Comparison of GLP-1 receptor agonists and other Glucose-Lowering agents on cardiovascular outcomes in individuals with type 2 diabetes and Obesity: A Spanish Real-World Population-Based study.

AIMS: Assess the impact of glucagon-like peptide receptor agonists (GLP-1RA) compared to other glucose-lowering agents on cardiovascular outcomes in individuals with type 2 diabetes and obesity in a Spanish metropolitan area. METHODS: A retrospective population-based type 2 diabetes cohort was identified from the Valencia Clinic-Malvarrosa Department electronic databases (2014-2019). Study groups included GLP-1RA, sodium-glucose co-transporter-2 inhibitors (SGLT2i), Insulin, and Miscellany (other glucose-lowering agents). 1:1:1:1 propensity score matching was conducted. The primary outcome was a composite of major adverse cardiovascular events (4-point MACE) comprising myocardial infarction, stroke, all-cause mortality, and heart failure. Secondary outcomes included individual 4-point MACE components. Hazard ratios were estimated using Cox regression analyses against the Miscellany group. RESULTS: From 26,944 subjects, 1,848 adults were selected per group. GLP-1RA did not show a significant reduction in 4-point MACE risk (HR 1.05 [95%CI 0.82-1.34]). SGLT2i significantly reduced the risk of heart failure (HR 0.16 [95%CI 0.05-0.54]) and atrial fibrillation (HR 0.58, [95%CI 0.35-0.95]). The Insulin group exhibited a higher risk for 4-point MACE and most individual outcomes compared to GLP-1RA and SGLT2i. CONCLUSIONS: Our findings do not provide evidence of a reduced cardiovascular risk, as assessed by 4-point MACE, with GLP-1RA. In contrast, SGLT2i demonstrated protective effects against heart failure and atrial fibrillation.

Towards a personalized health care using a divisive hierarchical clustering approach for comorbidity and the prediction of conditioned group risks.

The objective was to assess risk of hospitalization and mortality of comorbidities using divisive hierarchical risk clustering to advice clinical interventions. Subjects and Methods: Data from the EHR of a general population, 3799885 adults, followed by 5 years. Model were performed using Spark and Scikit-learn and accuracy for the models was analyzed. Results: The number of models generated depends in part on the number of chronic diseases included (ex testing a sample of six diseases, a total number of 397 models for all-cause mortality and 431 models for hospitalization). The estimated models offered an ordered selection for the relevant clinical variables and their estimated risk as a group and for the individual patient in the group. Accuracy was assessed according to age, sex and the cardinality of the comorbid groups. A mobile version and dashboard were developed. Conclusion: The software developed stratified hospital admission and mortality risk in clusters of chronic diseases, and for a given patient, it could advise intensifying treatment or reallocating the patient risk.

Real-World Evaluation of GLP-1 Receptor Agonist Therapy Persistence, Adherence and Therapeutic Inertia Among Obese Adults with Type 2 Diabetes.

INTRODUCTION: In type 2 diabetes (T2D), key barriers to optimal glycaemic control include lack of persistence with treatment, reduced medication adherence and therapeutic inertia. This study aimed to assess the impact of these barriers in obese adults with type 2 diabetes treated with a GLP-1 receptor agonist (GLP-1RA) and compare them against other glucose-lowering agents in a real-world setting. METHODS: A retrospective study was conducted using electronic medical records from 2014 to 2019 for adults with T2D at the Valencia Clínico-Malvarrosa Department of Health (Valencia, Spain). Four study groups were established: all GLP-1RA users, SGLT2i users, insulin users and other glucose-lowering agent users (miscellany group). To account for imbalance between groups, propensity score matching (PSM) including age, gender and pre-existing cardiovascular disease was performed. Chi-square tests were used for comparisons between groups. Time to first intensification was calculated using competing risk analysis. RESULTS: Among the 26,944 adults with T2D, 7392 individuals were selected following PSM, with 1848 patients in each group. At 2 years, GLP-1RA users were less persistent than non-users (48.4% versus 72.7%, p < 0.0001) but more adherent (73.8% versus 68.9%, respectively, p < 0.0001). A greater proportion of persistent GLP-1RA users than non-persistent users exhibited reduced HbA1c (40.5% versus 18.6%, respectively, p < 0.0001), but no differences in cardiovascular outcomes and death were found. Overall, therapeutic inertia was observed in 38.0% of the study population. The large majority of GLP-1RA users received treatment intensification, whereas only 50.0% of GLP-1RA non-users were intensified. CONCLUSION: Under real-life conditions, obese adults with T2D persistently treated with GLP-1RA showed improved glycaemic control. Despite benefits, persistence with GLP-1RA was limited after 2 years. Additionally, therapeutic inertia occurred in two out of three study participants. Strategies to facilitate medication adherence, persistence and treatment intensification in people with T2D should be made a priority in order to achieve and maintain glycaemic targets and improve outcomes in this population. TRAIL REGISTRATION: Study registered in clinicaltrials.org with the identifier NCT05535322.

Incidence and impact of atrial fibrillation in heart failure patients: real-world data in a large community.

AIMS: The objective of the present study is to assess the bidirectional association between heart failure (HF) and atrial fibrillation (AF) using real-world data. METHODS AND RESULTS: From an electronic health recording with a population of 3 799 885 adult subjects, those with prevalent or incident HF were selected and followed throughout a study period of 5 years. Prevalence and incidence of AF, and their impact in the risk for acute HF hospitalization, worsening renal function, ischaemic and haemorrhagic stroke, and all-cause mortality were identified. We analysed all incident and prevalent patients with HF and AF, 128 086 patients (S1), and subsequently analysed a subset of patients with incident HF and AF, 57 354 patients (S2). We analysed all incident and prevalent patients with HF and AF, 128 086 patients (S1), and subsequently a subset of patients with incident HF and AF, 57 354 patients (S2). The prevalence of AF was 59 906 (46.7%) of the HF patients, while incidence in the S2 was 231/1000 patients/year. In both cohorts, S1 and S2, AF significantly increases the risk of acute heart failure hospitalization [incidence 79.1/1000 and 97.5/1000 patients/year; HR 1.53 (1.48-1.59 95% CI) and HR 1.32 (1.24-1.41 95% CI), respectively], risk of decreased renal function (eGFR reduced by >20%) [66.2/1000 and 94.0/1000 patients/year; HR 1.13 (1.09-1.18 95% CI) and HR 1.22 (1.14-1.31 95% CI), respectively] and all-cause mortality [203/1000 and 294/1000 patients/year; HR 1.62 (1.58-1.65 95% CI) and HR 1.65 (1.59-1.70 95% CI), respectively]. The number of episodes of hospitalization for acute heart failure was also significantly higher in the AF patients (27 623 vs. 10 036, P < 0.001). However, the risk for ischaemic stroke was reduced in the AF subjects [HR 0.66 (0.63-0.74 95% CI)], probably due to the anticoagulant treatment. CONCLUSIONS: AF is associated with an increment in the risk of episodes of acute heart failure as well as decline of renal function and increment of all-cause mortality.

Real world data of anticoagulant treatment in non-valvular atrial fibrillation across renal function status.

The objective is to assess the impact of anticoagulant treatment in non-valvular atrial fibrillation (AF) and different categories of renal dysfunction in real world. Electronic Health recordings of patients with diagnosis of AF and renal function collected throughout 5 years and classified according to KDIGO categories. Stroke, transitory ischemic attack (TIA), intracranial hemorrhage and all-cause mortality were identified. Anticoagulant treatments during the study period were classified in untreated (never received therapy), VKA, NOAC and Aspirin. The risk of events was calculated by Cox-proportional hazard models adjusted by confounders. A total of 65,734 patients with AF, mean age 73.3 ± 10.49 years old and 47% females and follow-up of 3.2 years were included. KDIGO classification were: G1 33,903 (51.6%), G2 17,456 (26.6%), G3 8024 (12.2%) and G4 6351 (9.7%). There were 8592 cases of stroke and TIA, 437 intracranial hemorrhage, and 9603 all-cause deaths (incidence 36, 2 and 38 per 103 person/year, respectively). 4.1% of patients with CHA2DS2-VASc Score 2 or higher did not receive anticoagulant therapy. Risk of stroke, TIA, and all-cause mortality increased from G1 to G4 groups. Anticoagulant treatments reduced the risk of events in the four categories, but NOAC seemed to offer significantly better protection. Renal dysfunction increases the risk of events in AF and anticoagulant treatments reduced the risk of stroke and all-cause mortality, although NOAC were better than VKA. Efforts should be done to reduce the variability in the use of anticoagulants even in this high risk group.

Real-World Data of Anticoagulant Treatment in Non-valvular Atrial Fibrillation.

AIMS: To assess the impact of anticoagulant treatment on risk for stroke and all-cause mortality of patients with atrial fibrillation using real-world data (RWD). METHODS: Patients with prevalent or incident atrial fibrillation were selected throughout a study period of 5 years. Stroke, transitory ischemic attack, hemorrhagic stroke, and all-cause mortality were identified in the claims of the electronic health records (EHRs). Subjects were classified according to the anticoagulant treatment in four groups: untreated, vitamin K antagonists (VKAs), New Oral Anticoagulants (NOACs), and antiplatelet (AP). Risk of events and protection with anticoagulant therapy were calculated by Cox proportional hazard models adjusted by potential confounders. RESULTS: From a total population of 3,799,884 patients older than 18,123,227 patients with incident or prevalent atrial fibrillation (AF) were identified (mean age 75.2 ± 11.5 years old; 51.9% women). In a follow-up average of 3.2 years, 17,113 patients suffered from an ischemic stroke and transitory ischemic attack (TIA), 780 hemorrhagic stroke, and 42,558 all-cause death (incidence of 46, 8, 2, and 120 per 1,000 patients/year, respectively). Among CHA2DS2, VASc Score equal or >2, 11.7% of patients did not receive any anticoagulant therapy, and a large proportion of patients, 47%, shifted from one treatment to another. Although all kinds of anticoagulant treatments were significantly protective against the events and mortality, NOAC treatment offered significantly better protection compared to the other groups. CONCLUSION: In the real world, the use of anticoagulant treatments is far from guidelines recommendations and is characterized by variability in their use. NOACs offered better protection compared with VKAs.

Impact of Acute Hemoglobin Falls in Heart Failure Patients: A Population Study.

Aims: This study assessed the impact of acute hemoglobin (Hb) falls in heart failure (HF) patients. Methods: HF patients with repeated Hb values over time were included. Falls in Hb greater than 30% were considered to represent an acute episode of anemia and the risk of hospitalization and all-cause mortality after the first episode was assessed. Results: In total, 45,437 HF patients (54.9% female, mean age 74.3 years) during a follow-up average of 2.9 years were analyzed. A total of 2892 (6.4%) patients had one episode of Hb falls, 139 (0.3%) had more than one episode, and 342 (0.8%) had concomitant acute kidney injury (AKI). Acute heart failure occurred in 4673 (10.3%) patients, representing 3.6/100 HF patients/year. The risk of hospitalization increased with one episode (Hazard Ratio = 1.30, 95% confidence interval (CI) 1.19-1.43), two or more episodes (HR = 1.59, 95% CI 1.14-2.23, and concurrent AKI (HR = 1.61, 95% CI 1.27-2.03). A total of 10,490 patients have died, representing 8.1/100 HF patients/year. The risk of mortality was HR = 2.20 (95% CI 2.06-2.35) for one episode, HR = 3.14 (95% CI 2.48-3.97) for two or more episodes, and HR = 3.20 (95% CI 2.73-3.75) with AKI. In the two or more episodes and AKI groups, Hb levels at the baseline were significantly lower (10.2-11.4 g/dL) than in the no episodes group (12.8 g/dL), and a higher and significant mortality in these subgroups was observed. Conclusions: Hb falls in heart failure patients identified those with a worse prognosis requiring a more careful evaluation and follow-up.

Acute kidney injury in heart failure: a population study.

AIMS: The objective of the present study is to assess the prognostic value of acute kidney injury (AKI) in the evolution of patients with heart failure (HF) using real-world data. METHODS AND RESULTS: Patients with a diagnosis of HF and with serial measurements of renal function collected throughout the study period were included. Estimated glomerular filtration rate (GFR) was calculated with the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). AKI was defined when a sudden drop in creatinine with posterior recovery was recorded. According to the Risk, Injury, Failure, Loss, and End-Stage Renal Disease (RIFLE) scale, AKI severity was graded in three categories: risk [1.5-fold increase in serum creatinine (sCr)], injury (2.0-fold increase in sCr), and failure (3.0-fold increase in sCr or sCr > 4.0 mg/dL). AKI incidence and risk of hospitalization and mortality after the first episode were calculated by adjusting for potential confounders. A total of 30 529 patients with HF were included. During an average follow-up of 3.2 years, 5294 AKI episodes in 3970 patients (13.0%) and incidence of 3.3/100 HF patients/year were recorded. One episode was observed in 3161 (10.4%), two in 537 (1.8%), and three or more in 272 (0.9%). They were more frequent in women with diabetes and hypertension. The incidence increases across the GFR levels (Stages 1 to 4: risk 7.6%, 6.8%, 11.3%, and 12.5%; injury 2.1%, 2.0%, 3.3%, and 5.5%; and failure 0.9%, 0.6%. 1.4%, and 8.0%). A total of 3817 patients with acute HF admission were recorded during the follow-up, with incidence of 38.4/100 HF patients/year, 3101 (81.2%) patients without AKI, 545 (14.3%) patients with one episode, and 171 (4.5%) patients with two or more. The number of AKI episodes [one hazard ratio (HR) 1.05 (0.98-1.13); two or more HR 2.01 (1.79-2.25)] and severity [risk HR 1.05 (0.97-1.04); injury HR 1.41 (1.24-1.60); and failure HR 1.90 (1.64-2.20)] increases the risk of hospitalization. A total of 10 560 deaths were recorded, with incidence of 9.3/100 HF patients/year, 8951 (33.7%) of subjects without AKI episodes, 1180 (11.17%) of subjects with one episode, and 429 (4.06%) with two or more episodes. The number of episodes [one HR 1.05 (0.98-1.13); two or more HR 2.01 (1.79-2.25)] and severity [risk 1.05 confidence interval (CI) (0.97-1.14), injury 1.41 (CI 1.24-1.60), and failure 1.90 (CI 1.64-2.20)] increases mortality risk. CONCLUSIONS: The study demonstrated the worse prognostic value of sudden renal function decline in HF patients and pointed to those with more future risk who require review of treatment and closer follow-up.