bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conservative management of acute coronary syndromes in chronic kidney disease patients: a deadly sin
Authors: Gkini K.-P , Terentes-Printzios D , Aznaouridis K , Georgakopoulos C , Oikonomou D , Ioakeimidis N , Gardikioti V , Kallikazaros I , Tsioufis K , Vlachopoulos C 
Published: October 2021

Abstract

Background/Introduction
Chronic kidney disease (CKD) is associated with worse prognosis in acute coronary syndromes (ACS).

Purpose
We sought to investigate the prognostic effect of non-invasive management of ACS in CKD patients in a tertiary University Hospital.

Methods
Two hundred and one patients (mean age 66.5±13.6 years, 150 males) admitted to our Hospital with ACS from 2016–2017 were included in the study. Patients were followed for a median of 2 years post the index event. CKD was defined by an estimated glomerular filtration rate (eGFR) &lt;60 ml/min/m2, as assessed by the Modification of Diet in Renal Disease (MDRD) equation. We grouped patients into four groups according to their CKD status and whether they underwent coronary angiography or not. The primary outcome was all-cause death and secondary outcomes were cardiovascular and non-cardiovascular death.

Results
The majority of patients (n=120, 60%) presented with non-ST elevation ACS (NSTE-ACS), whereas 81 patients as ST-elevation myocardial infarction (STEMI) (40%). Fifty-four patients (27%) were identified as CKD patients (of whom 5 were on dialysis). Overall, 29 patients (14.4%) did not undergo coronary angiography. Patients at a higher age and with CKD were more likely to not undergo angiography. Thirty-seven (18.4%) died during follow-up (25 non-cardiovascular deaths and 12 cardiovascular deaths). Patients with conservative treatment and CKD had the worse prognosis (Hazard ratio [HR] =11.00, 95% Confidence intervals [CI] 4.00 to 30.24, p&lt;0.001) followed by non-CKD patients with conservative treatment (HR=4.37, 95% CI 1.20 to 15.90, p=0.025) compared to non-CKD patients treated invasively (reference group) after adjusting for age, gender, STEMI/NSTE-ACS diagnosis (Figure). Results were similar for non-cardiovascular death, whereas regarding cardiovascular death only the group with CKD and conservative treatment had a lower survival compared to the reference group (HR=26.5, 95% CI 2.9 to 241.7, p=0.004)

Conclusions
Patients with ACS and CKD are less likely to receive invasive management and have higher mortality from both cardiovascular and non-cardiovascular causes than patients without CKD. Conservative management of ACS was associated with higher long-term mortality versus invasive management in all patients, regardless of CKD status.

Funding Acknowledgement
Type of funding sources: None.
PCSK9 inhibitors associated hyperglycemic disorders: a real world, pharmacovigilance study
Authors: Goldman A G , Raschi E R , Cukierman-Yaffe T Y , Dankner R D , Shouval R S , Shechter M D , Ben-Zvi I B Z , Maor E M 
Published: October 2021

Abstract

Background
Initial genetic and biological studies indicated an association between proprotein-convertase subtilisin/kexin type 9 inhibitors (PCSK9i) and hyperglycemic disorders. However, subsequent clinical trials yielded inconsistent results, and real-world data are scant.

Purpose
We sought to assess the association of PCSK9i and hyperglycemic events in a real-world setting, using the FDA adverse event reporting system (FAERS).

Methods
The FAERS database (2015–2020) was retrospectively queried to assess reporting of PCSK9i-associated hyperglycemic events. Disproportionality analyses were performed using an adjusted odds ratio (adj.ROR), and the lower bound of the information component (IC) 95% credibility interval (IC025&gt;0 is deemed significant).

Results
The full database included 7,295,624 eligible patients, among them 71,748 reports of evolocumab and 15,976 of alirocumab. Compared to the full database, treatment with evolocumab, but not alirocumab, was associated with increased reporting of hyperglycemic events (n=1,587 [2.21%], adj.ROR = 1.24 [1.15–1.32], IC025 = 0.20; n=254 [1.59%], adj.ROR = 0.73 [0.60–0.88], IC025 = −0.38, respectively). Hyperglycemic events were primarily mild hyperglycemic disorders (n=1,262 [1.76%], adj.ROR = 1.56 [1.42–1.71], IC025 = 0.58), whereas diabetes was not over-reported (n=325 [0.45%], adj.ROR = 0.73 [0.63–0.86], IC025 = −0.82). Hyperglycemic events were over-reported with evolocumab versus ezetimibe (adj.ROR = 1.81 [1.06–3.07]), albeit were less frequently reported versus statins (adj.ROR = 0.44 [0.40–0.49]). Most of the hyperglycemic events occurred during the first six months of treatment and were reversible.

Conclusion
In a real-world setting, evolocumab (but not alirocumab) was consistently associated with mild hyperglycemic disorders, but not diabetes. Although initial monitoring is warranted, the favorable glycemic safety profile compared to statins supports their essential role in the management of lipid disorders. Potential different effects of evolocumab and alirocumab on glucose metabolism should be further evaluated prospectively.

Funding Acknowledgement
Type of funding sources: None.
The effect of glucagon-like peptide-1 receptor agonists on 24-hour ambulatory blood pressure: a meta-analysis
Authors: Patoulias D , Boulmpou A , Papadopoulos C E , Siskos F , Stavropoulos K , Tranidou A , Mouselimis D , Bakatselos S , Damianidis G , Doumas M 
Published: October 2021

Abstract

Background
Hypertension augments overall cardiovascular risk in patients with type 2 diabetes mellitus (T2DM), constituting a major additional burden for diabetic subjects; however, control rates of hypertension remain suboptimal. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), second-line treatment option for diabetics, have revolutionized the field of T2DM therapeutic management due to their pleiotropic effects, while they seem to hold multiple cardiovascular benefits. A few randomized controlled trials (RCTs) evaluated the effect of GLP-1RAs on ambulatory blood pressure (ABP). Ambulatory blood pressure monitoring (ABPM) provides a better method to predict long-term cardiovascular outcomes than office blood pressure.

Purpose
We sought to determine the effect of GLP-1RAs on ABPM, pooling data from relevant randomized controlled trials (RCTs).

Methods
We searched 2 major electronic databases, namely PubMed and Cochrane/CENTRAL, along with grey literature sources, for RCTs assessing the effect of various GLP-1RAs on ABP in patients with T2DM.

Results
After screening of the potentially eligible records, 7 RCTs were finally included in our meta-analysis (4 parallel-group and 3 cross-over). GLP-1RA treatment compared to placebo or active control resulted in a nonsignificant decrease in 24-h systolic blood pressure (MD=−1.57 mm Hg, 95% CI: −4.12 to 0.98, I2=63%) (Figure 1) and in 24-h diastolic blood pressure (MD=1.28 mmHg, 95% CI: −0.31 to 2.87, I2=49%) (Figure 2). No subgroup differences between the various GLP-1RAs were identified. More specifically, it was demonstrated that liraglutide once daily produced a non-significant decrease in 24-h systolic blood pressure (MD=−1.43 mm Hg, 95% CI: −5.24 to 2.38, I2=72%) and a non-significant increase in 24-h diastolic blood pressure (MD=1.47 mm Hg, 95% CI: −1.12 to 4.05, I2=61%), while data concerning the effect of once weekly dulaglutide and twice daily exenatide on ABPM were pooled from one RCT respectively (Figures 1, 2).

Conclusions
Antidiabetic treatment with GLP-1RAs does not influence either systolic or diastolic ABP in patients with T2DM.

Funding Acknowledgement
Type of funding sources: None. Figure 1Figure 2
Impact of antidiabetic treatment with dipeptidyl peptidase-4 inhibitors on the risk of cardiac arrhythmias among patients with type 2 diabetes mellitus
Authors: Boulmpou A , Patoulias D , Teperikidis E , Tsavousoglou C , Vergopoulos S , Toumpourleka M , Doumas M , Fragakis N , Vassilikos V , Papadopoulos C E 
Published: October 2021

Abstract

Introduction
Type 2 diabetes mellitus (T2DM) is considered as a global pandemic, comprising a significant, independent cardiovascular risk factor. Besides major adverse cardiovascular events, patients with T2DM experience an increased risk of heart rhythm disorders, nevertheless the exact mechanisms of arrhythmogenesis in the context of diabetes mellitus are still being under investigation. Dipeptidyl peptidase-4 (DPP-4) inhibitors represent a novel class of antidiabetic regimens with proved safety and efficacy among patients with T2DM and a series of randomized controlled trials (RCTs) addressing cardiovascular outcomes with DPP-4 inhibitors have been published. The exact effect of DPP-4 inhibitors on the arrhythmic burden among diabetic individuals is yet to be identified.

Purpose
In the present meta-analysis, we sought to determine the impact of antidiabetic treatment with DPP-4 inhibitors on the risk of various cardiac arrhythmias.

Methods
We searched PubMed for all published RCTs assessing cardiovascular outcomes after antidiabetic treatment with DPP-4 inhibitors. We extracted data regarding the risk for the following cardiac arrhythmias: atrial fibrillation, atrial flutter, atrial tachycardia, ventricular fibrillation, ventricular tachycardia, ventricular extrasystoles, supraventricular tachycardia, sinus node dysfunction, second degree atrioventricular block, complete atrioventricular block.

Results
Following a meticulous assessment of the available literature, we pooled data from 6 trials in a total of 52,520 patients. Antidiabetic treatment with DPP-4 inhibitors did not significantly affect the risk for atrial fibrillation (RR=0.95, 95% CI: 0.78–1.17, I2=0%) (Figure 1a). Of note, DPP-4 inhibitors were associated with a significant increase in the risk for atrial flutter, equal to 52% (RR=1.52, 95% CI: 1.03–2.24, I2=0%), as shown in Figure 2. Finally, DPP-4 inhibitors did not have a significant impact on the risk for any of the rest assessed major cardiac arrhythmias.

Conclusions
DPP-4 inhibitors do not seem to be associated with a significant risk for any major cardiac arrhythmias, except for atrial flutter.

Funding Acknowledgement
Type of funding sources: None. Figure 1Figure 2
The effect of one year treatment with GLP1-RA, SGLT2i and their combination on plasma levels of oxidative and antioxidative biomarkers
Authors: Ikonomidis I , Thymis J , Pavlidis G , Birba D , Kalogeris A , Kousathana F , Kountouri A , Korakas E , Kostelli G , Triantafyllou C , Triantafyllidi H , Andreadou I , Lambadiari V 
Published: October 2021

Abstract

Background/Introduction
Biomarkers of oxidative stress burden are found increased in Type-2 diabetes mellitus (T2DM) patients. An imbalance between oxidative and antioxidative plasma factors is implicated in the pathway of cardiovascular disease in diabetics. Novel antidiabetic agents with cardioprotective effects are glucagon like peptide-1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i).

Purpose
We investigated the effect of liraglutide (GLP1-RA),empagliflozin (SGLT-2i) and their combination on plasma levels of oxidative and antioxidative factors.

Methods
A hundred-sixty T2DM patients were randomly assigned and received: a) insulin (n=40), b) liraglutide (n=40), c) empagliflozin (n=40) and d) the combination liraglutide and empagliflozin (n=40) for 1 year. We measured at baseline and after 1 year of treatment the following antioxidative markers: a) Reducing Power (RP), b) 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), c) Total Antioxidant Capacity (TAC) and also Thiobarbituric acid reactive substances (TBARS) as a marker of oxidative burden.

Results
After 1 year of treatment all subjects achieved successful glycemic regulation, as estimated by Hemoglobin A1c (HbA1c) levels (8±0.5 vs 6.65±0.5, p&lt;0.05). Patients on the combination GLP1-RA + SGLT2i displayed greater reduction of TBARS (8.66±0.42 μmol/l vs 7.92±0.35 μmol/l, p&lt;0.05) and increase of ABTS (17.49 ±0.63 mmol/l vs 19.14 ±0.64 mmol/l, p&lt;0.05) compared with insulin-treated participants (8.85±0.41 μmol/l vs 8.83±0.44 μmol/l and 17.07 ±0.58 mmol/l vs 17.22 ±0.49 mmol/l, p=NS respectively). Patients treated on GLP1-RA or SGLT2i separately showed the same improving trend with the combination group in the abovementioned biomarkers but the changes were not so prominent. In the insulin group worsening of TAC was also noticed (0.92±0.02 mmol/l vs 0.89±0.01 mmol/l, p&lt;0.05). In the other biomarkers nonsignificant changes were observed for all groups. Furthermore the absolute change of HbA1c was correlated with the relative change of TBARS (r=0.419, p&lt;0.05)

Conclusion
One year treatment with the GLP1-RA liraglutide and SGLT2i empagliflozin resulted in improvement of plasma levels of oxidative and antioxidative biomarkers compared to administration of insulin and the changes were more outstanding in patients that received the combination of GLP1-RA and SGLT2i, despite similar glycemic regulation in all participants. Thus the favorable cardiovascular effects of these novel factors may be partly explained by alterations in equilibrium between oxidative and antioxidative circulating biomarkers.

Funding Acknowledgement
Type of funding sources: None.
Temporal trend of clinical events in patients with atrial fibrillation on edoxaban therapy: results from the non-interventional global ETNA-AF program
Authors: Dinshaw L , Chen C , De Caterina R , Jiang W , Kim Y.-H , Koretsune Y , Morrone D , Pecen L , Reimitz P.-E , Wang C.-C , Yamashita T , Unverdorben M , Kirchhof P 
Published: October 2021

Abstract

Background
Patients with atrial fibrillation (AF) who initiated vitamin K antagonist (VKA) were at highest risk of stroke and bleeding in the first few months of therapy. Understanding of the temporal trend of clinical events in AF patients on non-VKA oral anticoagulant (NOAC) therapy should aid therapeutic decisions.

Purpose
To evaluate the temporal trend of clinical events in AF patients receiving edoxaban in routine clinical practice in the Global ETNA-AF program.

Methods
Global ETNA-AF is a multicentre, prospective, noninterventional program evaluating the safety and effectiveness of edoxaban in patients from European and Asian countries. Thromboembolic, bleeding and death events were analysed separately for the 1st and 2nd year of the follow-up period, using a time-to-first-event estimation of cumulative incidence and annual rate via Kaplan-Meier method.

Results
A total of 27,617 patients were included in this analysis, 48.6% from Europe and 51.4% from Japan, Korea, and Taiwan. Baseline characteristics were consistent with typical AF population in real world studies (Table 1). Approximately 83% of patients received the recommended edoxaban dose. Annualized rates of ischaemic stroke and major bleeding (ISTH) were lower in the 2nd year than in the 1st year: ischaemic stroke 0.59% (95% CI, 0.50–0.70) vs 0.86% (95% CI, 0.75–0.98), p=0.015; major bleeding 0.87% (95% CI, 0.75–1.00) vs 1.15% (95% CI, 1.02–1.29), p=0.036. The trend toward lower rates of ischaemic stroke and major bleeding in the 2nd year was consistent across regions. All-cause mortality increased slightly from the 1st year to the 2nd year, which was not statistically significant and was not driven by cardiovascular (CV) mortality (Table 2).

Conclusion
In routine clinical practice in the Global ETNA-AF program, major bleeding and ischaemic stroke rates in &gt;27,000 patients on edoxaban therapy declined from 1st year to 2nd year. Further analyses will investigate whether such trend is influenced by selection for healthier patients over time. Longer follow-up is needed to better understand long-term trends.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Table 1. Baseline characteristicsTable 2. Annualised clinical event rates
Evaluating direct oral anticoagulants versus vitamin K antagonists for treatment of left ventricular thrombus: a systematic review and meta-analysis
Authors: Qiu Y , McEwen C , Bhagirath V , Chan N , Eikelboom J , Eikelboom R , Young J , Whitlock R , Belley-Cote E 
Published: October 2021

Abstract

Background/Introduction
Left ventricular thrombi are associated with high rates of stroke and systemic embolism (1). While vitamin K antagonists (VKAs) have historically been the anticoagulant of choice, they have a narrow therapeutic window and require frequent monitoring. Direct oral anticoagulants (DOACs) offer more predictable anticoagulation but the use of DOACs to treat left ventricular thrombus has not been well studied (1,2). Guideline recommendations around the topic are based on expert consensus and very low-quality evidence.

Purpose
This systematic review and meta-analysis compares DOACs or VKAs in the treatment of left ventricular thrombus. Outcomes of interest were stroke and systemic embolism, thrombus resolution, any bleeding, major bleeding, and mortality.

Methods
We searched CENTRAL, MEDLINE, EMBASE, CINAHL, ACPJC, and Web of Science for studies comparing DOACs and VKAs in the treatment of left ventricular thrombus. We also searched reference lists from included studies and relevant conferences' proceedings. Two reviewers independently screened titles and abstracts and then the full-text of potentially relevant citations in duplicate. They then extracted data and evaluated risk of bias in duplicate. The data was analyzed using Revman 5.3. We used the DerSimonian and Laird random-effects model to pool the weighted effect of estimates across all studies. The pooled relative risks (RRs) were calculated with corresponding 95% confidence intervals (CIs). We assessed the quality of evidence for each outcome using the Grading of Recommendations, Assessment, Development, and Evaluation approach.

Results
Of 443 citations screened, 12 observational studies (n=2,225) were included. We found no randomized controlled trial addressing the question. Most included studies were at high risk of bias due to unmatched baseline variables. We found no significant difference in any of our outcomes with DOACs versus VKAs: stroke and systemic embolism (RR 1.14, 95% CI [0.82, 1.58], p=0.43), thrombus resolution (RR 1.02, 95% CI [0.91, 1.15], p=0.69), any bleeding (RR 1.47, 95% CI [0.65, 3.33], p=0.36), major bleeding (RR 0.22, 95% CI [0.01, 4.21], p=0.32), and mortality (RR 0.99, 95% CI [0.67, 1.45], p=0.95). Evidence for each of these outcomes was of very low-quality due to risk of bias, inconsistency, and imprecision of the studies.

Conclusions
Very low quality evidence suggests no difference in outcomes with DOACs versus VKAs in the treatment of left ventricular thrombus. More robust data are needed to guide clinicians.

Funding Acknowledgement
Type of funding sources: None.
Effectiveness of direct oral anticoagulants in obese adults with atrial fibrillation: an overview examining the evidence from international systematic reviews and meta-analyses
Authors: Shaikh F , Wynne R , Castelino R L , Inglis S C , Ferguson C 
Published: October 2021

Abstract

Background
Obesity may influence the pharmacology of direct oral anticoagulants (DOAC) that are recommended by all international guidelines for stroke prevention in adults with atrial fibrillation (AF).

Purpose
To evaluate the safety and efficacy of DOACs in obese adults with AF.

Methods
Medline, CINAHL, Scopus, Web of Science, Cochrane Database, Johanna Briggs Institute, Embase, Psych Info and ProQuest were searched till April 2020. Only systematic reviews with meta-analyses, that were published after 2005 and were in the English language were included. Articles were screened by title and abstract, followed by full text assessment using the Covidence systematic review software. Data was extracted using a standardised extraction tool. AMSTAR-2® and ROBIS® tools were used for quality and risk of bias assessment. The entire process was undertaken by two investigators at each stage of the study selection, appraisal, and data extraction. Disagreements were resolved through consensus discussion with a third arbitrary investigator. Statistical analyses were performed using the DerSimonian and Laird method for random effects. Meta-analysis was performed using only randomised controlled trials from eligible systematic reviews at both 12 months and across the entire trial. Primary outcomes assessed was stroke (ischemic or haemorrhagic) or systemic or pulmonary embolism. Secondary outcomes assessed included all-cause mortality, transient ischemic attack, myocardial infarction, major bleed, all cause-hospitalisation, and cardiovascular mortality.

Results
Of the 8162 articles screened, a total of five systematic reviews were included in this overview. There was disagreement within the published reviews on the effect of DOAC in obesity. Four of the five reviews were of either “low” or “critically low” quality, with inconsistencies in data extraction and appropriateness of the included studies and statistical methods used in analysis. Data from only the RE-LY, AVERROES and ENGAGE AF-TIMI 48 trials, were available for the meta-analysis, which did not find any significant difference between all BMI groups for all outcomes, at both time points. However, analysis of the different weight groups versus normal weight, highlighted non-significant differences between the different DOACs.

Conclusion
There was no difference between the BMI classes in any of the outcomes assessed. However, the non-significant trends that were seen, suggests individual superiority of DOACs may exist within the obese adult populations. There is a need for prospective trials to evaluate which DOACs are safe and efficacious in the obese class III adults and at which dose.

Funding Acknowledgement
Type of funding sources: Other. Main funding source(s): Australian Government Research Training Program (RTP) Heart Foundation of AustraliaNational Health and Medical Research Council (NHMRC)