bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipid-lowering therapy with Inclisiran in the real-world setting: initial data from a national health care service
Authors: Zafrir B , Naoum I , Aker A , Saliba W 
Published: October 2024

Abstract

Introduction
Inclisiran, a first-in-class siRNA enabling long-term inhibition of PCSK9 synthesis, demonstrates good safety and efficacy profile in randomized clinical trials. Challenges for real-life use of inclisiran include limited access to therapy, injections by medical staff, lack of cardiovascular outcome data, and concern from adverse effects considering the novel mechanism and long-term activity. Real-life data on the potential to attain lipid-goals and reduce treatment gaps is lacking. We investigated the implementation of inclisiran in real-world clinical setting in Israel.

Methods
Data from a nationwide healthcare organization on patients initiating inclisiran therapy during the period of 3/2022-11/2023. Patients’ characteristics, efficacy, use of combination lipid-lowering therapies, and attainment of low-density lipoprotein cholesterol (LDL-C) goals, were evaluated.

Results
Inclisiran was initiated by 503 patients (57% women; mean age 66±11 years). Atherosclerotic cardiovascular disease was present in 54%, and peak historical LDL-C levels &gt;190 mg/dL documented in 64%. Prior exposure to PCSK9 monoclonal antibodies was evident in 28%. Follow-up lipid profile &gt;2 months after filling first prescription, was available in 397 patients (347 with ≥2 injections). In patients treated by inclisiran only (n=254), median LDL-C reduction from peak historical levels was 57% (IQR, 48%-67%), and from pre-injection levels 40% (19%-54%). In those with concomitant oral lipid-lowering therapies (n=143), median LDL-C reduction from peak levels was 66% (IQR, 55%-73%), and from pre-injection levels 46% (23%-59%) (Figure). LDL-C &lt;70 mg/dL was attained by 39% and LDL-C &lt;55 mg/dL by 21.9%. Of those treated with concomitant statin therapy, 38% attained LDL-C &lt;55 mg/dL. Overall, 6.5% did not persist with inclisiran therapy after initial injection.

Conclusions
In real-life practice, inclisiran showed good efficacy with positive short-term adherence. However, attainment rates of lipid-goals were suboptimal due to limited use of combination lipid-lowering therapy and high-rates of severe hypercholesterolemia in our patient population cohort.Waterfall Plot of LDL-C (%) Reduction
Efficacy of combination lipid lowering therapy in achieving low density lipoprotein cholesterol targets after one month of event in patients with acute coronary syndrome
Authors: Mahajan K , Mohite K , Himral S K , Dsouza S , Chandel P , Kapoor A , Patel P , Yadav R , Sharma J B , Puri R 
Published: October 2024

Abstract

Introduction
Rapid reduction in low-density lipoprotein cholesterol (LDL-C) levels reduces the risk of recurrent events in patients with acute coronary syndrome (ACS) with benefits proportional to LDL-C reduction. Early use of combination lipid-lowering therapy (LLT) is therefore recommended. Proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) combined with high-intensity statins (HIS) improve LDL-C goal attainment but are unaffordable for many patients in India and worldwide.

Purpose
We share our experience with the use of dual RE (rosuvastatin plus ezetimibe) and triple REB (rosuvastatin plus ezetimibe and bempedoic acid) combination LLT in patients admitted with ACS.

Methods
All ACS patients admitted to our institute over one year (January 2023 to December 2023) were considered in this retrospective analysis. Those with unavailable lipid profile reports, either at the time of ACS or at 1-month follow-up, were excluded. Clinical and laboratory details were obtained from hospital records. The primary objective was to assess the percentage change in LDL-C levels from index event to 4 weeks follow-up.

Results
A total of 299 patients were included, out of which 60 were on HIS alone, 71 were on RE, and 168 were on REB (Figure). The majority (99%) of patients in the REB group were statin naïve, compared to the other two groups. The baseline mean LDL-C levels at the time of the index event were 95.3+30.5, 103.2+39.6, and 115.6+32.9 mg/dl, respectively (p&lt;0.001) (Table). The mean LDL-C levels at four weeks post-ACS reduced to 52.9+21.2, 45.9+20.5, and 43.7+15.4 mg/dl, respectively (p&lt;0.01). The percentage reduction in LDL-C level was 44.4%, 55.5%, and 62.2%, respectively (p&lt;0.001). REB enabled 70.8% and 95.2% of patients to achieve the Lipid Association of India, and American College of Cardiology recommended LDL-C targets of &lt;50 mg/dl and &lt;70 mg/dl within 4 weeks. These target levels were achieved in 67.6% and 88.7% of patients on the dual RE therapy and 50% and 81.6% of patients, respectively, on HIS alone.

Conclusion
Our study demonstrates the capacity to rapidly achieve LDL-C goals after ACS with triple REB therapy, an affordable regimen compared to costly PCSK9i therapy.Figure.Lipid lowering strategies usedComparison of study groups
Predicting 1-year atrial fibrillation risk from a patch-based ambulatory ECG monitoring without atrial fibrillation
Authors: Gadaleta M , Harrington P , Okeson A , Hytopoulos E , Turakhia M P , Steinhubl S R , Quer G 
Published: October 2024

Abstract

Introduction
Early identification of atrial fibrillation (AF) can enable interventions that reduce cardiovascular events. However, AF remains undiagnosed in about 10-20% of affected individuals, and paroxysmal AF often remains undetected despite the use of in-clinic ECGs, consumer smartwatch ECGs, or ambulatory ECG monitoring. We therefore investigated whether ambulatory ECG patch-based monitoring without AF can predict AF in the subsequent 1-year post monitoring.

Purpose
This study aims to validate a machine-learning model for AF prediction within 1-year post-wear, based on the observation of non-AF single-lead ECG recordings.

Methods
We considered a clinically monitored cohort of 67,296 individuals wearing multiple single-lead ECG multi-day ambulatory monitoring patches as part of real-world care. For all selected individuals, the first patch recorded no occurrences of AF and was worn for a minimum of 6.5 days. We assess the risk of future AF based on the raw ECG, heartrate variability, frequency of ectopic beats, age and gender (ECG model), which is then compared with the risk assessment by a model based on age and gender (Baseline model). We then observe AF incidence on subsequent patches worn within one year from the first patch. We evaluated the model's accuracy by observing the number of AF cases identified (or missed) among the individuals with highest risk according to the model.

Results
In the clinically monitored cohort, a total of 3463 individuals experienced AF within the next year (incidence 5.1%) after a first AF-free monitoring period of a minimum 6.5 days. The receiver operating characteristic (ROC) curve shows an area under the curve (AUC) for the ECG model of 0.75 (95% CI: [0.74, 0.76]), and for the Baseline model of 0.66 (CI: [0.65, 0.67]). When selecting the top 20% (13,459) participants with the highest risk and verifying who developed AF in the following 1-year, we obtain positive prediction value (PPV) or precision of 12% and sensitivity (recall) of 46% for the ECG model (which correctly identifies 1,594 individuals with incident AF), and of 8% and 29%, respectively, for the Baseline model (p-value&lt;0.001). (Figure)

Conclusion
A machine learning model using as input an AF-free single-lead ECG can quantify the risk of observing AF in a population including individuals with low burdens of paroxysmal or new onset of AF within 1 year. Further research and validation are needed to enhance the interpretability and clinical applicability of the model, while prediction may be further improved with clinical AF diagnoses ascertained from other data sources. The findings of this study have important implications for the early detection and management of AF, potentially enabling earlier intervention and improved outcomes in individuals with undiagnosed AF.
Association of HbA1C with mortality and cardiovascular outcome in patients with type 2 diabetes using drugs with different hypoglycemic risk
Authors: Lin Y , Shao Y H , Huang L Y , Chen B L , Huang C Y 
Published: October 2024

Abstract

Background
Previous clinical trials showed that intensive glucose control did not reduce macrovascular events and mortality. It was speculated that severe hypoglycaemia contributed to these adverse outcomes. More contemporary clinical trials using newer anti-diabetic agents with less hypoglycaemic potential showed a linear relationship between major adverse cardiovascular events (MACE) and HbA1c reduction according to a meta-regression analysis.

Purpose
The aim of this study was to examine the association between clinical outcomes and HbA1c under different treatment backgrounds in the real-world setting. We hypothesised that when using drugs with minimal hypoglycaemic risk, lower HbA1c would be associated with better outcomes.

Methods
This was a retrospective population-based cohort study using a multi-centre electronic medical record database. Eligible patients were those diagnosed with type 2 diabetes between 2009 and 2020 who received non-insulin antidiabetic drugs. Patients were stratified into two groups based on the drugs received: drugs with high hypoglycaemic risk (sulphonylurea, meglitinide) and drugs with low hypoglycaemic risk (thiazolidinediones, acarbose, DPP4 inhibitors, GLP1 agonists, SGLT-2 inhibitors). Patients were excluded if they had received these drugs for less than 180 days or had received both high and low hypoglycaemic risk oral drugs simultaneously. HbA1c levels were assessed from the index date to the date of the interested outcome or the end of the study period (31 December 2021), whichever came first. The relationship between HbA1c and clinical outcomes was examined using a Cox proportional hazards model. The outcomes of interest included all-cause mortality and MACE.

Results
The study population consisted of 6,923 patients, including 3,639 high hypoglycaemic risk drug users and 3,284 low hypoglycaemic risk drug users. Patients with lower HbA1c levels during the follow-up period were older and frailer. After adjusting for baseline covariates, the association between the risk of death and HbA1c presented a U-shaped pattern, and this U-shaped association was similar in the two treatment cohorts (Table 1). On the other hand, the association between the risk of MACE and HbA1c presented a J-shaped pattern. In the high hypoglycaemic risk drug cohort, patients with the highest HbA1c levels (mean HbA1c 9.6%) were associated with a higher risk of MACE compared to the group with a mean HbA1c of 7.2% (hazard ratio [HR] 4.16, 95% confidence interval [CI] 2.07-8.37); lower HbA1c levels were not associated with a lower risk of MACE (Table 2). In contrast, in the low hypoglycaemic risk drug cohort, lower HbA1c levels were associated with a higher risk of MACE (HR 3.82, 95% CI 1.29-11.28).

Conclusion
Lower HbA1c levels were not associated with a lower risk of all-cause mortality and MACE. Furthermore, this phenomenon was independent of the hypoglycaemic risk of anti-diabetic drugs.
The effect of metformin use on the risk of atrial fibrillation in patients with type 2 diabetes: data from the UK biobank
Authors: Guo T S , Zhao C Y , Chen T , Tang M Y , Ning Y Y , Wang D L , Yuan Z Y , Li G 
Published: October 2024

Abstract

Objective
The present study aims to investigate the protective role of metformin against atrial fibrillation (AF) and stroke in type 2 diabetes (T2DM) patients treated with other antidiabetic medications.

Methods
We included 10,011 participants with T2DM from the UK biobank database, with a follow-up for new diagnoses of AF and stroke recorded until 2023. We employed logistic regression analysis and competing risk models to assess the association between metformin use and the incidence of AF or stroke.

Results
The cross-sectional analysis revealed that, compared with the use of other antidiabetics, metformin was associated with a lower prevalence of AF (odds ratio [OR] 0.71, 95% CI: 0.57–0.89) and stroke (OR 0.70, 95% CI: 0.56–0.86). In the competing risk model, compared to other antidiabetics, metformin may reduce the risk of AF (sub-hazard ratio [SHR] 0.86, 95% CI: 0.75–0.98) and stroke (SHR 0.62, 95% CI: 0.44–0.86) (Figure 1). Subgroup analysis indicated a significantly lower incidence of AF or stroke in patients under 65 years of age (SHRs were 0.80, 95% CI:0.67-0.96 for AF and 0.52, 95% CI: 0.34-0.81 for stroke) and in female patients (SHRs were 0.65, 95% CI:0.52-0.81 for AF and 0.53, 95% CI: 0.30-0.91 for stroke). Notably, metformin significantly reduced the incidence of AF in non-insulin users (SHR 0.80, 95% CI: 0.66-0.97) and the incidence of stroke in insulin users (SHR 0.55, 95% CI: 0.35-0.87) (Figure 2).

Conclusion
Our findings suggest that metformin use, in comparison to other antidiabetic medications, is associated with a reduced risk of AF and stroke, especially in non-insulin users for AF and insulin users for stroke.
Drug-drug interactions of empagliflozin and dapagliflozin
Authors: Stoellberger C , Finsterer J , Schneider B 
Published: October 2024

Abstract

Introduction
The sodium glucose co-transporter2-inhibitors dapagliflozin (Dapa) and empagliflozin (Empa), initially developed as antihyperglycemic agents, are increasingly also prescribed for non-diabetic patients with heart failure (HF). Glucuronidation by uridine-diphosphate glucuronosyltransferase (UGT)1A9 is the main mechanism of metabolism of Dapa, whereas Empa is eliminated mainly by excretion. Both Dapa and Empa are substrates of P-glycoprotein. The risk for drug-drug interactions (DDI) of Empa and Dapa is assumed to be low. Aim of this study was to summarize reports of DDI of Empa and Dapa from the literature.

Methods
Search-terms in PubMed were "drug-drug interaction" and AND "sodium glucose co-transporter2-inhibitors" OR "SGLT2" OR "dapagliflozin" OR "empagliflozin". The drugs were classified according the Anatomical Therapeutic Chemical (ATC) system. Included were randomized trials, pharmacovigilance studies, case series, case reports, studies in healthy subjects and in vivo data. The funding of the study and the disclosures of the authors were registered.

Results
In 45 reports DDI of Empa and Dapa with 29 drugs were described (Table). According to the ATC system, these were drugs for the alimentary tract and metabolism (n=5), blood and blood forming organs (n=2), cardiovascular system (n=11), genitourinary system and sex hormones (n=2), antiinfectives (n=2), antineoplastic and immunomodulating agents (n=3), musculo-skeletal system (n=2) and nervous system (n=2). The reports comprised studies in healthy subjects (n=28), case reports (n=7), case series (n=6), pharmacovigilance studies (n=2), a subgroup analysis of a randomized trial (n=1) and in vivo data (n=1). Most of the reports found no clinically relevant DDI (n=32).
Dapa and Empa both had a synergistic diuretic effect with bumetanide, and led to severe infections when combined with the interleukin-17-inhibitors secukinumab or ixekizumab. Empa administered with intravenous iron was reported to increase cell-iron availability, with lithium to reduce lithium exposure and with valproate to increase valproate exposure. Dapa administered with sacubitril-valsartan was reported to lead to severe hypotension, with linezolid to pancytopenia, with donafenib to an increased exposure to donafenib, with rifampicin to a reduction and mefenamic acid to an increase in Dapa exposure.
Of the 45 reports, 33 were funded by a pharmaceutical company marketing Dapa or Empa and 33 had authors with conflicts of interest with pharmaceutical companies marketing Dapa or Empa.

Conclusions
Most data about DDI of Empa and Dapa derive from studies in healthy subjects and from the marketing companies. The clinical relevance DDI of Empa and Dapa in polymorbid patients with polymedication is largely unknown. There is an urgent need for independent studies on DDI of these drugs in diabetic and non-diabetic patients with HF.Table
Use of new antidiabetic drugs in patients with cardiovascular diseases - real life data
Authors: Vucak J V , Corak N C 
Published: October 2024

Abstract

Introduction and aim
Cardiovascular diseases (CVD) are among the most common and significant complications of type 2 diabetes mellitus (T2DM). Despite significant therapeutic progress in the prevention of CVD, T2DM remains a leading cause of major adverse cardiac events (MACE). Patients with T2DM and clinical manifestations of atherosclerotic CVD, or those at high risk of developing it, should receive cardioprotective and nephroprotective medications such as GLP-1 receptor agonists (GLP-1) and SGLT-2 inhibitors (SGLT2). This study aims to determine to what extent patients undergoing treatment at the general practitioner (GP) level comply with the recommendations.

Methodology
Retrospectively, in the period January 2022 to September 2023, records in the EHR were reviewed in the five GP offices. For all patients ( ≥18 years) with DMT2, all demografic as well as data on chronic therapy, stage of chronic kidney disease (CKD), presence of any cardiovascular (CV) risk factors and/or history of cardiovascular diseases (CVD), and the therapy applied were observed.

Results
A total of 6,941 patients' data were reviewed, out of which 483 (6.96%) had a diagnosis of DMT2. Table 1. shows the characteristics of the study population. Table 2. presents the values of HbA1c according to the criteria of good, acceptable, and poor DMT2 control, as well as the CKD stage by eGFR. Among the associated comorbidities, the most common was arterial hypertension, observed in 79.5% of the participants, followed by obesity in 28.2%. In terms of the applied therapy, the majority of participants were on metformin (76.8%). There were no significant differences in body mass index (BMI) and glycemic control between the group with and without CVD. However, compared to the group without CVD, patients with both DMT2 and CVD had a higher frequency of SGLT2 inhibitors (27% vs. 18.5%) [chi²=4.336, df=1, p=0.032] and GLP-1 receptor agonists (10.7% vs. 4.6%) [chi²=6.336, df=1, p=0.012] use, but a lower frequency of metformin (67.9% vs. 81.2%) [chi²=10.510, df=1, p=0.001].

Discussion
According to current guidelines, all patients with CVD and CKD should have SGLT2 inhibitors and/or GLP-1 receptor agonists in their therapy. Comparing our study with the CAPTURE study, our patients were older and had slightly fewer associated CVD (38.7% vs. 32.9%). According to the CAPTURE study, less than 25% of patients with DMT2 in therapy have an antidiabetic medication with proven cardiovascular benefit, while in our sample, this was the case for 31.4% of the participants. This suggests that progress is being made, but it is still insufficient.

Conclusion
Over the past decade, there has been a rapid increase in knowledge regarding the appropriate treatment and management of risk factors in the population of individuals with DMT2. Although new insights are continuously incorporated into guidelines, our study shows that implementation in practice lags.
Temporal trends and regional differences of initial oral antiarrhythmic drug options in patients with new-onset atrial fibrillation: a report from the GLORIA-AF registry
Authors: Huang B , Lam H M , Ishiguchi H , Liu Y , Chao T F , Olshansky B , Huisman M , Lip G 
Published: October 2024

Abstract

Background
New-onset atrial fibrillation (AF) is common and antiarrhythmic drugs (AADs) are commonly used for treating such patients. However, whether there are temporal changes and regional differences in the choice of AADs in direct acting non-vitamin K oral anticoagulants (DOACs) era is less studied.

Purpose
The present study aimed to analyze the temporal trends and regional differences of initial oral AAD options in patients with new-onset AF in the GLORIA-AF registry, based on a proposed modernized classification of AADs in 2018 (Circulation, 2018, PMID: 30354657). AADs involved in the present study included traditional Vaughn-Williams Class I to Class IV AAD, Class IId AAD (digoxin), and Class VII AAD, which acts on the upstream of arrhythmia including angiotensin converting enzyme inhibition, angiotensin receptor blocker, and stains.

Methods
Temporal changes regarding the AAD use between the two phases of GLORIA-AF and regional differences of AADs choice were investigated. Factors associated with the choice of different AADs were established by multivariate logistic regression.

Results
Among the 36,617 participants in the GLORIA-AF registry, 33,208 (90.7%) were prescribed with AADs: 74.0% were rate control and 10.2% were rhythm control, and among the prescribed AADs, single and dual AADs were used in 73.3% and 24.9%, respectively. Moreover, 70.5% patients received upstream target modulators (Class VII AAD). Class IIa AADs (beta-blockers) were the most commonly prescribed AAD and slightly increased from Phase II (60.58%) to Phase III (62.91%) while the use of Class IId AAD (e.g. digoxin) decreased regardless of single or combined use. AADs use varied significantly among regions but the temporal trends and regional differences were similar with that of the overall cohort. Age, gender, comorbidities, admission signs, region, and concomitant medications (e.g. anticoagulants) were associated with the choices of different AADs.

Conclusions
In the DOAC era, new-onset AF patients receiving AAD commonly included upstream therapy. Rate control was still the dominant strategy for patients with new-onset AF but the use of Class IId AAD significantly decreased with the increased use of Class IIa AAD. The choice of AADs demonstrated significant regional differences and concomitant anticoagulants played important roles.Temporal trends in GLORIA-AFComparisons of AADs use in GLORIA-AF