoms were enrolled in this prospective study. Cardiological evaluation was performed with electrocardiogram and transthoracic echocardiogram. The presence of hypertension, dyslipidemia, diabetes, and smoking status were ascertained. The patients were grouped according to their Gensini scores and gender. Genetic analysis of the PON1 gene L55M polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: We determined that the LL genotype was more prevalent in patients with Gensini score higher than or equal to 20 (p=0.026) and that this correlated with severe atherosclerotic coronary artery lesions in both gender groups, reaching a statistical significance in the female subjects (p=0.038). CONCLUSION: It was thought that the PON1 gene L55M polymorphism plays a significant role in CAD progression, especially in females.