bluuebunny/crossref_metadata_2025 huggingface dataset:
Combination of nicorandil and beta-adrenergic receptor blockers in patients with coronary heart disease: a real-world observational study
Authors: Zhou N , Cheng J , Qiu L , Zhang Z X , Li N , Shu H Y , Xiao Z C
Published: November 2023

Background and objective

Nicorandil and beta-adrenergic receptor blockers (BBs) are commonly used anti-anginal drugs. However, the effect of combined nicorandil and BBs compared with that of BBs alone on long-term clinical outcomes in patients with coronary heart disease (CHD) remains undetermined. Accordingly, a real-world observational study was performed to assess the long-term potential of nicorandil combined with BBs in Chinese patients with CHD.

Methods

A multicenter retrospective cohort study involving two tertiary healthcare institutions in our city was performed. Adult patients who had been hospitalized for CHD and treated for angina with a combination of nicorandil and BBs or BBs alone between August 2002 and March 2020 were included. The effect of different treatments on the cumulative incidence of major adverse cardiovascular events (MACE) and their components (myocardial infarction [MI], stroke, and all-cause mortality) within a follow-up duration of 2.5 years were analyzed using Kaplan–Meier survival curves. An inverse probability of treatment weighting (IPTW) method was used to adjust for the possible effect of confounding factors. The hazard ratio (HR) and corresponding 95% confidence interval (CI) were calculated using a Cox regression analysis. Sensitivity analyses based on IPTW with trimming or limited to patients admitted after January 1, 2012, were performed to evaluate the robustness of the findings.

Results

Overall, 4,669 patients receiving the combined treatment and 12,243 receiving BBs alone were included. After IPTW, the results demonstrated that the combined treatment was associated with a significantly reduced incidence of MACE (HR 0.80, 95% CI: 0.73–0.87, P < 0.0001)(Figure 1) and stroke (HR 0.48, 95% CI 0.42–0.54) but not of MI (HR 1.03, 95% CI 0.92–1.15) or all-cause mortality (HR 0.93, 95% CI 0.64–1.37). Interaction analyses were performed for the following subgroups: age (younger than 65 or is and older than 65 years), gender, acute coronary syndrome (ACS), smoking, drinking, revascularization, diabetes and hypertension, and showed a favorable consistency with the primary outcome (Figure 2).

Conclusion

A combined anti-angina treatment of nicorandil and BBs may be more effective than a treatment of BBs alone in reducing the long-term incidence of MACE in patients with CHD.The Kaplan-Meier curves of the outcomesThe forest plot of the subgroup analysis
Clopidogrel vs. aspirin in the chronic maintenance period following percutaneous coronary intervention in high thrombotic and high bleeding risk patients:sub-analysis of the HOST-EXAM Extended study
Authors: Chung J , Kang J , Lee H , Hwang D , Park K W , Yang H M , Han J K , Shin E S , Koo B K , Kim H S
Published: November 2023

Background

The HOST-EXAM Extended study evaluated the long-term follow-up results of the original HOST-EXAM trial, which demonstrated that clopidogrel monotherapy was associated with a lower risk of thrombotic and bleeding events compared to aspirin monotherapy. However, the optimal single antiplatelet agent during the chronic maintenance period in patients with high thrombotic risk and/or high bleeding risk has not been assessed.

Purpose

This study aimed to compare the efficacy of clopidogrel versus aspirin monotherapy in patients with high thrombotic risk and/or high bleeding risk who were stabilized after percutaneous coronary intervention (PCI) with drug-eluting stents (DES).

Methods

A post-hoc subgroup analysis of the HOST-EXAM Extended study was conducted. High thrombotic risk was defined as patients who had at least one of the following procedural features: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or chronic total occlusion. High bleeding risk was defined according to the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium bleeding type 3 or 5. Clinical outcome was analyzed according to the patients’ initial thrombotic and bleeding risk.

Results

Among the total population, 28.2% had high thrombotic risk and 27.0% had high bleeding risk. Patients with high thrombotic risk was not associated with a higher risk of primary endpoint, whereas those of high bleeding risk was associated with a increased risk of the clincical event (Hazard ratio [HR] 2.70, 95% Confidence interval [CI] 2.29-3.18, Log-rank p < 0.001). Clopidogrel consistently reduced the risk of primary endpoint, regardless of the presence of high thrombotic risk or high bleeding risk (Absolute risk difference [ARD] 7.5%, 95% CI 2.7-12.3, HR 0.59, 95% CI 0.43-0.82, Log-rank p=0.001 vs ARD 4.1%, 95% CI 1.5-6.7, HR 0.78, 95% CI 0.66-0.92, Log-rank p=0.004 with or without high thrombotic risk, respectively. P-interaction=0.133; ARD 9.2%, 95% CI 2.4-16.0, HR 0.71, 95% CI 0.55-0.92, Log-rank p=0.008 vs ARD 4.0%, 95% CI 1.6-6.4, HR 0.74, 95% CI 0.60-0.90, Log-rank p=0.003 with or without high bleeding risk, respectively. P-interaction=0.860; Figure 1). The beneficial effect of clopidogrel was consistent across patients divided into four groups based on the presence or absence of high thrombotic risk and high bleeding risk (Figure 2).

Conclusion

In chronic maintenance period of patients who received PCI with DES, the beneficial effect of clopidogrel was maintained in patients regardless of the presence or absence of high thrombotic risk and high bleeding risk.
Non-clinical evaluation of YN001-a promising drug for atherosclerotic therapy by targeted delivery system
Authors: Ma Q , Zhang W E I , Li Y I N G , Sun J F , Chen Y A N , Wu S J , Zhou W X , Wang Z J , Yang S W , Su H F , Ren X M , He C Q , Jiang M J , Chen X M , Zhou Y J
Published: November 2023

Background

Atherosclerosis (AS) is a systemic disease and the common cause of heart attacks, strokes and peripheral vascular disease collectively referred to as cardiovascular diseases (CVD). In AS plaques, CD44 is upregulated and functionally activated on vascular endothelial cells, smooth muscle cells, and macrophages.

YN001 is a liposome encapsulated Rosuvastatin calcium which was initially approved for the reduction of cholesterol levels and slowing the progression of atherosclerosis. YN001 is being developed for the treatment of AS by targeted enrichment of Rosuvastatin in the local atherosclerotic plaques by CD44 active targeting ability of HPD, one of the components of liposome.

Purpose

Investigating pharmacology, PK and toxicity of YN001 to evaluate its clinical use potential for AS patients.

Results

As expected, YN001 could bind to CD44 with KD as 485.5pm while there’s no binding affinity of non-targeted liposome (encapsulate Rosuvastatin without HPD). In stimulated human macrophages in which CD44 was overexpressed, YN001 showed enhanced uptake and higher cholesterol effluxion ability than Rosuvastatin, meanwhile more MCP-1 reduction was also observed. In ApoE AS mice model, single YN001 administration showed much higher drug concentrations in the plaque of aortas compared to Rosuvastatin (oral or iv) or non-targeted liposome which demonstrated targeted enrichment ability by HPD. With repeat treatment of YN001 at 5mg/kg in AS mice model, atherosclerotic plaque weight decreasing and plaque area reduction were observed, following MCP-1 reduction. YN001 may down-regulate the expression of inflammatory signaling pathways, such as chemokine-related signaling pathway to reduce the inflammatory response of atherosclerotic plaques to decrease plaque levels. In pharmacokinetic studies in rats and dogs, YN001 had much higher exposure in plasma and prolonged existence compared to Rosuvastatin i.v administration. A comprehensive safety evaluation package was performed in rats and dogs including safety pharmacology, general toxicity, genotoxicity, immunotoxicity and local tolerance. Results showed YN001 has promising safety with NOAEL as 40mg/kg in both or rats and dogs.

Conclusion

YN001 demonstrated excellent efficacy in AS model, a favorable pharmacokinetic and safety profiles in rats and dogs. These support its FDA IND approval and phase I study is ongoing to investigate further character in clinical.Efficacy and pharmacokinetics resultsSafety evaluation
Current use of antiplatelet therapy in the management of acute myocardial infarction: overview of the FRENCHIE national registry
Authors: Gautier A , Ducrocq G , Danchin N , Simon T , Nekrouf C , Rousseau A , Cottin Y , Coste P , Prunier F , Cayla G , Lemesle G , Angoulvant D , Steg P G
Published: November 2023

Background

There are many options for antiplatelet therapy (APT) at various stages in the management of acute myocardial infarction (MI) but few contemporary data regarding use in routine clinical practice in unselected patients.

Purpose

to describe the contemporary use of APT treatments in unselected MI patients.

Methods

FRENCHIE (FRENch CoHort of myocardial Infarction Evaluation) is a multicenter observational study (38 centers in France) consecutively enrolling patients with spontaneous MI whose symptoms were < 48 hours. Exclusion criteria were age < 18 years, no health coverage, unstable angina and procedure-related MI.

Results

Between September 2019 and December 2020, 10190 patients with MI were enrolled. Complete data on APT use were available for 9842 patients. Of these, 54.5% had ST elevation myocardial infarction (STEMI) and 45.5% non-STEMI (NSTEMI). During the first 24 hours, APT use for STEMI and NSTEMI patients, was as follows, respectively: acetylsalicylic acid (ASA) 95.1% and 88.8%, clopidogrel 12.4% and 17.7%, ticagrelor 79.5% and 55.0%, prasugrel 4.8% and 3.6%, GPIIb-IIIa inhibitors 23.8% and 6.5%, Cangrelor 1.1% and 0.8%. Among STEMI patients, 3.2% had undergone thrombolysis, 92.2% primary percutaneous coronary intervention (pPCI) and 4.5% did not have reperfusion during acute phase management. The use of ASA was similar regardless of the initial reperfusion strategy, but that of P2Y12 inhibitors (P2Y12i) was different. Clopidogrel was mainly used in case of thrombolysis, 69.6% of cases, while ticagrelor was mainly used in case of pPCI or medical treatment alone, respectively in 83.9% and 59.7% of cases. GPIIb-IIIa inhibitors were used in 9.3%, 26.2% and 11.4% in patients who had undergone thrombolysis, pCI and medical treatment respectively. At hospital discharge, APT use was as follows, respectively for STEMI and NSTEMI patients: ASA 94.6% and 91.2%, clopidogrel 14.7% and 21.8%, ticagrelor 72.6% and 54.9%, prasugrel 6.9% and 5.7%. The first P2Y12i administered was different from that retained at discharge in 15.4% of STEMI and 12.5% of NSTEMI patients. The most common scenario was switching from ticagrelor to clopidogrel in 64.2% of STEMI patients and 57.2% of NSTEMI patients. No P2Y12i was prescribed at discharge in 3.6% of STEMI patients and 11.3% of NSTEMI patients.

Conclusion

In contemporary practice in France, P2Y12i use was different according to MI type and to initial reperfusion strategy. GPIIb-IIIa inhibitors were used in more than a quarter of STEMI patients with pPCI. Switching between P2Y12i occurred in 1/8 of patients before discharge and deserves further investigation.
Meta-analysis of 3-month vs 12-month dual anti-platelet therapy after percutaneous coronary intervention
Authors: Gerardo F , Fialho I , Passos M , Mateus C , Miranda I , Lima Lopes J , Faria D
Published: November 2023

Background

The optimal duration of dual antiplatelet therapy (DAPT) in the era of second generation drug-eluting stents is a matter of debate as increasing evidence suggests that shorter periods of DAPT are feasible and reduce bleeding events. However, the non-inferiority design of the published trials regarding ischemic events still raises doubt on its effectiveness.

Methods

We performed a meta-analysis to evaluate short-term (≤ 3 months) vs long-term (≥ 12 months) DAPT after percutaneous coronary intervention (PCI). PubMed, Embase and Cochrane Central were searched from inception to February 2023 to identify randomized controlled trials that compared outcomes of patients between these two regimens. Primary outcome of interest included a composite of ischemic events (cardiovascular death, myocardial infarction, re-revascularization and stroke) and secondary outcome was major bleeding as assessed by Bleeding Academic Research Consortium (BARC) classification ≥ 3 after 1 year of follow up. Event rates were extracted and Mantel-Haenszel fixed-effects

model was used to perform the meta-analysis.

Results

We identified a total of 5 trials with 18.682 randomized patients. The use of short-term DAPT was not associated with increased risk of ischemic events (0.90 [0.75-1.08], p=0.250; Figure 1) and was associated with reduced risk of major bleeding (0.74 [0.65-0.84], p<0.001; Figure 2).

Conclusion

The present meta-analysis provides an updated data on the use of DAPT duration. Short-term DAPT appears to be equivalent to long-term DAPT regarding ischemic risk and a superior strategy in optimizing bleeding risk reduction.Forest plot of ischemic outcomesForest plot of bleeding outcomes
Cardioprotective potential of exosomes derived from blood outgrowth endothelial cells in ischemic cardiomyopathy
Authors: Wu M , Wibowo A , Delrue L , Veltman D , Vanhaverbeke M , Trenson S , Gillijns H , Caluwe E , Pokreisz P , Luttun A , Bartunek J , Janssens S
Published: November 2023

Introduction

Blood outgrowth endothelial cell (BOEC)-derived exosomes can effectively induce vascular network formation in vitro and mediate therapeutic neovascularization in a skin wound healing model. We hypothesized that BOEC-derived exosomes can enhance myocardial repair in mice after ischemia-reperfusion (I/R) injury.

Methods

BOECs were isolated and culture-expanded from peripheral blood of patients with severe ischemic cardiomyopathy (ICMP) in normoxic and hypoxic (1% O2) conditions. Exosomes were isolated from the medium by differential ultracentrifugation, and their size, number, and surface markers were determined by nano tracking analysis (NTA) and immunoblot analysis. Myocardial infarction (MI) was induced via transient LAD ligation for 60 min followed by reperfusion. BOEC-derived exosomes and were resuspended in small fractions (120x10^8 particles per 10 µl) 2.5 µl 4 aliquots were injected under direct vision into the epicardial wall of the peri-infarct region. One month later, left ventricular (LV) structure and function were analyzed using a 7T Bruckner MRI with commercial software Segment in mice that received exosome injections or placebo injections (n=10 and n=8, respectively).

Results

Quantification of exosomes by NTA showed higher concentrations in the medium of BOECs cultured in hypoxia. Immunoblot analysis confirmed robust expression of exosome markers TSG101 and Flotilin-1. One month after intramyocardial exosome injections, heart rate, LV volumes or LV ejection fraction were similar between mice receiving myocardial exosomes injections (n=10) in the border zone as compared to those receiving placebo (n=8). However, in vivo exosome transfer mediated favorable structural remodeling after MI with lower LV mass indices (p=0.01) and better preserved regional wall thickness in all 4 segments receiving exosomes aliquots (p<0.05) (Figure).

Conclusions

Our results suggest that BOEC-derived exosomes have favorable post-infarction myocardial structural remodeling. Exosomes may constitute an attractive cell-free therapeutic modality.Figure
Drug-interacting gene expression levels differ between atherosclerotic plaque subtypes
Authors: Palm K , Marsman J , Boltjes A , De Borst G J , De Kleijn D P V , Den Ruijter H M , Van Steenbeek F G , Mokry M , Pasterkamp G , Engels S
Published: November 2023

Background

Recent transcriptomic-based clustering of human atherosclerotic plaques revealed that plaques have a diversity and complexity that cannot be accurately described by classical concepts. Previous plaque RNA sequencing that we performed identified five major plaque types that reflect the severity of the atherosclerotic disease. These include the following plaque subtypes: 0. Fibro-collagenous, 1. Intermediate, 2. Lipo-necrotic, 3. Fibro-inflammatory, and 4. Fibro-cellular. We hypothesised that identifying these different plaque types could explain differential responses following drug treatment.

Objective

To assess differential expression levels of drug-responsive genes between the earlier described five plaque subtypes. For this pilot experiment, we selected genes that are differentially expressed after colchicine treatment in smooth muscle cells and endothelial cells.

Methods

A web-based search identified 46 published colchicine interacting genes. Colchicine was also applied to smooth muscle and endothelial cells to identify direct-effect genes via differential gene expression analysis. Differences in gene expression between plaque types were assessed for those genes that were considered drug-responsive. Finally, to model the effect of colchicine on an atherosclerotic plaque, we projected the in vitro derived expression changes onto the gene expression data from carotid plaques of 654 patients that participated in the ATHERO-EXPRESS study.

Results

34 out of the 46 publicly known colchicine interacting genes were differently expressed between plaque types (Figure 1). These genes included established determinants of cell motility and atherosclerosis development (SCD, ITGB1, Tubulins). Furthermore, in-silico colchicine treatment revealed colchicine's strong effect on the atherosclerotic plaques' transcriptome. We are currently assessing if these perturbations may lead to changes in plaque subtypes.

Conclusion

The pilot data demonstrated major differences in drug-interacting gene expression levels in advanced atherosclerotic lesions. Therefore, novel and standard drugs used to treat atherosclerosis may have varying effects depending on the atherosclerotic plaque subtype.Figure 1
Baseline characteristics of patients enrolled in the EMPACT-MI trial
Authors: Butler J
Published: November 2023

Background

Empagliflozin has been shown to reduce the risk of adverse cardiovascular (CV) outcomes in patients with type 2 diabetes (T2DM) and in those with heart failure (HF). The impact of empagliflozin in post-acute myocardial infarction (AMI) patients is unknown.

Methods and Results

The Study to Test the Effect of Empagliflozin on Hospitalization For Heart Failure And Mortality In Patients With Acute Myocardial Infarction (EMPACT-MI) trial screened 6610 participants with AMI and 6522 were randomized to empagliflozin or placebo in addition to standard of care. Patients were eligible for enrollment if they had no history of HF, had been hospitalized with a AMI and had either acute signs or symptoms of congestion that required treatment, and/or a newly depressed LVEF<45%. Patients were also required to have at least one additional risk factor (enrichment criterion). The median (interquartile range) age of trial population was 64 (56-71) years and 75.1% were male. Major comorbidities included hypertension (69.1%), atrial fibrillation (10.9%), prior myocardial infarction (13.0%), and type 2 diabetes (31.7%). The majority (74.3%) of patients presented with an ST elevation myocardial infarction. Overall, 56.9% of patients randomized had acute signs or symptoms of congestion that required treatment, and 78.3% had newly developed left ventricular systolic dysfunction with ejection fraction <45%. Key characteristics of EMPACT-MI patient population are presented on the figure 1.

Conclusion

EMPACT-MI has randomized 6522 patients with acute MI. EMPACT-MI will establish the benefit and risks of empagliflozin in these patients.
3-dimensional ct versus angiography guided pci for ostial rca lesions
Authors: Van Den Buijs D M F , Poels E M , Willems E , Cottens D , Ferdinande B , Vrolix M , Dens J , Ameloot K
Published: November 2023

Background

Geographical stent-ostium mismatch is an important predictor of target lesion failure (TLF) after PCI of an aorto-ostial right coronary artery (RCA) lesion.

Purpose

We hypothesize that a pre-procedural 3-dimensional coronary CT angiography (3DCT) to determine the optimal C-arm angle of the X-ray system with the most accurate visualization of the aorto-ostial angle could allow optimal stent implantation at the level of the ostium and avoid excessive use of radiation and contrast.

Methods

This is a single centre trial randomizing 30 patients with an indication for non-emergent PCI of an ostial RCA lesion between 3DCT (intervention group) versus angiography guided strategy (control group). While in the control group the C-arm angle was at the operators’ discretion, in the intervention group the angle was determined based on a pre-PCI CT scan with 3D reconstruction using Materialise Mimics Innovation Suite software.

A pre- and post-PCI IVUS is performed in all patients and analyzed by a blinded core lab. The primary endpoint is absence of geographical mismatch on IVUS defined as full stent coverage of the ostium and maximal aortic protrusion equal or less than 3mm. Secondary, we also aim to investigate whether a pre-procedural 3DCT may reduce procedural radiation, contrast use, may predict IVUS parameters (minimal luminal area (MLA), calcification), stent sizing and may promote stent expansion. Finally, MACE rate is evaluated at 1 month.

Results

The full patient dataset (n=30) including primary and all secondary endpoints will be available for presentation at the ESC congress. Currently, 27 patients were randomized. An interim analysis shows the following findings.

There is significant patient heterogeneity considering the optimal angle for stent implantation, underscoring the potential benefit for individualized pre-procedural CT planning. In general, more extreme LAO angles were used in patients randomized to the intervention group (picture 1).

While the stent was implanted in optimal position in 13/13 (100%) patients randomized to the intervention group, geographical stent mismatch was present in 5/14 (36%) patients randomized to the control group (interim p-value 0.07) (picture 2).

The number of cine acquisitions performed before stent implantation (1±1.87 vs. 3.5±0.60; p=0.0007), the amount of contrast used (60±24.5 vs. 114±37.8 mL; p=0.0002), radiation dose (209 [186,315] vs. 497 [411,678] mGy; p=0.01) and procedure time (30 [20,38] vs. 50 [39,66] min; p=0.005) were significantly lower in patients randomized to the intervention group.

There was a highly significant correlation between the calcium arc determined by CT and IVUS (R² = 0.84). No MACE occurred at 1 month.

Conclusion

We showed that pre-procedural CT planning for PCI of aorto-ostial RCA lesions allowed for optimal stent positioning while reducing procedure time, contrast and radiation use.Picture 1Picture 2
Incidence and prediction of periprocedural myocardial infarction in elective PCI: the ALPHEUS-MI sub-study
Authors: Montalescot G , Georges J L , Bellemain-Appaix A , Hauguel-Moreau M , Le Breton H , Saint-Etienne C , Caussin C , Montsegu J , Cayla G , Beygui F , Range G , Motovska Z , Portal J J , Vicaut E , Silvain J
Published: November 2023

Background

PCI-related myocardial infarction (MI) or injury are frequent events that have been shown to be associated with long-term ischemic outcomes and mortality. Determinants of these events with the validated definition of PCI-related myocardial infarction (MI) or injury are not well documented in contemporary elective PCI.

Methods

The ALPHEUS-MI study is a prespecified analysis of the ALPHEUS randomized trial conducted in 49 centers of two European countries which recruited 1910 patients with chronic coronary syndrome undergoing elective PCI. We analyzed the rate and predictors of periprocedural myocardial necrosis using the primary and secondary endpoint of the ALPHEUS trial (3rd and 4th universal definition of MI) and the ARC2/SCAI definitions. Multivariable model including patient’s demographic, angiographic and procedural characteristics were performed for each definition to determine predictors of periprocedural events.

Findings : The primary endpoint of the ALPHEUS trial (type 4a MI or major myocardial injury) occurred in 35.85% of the patients (3rd universal definition of MI); the secondary endpoint of the ALPHEUS trial (type 4a MI and any myocardial injury) occurred in 77.21% of the patients (4th universal definition of MI); significant periprocedural myocardial injury occurred in 3.24% of the patients (ARC2/SCAI definition) and periprocedural MI (ARC2/SCAI definition) in 2.02% of the patients. The rate of events followed a stepwise increase according to the number of high-risk features with all definitions (figure). High risk features were characterized by patients’ characteristics, the complexity of the coronary lesion (anatomy and atheroma burden) and the complexity of the PCI procedure itself. The only common predictor of MI or myocardial injury present with the 4 definitions was the total length of stent implanted (>60mm) ; adjOR 3.23 (2.49-4.18) p<0,001 (type 4a MI/major injury 3rd UDMI ) , adjOR 3.82 (2.51-5.8) p<0,001 (type 4a MI/any injury 4th UDMI) , adjOR 2.2 (1.24-3.91) p=0,007 (myocardial injury ARC2/SCAI) and adjOR 6.0 (3.04-11.9) p<0,001 (MI ARC2/SCAI).

Conclusion

Whatever definition of type 4aMI and myocardial injury, the strongest predictor of myocardial necrosis seems to be the length of stent implanted which reflects both the severity of atheroma burden and the complexity of PCI.
Intravascular ultrasonography guided percuatneous coronary intervention with everolimus-eluting stents or bypass surgery for multivessel coronary artery disease: post-hoc analysis of the BEST study
Authors: Lee J , Kim H , Choi Y , Ahn J M , Kang D Y , Kim M J , Park D W , Park S J
Published: November 2023

Background

Previous studies suggested that intravascular ultrasonography (IVUS)-guided percutaneous coronary intervention (PCI) improved clinical outcomes compared with coronary angiography (CAG)-guided PCI in complex coronary artery disease.

Objectives

We compared long-term clinical outcomes of IVUS-guided PCI with everolimus-eluting stent and coronary-artery bypass grafting (CABG) in multivessel coronary disease (MVD).

Methods

Among 880 patients with MVD enrolled in the BEST Extended Follow-up study, 333 patients underwent IVUS-guided PCI and 131 patients underwent CAG-guided PCI, which were compared with 401patients underwent CABG. The primary endpoint was the composite of death from any cause, myocardial infarction, or target-vessel revascularization during a median follow-up of 11.8 years (interquartile range, 10.6 to 12.5 years).

Results

During an extended follow-up, primary endpoint occurred in 75 patients (22.8%) in the IVUS-guided PCI group, in 58 patients (44.38%) in the CAG-guided PCI group, and in 95 patients (24.0%) in the CABG group. Compared with the CABG group, the IVUS-guided PCI group had a similar rate of primary endpoint (adjusted hazard ratio [HR], 1.013; 95% confidence interval [CI], 0.747-1.374; P=0.93), whereas the CAG-guided PCI group had a significantly higher risk of clinical events (adjusted HR, 2.231; 95% CI, 1.582-3.145; P<0.001). Similarly, whereas the IVUS-guided PCI group had similar rate (adjusted HR, 0.845; 95% CI, 0.605-1.181; P=0.324), the CAG guided PCI group had the significantly higher rate of the safety composite of death, stroke and myocardial infarction (adjusted HR, 2.016; 95% CI, 1.405-2.895; P<0.001) compared with the CABG group. However, both IVUS- and CAG-guided PCI groups had significantly higher rate of any repeat revascularization than CABG group. Conclusions In patients with MVD, IVUS-guided PCI appeared to be an safe and effective alternative to CABG. This study advocated the routine use of intravascular imaging during PCI for MVD.KM curve of outcomesPrimary and secondary outcome
Effects on re-endothelialisation with Bydureon treatment add on to insulin versus insulin alone, both in combination with metformin in type 2 diabetic subjects: Rebuild study
Authors: Santos-Pardo I , Witt N , Nystrom T
Published: November 2023

Background

Patients with type 2 diabetes (T2D) have a higher risk of in-stent restenosis and stent thrombosis following a percutaneous coronary intervention1. The key mechanism for preventing these events after stenting is a restored and well-functioning neo-endothelium2. Several large, randomized trials have shown cardioprotective effect of Glucagon Like Pepetide-1 receptor (GLP-1R) agonists therapy lowering the risk of major adverse cardiovascular events. In addition, activation of GLP-1R has been suggested to induce several effects on the vasculature3 that may reduce not only the risk of atherosclerosis progression, but even the risk of stent failure following an angioplasty.

Purpose

To evaluate the potential beneficial effect of the GLP-1R agonist Bydureon in the endothelialisation of modern drug-eluting stents (DES) in patients with T2D.

Methods

38 subjects with T2D and coronary artery disease who were eligible for revascularisation with implantation of DES were included and randomized to either treatment with Bydureon (once weekly) over the standard treatment, or to standard treatment alone. After 12 weeks, a new coronary angiography was performed to evaluate the coverage of the DES and the presence of neo-atherosclerosis by optical coherence tomography. The main outcome was the percentage of stent coverage at 12 weeks. Descriptive data is shown as median (percentile 25th- 75th).

Results

The two groups were well balanced regarding baseline clinical characteristics (Table). Neo-intimal coverage could be assessed in all 33 subjects that completed follow-up. DES coverage was 95% (88.7-98.5%) in the Bydureon group and 91.4% (88.8-98.5%) in the Control group (p=0.692). There were no significant differences between groups neither in the thickness of neo-intima (0.2 mm in both groups, p=0.471), nor the maximal in-stent obstruction by neo-intima (15.5% in Bydureon group vs 14.7% in Control group, p= 0.801). Weight decrease was greater in Bydureon group compared to Control group (-7.8 kg vs +0.14 kg, p=0.014), and so was also HbA1c reduction (-11.4 mmol/mol vs -4.7 mmol/mol, p=0.001). No significant differences were detected on the rate of target lesion revascularisation between groups (p=0.224).

Conclusion

Twelve weeks treatment with Bydureon did not lead to a significantly better stent coverage in patients with T2D. No significant differences in the occurrence of neo-atherosclerosis were detected between groups.Table:Baseline clinical characteristicsImage:Diagram of Methods and Results
Impact of repeat revascularization within 5 years on 10-year mortality after percutaneous or surgical revascularization
Authors: Wang R , Lunardi M , Hara H , Gao C , Ono M , Davierwala P , Geuns R J , Kappetein A P , Head S J , Thuijs D J F M , Tao L , Garg S , Onuma Y , Wijns W , Serruys P W
Published: November 2023

Background

The SYNTAX trial demonstrated negative impact of repeat revascularization (RR) on 5-year outcomes following percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in patients with three-vessel (3VD) and/or left main coronary artery disease (LMCAD). We aimed to investigate the impact of RR within 5 years, on 10-year mortality in patients with 3VD and/or LMCAD after PCI or CABG.

Methods

The SYNTAXES study evaluated the vital status out to 10 years of patients with 3VD and/or LMCAD. Patients were stratified by RR within 5 years and randomized treatment. The association between RR within 5 years and 10-year mortality was assessed.

Results

A total of 330 (220 RR after initial PCI and 110 RR after initial CABG) out of 1800 patients (18.3%) underwent RR within 5 years from initial revascularization. RR occurred more frequently after initial PCI than after initial CABG (25.9% vs 13.7%, p<0.001). Overall, 10-year mortality was comparable between patients undergoing RR and those not (28.2% vs 26.1%, adjusted HR: 1.17, 95% CI: 0.93-1.48,

p=0.187). Among patients requiring RR, those who underwent PCI as initial revascularization had a higher risk of 10-year mortality compared to initial CABG (33.5% vs 17.6%, adjusted HR: 2.09, 95% CI: 1.21-3.61, p=0.008).

Conclusions

In the SYNTAXES study, RR within 5 years had no impact on 10-year all-cause death in the population overall. Among patients requiring any repeat procedures, 10-year mortality was higher after initial treatment with PCI than after CABG. These exploratory findings should be investigated with larger populations in future studies.Graphic Abstract
Association of liver dysfunction with outcomes after percutaneous coronary intervention - a systematic review and meta-analysis
Authors: Caldonazo T , Kirov H , Pompeu Sa M , Tasoudis P , Shanaah A , Haji D , Doenst T
Published: November 2023

Background

Liver dysfunction is currently receiving renewed attention as a major risk factor in patients undergoing cardiac surgery, including surgical treatment of coronary artery disease (CAD). Since percutaneous coronary intervention (PCI) for CAD treatment is much less invasive, the influence of liver dysfunction on outcomes after PCI may not be relevant.

Purpose

To assess the association of liver dysfunction with PCI outcomes.

Methods

We systematically searched three libraries (MEDLINE, Web of Science and The Cochrane Library) selecting all studies including patients with liver dysfunction who underwent PCI. A meta-analysis of studies comparing outcomes in patients with and without liver dysfunction who underwent PCI was performed. Primary outcome was short-term mortality. Secondary outcomes were major adverse cardiovascular events (MACE), bleeding and acute kidney injury. Random-effects model was performed.

Results

Five studies were selected and the data from 10,710,317 patients were included in the final analysis. Included studies were published between 2015 and 2021, all were observational risk-adjusted cohort studies, and two were national databases. In comparison with the absence of liver dysfunction, patients with liver dysfunction were associated with higher short-term mortality (OR, odds ratio: 2.97, 95% CI, confidence interval: 1.23-7.18, p=0.02), higher MACE (OR 1.42, 95%CI 1.08-1.87, p=0.01), and higher bleeding rates (OR 2.23, 95%CI 1.65-3.00, p<0.01). There was no significant difference regarding acute kidney injury (OR 1.20, 95%CI 0.50-2.87, p=0.69).

Conclusions

The analysis suggests that liver dysfunction is a major risk factor in patients undergoing PCI. It is independently associated with higher risk of short-term mortality and also with an increased occurrence of MACE and bleeding, without significantly affecting renal function.
The triglyceride-glucose index might be a better indicator for predicting poor cardiovascular outcomes in chronic coronary syndrome
Authors: Erdogan A , Inan D , Genc O , Yildiz U , Genc D , Demirtola A Y S E I , Cetin I , Guler Y , Tekin A L I F , Bartucu S , Guler A , Karagoz A
Published: November 2023

Background

Abnormal glucose, and lipid metabolism all play major roles in the process of atherogenesis and are thus substantial risk factors for the development of coronary artery disease.

Purpose

We sought to investigate whether the triglyceride-glucose index (TyG) and the Atherogenic Index of Plasma (AIP), surrogates for atherosclerosis, are linked to major adverse cardiovascular events (MACE) in patients with Chronic Coronary Syndrome (CCS).

Methods and Results

Seven hundred ten-five consecutive patients with intermediate risk for CCS who presented to the outpatient clinic between June 2020 and August 2022 were included retrospectively. MACE included non-fatal myocardial infarction, heart failure, cerebrovascular events, non-cardiac mortality, and cardiac mortality. The composite of MACE was determined to be the primary outcome at follow-up after discharge. Secondary outcomes were defined as each individual parameter of MACE. For the primary outcome's time-to-event analysis, the Kaplan-Meier plots, and Cox proportional hazard models were done.The overall population’s median age was 55 years, with males accounting for 58%. The median follow-up time was 17 months. On multivariate cox regression analysis, age, hypertension, Coronary Artery Disease-Reporting and Data System score, and TyG index were found to be independent predictors of the primary outcome. The primary outcome rate was higher in individuals with high TyG than in those with low TyG (18.7% vs 3.8%, p<0.001). Likewise, patients with high TyG had statistically higher rates of cerebrovascular events, heart failure, non-fatal MI, non-cardiac mortality, and cardiac mortality than the latter.

Conclusion

We found that the TyG might predict poor cardiovascular outcomes in CCS patients.Table 1Figure 1
Post-menopause women show increased levels in risk prediction scores with age as dependent variable
Authors: Dannenberg L , Chavez-Talavera O , Kielb J , Glugla S , Shahjerdi K , Saffak S , Weber J , Baensch L , Riek S , Celik A , Neizel-Wittke M , Zeus T , Kelm M , Polzin A
Published: November 2023

Background

Men and women differ in outcome after percutaneous coronary intervention (PCI). However, frequently used scores for ischemic risk prediction in patients with cardiovascular disease do not include sex related factors. In this study, we aimed to analyze sex related differences in risk score prediction in patients after PCI in dependence from age-determined menopause.

Methods

In this mono-center analysis, we compared frequently used risk prediction scores for post PCI patients (GRACE [Global Registry of Acute Coronary Events], PRECISE-DAPT [PREdicting bleeding Complications In patients undergoing Stent implantation and subsEquent Dual Antiplatelet Therapy], NCDR-mortality and PARIS [Patterns of Non-Adherence to Anti-Platelet Regimen in Stented Patients]-thrombotic score) in male versus female post PCI patients in dependence from menopause (age determined) and age itself. Three-year follow-up was conducted to assess the incidence of MACCE (major adverse cerebro- and cardiovascular events) including all-cause mortality, myocardial infarction and stroke. Receiver operating characteristic (ROC) analysis was conducted to analyze predictive capacity of each score.

Results

1,001 patients post PCI were included (38% chronic coronary syndrome [CCS], 61% acute coronary syndrome [ACS]). Out of these, 765 were male and 306 were female. Women were slightly older (68.1±11.5 vs. 73.3±11.3 years, p<0.0001). Male and female patients did not differ in achieved levels of risk score below the age of 55. In contrast, in the subgroups >55 years, GRACE, PD-DAPT and NCDR Mortality scores were higher in woman compared to men (GRACE – 120.5±27.89 vs. 128.5±29.97, p<0.0001; PD-DAPT – 26.46±13.13 vs. 30.66±12.76, p<0.001; NCDR Mortality – 345.79±18.33 vs. 40.8±20.62, p<0.0001). Interestingly, PARIS thrombotic score was reduced (4.02±2.28 vs. 3.6±2.3, p=0.027). After Propensity score matching for age, GRACE, PD-DAPT and NCDR Mortality did no longer differ whereby PARIS thrombotic was reduced in female patients in this analysis as well. ROC revealed a moderate predictive capacity for MACCE for all scores in this post PCI cohort with a numerically higher predictive capacity for women (GRACEAUC – 0.625 vs. 0.662; PD-DAPTAUC 0.589 vs. 0.660, NCDR-mortalityAUC 0.625 vs. 0.667; PARIS-thromboticAUC 0.594 vs. 0.638).

Conclusion

In this single center analysis of post PCI patients with ACS and CCS, we could reveal that the GRACE, PD-DAPT and NCDR-mortality risk scores show higher values in post-menopause women compared to men whereby the PARIS-thrombotic score was reduced. We revealed age as major driver for this discrepancy. Moreover, women showed a numerically higher predictive accuracy for the occurrence of MACCE in line with the demonstrated worse outcome after PCI in several cohorts.
Synergistic adverse impact of diabetes and chronic kidney disease on cardiovascular mortality in patients underwent percutaneous coronary intervention
Authors: Moriya S , Iwata H , Chikata Y , Funamizu T , Doi S , Endo H , Okai I , Wada H , Naito R , Ogita M , Dohi T , Okazaki S , Miyauchi K , Daida H , Minamino T
Published: November 2023

Background

Diabetes and chronic kidney disease (CKD) are frequently complicated each other. While approximately 40% of patients have diabetes among those with CKD, it is the most major (40-50%) and clinically important complication of diabetic patients which critically effects on their quality of life and outcomes. Moreover, numerous previous evidence has indicated the adverse prognostic impact by each of diabetes and CKD particularly in the secondary prevention of patients with established coronary artery disease (CAD). Nevertheless, to date, limited data is available regarding the synergistic impact of these two major risk factors on outcomes of patients with CAD.

Purpose

We studied the synergistic adverse effects of diabetes and chronic kidney disease on cardiovascular mortality in patients undergoing percutaneous coronary intervention (PCI).

Methods

This study is a part of a single-center prospective registry database of patients underwent PCI, which launched at 1984. A total of 4880 patients who underwent their first PCI (index PCI) at our university hospital between 2000 and 2018 were enrolled for the study. Participants were divided into 4 groups by the presence or absence of CKD and DM: DM−/CKD− (n=2028, 41.6%), DM+/CKD− (n=1411, 28.9%), DM−/CKD+ (n=754, 15.5%), and DM+/CKD+ (n=687, 14.1%). The endpoint was set as cardiovascular-related death (CV death). The median follow-up duration was 5.2 years since PCI procedure.

Results

During follow-up, 288 (5.9%) CV deaths were identified, in which 79.1% had DM or CKD. Unadjusted Kaplan-Meier curves showed patients with DM+/CKD+ had a significantly higher cumulative incidence of CV death compared to those with DM-/CKD- (log-rank p<0.0001) and DM-/CKD+ (p=0.03) (Figure 1). Moreover, multivariate Cox-proportional hazard analysis set DM-/CKD- as a reference and adjusted by age, gender, body mass index, hemoglobin, ejection fraction, acute coronary syndrome, statin and smoking history showed significantly increased risk of having both of diabetes and CKD (Hazard ratio (HR) and 95% confidence interval (CI) of DM and CKD: 3.1,: 1.9-5.1, p<0.0001) than having each of these (HR and 95% CI of DM alone: 1.2, 0.7-2.0, p=0.5, and of CKD alone: 1.8, 1.1-3.0, p=0.02 (Figure 2).

Conclusions

Findings in the present study indicated that CKD is a significant risk for CV death in patients following PCI, while only DM without CKD was not a significant risk factor in this population. Moreover, the risk for CV death was synergistically increased, when a patient had both of DM and CKD, compared to having each of these.Kaplan-Meier curves in CV deathAdjusted Cox hazard model in CV death
Iron deficiency and association with mortality in patients with coronary artery disease
Authors: Corballis N , Merinopoulos I , Gunawardena T , Tsampasian V , Bhalraam U , Fish J , Eccleshall S , Vassiliou V , Reinhold J
Published: November 2023

Background

Iron is essential for a number of metabolic and physiological processes and the role of iron deficiency (ID) as an adverse prognostic indicator in heart failure is well established. The suitability of the international guideline definition for prognosticating adverse events in heart failure has recently been brought into question due to the inclusion of ferritin, given its reduced specificity during intercurrent inflammation. As inflammation plays an active role in coronary disease, and acute coronary syndromes in particular, we sought to further explore whether ID according to the current guideline definition or alternative definitions without reliance on ferritin is a predictor of clinical outcomes in patients with coronary artery disease.

Purpose

The aims are to assess whether a)ID is associated with increased all-cause mortality in patients with coronary artery disease requiring percutaneous coronary intervention (PCI) and b) whether different definitions of ID have a stronger association with mortality in these patients.

Methods

All patients in a UK PCI registry who had full iron studies within thirty days of their index procedure were included. ID was defined according to three different criteria: 1) International guideline criteria (ferritin <100 ng/ml or transferrin saturations (TSATs) <20% if ferritin 100-299 ng/ml), 2) TSATs <20%, or 3) serum iron <13μmol/L. Mortality data was obtained from Hospital Episodes Statistics. Ethical approval was obtained from the Northwest Haydock Research Committee.

Results

Some 390 patients were included in this analysis. The mean age was 72.5 (62-86) and 33.0% were female. 28.7% of patients presented with a STEMI, 39.7% with an acute coronary syndrome and 31.5% had stable angina.

ID according to the serum iron and TSAT definitions were associated with increased all-cause mortality, HR 1.61 (CI 1.07-2.41), p=0.02 and HR 1.64 (CI 1.13-2.37), p=0.009 respectively. However, ID as determined by the international guideline definition was not predictive of increased all-cause mortality, HR 0.99 (CI 0.69-1.42), p=0.97.

Conclusions

Here we show that ID, defined by serum iron and TSATs but not by the current guideline definition of ID, is associated with increased all-cause mortality in patients with coronary artery disease, undergoing PCI. A randomised controlled trial into treating ID in patients with coronary disease is warranted to determine whether intravenous iron replacement is beneficial in this patient group. The current study supports the growing evidence that alternatives to the current guideline definition of ID may be better suited to identify patients with adverse prognosis and who, in turn, may benefit most from intravenous iron replacement therapy.