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Öğe Deciphering mortality risk of diabetes medications in heart failure patients with diabetes mellitus under triple guideline-directed medical therapy(Elsevier Ireland Ltd, 2024) Colluoglu, Inci Tugce; Celik, Ahmet; Ata, Naim; Ural, Dilek; Sahin, Anil; Ulgu, Mustafa Mahir; Kanik, Emine ArzuBackground: Scientific evidence regarding the impact of different combinations of diabetes medications in heart failure patients with diabetes mellitus (HFwDM) remains limited. Aim: We aimed to investigate the effect of monotherapy and combination therapy for DM on all -cause mortality in HFwDM under triple guideline -directed medical therapy (GDMT). Method: This nationwide retrospective cohort study included adult HFwDM under triple GDMT between January 1, 2016 and December 31, 2022.We collected the data from the National Electronic Database of the Turkish Ministry of Health.We created various combination including different diabetes medications based on the current guidelines for DM.The primary endpoint was all -cause mortality. Results: A total of 321,525 HFwDM under triple GDMT (female:49%, median age:68[61 -75] years) were included. The highest rate of prescribed combination therapy was metformin and sulfonylureas ( n = 55,266). In Cox regression analysis, ins & uuml;lin monotherapy had the highest risk for all -cause mortality (HR:2.25, 95CI%:2.062.45), whereas combination therapy including metformin, SGLT2i, and sulfonylureas provided the most beneficial effect on survival (HR:0.29, 95CI%:0.22 -0.39) when compared to patients not receiving diabetes medication. Among patients taking diabetes medications, the inclusion of SGLT2i demonstrated a survival benefit ( p < 0.05), despite concurrent use of volume -retaining medications such as insulin and thiazolidinediones. Conversely, combinations of diabetes medications without SGLT2i did not demonstrate any survival benefit compared to patients not taking diabetes medication ( p > 0.05). Conclusion: This study underscored the use of SGLT2i as monotherapy or as a part of combination diabetes medications to improve survival among HFwDM, while also highlighting that combinations lacking SGLT2i did not confer any survival benefit.Öğe Epidemiology of heart failure in Turkiye(Tubitak Scientific & Technological Research Council Turkey, 2024) Ata, Naim; Colluoglu, Inci Tugce; Sahin, Anil; Yilmaz, Mehmet Birhan; Nalbantgil, Sanem; Birinci, Suayip; Ulgu, Mustafa MahirBackground/aim: The epidemiological data on heart failure (HF) vary between regions within the same country. We aimed to investigate the epidemiological data on HF in Turkiye across all age groups regarding seven geographical regions. Materials and methods: We included all patients from the Turkish population who received a first diagnosis of HF between January 1, 2016 and December 31, 2022, using ICD-10 codes from the National Electronic Healthcare Database. The data were categorized by seven geographical regions of Turkiye. Results: The median age of index diagnosis of HF was 70 (60-78) years in all age groups and 4 (1-12) years in pediatric population. The prevalence rate of HF was the highest in the Black Sea Region at 3.103%, while the Southeastern Anatolia Region exhibited the lowest at 1.436%. In all age groups, female patients with HF were older and had a higher prevalence rate across all geographical regions than male patients. From 2017 to 2021, incidence rates of HF declined to 3.0 per 1000 person years, with a consistent decrease for each geographical region. The highest incidence rates of HF were seen in the Black Sea Region, while the Southeastern Anatolia Region had the lowest. Evaluating pediatric population with HF, prevalence of HF was 0.81 per 1000 people (female children: 0.77 per 1000 people, male children: 0.84 per 1000 people). Female children with HF demonstrated the highest prevalence in the Central Anatolia Region with a rate of 1.04 per 1000 people, while male pediatric population with HF exhibited the greatest prevalence of HF in the Mediterranean Region, reaching 0.89 per 1000 people. The lowest prevalence of children with HF in both sexes was observed in the Eastern Anatolia Region (female children: 0.62 per 1000 people, male children: 0.48 per 1000 people). Conclusion: Despite regional variations, prevalence of HF in Turkiye's regions aligns with global trends. Sex-based differences in HF prevalence were evident across all age groups, including pediatric population. Incidence rates of HF in each region exhibited a substantial decline by 2021.Öğe Exploring Regional Disparities in Heart Failure Epidemiology and Outcomes: A Comprehensive Study Across Geographical Regions in Türkiye(Galenos Publ House, 2024) Sahin, Anil; Coellueoglu, Tugce; Celik, Ahmet; Ata, Naim; Yilmaz, Mehmet Birhan; Ural, Dilek; Kanik, ArzuBackground: Heart failure (HF) is a common condition that affects 1-3% of the general population. Its prevalence exhibits notable international and intranational disparities, partly explained by socioeconomic status, religion, ethnic diversity, and geographic factors. A comprehensive understanding of the epidemiological symptoms of HF in different regions of Turkiye has yet to be revealed. Aims: To examine epidemiological data from 2016 to 2022, focusing on crucial patient characteristics and geographical regions, to determine the incidence and prevalence of HF in Turkiye across seven diverse geographical regions.Study Design: A nationwide population-based retrospective cohort study.Methods: The comprehensive National Electronic Database of the Turkish Ministry of Health was used in this study to obtain data that covers the whole Turkish population from January 1, 2016, to December 31, 2022. The International Classification of Diseases-10 (ICD-10) codes were used to identify adults with HF (n = 2,701,099) and associated comorbidities. Turkiye is divided into seven geographically distinct regions. Epidemiological characteristics and survival data of these regions were analyzed separately. All-cause mortality was set as the primary outcome. Results: In , the total estimated prevalence of adult patients with HF is 2.939%, ranging from 2.442% in Southeastern Anatolia to 4.382% in the Black Sea Region. Except for the Eastern Anatolia Region, the three most often reported comorbidities were hypertension, dyslipidemia, and anxiety disorders. The rates of prescribing guideline-directed medical therapy (GDMT) for HF and other medications varied significantly. GDMT prescription rates were lowest in the Eastern Anatolia Region (82.6% for beta-blockers, 48.7% for RASi, 31.8% for mineralocorticoid receptor antagonists, and 9.4% for SGLT2i). The Mediterranean and Aegean regions had the highest median N-terminal brain natriuretic peptide (NT-proBNP) levels of 1,990,0 pg/ml (518.0-6,636,0) and 1,441,0 pg/ml (363.0-5,000,0), respectively. From 2016 to 2022, 915,897 (33.9%) of 2,701,099 patients died. The Eastern Anatolia Region had the lowest all-cause mortality rate of 26.5%, whereas the Black Sea Region had the highest all-cause mortality rate of 35.3%.Conclusion: Our real-world analysis revealed geographic disparities in HF characteristics, such as decreased mortality in socioeconomically challenged regions. Higher stress susceptibility in developed regions may increase the likelihood of adverse outcomes.Öğe Impact of implantable cardioverter defibrillators on mortality in heart failure receiving quadruple guideline-directed medical therapy: a propensity score-matched study(Bmc, 2024) Sahin, Anil; Celik, Ahmet; Ural, Dilek; Colluoglu, Inci Tugce; Ata, Naim; Kanik, Emine Arzu; Ulgu, Mustafa MahirBackgroundIn the contemporary management of heart failure with reduced ejection fraction (HFrEF), the recommended quadruple guideline-directed medical therapy (GDMT) consists of angiotensin receptor-neprilysin inhibitor (ARNI), evidence-based beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), and sodium-glucose cotransporter-2 inhibitors (SGLT-2i). This study explored the impact of adding implantable cardioverter-defibrillator (ICD) therapy to this comprehensive regimen in HFrEF patients.MethodsUtilizing deidentified data from the National Electronic Database of the Turkish Ministry of Health, we conducted a nationwide retrospective cohort study on 5450 HFrEF patients receiving quadruple GDMT, including ARNI. Among them, 709 patients underwent additional ICD or cardiac resynchronization therapy defibrillator (CRT-D) implantation. Propensity score matching ensured balanced baseline characteristics between groups. Primary endpoint was determined as all-cause mortality.ResultsIn the matched cohort, all-cause mortality occurred in 108 out of 619 patients (17.4%) in the GDMT group and 101 out of 619 patients (16.3%) in the ICD group, with a hazard ratio (HR) of 0.74 and a 95% confidence interval (CI) ranging from 0.57 to 0.98. The median follow-up time was 1365 days in the matched cohort, 1283 days in the GDMT group. Subgroup analyses consistently demonstrated benefits, particularly among individuals aged 61 years and older (HR: 0.60, 95% CI: 0.42-0.87, p = 0.006), those with sinus rhythm (HR: 0.55, 95% CI: 0.34-0.89, p = 0.013), individuals not using amiodarone (HR: 0.61, 95% CI: 0.42-0.89, p = 0.011), and those with an estimated glomerular filtration rate lower than 61.9 (HR: 0.66, 95% CI: 0.48-0.91, p = 0.011).ConclusionsThis study may offer a glimmer of hope that even after achieving the best current optimal medical therapy, the addition of device therapy could still yield positive outcomes in the management of patients with HFrEF.Öğe In Response to The Importance of Age Standardisation in Comparing Regional Inequalities(Galenos Publ House, 2025) Sahin, Anil; Colluoglu, Tugce; Celik, Ahmet; Ata, Naim; Yilmaz, Mehmet Birhan; Ural, Dilek; Kanik, Arzu[No abstract available]Öğe Medical and advanced heart failure therapies in Türkiye(Tubitak Scientific & Technological Research Council Turkey, 2024) Nalbantgil, Sanem; Demir, Emre; Celik, Ahmet; Colluoglu, Inci Tugce; Ata, Naim; Yilmaz, Mehmet Birhan; Sahin, AnilBackground/aim: Effective management of heart failure involves evidence-based use of multiple medications and their combinations. Furthermore, dosage escalation of the recommended medications is advised. In cases of advanced heart failure, long-term mechanical assistance devices or heart transplantation surgery may be necessary. Socio-economic disparities create unequal opportunities for people to access these treatments. The study aimed to analyze and compare medical and advanced heart failure treatments recommended by guidelines across various regions in T & uuml;rkiye. Materials and methods: About 85 million citizens medical treatment records were utilized between January 1, 2016, and December 31, 2022. Medical and heart replacement treatment opportunities for heart failure in T & uuml;rkiye were evaluated in the general population and across different geographical regions. Results: According to this study, beta-blockers were the most commonly prescribed medication for heart failure in T & uuml;rkiye. This was followed by angiotensin-converting enzyme inhibitors at 44% and mineralocorticoid receptor antagonists at 38.9%. However, only 0.6% of patients used angiotensin receptor blocker-neprilysin inhibitors. Despite the high incidence of diabetes mellitus among heart failure patients, only 11% used sodium-glucose cotransporter two inhibitors. The study also found that using an implantable cardioverter defibrillator (ICD) was 0.8%, and cardiac resynchronization therapy (CRT) was 0.3% among all intracardiac device treatments. Heart replacement therapies, cardiac transplantation surgery, and long-term left ventricle-assisted device (LVAD) surgery had very low rates. Conclusion: The use of guideline-directed medical therapy is not optimal in T & uuml;rkiye and varies across different geographical regions. It is a fact that heart transplant or LVAD surgery, CRT, and ICD implantation rates in T & uuml;rkiye are significantly lower than those in developed countries, regardless of geographical region.Öğe Navigating Heart Failure: Unveiling Sex Disparities in Guideline-Directed Medical Therapy Combinations(Excerpta Medica Inc-Elsevier Science Inc, 2024) Celik, Ahmet; Sahin, Anil; Ata, Naim; Colluoglu, Inci Tugce; Ural, Dilek; Kanik, Emine Arzu; Ayvali, Mustafa OkanMajor heart failure (HF) trials remain insufficient in terms of assessing the differences in clinical characteristics, biomarkers, treatment efficacy, and safety because of the underrepresentation of women. The study aimed to present sex-related disparities in HF management, including differences in demographics, co-morbidities, cardiac biomarkers, prescribed medications, and treatment outcomes. The study utilized anonymized data from and December 31, 2022. The cohort analysis included 2,501,231 adult patients with HF. Specific therapeutic combinations were analyzed using a Cox regression model to obtain relative risk reduction for all-cause death. The primary end point was all-cause mortality. In the cohort, 48.7% (n = 1,218,911) were male, whereas 51.3% (n = 1,282,320) were female. Female patients exhibited a higher median age (71 vs 68 years) and manifested higher prevalence of diabetes mellitus, anemia, atrial fibrillation, anxiety, and ischemic stroke. Male patients demonstrated higher rates of previous myocardial infarction, dyslipidemia, chronic obstructive pulmonary disease, and chronic kidney disease. Higher concentrations of natriuretic peptides were observed in female patients. Renin-angiotensin aldosterone inhibitor, b blockers, mineralocorticoid receptor antagonists, sodium/glucose cotransporter 2 inhibitor (SGLT2i), and ivabradine were more commonly prescribed in male patients, whereas loop diuretics, digoxin, and ferric carboxymaltose were more frequent in female patients. Male patients had higher rates of cardiac resynchronization therapy and implantable cardioverter defibrillator implantation rates. All-cause mortality and hospitalization rates were higher in male patients. Compared with monotherapy, all combinations, including SGLT2i, showed a beneficial effect on all-cause mortality in both female and male patients with HF. In hospitalized patients with HF, the addition of digoxin to renin-angiotensin aldosterone inhibitor, mineralocorticoid receptor antagonists, and b blockers was superior to monotherapy regarding all-cause mortality in female patients with HF compared with male patients with HF. In conclusion, this study highlights that sex-specific responses to HF medication combinations compared with monotherapy and differences in co-morbidities underscore the importance of tailored management strategies. Digoxin showed a contrasting effect on allcause mortality between both sexes after hospitalization, whereas SGLT2i exhibited a consistent beneficial effect in both sexes when added to all combinations. (c) 2024 Elsevier Inc. All rights reserved. (Am J Cardiol 2024;216:27-34)Öğe Real-Life Individual Comparison of Sodium-Glucose Cotransporter-2 Inhibitors in Patients with Heart Failure and Diabetes Mellitus(Adis Int Ltd, 2025) Yilmaz, Mehmet Birhan; Celik, Ahmet; Colluoglu, Tugce; Sahin, Anil; Ural, Dilek; Kanik, Arzu; Ata, NaimBackgroundSodium-glucose cotransporter-2 inhibitors (SGLT2is) are breakthrough agents for the treatment of type 2 diabetes mellitus (T2DM) and heart failure (HF). However, among patients with HF and T2DM, some uncertainty remains about individual comparisons, including dosing.ObjectivesWe aimed to make a real-life individual comparison of SGLT2is among patients with HF and T2DM.MethodsThis was a subgroup analysis of the Turkish Ministry of Health's National Electronic Database for adult patients with HF (TRends-HF). All-cause mortality (ACM) data up to 7 years were evaluated. Patients with HF and T2DM who were prescribed an SGLT2i were identified, and individual doses of empagliflozin 25 mg, empagliflozin 10 mg, and dapagliflozin 10 mg were compared. For individual comparisons, propensity score-matching analysis was generated as 1:1:1, and disease-modifying therapies (DMTs) for HF were considered.ResultsIn the triple-matched cohort, 1-, 5-, and 7-year survival rates were 95%, 81%, and 76% versus 94%, 78%, and 72% versus 94%, 80%, and 75% for empagliflozin 25 mg, empagliflozin 10 mg, and dapagliflozin 10 mg, respectively. Among patients who were on triple DMT for HF, 1-, 5-, and 7-year survival rates were 95%, 78%, and 70% for empagliflozin 25 mg, 95%, 74%, and 66% for empagliflozin 10 mg, and 94%, 77%, and 69% for dapagliflozin, respectively. Annual emergency department visits were slightly lower with empagliflozin 10 mg and dapagliflozin 10 mg than with empagliflozin 25 mg. A greater proportion of patients on dapagliflozin 10 mg did not experience hospitalization during the 7-year follow-up compared with both doses of empagliflozin, albeit with a small effect size.ConclusionAmong patients with HF and T2DM, SGLT2is are instrumental, and empagliflozin 10 mg remains significantly inferior to dapagliflozin 10 mg and empagliflozin 25 mg in terms of 5- and 7-year ACM.Öğe Timing and Adherence Matter for Sodium-Glucose Cotransporter-2 Inhibitors in Heart Failure(Wiley, 2025) Yilmaz, Mehmet Birhan; Celik, Ahmet; Sahin, Anil; Colluoglu, Tugce; Ural, Dilek; Kanik, Arzu; Ata, NaimBackground It is imperative to maintain the use of sodium-glucose cotransporter-2 inhibitors (SGLT-2is) in patients with diabetes both after the index diagnosis of heart failure (HF) and even prior to the index diagnosis of HF. We aimed to investigate whether timing of SGLT-2 is before the index diagnosis of HF, and second, adherence to SGLT-2is in the form of the proportion of days covered metric matter in patients with HF and diabetes. Methods and Results All-cause death up to 7 years were evaluated in HF with diabetes from the subgroup analysis of TRends-HF (TRends in Heart Failure in T & uuml;rkiye). Patients with HF and diabetes, who were prescribed an SGLT-2i either before or after the index diagnosis of HF were identified, categorized according to duration of exposure before the index HF diagnosis and according to proportion of days covered after the index diagnosis of HF, and compared with nonusers. There were 1 229 833 patients with HF and diabetes in the cohort. A total of 247 987 were on an SGLT-2i and had available timing data, and 14.06% had SGLT-2i on board before the index HF diagnosis. Median duration of SGLT-2i exposure before the index HF diagnosis was 417 days. Prognosis was the best among patients with diabetes who were prescribed an SGLT-2i before the index diagnosis of HF with an exposure more than median duration. Of note, among patients who were prescribed an SGLT-2i after the index HF diagnosis; there was a numerically graded increase in all-cause mortality rate such that a >10% decrease in SGLT-2i proportion of days covered was associated with a 59% increase in all-cause death (hazard ratio, 1.21-2.09). Conclusions Regardless of time or adherence, SGLT-2is offer a remarkable all-cause death benefit to patients with HF and diabetes. SGLT-2is' all-cause death benefit for patients with HF and diabetes was greatest when it was prescribed before the HF index diagnosis. Poor adherence to SGLT-2is was associated with worsening survival in patients with HF and diabetes following the diagnosis of index HF.Öğe Trends in heart failure between 2016 and 2022 in Türkiye (TRends-HF): a nationwide retrospective cohort study of 85 million individuals across entire population of all ages(Elsevier, 2023) Celik, Ahmet; Ural, Dilek; Sahin, Anil; Colluoglu, Inci Tugce; Kanik, Emine Arzu; Ata, Naim; Arugaslan, EmreBackground Data on the burden of heart failure (HF) outside western countries are limited, but available data suggest it may present differently in other countries. The aim of this study was to examine the incidence, prevalence, and survival rates of HF in Turkiye, with a specific focus on how these rates vary according to age, sex, comorbidities, and socioeconomic status (SES).Methods We harnessed the extensive National Electronic Database of the Turkish Ministry of Health, covering Turkey's entire population from January 1, 2016, to December 31, 2022, to identify 2,722,151 cases of HF and their associated comorbidities using ICD-10 codes. Analyzing the primary endpoint of all-cause mortality, our study utilized anonymized data to examine patient demographics, comorbidities, socioeconomic status, and survival patterns, employing statistical techniques to delve into relationships and trends. The data were segmented by gender, socioeconomic status, and age, involving cross-tabulations and statistical metrics to explore connections, odds ratios, and survival rates.Findings The estimated prevalence of HF was 2.114% in Turkiye at the end of 2022, with an annual incidence ranging between 3.00 and 6.06 per 1000 person years. Females were older than males (69.8 +/- 13.9 years vs. 66.8 +/- 13.9 years, respectively). The most common comorbidities were congenital heart diseases and anemia under the age of 20, and hypertension and atherosclerotic cardiovascular disease in the adult population. Only 23.6% (643,159/2,722,151) of patients were treated with any triple guideline-directed medical therapy (GDMT) and 3.6% (96,751/2,722,151) of patients were on quadruple GDMT. The survival rates for patients with HF at 1, 5, and 7 years were 83.3% (95% CI: 83.2-83.3), 61.5% (95% CI: 61.4-61.6), and 57.7% (95% CI: 57.6-57.8) among females, and 82.1% (95% CI: 82.0-82.2), 58.2% (95% CI: 58.1-58.3), and 54.2% (95% CI: 54.0-54.3) among males. Despite a tendency for an increase from the highest to the lowest SES, the prevalence of HF and mortality were paradoxically lowest in the lowest SES region.Interpretation The prevalence, incidence, and survival rates of HF in Turkiye were comparable to western countries, despite the notable difference of HF onset occurring 8-10 years earlier in the Turkish population. Drug usage statistics indicate there is a need for effective strategies to improve treatment with GDMT.
