Stent Thrombosis Research Articles

Stent strategies: Endothelial progenitor cell coated stents vs sirolimus eluting stents in a pairwise meta-analysis

BackgroundEndothelial progenitor cells (EPCs) capturing stents were developed to enhance endothelial repair and reduce the risk of stent thrombosis, addressing limitations of Sirolimus-Eluting Stents (SES). This study aims to compare the safety and efficacy of EPC stents versus SES in patients undergoing percutaneous coronary intervention (PCI). MethodsWe performed a meta-analysis following PRISMA guidelines in patients undergoing PCI treated with Sirolimus eluting stent (SES) vs the use of EPC stents and recognized 8 clinical trials with patients undergoing PCI and reporting outcomes such as Target Lesion Failure (TLF), stent thrombosis, and revascularisation. Relative risks were calculated using a random effects model and heterogeneity was assessed with I^2 statistics. ResultsThe EPC group showed higher incidence of TLF (RR ​= ​1.28), MI(RR ​= ​1.10), and cardiac death (RR ​= ​1.19) compared to SES, though these differences were not statistically significant. Revascularisation rates were significantly higher in EPC group with TVR (RR ​= ​1.60) and TLR(RR ​= ​2.20) while stent thrombosis was lower (RR ​= ​0.93). ConclusionThe results of this EPC study reveals that while EPC stents show promise in revascularisation and lowering stent thrombosis, they are also associated with higher incidence of adverse events. The utility of EPC, especially vast reendothelialization, may have niche applications but their full potential can be realized with more rigorous trials as a clear advantage over SES remains lacking.

The prognosis of acute myocardial infarction due to stent thrombosis after 2nd generation drug eluting stents era (comparative study with acute myocardial infarction due to plaque rupture or erosion)

Abstract Backgrounds Stent thrombosis (ST) is a rare complication after percutaneous coronary intervention (PCI), and more than 70% of ST cases result in acute myocardial infarction (AMI). Although a new generation of drug-eluting stents (DES) and newer antiplatelet therapies have been shown to reduce the incidence of ST, ST-related AMI continues to be observed in contemporary practice. The prevalence and prognosis of ST results in AMI have not been well evaluated after the 2nd generation DES (G2-DES) era. Purpose The purpose of this study was to evaluate the prevalence and prognosis of AMI due to ST after the G2-DES era compared with AMI due to plaque rupture or erosion. Methods Among 6601 AMI patients enrolled in the Mie ACS registry from January 2013 to November 2022, 6273 AMI patients with AMI due to ST(ST) and AMI due to plaque rupture and erosion (AMI:P) were included for this analysis after excluding other types of AMI. ST was confirmed by angiography. The primary endpoint was defined as all-cause mortality, and revascularization after PCI for AMI was also evaluated. Results Seventy-eight patients, or 1.2% of all AMI in this study, had AMI due to ST, including early ST n=13 (16.7%), late ST n=4 (5.1%), and very late ST n=61 (78.2%). Stent types were G2-DES n=35 (44%), G1-DES n=18 (23.1%), bare metal stent (BMS) n=12 (15.4%), and unknown n=13 (16.7%). According to the KM survival curve, the 30-day mortality rate of ST was 2.6%, while the AMI:P rate was 6.7%, which was not statistically significant, but the ST was half the mortality rate. Furthermore, in the landmark analysis, the 2-year mortality rates were 6.2% for ST and 7.0% for AMI:P (P=0.66, Figure 1). ST was not an independent predictor of poor prognosis by multivariate Cox regression analysis. Even after the propensity score matching analysis as a sensitivity analysis, ST was not an independent predictor of poor prognosis in AMI patients. Among ST patients, 82.2% were treated with balloon angioplasty (without additional stenting) at the time of AMI, whereas 9.7% of AMI:P patients were treated with balloon angioplasty (P<0.001). Compared to patients with AMI:P, patients with ST had a higher incidence of revascularization after PCI for AMI within 2 years (21.8% vs. 11.2%; P=0.02, Figure 2A). Multivariate Cox regression analysis also showed that ST was an independent predictor of revascularization after PCI for AMI with a hazard ratio of 2.00 (P<0.01, Figure 2B). Conclusion The prognosis of ST patients tended to be better than that of AMI:P patients. The proportion of ST in AMI has decreased in the G2-DES era, and the higher proportion of VLST in ST suggests that its prognosis may be better than that of AMI:P . However, the rate of revascularization is higher in ST patients because stenting was not performed in the acute phase of PCI for AMI, and the appropriate use of stents depending on the type of ST may lead to a reduction in revascularization.Figure1Figure2

One year incidence of events after definite coronary stent thrombosis: a retrospective vs prospective comparison and a conglomerate determination of prognostic factors of mortality

Abstract Background Although many studies analysed the predictive factors of coronary stent thrombosis (ST), there are few data on prognostic factors of clinical outcomes after definite ST. The purpose of the current study was to analyse clinical presentation and outcomes at one year after definite coronary ST in two distinct cohorts: a retrospective cohort and a prospective cohort and to determine the prognostic factors. Methods Among 22’039 consecutive patients treated between January 2008 and December 2021, 275 patients presented a definite ST and were included in this study (retrospective cohort n=83 and prospective cohort n=192). Baseline characteristics, clinical ST presentation and 1-year outcomes were analysed between the two cohorts using SPSS Software. According to the obtained results data of both cohorts were pooled and prognostic factors of clinical outcomes determined using multivariate analysis. Results There was no statistical difference between the two cohorts concerning baseline characteristics and clinical ST presentation. All-cause mortality and MACE rate up to 1 year follow-up did not differ either among cohorts (16.9% vs 14.6%, p=0.764 for mortality (Figure 1) and 26.5% vs 24% p=0.766 for MACE). Multivariate analysis of the aggregated data of both prospective and retrospective cohorts revealed age (OR: 1.05 95% CI [1.02;1.09]; p=0.0016), early stent thrombosis (OR: 3.3 95% CI [1.52;7.15] p=0.002), severe renal failure (OR: 3.37 95% CI [1.35;8.42] p=0.009), clinical presentation (cardiogenic shock [OR: 2.92 95% CI {1.17;7.28} p=0.02] and cardiac arrest [OR: 15.3 95% CI {6.62;35.39} p<0.0001]) as strongly associated with a higher risk of death at 1 year whereas higher LVEF was a protective factor (OR: 0.922 95% CI [0.891; 0.955] p<0.0001). Conclusion Comparing retrospectively collected data versus prospectively collected data for definite ST showed very similar data concerning qualitative variables (e.g. baseline characteristics and clinical presentation of ST) suggesting feasibility of data pooling to determine prognostic factors of clinical outcome at one year. Prognostic factors influencing one-year all-cause mortality were age, early ST thrombosis, renal failure, residual LVEF and clinical presentation.Figure 1

A meta-analysis of randomised controlled trials comparing optical coherence tomography-guided against angiography-guided revascularisation

Abstract Optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) offers more in-depth assessment of plaque morphology, vessel sizing and post-PCI stent deployment characteristics than angiography guidance alone. Previous studies have demonstrated superiority of OCT-guided compared to angiography-guided PCI in stent implantation and expansion, with no difference in safety outcomes. Despite this, adoption of OCT-guided PCI remains low in clinical practice due to its increased procedural time, larger contrast volume, and added cost. Two large multicentre international randomised controlled trials (RCTs) were recently published. We therefore aimed to perform an up-to-date meta-analysis of RCTs comparing OCT-guided revascularisation against angiography-guided revascularisation on hard clinical outcomes. A comprehensive search of PubMed/MEDLINE and Ovid/Embase was performed, of which only RCTs were included. Two authors identified relevant articles and extracted the data independently. Any disagreements were resolved by a third author. Clinical outcome data was extracted from each study and then pooled to determine the overall risk ratio (RR) and confidence interval (CI) collectively. This was calculated with random-effects model using the Mantel-Haenszel method. All reported P values are two-sided, with significance set at P<0.05. A total of ten RCTs involving a total of 5062 patients were included. After an average follow-up of 20 months, there was no significant difference in the trial-defined composite endpoint between OCT-guided versus angiography guided revascularisation [6.8% versus 7.9%, RR 0.85, 95% CI (0.69 to 1.03), P=0.10, heterogeneity (I2)=0%]. There was also no significant difference in cardiac death [1.0% versus 1.6%, RR 0.61, 95% CI (0.36 to 1.02), P=0.06, heterogeneity (I2)=0%, Figure 1a], myocardial infarction [3.2% versus 3.7%, RR 0.86, 95% CI (0.65 to 1.15), P=0.31, I2=0%, Figure 1b] and target lesion or vessel repeat revascularisation [3.8% versus 4.1%, RR 0.95, 95% CI (0.72 to 1.25), P=0.70, I2=0%, Figure 1c] between the two arms. However, the OCT-guided revascularisation arm was associated with a significantly lower rate of stent thrombosis [0.8% versus 1.5%, RR 0.57, 95% CI (0.33 to 0.97), P=0.04, I2=0%, Figure 1d] than the angiography-guided revascularisation arm. The number-needed-to-treat (NNT) by OCT-guided revascularisation to reduce one additional stent thrombosis event was 143. In conclusion, our findings show the use of OCT-guided revascularisation led to a significant reduction in stent thrombosis compared to angiography-guided revascularisation, but there was no difference in cardiac death, myocardial infarction and repeat revascularisation. The NNT for stent thrombosis was 143 patients. Further research is needed to identity those subgroups most likely to benefit from OCT-guided revascularisation before it can be more widely adopted to significantly impact on clinical care.

Clinical outcomes of risk score-guided dual antiplatelet therapy in patients with acute coronary syndrome who underwent percutaneous coronary intervention

Abstract Objective We aimed to investigate the effect of risk score-guided dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) from real-world clinical practice in Korea. Methods 984 patients with ACS undergoing PCI with bioabsorbable-polymer everolimus eluting stent were enrolled from 20 hospitals in the multicenter, observational study. The analysis was conducted on 834 patients who took medications according to risk score-guided DAPT and were follow-up after 1 year. GRACE score and PRECISE-DAPT score were used for risk score-guided DAPT and medication for antiplatelets was conducted as follow (Figure 1). Results The mean age was 64.0 ± 10.5 years, 77.6% were men. 43.7% had acute myocardial infarction, 62.5% hypertension and 37.6% diabetes. Multivessel and left main artery disease were about in 56.2%. Trans-radial PCI was performed in 76.3%. Aspirin was taken in almost all patients (99.1%) and clopidogrel was most frequently prescribed as a DAPT (clopidogrel 64.9%, Ticagrelor 28.1%, prasugrel 6.6%). All-cause mortality and NACE (consisting of all-cause mortality, myocardial infarction, revascularization, stent thrombosis, stroke, and major/minor bleeding) were 1.2%, and 5.4% respectively at 1 year. Stent thrombosis was occurred only in 4 patients (0.5%). Bleeding complications were developed in 19 case (2.3%). Among the bleeding sites, the access site was the most common 7 (0.8%), followed by the gastrointestinal tract 4 (0.5%). Major bleeding was occurred (BARC types 3 to 5 bleeding) in 3 cases (0.4%) and BARC type 2 was most common (1.2%) (Figure 2 and Table 1). Conclusion Bleeding complications and ischemic events were very low in real-world patients with ACS undergoing PCI during 1 year follow-up, when the management was performed according to the risk scoring-guided DAPT.Figure 1Figure 2 and Table 1

Clinical impact of systemic inflammation across the spectrum of different high-sensitivity CRP values in patients undergoing percutaneous coronary intervention

Abstract Background Systemic inflammation enhances atherosclerosis progression and is a well-established determinant of cardiovascular risk. High-sensitivity C-reactive protein (hsCRP), the most widely available biomarker of inflammation, has indeed been associated with the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) in patients undergoing percutaneous coronary intervention (PCI). However, some heterogeneity exists in the threshold to define high hsCRP associated with increased cardiovascular risk, with the 2 and 3 mg/L cut-offs being used more commonly. Purpose We aimed to evaluate the clinical impact of systemic inflammation in patients undergoing PCI across the spectrum of baseline hsCRP values. Methods We retrospectively evaluated consecutive patients undergoing PCI with drug-eluting stent implantation from 2012 to 2022 at Mount Sinai Hospital (NY, USA). We excluded patients presenting with acute myocardial infarction or active cancer and those for whom baseline hsCRP was not available or was above 10 mg/L. Patients were stratified into three groups according to baseline hsCRP levels: <2.0, 2.0 to 3.0, and >3.0 mg/L. We estimated the risk of 12-month adverse events using the lowest hsCRP group (<2.0 mg/L) as reference. The primary endpoint was MACCE, defined as the composite of all-cause death, myocardial infarction (MI), or stroke. Secondary endpoints were MACCE individual components, target vessel revascularization (TVR), stent thrombosis and bleeding. Results A total of 10,811 patients were included in the analysis. Of these, 6,210 (57.4%) had hsCRP <2.0 mg/L, 1,624 (15.0%) between 2 and 3 mg/L and 2,977 (27.6%) >3.0 mg/L. Incidence of anemia, diabetes mellitus, peripheral and cerebrovascular artery disease, atrial fibrillation and chronic kidney disease increased stepwise across hsCRP groups. Moreover, patients with higher hsCRP tended to present more frequently with unstable angina and higher baseline LDL cholesterol levels. As regards procedural variables, coronary artery disease severity and PCI complexity did not differ significantly across groups. When compared with patients with hsCRP < 2, hsCRP > 3 mg/L was associated with a greater adjusted risk of MACCE (4.9% vs 2.4%; HR 1.75 % CI 1.35 - 2.28), all-cause death (2.5% vs 0.9%, HR 2.34, 95%CI 1.57-3.47) and MI (2.5% vs 1.3%; HR 1.58 95%CI 1.11-2.26) (Figure 1). Risks of stroke, TVR, stent thrombosis and bleeding did not significantly differ across hsCRP groups (Table 1) Conclusions In patients undergoing PCI, elevated hsCRP values exceeding 3 mg/L exhibit a more robust association with the risk of MACCE and all-cause mortality, as compared with both hsCRP < 2.0 and between 2.0 and 3.0 mg/L. In this context, the use of hsCRP might improve the stratification of patients associated with higher inflammatory burden.

Choosing the most effective and safest P2Y12 Inhibitor for use in >70-year-old acute coronary syndrome patients: a network meta-analysis

Abstract Background Acute coronary syndrome (ACS) represents a significant health burden, especially in elderly patients. Antiplatelet therapy forms the cornerstone of medical treatment for ACS, prasugrel and ticagrelor are preferred for their rapid action and proven efficacy. Despite their benefits, the comparative effectiveness and safety of prasugrel, ticagrelor, and clopidogrel, especially in elderly ACS patients, represents a true gap of knowledge. Aim This study aims to compare the efficacy and safety of prasugrel, ticagrelor, and clopidogrel in elderly patients with ACS, focusing on outcomes such as major adverse cardiovascular events (MACE), stroke, major or moderate bleeding, myocardial infarction (MI), all-cause mortality, cardiac mortality, revascularization, and stent thrombosis. Methods We conducted a comprehensive literature search across PubMed, Web of Science, Cochrane, Scopus, and ClinicalTrials.gov. Thirty-seven studies were included in our network meta-analysis (NMA), with data extracted on various outcomes. Data reported as relative risks (RRs) with 95% confidence intervals. Results Our NWM revealed that there is no significant difference in the incidence of MACE between prasugrel and ticagrelor or clopidogrel (RR 0.91 [0.67, 1.25] and RR 0.86 [0.64, 1.15], respectively). Stroke outcomes also showed no significant difference (RR 0.88 [0.60, 1.28] for prasugrel vs. ticagrelor; RR 0.73 [0.52, 1.02] for prasugrel vs. clopidogrel). Ticagrelor compared to clopidogrel significantly increased the risk of major or moderate bleeding (RR 1.23 [1.08, 1.39]). Significantly decreased risks of cardiac mortality were found for prasugrel and ticagrelor compared to clopidogrel (RR 0.88 [0.78, 0.98] and OR 0.81 [0.73, 0.90], respectively). Prasugrel significantly reduced the risk of revascularization compared to ticagrelor and clopidogrel (RR 0.57 [0.42, 0.78] and RR 0.75 [0.64, 0.88], respectively). For stent thrombosis, prasugrel and ticagrelor both showed significantly decreased risks compared to clopidogrel (RR 0.71 [0.55, 0.92] and RR 0.76 [0.62, 0.93], respectively). for MI, no significant difference was observed between prasugrel and ticagrelor (RR 0.88 [CI 0.64-1.20]), prasugrel and clopidogrel (RR 0.81 [0.60-1.09]), or ticagrelor and clopidogrel (RR 0.92 [CI 0.73-1.16]). Similarly, all-cause mortality rates did not significantly differ, with an RR of 0.93 [0.68-1.27] for prasugrel vs. ticagrelor, and an RR of 0.80 [0.61-1.06] for prasugrel vs. clopidogrel. Conclusion Our NMA suggests that while there are no significant differences among prasugrel, ticagrelor, and clopidogrel in reducing the risk of MACE, stroke, MI, and all-cause mortality in elderly ACS patients, ticagrelor may increase the risk of bleeding. Prasugrel and ticagrelor offer advantages in reducing cardiac mortality, revascularization, and stent thrombosis.

Markers of coagulation and early coronary stent thrombosis

Abstract Background Acute stent thrombosis is a rare but deleterious event after percutaneous coronary intervention (PCI). Hemostatic factors such as D-Dimer, fibrinogen, and platelet count have emerged as potential indicators of increased thrombotic risk. However, data regarding the association with early stent thrombosis (ST) is sparse. Purpose The aim of this study was to investigate whether markers of coagulation are associated with increased risk of early (< 30 days after PCI) ST. Methods Within a prospective single-center registry, we retrospectively analyzed the association between pre-procedural platelet count, plasma levels of fibrinogen and D-Dimer with the occurrence of early ST within 30 days after PCI. Results We included 10,714 consecutive patients who underwent percutaneous coronary intervention (PCI) with implantation of drug-eluting stents (DES). Pre-procedural measurements of platelet count, fibrinogen and D-Dimer was available in 6,337, 6,155 and 956 patients, respectively. The number of definite early ST within 30 days was 58 (0.92 %). Pre-procedural platelet count (p<0.05) and plasma levels of fibrinogen (p<0.05) were significantly higher in patients with early ST as compared to patients without ST. Whereas D-Dimer was not associated with early ST, patients in the fifth quintile of platelet count had a significant increased risk for early ST (HR 2.43; 95% CI 1.43 - 4.14; p=0.001) as compared to patients in the lower four quintiles and patients in the fifth quintile of fibrinogen had a significant increased risk for early ST (HR 1.86; 95% CI 1.07 – 3.26; p<0.05) as compared to patients in the lower four quintiles. These associations were independent of clinical risk factors, the presence of acute coronary syndromes and the number of stents. Conclusions Pre-procedural platelet count and plasma levels of fibrinogen are associated with the risk of early ST in patients after implantation of DES. Device-level risk factors like stent-type or size and procedure-level risk factors like peri-interventional medication and complications during stent apposition are associated with ST. Platelet count and plasma levels of fibrinogen may be additional patient-level risk factors that have to be taken in account in the development of future personalized strategies to prevent these rare but deleterious complications.

Risk score guided dual antiplatelet therapy duration in patients with acute coronary syndrome: insights from the FORCE-ACS registry

Abstract Background The use of risk scores to guide the duration of dual antiplatelet therapy(DAPT) in patients with acute coronary syndrome(ACS) is recommended in current guidelines, however clinical data on the impact of its prospective use is lacking. Purpose To compare risk-score guided DAPT duration to standard of care in ACS patients. Methods Since 2015, patients with ACS are enrolled in the prospective FORCE-ACS registry. In 2018, we implemented a risk score-guided approach for DAPT duration. In this analysis, we compared patients in which DAPT duration was guided by bleeding and ischemic risk assessment using PRECISE-DAPT-scores and DAPT-scores to a standard treatment group in a 1:4 ratio. In risk score-guided patients, high bleeding risk patients(HBR) were advised short DAPT(≤6 months); patients without HBR or high ischemic risk(HIR) were advised 12 months DAPT; and patients without HBR but with HIR were advised prolonged DAPT(≥30 months). In the standard treatment group DAPT duration was left at the discretion of the treating physician. Exclusion criteria included no DAPT or oral anticoagulation at discharge or implanted bio-vascular stents. Primary outcome was a composite of all-cause mortality, myocardial infarction(MI), stent thrombosis(ST), stroke and Bleeding Academic Research Consortium(BARC) 3 or 5 bleeding; a secondary composite ischemic outcome consisted of cardiovascular mortality, MI, ST and ischemic stroke. Kaplan-Meier plots with log-rank testing and Cox proportional hazard regression after adjustment of potential confounders were performed for the primary outcome. Sensitivity analyses were performed for patients included after implementation of the risk score-guided approach and for censoring events within the first six months. Results Between 2015 and 2020 8,009 patients were enrolled in the FORCE-ACS registry, of which 5,518 patients were included for analysis. The risk-score guided group(n=1,200) more often presented with ST-elevation MI, percutaneous coronary intervention or optimal medical therapy, while standard treatment patients(n=4,318) were older, more often had prior MI, prior revascularization, received coronary artery bypass grafting or conservative management. In the risk-score guided group, 15.7% had HBR, 46.4% were without HBR or HIR, and 37.9% showed HIR without HBR. The primary outcome was 6.3%(n=75) in risk score-guided patients versus 14.8%(n=637) in the standard treatment group (adjusted hazard ratio(HR) 0.47 [95%CI 0.36–0.61], p<0.001). These results remained consistent after sensitivity analyses (fig 1B). Both the composite ischemic outcome(HR 0.54 [95%CI 0.41–0.72] p<0.001) and BARC 3 or 5 bleeding (HR 0.23 [95%CI 0.08-0.63], p=0.004) were significantly lower in risk score-guided patients compared to the standard treatment group. Conclusion In this prospective analysis, risk-score guided DAPT duration showed a significant reduction of both ischemic and bleeding events compared to standard treatment.

To shock or to drill: comparison of intravascular lithotripsy and rotational atherectomy - a meta-analysis

Abstract Background Coronary intravascular lithotripsy (IVL) and rotational atherectomy (RA) are potent tools for calcified plaque modification before stenting. While IVL uses pressure waves to breakup calcium, RA mechanically disrupts calcium to promote vascular compliance. It is unclear if one has superior clinical outcomes than the other for calcified coronary lesion preparation before percutaneous coronary intervention (PCI). Methods All relevant studies from PubMed and Embase were included with patients (age >18 years) undergoing PCI for calcified coronary plaque treated with either IVL or RA. All-cause mortality, target lesion revascularization (TLR), and major adverse cardiovascular events (MACE) (mortality, myocardial infarction, TLR, stroke, and in-stent thrombosis) were assessed. The pooled odds ratio (OR) for binary outcomes was computed using the Mantel-Haenszel method. Random effects model was used with 95% confidence interval (CI) for statistical significance. Heterogeneity was marked by Higgins I-squared (I2) statistic. Analysis was done on Comprehensive R Archive Network in R (CRAN-R) software. Results Three studies were included (IVL n=351, RA n=118). Compared to RA, IVL had similar all-cause mortality (OR 1.0, CI 0.3-3.0, p 0.9), TLR (OR 2.1, CI 0.26-18.2, p 0.4), and MACE (OR 2.0, CI 0.9-4.1, p 0.6). There was a trend towards favorable outcomes for RA, although statistically insignificant (figure 1). Conclusion For patients undergoing PCI for calcified coronary lesions, IVL and RA demonstrated comparable clinical outcomes including all-cause mortality. Large-scale prospective studies are needed to understand the differences in clinical outcomes.

The long-term clinical benefit of early versus delayed invasive strategies in elderly patients with non-ST-segment elevation myocardial infarction who have undergone percutaneous coronary intervention

Abstract Background The data regarding long-term outcomes of early versus delayed invasive strategies in elderly patients who have undergone percutaneous coronary intervention (PCI) for non-ST-segment elevation myocardial infarction (NSTEMI) is limited. Purpose We aimed to investigate the long-term clinical benefit of early versus delayed invasive strategies in elderly patients who underwent PCI for NSTEMI. Methods From a nationwide, prospective, real-world registry of 13,104 patients with acute myocardial infarction (MI) who underwent PCI, 2818 elderly patients (aged ≥70 years) who underwent PCI for NSTEMI were included. Of these, 2299 patients were treated with an early invasive strategy (early invasive group), and 519 were treated later (delayed invasive group). The incidence of major adverse cardiac events (MACE; all-cause death, recurrent MI, any revascularization, stroke, readmission due to heart failure [HF], or definite/probable stent thrombosis [ST]) and the components of MACE were compared using multivariable Cox regression, propensity score (PS) matched, and PS-adjusted analyses. Results During a median follow-up of 1047 days, MACE, all-cause death, and cardiac death occurred in 1018 (36.1%), 660 (23.4%), and 423 patients (15.0%), respectively. The early invasive group showed significantly lower risks of MACE (entire: 35.0% vs. 41.2%, hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.66-0.90, p=0.001; PS-matched: n=984, 33.3% vs. 40.8%, HR 0.75, 95% CI 0.62-0.91, p=0.005), all-cause death (entire: 22.5% vs. 27.4%, HR 0.76, 95% CI 0.63-0.92, p=0.004; PS-matched: 21.8% vs. 27.2%, HR 0.75, 95% CI 0.58-0.90, p=0.005), cardiac death (entire: 13.8% vs. 20.2%, HR 0.64, 95% CI 0.51-0.79, p<0.001; PS-matched: 13.1% vs. 19.4%, HR 0.67, 95% CI 0.55-0.86, p=0.011), and readmission due to HF (entire: 6.5% vs. 9.2%, HR 0.64, 95% CI 0.46-0.89, p=0.007; PS-matched: 6.7% vs. 9.4%, HR 0.68, 95% CI 0.51-0.96, p=0.017) than the delayed invasive group. There were no significant differences in the risks of recurrent MI, any revascularization, stroke, and definite/probable ST between the groups. Furthermore, in patients aged ≥80 years, the early invasive group had significantly reduced rates of MACE (42.9% vs. 49.5%, HR 0.71, 95% CI 0.55-0.91, p=0.039), all-cause death (31.7% vs. 39.0%, HR 0.71, 95% CI 0.55-0.92, p=0.010), and cardiac death (20.9% vs. 31.0%, HR 0.59, 95% CI 0.44-0.80, p=0.001) compared to the delayed invasive group. Conclusions In elderly patients with NSTEMI, an early invasive intervention strategy was associated with favorable long-term clinical outcomes compared to a delayed invasive intervention strategy.

One-year clinical outcome of aspirin-free prasugrel monotherapy following stent implantation in patients with chronic coronary syndrome: insight from ASET-JAPAN study

Abstract Background Single antiplatelet therapy with a potent P2Y12 inhibitor without aspirin after coronary stent implantation may provide an adequate balance between ischemic and bleeding risks in selected patients. The 3-month follow-up of the Acetyl-Salicylic Elimination Trial (ASET)-Japan pilot study demonstrated the feasibility and safety of Prasugrel monotherapy without aspirin after successful percutaneous coronary intervention (PCI) in selected patients with chronic coronary syndrome (CCS). Purpose The current study aimed to evaluate the 1-year clinical outcome in the ASET-Japan. Methods The ASET-Japan pilot study was designed to demonstrate the feasibility and safety of the approved dose of prasugrel monotherapy in Japan without aspirin after optimal PCI with a platinum-chromium everolimus-eluting stent in CCS population. After successful procedure, all patients were treated with a locally approved maintenance dose of 3.75 mg/day of Prasugrel monotherapy up to 3-month. After 3-month, the choice of antiplatelet therapy was left to the discretion of the investigators. Patients were followed up to 1 year. The target lesion-related endpoint was a composite of cardiac death, spontaneous target-vessel myocardial infarction (MI) >48 h after the index PCI or clinical-driven target lesion revascularisation. Patient-Oriented Composite Endpoint (POCE) was defined as a composite of all cause mortality, any stroke, any MI and any revascularisation. Spontaneous MI was defined according to Forth universal definition. The event rate was estimated by the Kaplan-Meier method. The event was adjudicated by an independent clinical event committee. Results A total of 208 patients were enrolled in the study. The average anatomical SYNTAX score was 7.96 (±4.6). After procedure, prasugrel monotherapy was immediately initiated. After 3-month, Prasugrel monotherapy was continued in 88.6% up to 1-year. Aspirin monotherapy was prescribed to 10 patients (5.0%), while 6 patients (3.0%) were on DAPT at 1-year. All-cause mortality rate was 1.49%, with no occurrence of cardiovascular death. Revascularisation occurred in 4.0% (n=8) with no occurrence of TLR, while one patient (0.5%) underwent a clinical driven target vessel revascularisation. In summary, 7 out of 8 revascularisations were non-target vessel revascularisation (6 clinically-driven non-TVR). Spontaneous non TV-MI occured in 0.5% (n=1) of patients. There was no definite/probable stent thrombosis up to 1 year. The target lesion related endpoint rate at 1-year was 0%, whereas 1-year POCE rate was 7.0% (n=14). Conclusion Discontinuation of Aspirin and Prasugrel monotherapy at a low maintenance dose of 3.75 mg/day following an angiographically successful stent deployment was feasible and safe in selected patients with CCS and low SYNTAX score. This safety profile is confirmed at 1 year while the investigators, in their large majority and at their own discretion, had maintained the prasugrel treatment.

Impact of moderate to severe anemia on clinical outcomes in patients with atrial fibrillation and coronary artery disease requiring percutaneous coronary intervention

Abstract Background In patients with coronary artery disease undergoing percutaneous coronary intervention (PCI), anemia is one of the important risk factors for thrombotic events as well as bleeding events. In patients with atrial fibrillation (AF), on the other hand, a similar relationship between anemia and the increased risks of mortality, cardiovascular events, or bleeding events has been reported. Purpose The purpose of this study was to evaluate the impact of anemia on clinical outcomes in patients with AF undergoing PCI, who required intensive antithrombotic therapy with a combination of anticoagulants and antiplatelet agents, using a multicenter registry database. Methods Patients with AF undergoing PCI at 15 institutions between January 2015 and March 2021 were included in this analysis. Based on the baseline hemoglobin levels, moderate to severe anemia was defined as hemoglobin levels <11 g/dL, and mild anemia was defined as hemoglobin levels 11-12.9 g/dL for men and 11-11.9 g/dL for women. Clinical outcomes within 1 year, including major adverse cardiovascular events (MACE: all-cause death, myocardial infarction, stent thrombosis, and stroke) and major bleeding events (BARC 3 or 5), were compared among patients with moderate/severe anemia, mild anemia, and no anemia. Results In a total of 746 enrolled patients, 119 (16.0%) and 168 (22.5%) patients presented with moderate/severe and mild anemia. The incidence of MACE (22.5%, 11.0%, and 9.1%, log-rank p<0.001) as well as major bleeding events (10.7%, 6.5%, and 2.7%, log-rank p<0.001) was the highest in the moderate/severe anemia group compared with the mild and no anemia groups (Figure 1). In multivariable Cox regression analyses, moderate/severe anemia (p=0.008), severe chronic kidney disease (p=0.019), and acute coronary syndrome (p=0.049) were independently associated with MACE. For major bleeding events, moderate/severe anemia (p=0.031) and platelet count (p=0.021) were independent predictors. Conclusions Moderate/severe anemia was significantly associated with the higher incidence of MACE as well as major bleeding events compared with mild and no anemia in AF patients undergoing PCI.Figure 1

Sex differences in clinical data and long-term outcomes of elderly patients with acute myocardial infarction presenting with cardiogenic shock undergoing percutaneous coronary intervention

Abstract Background Data on contemporary clinical practice and long-term outcomes for sex differences in elderly patients with acute myocardial infarction (MI) who have undergone percutaneous coronary intervention (PCI) presenting with cardiogenic shock (CS) is limited. Purpose This study aimed to investigate contemporary clinical data and long-term clinical outcomes according to sex differences in elderly patients undergoing PCI for acute MI complicated by CS. Methods We analyzed data from a nationwide, prospective, and real-world registry comprising elderly patients (≥65 years) with acute MI who have undergone PCI and presented with CS. Of the 540 patients included, 228 were women, and 312 were men. We compared major adverse cardiac events (MACE; all-cause death, recurrent MI, any revascularization, stroke, heart failure [HF] readmission, or definite/probable stent thrombosis [ST]) and the components of MACE between the groups using multivariable Cox regression, propensity score (PS) matching, and PS-adjusted analyses. Results Compared to men, women were younger and had higher incidences of hypertension and elevated pro-BNP levels. No significant differences were observed in other cardiovascular risk factors, left ventricular systolic function levels, or adherence to guideline-directed medical therapy between the groups. Over a median follow-up of 1035 days, MACE, all-cause death, and cardiac death occurred in 257 (47.6%), 212 (39.3%), and 170 (31.5%) patients, respectively. Women exhibited significantly increased risks of MACE (overall: 53.5% vs. 43.3%, hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.59-0.97, p=0.023; PS-matched: n=368, 52.3% vs. 41.8%, HR 0.73, 95% CI 0.53-0.94, p=0.033), all-cause death (overall: 44.7% vs. 35.3%, HR 0.77, 95% CI 0.58-0.97, p=0.032; PS-matched: 42.8% vs. 33.4%, HR 0.71, 95% CI 0.54-0.95, p=0.041), cardiac death (overall: 35.1% vs. 28.8%, HR 0.81, 95% CI 0.60-0.97, p=0.048; PS-matched: 34.4% vs. 26.9%, HR 0.78, 95% CI 0.54-0.95, p=0.043) compared to men. There were no significant differences in the risks of recurrent MI, any revascularization, stroke, HF readmission, and definite/probable ST between the groups. Conclusions In this nationwide registry, women compared to men exhibited increased risks of long-term clinical outcomes in elderly patients with acute MI who have undergone PCI presenting with CS.

Comparison of ridaforolimus-eluting and zotarolimus-eluting coronary stents: 5-Year outcomes from the BIONICS and NIREUS trials

Abstract Introduction Despite similarities between different modern drug eluting stents (DES), their comparative short and long-term safety and efficacy has generated much interest and yielded conflicting results. The BIONICS and the NIREUS randomized clinical trials showed non-inferiority of the Ridaforolimus eluting stent (RES) compared to the Zotarolimus-eluting stent (ZES) with respect to 1-year target lesion failure (TLF) and 6-month angiographic late lumen loss. Aim To evaluate clinical outcomes between treatment groups over 5 years follow-up Methods BIONICS and NIREUS were prospective, randomized, single-blind multicenter trials comparing RES and ZES in patients undergoing PCI. Patients were blinded to treatment assignment and randomized to RES or ZES in a 1:1 fashion in BIONICS, and in 2:1 fashion in NIREUS. Clinical events were assessed during hospital stay, at 30 days, 1 year, and yearly thereafter, up to 5 years. The The primary endpoint in the current study was the 5-year rate of target lesion failure (TLF). Results The study population included 2221 patients enrolled in the BIONICS (n=1919) and NIREUS (n=302) studies. Median follow-up was 1822 days (interquartile range 1783 to 1847 days). Mean age was 63.2±10.3 years, and most patients were men (79.7%). Clinical presentation with ACS was similar between groups (38.9% versus 37.9%, RES versus ZES, respectively, p=0.38). Procedural characteristics were similar for patients treated with RES and ZES. A mean of 1.6±0.9 and 1.5±0.8 stents were implanted in RES and ZES patients, respectively, p=0.08. Post dilatation was performed more frequently in the RES group (63.3% versus 60.1%, p=0.02) and procedure duration was longer in RES versus ZES patients (47.0±31.8 minutes versus 44.6±29.2 minutes, p=0.01). Device success was high in both groups but slightly higher in the ZES group (98.2% versus 99.5% for RES and ZES, respectively, p=0.002) yet with similar procedural success (97.9% versus 97.3%, p=0.49). At 5 years, the primary endpoint of TLF was similar between treatment groups (12.2% RES versus 11.3% ZES, p=0.52). Rates of TLR (7.6% RES versus 6.8% ZES, p=0.42), target vessel-related MI (4.8% RES versus 4.9% ZES, p=0.95) and stent thrombosis (0.9% RES versus 0.9% ZES, p=0.87), also did not differ between groups. Target vessel revascularization (TVR) and cardiac death were higher among the RES group (12.3% versus 9.5% p=0.037, and 3.6% versus 2.2 % p=0.042, respectively). However, after correction for baseline characteristics there was no significant difference in cardiac death between groups. Conclusions In a pooled analysis of two randomized trials, 5-year clinical outcomes were similar between patients undergoing PCI with RES and ZES. These results support the long-term safety and efficacy of RES for the treatment of patients with coronary artery disease.Central illustrationZES vs. RES

Routine HbA1c screening identifies de novo (pre)diabetes mellitus in 37% of ACS patients which comes with an even higher ischemic risk compared to known diabetes mellitus

Abstract Background Diabetes is a prominent risk factor for coronary artery disease (CAD). By exacerbating the progression of CAD, it puts these patients at increased risk of acute coronary syndrome (ACS) and recurrent ischemic events. It is therefore important to identify hyperglycaemic individuals and to treat them accordingly. However, in daily practice it is seen that a subsequent proportion of people with diabetes is undiagnosed. Purpose The aim of this research is to gain insight in the prevalence of patients with de novo (pre)diabetes, the treatment, and the risk of major adverse cardiac and cerebrovascular events (MACCE) compared to patients with known diabetes in an ACS cohort treated by percutaneous coronary intervention (PCI). Methods The Southeast Netherlands Heart Registry (ZON-HR) is an ongoing, multicentre registry collecting data of patients who underwent a PCI procedure. Of this cohort, patients presenting with ACS and measured HbA1c concentrations (on admission) were selected (N=1507). Patients with diagnosed diabetes are considered well-regulated when HbA1c <53 mmol/mol. Patients undiagnosed with diabetes were divided into three groups: HbA1c concentration <42 mmol/mol (normal), HbA1c 42-47 mmol/mol (pre-diabetes) and HbA1c ≥48 mmol/mol (diabetes). The rates of 30-day repeated myocardial infarction (MI), unplanned revascularisation, ischemic CVA, stent thrombosis, and cardiovascular mortality were determined, separately and combined as MACCE in patients with known diabetes compared to prediabetes and diabetes de novo. Results In the selected population, 28.5% of the patients were previously diagnosed with diabetes, which was well-regulated in only 30.2% of these patients. Of the patients not previously diagnosed, 23.1% and 14.4% had pre-diabetic and diabetic HbA1c concentrations, respectively. In 56.1% of patients with de novo diabetes, no glucose-lowering medication was prescribed at discharge (Table 1). At 30-day follow-up, de novo diabetes patients had increased rates of MACCE compared to patients with known diabetes (HR: 3.51, 95%CI 1.48-8.52) after multivariate analysis which corrected for differences at baseline (Figure 1). In addition, a significant increase in unplanned revascularisation (p=.014) and MI (p=.037) was found between de novo diabetes and known diabetes patients. Conclusions Almost half of the ACS patients in this cohort had either poorly regulated diabetes (305 patients) or was undiagnosed with (pre)diabetes while having an increased HbA1c concentration on admission (401 patients). Despite routine HbA1c screening, a subsequent part of these patients is not adequately treated for (pre)diabetes, especially the de novo diabetes patients. By this group, an even larger rate of MACCE was found, compared to the already established risk of diabetes in ACS. Therefore, active screening and treatment (as recommended in the guidelines) should get more attention to improve outcomes in these high-risk patients.Table 1:ACS population based on HbA1cFigure 1:Survival curves of 30D MACCE

Risk stratification using the academic research consortium high bleeding risk criteria in patients with atrial fibrillation undergoing percutaneous coronary intervention

Abstract Background Previous studies have reported that the academic research consortium high bleeding risk (ARC-HBR) criteria are useful to predict the risk of bleeding events in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). However, there are few studies investigating the predictive value of the ARC-HBR criteria in patients with atrial fibrillation (AF) undergoing PCI. Purpose The purpose of this study was to investigate whether the ARC-HBR criteria can be applied to long-term risk stratification in patients with AF undergoing PCI. Methods Patients with AF undergoing PCI at 15 institutions between January 2015 and March 2021 were enrolled. The ARC-HBR score was calculated by assigning 1 point for each major criterion and 0.5 points for each minor criterion. Clinical outcomes within 1 year, including major adverse cardiovascular events (MACE: all-cause death, myocardial infarction, stent thrombosis, and stroke) and major bleeding events (BARC 3 or 5), were evaluated. Results A total of 723 patients were included in this analysis. The best cut-off values of J-HBR score determined by ROC curve analysis to predict MACE and major bleeding events were both 3.0. Of 723 patients, 161 (22.3%) had ARC-HBR score ≥3.0. In Kaplan-Meier curve analyses, the incidence of MACE as well as major bleeding events was significantly higher (log-rank p<0.001 and p=0.010) in patients with ARC-HBR score ≥3.0 compared to those with ARC-HBR score <3 (Figure 1). Conclusion The ARC-HBR score may be useful in assessing the risk of MACE, including thrombotic events, as well as bleeding events in AF patients undergoing PCI.Figure 1

Real-world evidence supports superior efficacy of prasugrel over ticagrelor in individuals with acute coronary syndrome

Abstract Background In patients with acute coronary syndrome (ACS) undergoing invasive treatment, ticagrelor and prasugrel are guideline-recommended P2Y12 receptor inhibitors. Preference for one of the two drugs is under debate although the ISAR-REACT5 trial revealed advantages for prasugrel. This real-world data study evaluated the efficacy and safety of ticagrelor versus prasugrel in individuals with ACS undergoing invasive treatment by emulating a target trial analogous to ISAR-REACT5. Methods Following the Population, Intervention, Comparator, Outcome, and Timing (PICOT) framework, within a German health claims database, we adapted the inclusion and exclusion criteria from ISAR-REACT5 and identified a 1:1 propensity score-matched cohort with ACS being treated after hospital discharge with either ticagrelor or prasugrel (n=9,380, each). End points were defined as in ISAR-REACT5 at 1-year follow-up. Additionally, subgroup analyses of individual ACS components ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI) and unstable angina (UA) were conducted. Results The primary composite end point occurred in 9.2% of ticagrelor and 7.4% of prasugrel treated individuals (hazard ratio 1.22; 95% confidence interval 1.10-1.35). Likewise, the secondary end points MI and stroke occurred significantly more often in the ticagrelor arm. All-cause mortality, stent thrombosis, and the safety end point bleeding revealed no significant differences. Subgroup analysis revealed superiority for prasugrel particularly in individuals with STEMI. Statistically, test results and hazard ratios of this real-world data study were in agreement with the findings of ISAR-REACT5. Conclusions With over four times the cohort size of ISAR-REACT5, this study indicates superior efficacy of prasugrel over ticagrelor in individuals with ACS undergoing invasive strategy.Cumulative incidence of primary endpointGraphical abstract

Drug eluting stents trigger the secretion of inflammatory proteins in an experimental in vitro study

Abstract Introduction Ischemic cardiovascular diseases commonly appear following the occlusion of one or more of the coronary arteries. Drug eluting stents (DES) constitute the gold standard to help to keep open the arteries and maintain the blood flow. After their placement into the coronary arteries, they stay in direct contact with the blood stream, disturbing the physiological conditions and interacting with several cells and proteins within the surrounding blood and vessel wall. Besides the beneficial effects of DES, their clinical application is also associated with complications, such as (late) stent thromboses. Previous studies have shown that thrombosis and inflammation are tightly linked with each other by activating inflammatory cells and secreting cytokines and chemokines to further promote an inflammatory surrounding. However, the influence of DES and their components on the inflammatory cascade and their corresponding players was not investigated yet. Methods To investigate the inflammatory secretome in response to DES, we performed an in vitro study with isolated human peripheral blood mononuclear cells (PBMCs). Therefore, PBMCs were isolated from the whole blood of four healthy volunteers. In total, 63 stents were used in the study, including Medtronic Resolute Onyx (n=37), Abbott XIENCE Sierra (n=5), Boston Scientific SYNERGY (n=4), Terumo Ultimaster (n=3), and Biotronik Orsiro (n=14). We measured the secretion of cytokines and chemokines, including IL-1β, IL-6, TNF-α, IL-8, and IL-12, as well as ICAM-1, VCAM-1, and MCP-1 by commercially available enzyme-linked immunosorbent assay (ELISA). Results Our results showed that DES significantly increase the secretion of the cytokines IL-1β (p=0.0005), and IL-6 (p=0.0002), as well as the chemokine IL-8 (p=0.0010). Additionally, we also detected an elevation of the reaction product ICAM-1 (p=0.0003). Further analyses resulted in a reduced secretion of IL-1β, IL-6, TNF-α, IL-8, and ICAM-1 into the cells’ supernatants in response to Resolute Onyx stents, in comparison to the other stents. Moreover, multiple regression analysis revealed a high dependency of the inflammatory reaction on the elution drug, the polymer type and the stent’s length. Additionally, the material of the stent platform, as well as the polymer thickness further have impact on the cytokine and chemokine response of PBMCs. Conclusion Our study indicate that DES by themselves trigger an inflammatory reaction of blood cells by the secretion of cytokines and chemokines. Furthermore, we provided first insights into the composition of the inflammosome in response to DES. A triggered inflammation may increase the vulnerability for complications and the failure of the DES. As these complications were already observed in clinical studies, our results would potentially provide predictions about the application of certain DES designs and may help to choose the appropriate stents in the clinical setting.

Clinical impact of perfusion balloon for ST-segment elevated myocardial infarction: RYUSEI study

Abstract Background Drug-eluting stents have significantly contributed to reducing mortality in patients with ST-segment elevation myocardial infarctions (STEMIs), but slow flow/no-reflow phenomenon and in-stent restenosis are still clinical problems. On the other hand, perfusion balloons (PBs) can compress thrombi and ruptured plaque for long inflation without ischemia and can be used as a delivery device for infusion of nitroprusside to distal risk area during ballooning. Purpose We conducted RYUSEI (Reduction of risk bY perfUsion balloon for ST-segment Elevated myocardial Infarction) study to evaluate whether PBs before stenting are more effective than conventional stenting for STEMIs. Methods We divided consecutive patients with STEMIs who underwent optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) into PB group who were treated with PBs before stenting and the conventional PCI (CP) group. In PB group, we inflated PB at the culprit lesion for five minutes to compress thrombi and ruptured plaque as a pre-stent lesion modification. In addition, an intra-coronary injection of nitroprusside (total dose: 120 µg; slow bolus injection of 24 µg/5mL every minute [5 times]) into the distal vascular bed to the culprit lesion through the PB was performed during a 5-minute PB ballooning. We compared clinical results including slow flow/no-reflow phenomenon, OCT findings, and one-year clinical events including cardiac death, target vessel-related myocardial infarctions, target lesion revascularization and stent thromboses between the two groups. Results We finally analyzed 34 patients in PB group and 90 in CP group. After propensity score matching, PB and CP groups consisted of 23 patients, respectively. In the propensity score-matched cohort, there were no significant differences of the patients’ backgrounds and lesion and procedural characteristics between the two groups. In the cohort, regarding post PCI angiographic and OCT findings, the incidence of slow flow/no-reflow phenomenon and maximum protrusion area detected by OCT were significantly lower (P=0.047 and P=0.019, respectively) and TIMI flow grade 3 was significantly higher (P=0.022) in the PB group than CP group while the other parameters were similar (Table). Kaplan-Meier analysis revealed a significantly better one-year clinical outcome in PB group than CP group (p=0.038) (Figure). Conclusions The RYUSEI study revealed a pre-stent lesion modification in addition to nitroprusside infusion using PB is useful to achieve better clinical course in STEMI patients.Post PCI Angiographic and OCT FindingsComparison of One-year Clinical Outcome