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Contrast-induced nephropathy (CIN) impairs clinical outcome in patients undergoing angiographic procedures. The aim of this study was to investigate whether short-term high-dose atorvastatin load decreases the incidence of CIN after percutaneous coronary intervention (PCI). Statin-naive patients with acute coronary syndrome undergoing PCI (n = 241) randomly received atorvastatin (80 mg 12 hours before intervention with another 40-mg preprocedure dose, n = 120) or placebo (n = 121). All patients had long-term atorvastatin treatment thereafter (40 mg/day). Primary end point was incidence of CIN defined as postintervention increase in serum creatinine ≥0.5 mg/dl or >25% from baseline. Five percent of patients in the atorvastatin arm developed CIN versus 13.2% of those in the placebo arm (p = 0.046). In the atorvastatin group, postprocedure serum creatinine was significantly lower (1.06 ± 0.35 vs 1.12 ± 0.27 mg/dl in placebo, p = 0.01), creatinine clearance was decreased (80.1 ± 32.2 vs 72.0 ± 26.6 ml/min, p = 0.034), and C-reactive protein peak levels after intervention were decreased (8.4 ± 10.5 vs 13.1 ± 20.8 mg/l, p = 0.01). Multivariable analysis showed that atorvastatin pretreatment was independently associated with a decreased risk of CIN (odds ratios 0.34, 95% confidence interval 0.12 to 0.97, p = 0.043). Prevention of CIN with atorvastatin was paralleled by a shorter hospital stay (p = 0.007). In conclusion, short-term pretreatment with high-dose atorvastatin load prevents CIN and shortens hospital stay in patients with acute coronary syndrome undergoing PCI; anti-inflammatory effects may be involved in this renal protection. These results lend further support to early use of high-dose statins as adjuvant pharmacologic therapy before percutaneous coronary revascularization. [ABSTRACT FROM AUTHOR]

Aortic valve calcification (AVC) has been explored as a powerful predictor of procedural complications in patients undergoing transcatheter aortic valve implantation (TAVI). However, little evidence exists on its impact on intra-annular devices' performance. We aimed to investigate the impact of AVC burden and distribution pattern on the occurrence of paravalvular leak (PVL), conduction disturbances requiring permanent pacemaker implantation (PPI) and 30-day clinical outcomes in patients undergoing TAVI with a self-expanding, intra-annular device. According to AVC, 103 patients enrolled in a single medical centre from November 2019 to December 2022 were divided into tertiles. Valve Academic Research Consortium (VARC)-3 definitions were used to classify procedural complications and outcomes. Patients in the highest AVC tertile showed an increased occurrence of mild or more PVL and conduction disorders (p < 0.001 and p = 0.006). AVC tertiles (highest tertile) emerged as an independent predictor of PVL (OR 7.32, 95%CI 3.10-17.28, p < 0.001) and post-TAVI conduction disturbances (OR 3.73, 95%CI 1.31-10.60, p = 0.013) but not of PPI (OR 1.44, 95%CI 0.39-5.35, p = 0.579). Considering calcium distribution, ROC analyses revealed that annular AVC but not left ventricle outflow tract (LVOT) calcium burden significantly indicated the development of PVL (AUC 0.863, 0.77-0.93, p < 0.001) and conduction disorders/PPI (AUC 0.797, 0.70-0.89, p < 0.001 and 0.723, 0.58-0.86, p = 0.018, respectively). After adjustment for age and sex, the highest tertile remained an independent predictor of the 30-day composite outcome (death, myocardial infarction, stroke, major vascular complications, type 3/4 bleedings, acute kidney injury, PPI and ≥ moderate PVL) (OR 3.26; 95%CI 1.26-8.40, p = 0.014). A higher AVC is associated with an increased risk of PVL and conduction disturbances after TAVI with a self-expanding, intra-annular device. However, our findings suggest a minor role for LVOT calcification compared with annular AVC in the performance of this specific prosthesis., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

To evaluate if integrating platelet reactivity (PR) evaluation in the original age, creatinine and ejection fraction (ACEF) score could improve the diagnostic accuracy of the model in patients with stable coronary artery disease (CAD). We enrolled patients treated with percutaneous coronary intervention between 2010 and 2011. High PR was included in the model (PR-ACEF). Co-primary end points were a composite of death/myocardial infarction (MI) and major adverse cardiovascular events (MACE). Overall, 471 patients were enrolled. Compared to the ACEF score, the PR-ACEF showed an improved diagnostic accuracy for death/MI (AUC 0.610 vs 0.670, p < 0.001) and MACE (AUC 0.572 vs 0.634, p < 0.001). These findings were confirmed using internal validation with bootstrap resampling. At 5 years, the PR-ACEF value > 1.75 was independently associated with death/MI [HR 3.51, 95% CI (1.97-6.23)] and MACE [HR 2.77, 95% CI (1.69-4.53)]. The PR-ACEF score was effective in improving the diagnostic performance of the ACEF score at the long-term follow-up., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Coronary chronic total occlusions (CTO) are an increasingly frequent entity in clinical practice and represent a challenging percutaneous coronary intervention (PCI) scenario. Despite data from randomized trials that have not yet demonstrated a clear benefit of CTO recanalization, the widespread of CTO-PCI has substantially increased. The improvement in operators' techniques, equipment, and training programs has led to an improvement in the success rate and safety of these procedures, which will represent an important field of future development of PCI. The present review will summarize clinical outcomes and technical and safety issues of CTO revascularization with the aim to guide clinical daily cath-lab practice.

Takotsubo syndrome (TTS) is a clinical condition characterized by temporary regional wall motion anomalies and dysfunction that extend beyond a single epicardial vascular distribution. Various pathophysiological mechanisms, including inflammation, microvascular dysfunction, direct catecholamine toxicity, metabolic changes, sympathetic overdrive-mediated multi-vessel epicardial spasms, and transitory ischemia may cause the observed reversible myocardial stunning. Despite the fact that TTS usually has an acute coronary syndrome-like pattern of presentation, the absence of culprit atherosclerotic coronary artery disease is often reported at coronary angiography. However, the idea that coronary artery disease (CAD) and TTS conditions are mutually exclusive has been cast into doubt by numerous recent studies suggesting that CAD may coexist in many TTS patients, with significant clinical and prognostic repercussions. Whether the relationship between CAD and TTS is a mere coincidence or a bidirectional cause-and-effect is still up for debate, and misdiagnosis of the two disorders could lead to improper patient treatment with unfavourable outcomes. Therefore, this review seeks to provide a profound understanding of the relationship between CAD and TTS by analyzing potential common underlying pathways, addressing challenges in differential diagnosis, and discussing medical and procedural techniques to treat these conditions appropriately.

Background and Aims: Leptin is a hormone involved in the regulation of food intake. Previous studies suggested an interplay between leptin, platelet aggregation, and cardiovascular outcome but this issue was not investigated in vivo in patients treated with percutaneous coronary intervention (PCI). We designed a study to evaluate the possible relation between leptin, cardiovascular outcome, and platelet reactivity (PR) in patients undergoing PCI., Methods: 155 PCI patients had preprocedural measurements of PR and leptin plasma levels. The latter were assessed by ELISA. Hyperleptinemia was defined as leptin levels ≥14 ng/ml. PR was evaluated by the VerifyNowP2Y12 assay and expressed as P2Y12 reaction units (PRU). Patients were divided into three groups based on PR values and defined as low (LPR), normal (NPR), and high (HPR). Patients were followed for up 8 years. The primary endpoint was the incidence of Major Acute Cardiac Events (MACE) at long-term follow-up according to leptin groups. Secondary endpoints were the evaluation of leptin levels according to PR groups and the incidence of periprocedural myocardial infarction (PMI) according to leptin groups., Results: Long-term follow-up was completed in 140 patients. Patients with hyperleptinemia experienced a higher MACE rate than the normoleptinemic group (HR 2.3; CI 95% 1.14-4.6, P = 0.02). These results remained unchanged after adjusting for Body Mass Index, hypertension, and gender. Leptin levels were significantly different among groups of PR (P = 0.047). Leptin levels were higher in the HPR group (12.61 ± 16.58 ng/ml) compared to the LPR group (7.83 ± 8.87 ng/ml, P = 0.044) and NPR group (7.04 ± 7.03 ng/ml, P = 0.01). The rate of PMI was higher in hyperleptinemia patients (15.1% vs. 6.5%, P = 0.22)., Conclusions: This study suggests that high leptin levels are associated with a worse clinical outcome in patients undergoing PCI and with HPR. Further studies are needed to define better the pathophysiological pathways underlying this association., Competing Interests: Declaration of competing interest All authors have nothing to declare concerning the present manuscript., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Atherosclerosis is the leading cause of death worldwide, especially in patients with type 2 diabetes mellitus (T2D). GLP-1 receptor agonists and DPP-4 inhibitors were demonstrated to play a markedly protective role for the cardiovascular system beyond their glycemic control. Several cardiovascular outcome trials (CVOT) reported the association between using these agents and a significant reduction in cardiovascular events in patients with T2D and a high cardiovascular risk profile. Moreover, recent evidence highlights a favorable benefit/risk profile in myocardial infarction and percutaneous coronary revascularization settings. These clinical effects result from their actions on multiple molecular mechanisms involving the immune system, platelets, and endothelial and vascular smooth muscle cells. This comprehensive review specifically concentrates on these cellular and molecular processes mediating the cardiovascular effects of incretins-like molecules, aiming to improve clinicians' knowledge and stimulate a more extensive use of these drugs in clinical practice as helpful cardiovascular preventive strategies.

Background: Clinical outcomes of patients suffering periprocedural myocardial injury and undergoing incomplete revascularization (IR) following percutaneous coronary intervention (PCI) has never been investigated., Objective: To investigate the relationship between different thresholds of post-PCI cardiac troponin (cTn) elevation and revascularization completeness in determining long-term clinical outcomes., Methods: Patients were stratified in tertiles according to preprocedural SYNTAX score (SS) (low: 0-6; medium: >6-11; high: >11) and residual SS (low: 0-4; medium: >4-8; high: >8). IR was defined by a rSS value >4. Three thresholds of myocardial injury were pre-specified: 5×, 35× and 70× 99th percentile upper reference limit (URL) increase of baseline cTn. Primary outcome was a composite of major adverse cardiac events (MACE) at two years of follow-up., Results: 1061 patients undergoing PCI for stable coronary artery disease were enrolled. IR occurred in 249 (23.4 %) and major myocardial injury in 540 (50.9 %). Patients belonging to the highest tertile of SS showed an increased risk of experiencing IR and periprocedural myocardial injury. Two-year follow-up was available in 869. At multi-variate Cox's regression analysis, patients undergoing IR + cTn > 35 × URL and IR + cTn > 70 × URL showed an increased risk of MACE [HR 2.30 (1.19-4.41) and HR 3.20 (1.38-7.41); respectively]., Conclusions: Periprocedural myocardial injury is critically associated with MACE at two-year follow-up in patient treated with PCI who achieve IR. Despite conflicting evidence exists regarding the influence of periprocedural myocardial injury on clinical outcomes, patients undergoing IR seem to represent a high-risk subgroup., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Abstract: Contrast-induced acute kidney injury (CI-AKI) is a serious complication in patients undergoing diagnostic or therapeutic procedures that require contrast use and negatively affects the long-term outcomes. Patients with type 2 diabetes mellitus (DM), particularly those who have already developed diabetic nephropathy (DN), are more susceptible to contrast-induced renal damage. Indeed, contrast media amplify some pathological molecular and cellular pathways already in place in the DN setting. In recent years, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have triggered a paradigm shift in managing patients with type 2 DM, reducing cardiovascular and renal adverse events, and slowing DN development. Some evidence also suggests favorable effects of SGLT2i on acute kidney injury despite the initial alarm; however, little data exist regarding CI-AKI. The present review provides an updated overview of the most recent experimental and clinical studies investigating the beneficial effects of SGLT2i on chronic and acute renal injury, focusing on their potential role in the development of CI-AKI. Thus, we aimed to expand the clinicians' understanding by underscoring new opportunities to prevent this complication in the setting of DM, where effective preventive strategies are still lacking., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Percutaneous coronary intervention (PCI) is frequently complicated by type 4a myocardial infarction (MI), which is associated with an increased risk of mortality. We assessed the usefulness of the angiography-derived hemodynamic index (ADDED), which is based on the extent of myocardium at risk and on the anatomical lesion severity, in predicting type 4a MI in patients with chronic coronary syndrome (CCS) undergoing PCI. We enrolled 442 patients treated with single-vessel PCI. The ADDED index was calculated as the ratio of the Duke Jeopardy Score to the minimum lumen diameter assessed with quantitative angiography analysis. Type 4a MI was defined according to the 4th Universal Definition of MI. The overall population was divided into tertiles of ADDED index. Type 4a MI occurred in 5 patients (3.3%) in the ADDED-low tertile, 8 (5.5%) in the ADDED-mid tertile, and 26 (17.7%) in the ADDED-high tertile (p < 0.0001). At ROC curve analysis, the ADDED index could significantly discriminate between patients with and without type 4a MI (area under the curve 0.745). At multivariate analysis, an ADDED index value > 5.25 was the strongest independent predictor type 4a MI. Our results support the role of the ADDED index as a predictor of type 4a MI in patients with CCS treated with elective PCI of a single vessel. Whether a selective use of additional preventive measures in patients considered at high risk based on ADDED index values may improve peri-procedural and long-term outcomes remains to be tested in dedicated investigations., (© 2022. Springer Japan KK, part of Springer Nature.)

Evidence assessing potential diurnal variations of platelet reactivity in patients on clopidogrel treated with elective percutaneous coronary intervention (PCI) for chronic coronary syndrome (CCS) are currently lacking. We prospectively enrolled 15 patients affected by stable coronary artery disease (CAD) previously treated with elective PCI and on clopidogrel for at least 8 days (administered at 8 a.m.). A significant heterogeneity in diurnal levels of ADP-dependent platelet aggregation was found (p = 0.0004), with a peak of platelet reactivity occurring at the 6 a.m. assessment, which resulted significantly increased compared to the afternoon (6 p.m.) evaluation (255 ± 66 vs 184 ± 67, p = 0.002). In addition, at the early-morning evaluation a considerably high proportion of patients with high platelet reactivity (53.3%) were observed. In conclusion, clopidogrel-induced platelet inhibition in patients with CCS after elective PCI follows a circadian rhythm, thus suggesting that a consistent and durable antiplatelet inhibition is often failed with standard clopidogrel administration at morning., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Coronary artery disease (CAD) remains one of the most important causes of morbidity and mortality worldwide, and revascularization through percutaneous coronary interventions (PCI) significantly improves survival. In this setting, poor glycaemic control, regardless of diabetes, has been associated with increased incidence of peri-procedural and long-term complications and worse prognosis. Novel antidiabetic agents have represented a paradigm shift in managing patients with diabetes and cardiovascular diseases. However, limited data are reported so far in patients undergoing coronary stenting. This review intends to provide an overview of the biological mechanisms underlying hyperglycaemia-induced vascular damage and the contrasting actions of new antidiabetic drugs. We summarize existing evidence on the effects of these drugs in the setting of PCI, addressing pre-clinical and clinical studies and drug-drug interactions with antiplatelet agents, thus highlighting new opportunities for optimal long-term management of these patients.

The relation between diabetes mellitus (DM) and bleeding complications after percutaneous coronary intervention (PCI) is controversial. This study investigates the role of low platelet reactivity (LPR) in the bleeding risk stratification of patients who underwent PCI according to DM status. A total of 472 patients who underwent PCI on aspirin and clopidogrel were included retrospectively. Platelet reactivity was assessed using the VerifyNow P2Y(12) assay. LPR was defined as platelet reactivity unit ≤178. The primary end point was the occurrence of any bleeding at 5 years stratified by DM status and LPR. DM was present in 30.5% of patients. LPR was less frequent in patients with DM (p = 0.077). Overall, 11.9% of patients experienced a bleeding complication at 5 years. The incidence of bleeding did not differ in subjects with and without DM (p = 0.24). LPR had a similar value for stratifying the increased bleeding risk in patients with and without DM (interaction p between DM and LPR 0.69). A stepwise increase in the crude rates of bleeding complications was observed across patients with and without LPR and DM (log-rank p = 0.004), with those affected by both conditions having the highest crude incidence rate. In conclusion, on top of aspirin, approximately 1/3 of patients who underwent PCI on clopidogrel have LPR. Assessment of LPR provides a significant incremental value for predicting bleeding irrespective of DM status. Although the presence of DM per se does not increase the incidence of hemorrhagic complications, the coexistence of DM and LPR identifies the subgroup with the highest bleeding risk., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Despite the significant reduction of the overall burden of cardiovascular diseases (CVD), valvular heart disease (VHD) still represents an important cause of CVD morbidity and mortality. While the number of patients with prosthetic heart valves (PHV) is increasing, management of antithrombotic therapy in this setting remains particularly challenge. This happens also because the scientific guidelines and consensus documents rely on limited evidences. Nevertheless, the evolution in prostheses' materials, the spread of transcatheter interventions, and the introduction of direct oral anticoagulants (DOACs), altogether led to a scientific renaissance of this field. Our purpose is to examine and discuss the available evidences on the use of antithrombotic treatments in patients with mechanical and biological PHV, with the aim to provide a practical tool for decision making in every day clinical practice., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims: To investigate the levels of platelet reactivity and the impact of high platelet reactivity (HPR) on long-term clinical outcomes of complex higher-risk and indicated patients (CHIP) with stable coronary artery disease (CAD) treated with elective percutaneous coronary intervention (PCI)., Methods: We enrolled 500 patients undergoing elective PCI for stable CAD and treated with aspirin and clopidogrel. Patients were divided into four groups based on the presence of CHIP features and HPR. Primary endpoint was the occurrence of major adverse clinical events (MACE) at 5 years., Results: The prevalence of HPR was significantly greater in the CHIP population rather than non-CHIP patients (39.9% vs 29.8%, P = 0.021). Patients with both CHIP features and HPR showed the highest estimates of MACE (22.1%, log-rank P = 0.047). At Cox proportional hazard analysis, the combination of CHIP features and HPR was an independent predictor of MACE (hazard ratio 2.57, 95% confidence interval 1.30-5.05, P = 0.006)., Conclusion: Among patients with stable CAD undergoing elective PCI and treated with aspirin and clopidogrel, the combination of CHIP features and HPR identifies a cohort of patients with the highest risk of MACE at 5 years, who might benefit from more potent antiplatelet strategies., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background: Ranolazine is a second-line drug for the management of chronic coronary syndromes (CCS). Glucose-lowering and endothelial effects have also been reported with this agent. However, whether ranolazine may improve short-term glycemic variability (GV), strictly related to the prognosis of patients with type 2 diabetes (T2D), is unknown. Thus, we aimed to explore the effects of adding ranolazine to standard anti-ischemic and glucose-lowering therapy on long- and short-term GV as well as on endothelial function and oxidative stress in patients with T2D and CCS., Methods: Patients starting ranolazine ( n = 16) were evaluated for short-term GV, haemoglobin 1Ac (Hb1Ac) levels, endothelial-dependent flow-mediated vasodilation (FMD), and oxidative stress levels at enrolment and after 3-month follow-up. The same measurements were collected from 16 patients with CCS and T2D that did not receive ranolazine, matched for age, gender, and body mass index., Results: A significant decline in Hb1Ac levels was reported after 3-month ranolazine treatment (mean change -0.60%; 2-way ANOVA p = 0.025). Moreover, among patients receiving ranolazine, short-term GV indexes were significantly improved over time compared with baseline ( p = 0.001 for time in range; 2-way ANOVA p = 0.010). Conversely, no significant changes were reported in patients without ranolazine. Finally, greater FMD and lower oxidative stress levels were observed in patients on ranolazine at 3 months., Conclusions: Ranolazine added to standard anti-ischemic and glucose-lowering therapy demonstrated benefit in improving the glycemic status of patients with T2D and CCS. How this improvement contributes to the overall myocardial benefit of ranolazine requires further studies., Competing Interests: The authors declare that they have no conflict of interest related to the content of the manuscript., (Copyright © 2021 Annunziata Nusca et al.)

We investigated the interaction between chronic kidney disease (CKD) and high platelet reactivity (HPR) in determining long-term clinical outcomes following elective PCI for stable coronary artery disease (CAD). A total of 500 patients treated with aspirin and clopidogrel were divided based on the presence of CKD (defined as glomerular filtration rate of < 60 ml/min/1.73 m 2 ) and HPR (defined as a P2Y12 reaction unit value ≥ 240 at VerifyNow assay). Primary endpoint was the occurrence of major adverse clinical events (MACE) at 5 years. Patients with both CKD and HPR showed the highest estimates of MACE (25.6%, p = 0.005), all-cause death (17.9%, p = 0.004), and cardiac death (7.7%, p = 0.004). The combination of CKD and HPR was an independent predictor of MACE (HR 3.12, 95% CI 1.46-6.68, p = 0.003). In conclusion, the combination of CKD and HPR identifies a cohort of patients with the highest risk of MACE at 5 years., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We evaluated the predictive power of age, creatinine, and ejection fraction (ACEF) score on mortality at 5-year follow-up in a population of 471 patients with chronic coronary syndrome (CCS) treated with percutaneous coronary intervention (PCI). Patients in the ACEF-High tertile showed the highest incidence of death at 5 years (15.7% vs. 2.6% in ACEF-Low and 4.3% in ACEF-Mid; log rank p<0.001). The ACEF score could significantly discriminate between patients who died and those who were still alive at 5 years (AUC 0.741, 95% CI 0.654-0.828), and an ACEF score >1.32 was identified as the optimal cutoff point to predict 5-year mortality (sensitivity 74%, specificity 68%). An ACEF score >1.32 was an independent predictor of 5-year mortality (HR 5.77, 95% CI 2.70-12.31; p<0.001). Our study shows that the ACEF score can predict mortality at 5-year follow-up in patients with CCS treated with PCI., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The Mehran score is the most widely accepted tool for predicting contrast-induced acute kidney injury (CI-AKI), a major complication of percutaneous coronary intervention (PCI). Similarly, abnormal fasting pre-procedural glycemia (FPG) represents a modifiable risk factor for CI-AKI, but it is not included in current risk models for CI-AKI prediction. We sought to analyze whether adding FPG to the Mehran score improves its ability to predict CI-AKI following PCI. We analyzed 671 consecutive patients undergoing PCI (age 69 [63,75] years, 23% females), regardless of their diabetic status, to derive a revised Mehran score obtained by including FPG in the original Mehran score (Derivation Cohort). The new risk model (GlyMehr) was externally validated in 673 consecutive patients (Validation Cohort) (age 69 [62,76] years, 21% females). In the Derivation Cohort, both FPG and the original Mehran score predicted CI-AKI (AUC 0.703 and 0.673, respectively). The GlyMehr score showed a better predictive ability when compared with the Mehran score both in the Derivation Cohort (AUC 0.749, 95%CI 0.662 to 0.836; p = 0.0016) and the Validation Cohort (AUC 0.848, 95%CI, 0.792 to 0.903; p = 0.0008). In the overall population (n = 1344), the GlyMehr score confirmed its independent and incremental predictive ability regardless of diabetic status (p ≤0.0034) or unstable/stable coronary syndromes (p ≤0.0272). In conclusion, adding FPG to the Mehran score significantly enhances our ability to predict CI-AKI. The GlyMehr score may contribute to improve the clinical management of patients undergoing PCI by identifying those at high risk of CI-AKI and potentially detecting modifiable risk factors., Competing Interests: Disclosures The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: While the superiority of reabsorbable-polymer drug-eluting stents (RP-DES) over bare-metal stents and first-generation durable-polymer (DP)-DES has been largely established, their advantage compared with new-generation DP-DES is still controversial. This study aimed was to compare clinical outcomes of all-comer patients undergoing percutaneous coronary intervention (PCI) with new generation DP-DES or RP-DES implantation., Methods: We prospectively enrolled 679 consecutive patients treated with PCI with RP-DES or DP-DES. The primary endpoint was the 1-year incidence of major adverse clinical events (MACE), a composite of death, myocardial infarction (MI), and target vessel revascularization (TVR). Target lesion revascularization (TLR) and definite stent thrombosis were also recorded., Results: A total of 439 (64.6%) received RP-DES and 240 (36.4%) received DP-DES. No significant difference in the incidence of MACE (5.9 vs. 4.9%; hazard ratio, 1.23; 95% confidence interval (CI), 0.61-2.49; P = 0.569), death (1.8 vs. 1.7%; hazard ratio, 1.09; 95% CI, 0.33-3.64; P = 0.882), MI (2.3 vs. 2.1%; hazard ratio, 1.05; 95% CI, 0.36-3.08; P = 0.927), TVR (2.3 vs. 1.3%; hazard ratio, 1.70; 95% CI, 0.47-6.20; P = 0.418), TLR (1.4 vs. 0.4%; hazard ratio, 3.06; 95% CI, 0.37-25.40; P = 0.301), and definite stent thrombosis (0.5 vs. 0.4%; hazard ratio, 1.09; 95% CI, 0.10-12.10; P = 0.942) was observed between RP-DES and DP-DES patients at 1-year follow-up. These results were confirmed in a propensity score-matched cohort (n = 134 per group)., Conclusion: In our registry including a real-world population of all-comer patients undergoing PCI, RP-DES, or durable polymer-DES showed similar efficacy and safety at a 1-year follow-up., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background Women represent an increasing percentage of interventional cardiologists in Italy compared with other countries. However, gaps exist in understanding and adapting to the impact of these changing demographics. Methods and Results We performed a national survey to analyze demographics, gender-based professional difference, needs in terms of catheterization laboratory (Cath-Lab) abstention, and radiation safety issues in Italian Cath-Lab settings. A survey supported by the Italian Society of Interventional Cardiology (Società Italiana di Cardiologia Interventistica-Gruppo Italiano di Studi Emodinamici SICI-GISE) was mailed to all SICI-GISE members. Categorical data were compared using the χ 2 test. P <0.05 was considered significant. There were 326 respondents: 20.2% were <35 years old, and 64.4% had >10 years of Cath-Lab experience. Notably, 26.4% were women. Workload was not gender-influenced (women performed "on-call" duty 69.8% versus men 68.3%; P =0.97). Women were more frequently unmarried (22.1% women versus 8.7% men; P =0.002) and childless (43.9% versus 56.1%; P <0.001). Interestingly, 69.8% of women versus 44.6% of men ( P <0.001) argued that pregnancy/breastfeeding negatively impacts professional skill development and career advancement. For Cath-Lab abstention, 38.9% and 69.6% of respondents considered it useful to perform percutaneous coronary intervention robotic simulations and "refresh-skill" sessions while they were absent or on return to work, respectively, without gender differences. Overall, 80% of respondents described current radioprotection counseling efforts as inadequate and not gender specific. Finally, 26.7% faced some type of job discrimination, a significantly higher proportion of whom were women. Conclusions Several gender-based differences exist or are perceived to exist among interventional cardiologists in Italian Cath-Labs. Joint strategies addressing Cath-Lab abstention and radiation exposure education should be developed to promote gender equity in interventional cardiologists.

Diabetes mellitus (DM) is an independent predictor of adverse outcomes in patients with coronary artery disease (CAD). We investigated the interaction between DM and high platelet reactivity (HPR) in determining long-term clinical outcomes after percutaneous coronary intervention (PCI). We enrolled 500 patients who were divided based on the presence of DM and HPR. Primary endpoint was the occurrence of major adverse clinical events (MACE) at 5 years. Patients with both DM and HPR showed the highest estimates of MACE (37.9%, log-rank p < 0.001), all-cause death (15.5%, log-rank p = 0.022), and non-fatal myocardial infarction (25.9%, log-rank p < 0.001). At Cox proportional hazard analysis, the coexistence of DM and HPR was an independent predictor of MACE (HR 3.46, 95% CI 1.67-6.06, p < 0.001). Among patients with stable CAD undergoing elective PCI and treated with aspirin and clopidogrel, the combination of DM and HPR identifies a cohort of patients with the highest risk of MACE at 5 years.

Background: The management of antithrombotic therapy in patients undergoing percutaneous coronary intervention (PCI) with an indication for long-term oral anticoagulant therapy (OAT) is still a matter of debate. We aim to evaluate the safety and the efficacy of dual therapy (DT) compared to triple therapy (TT) in this clinical setting., Methods: A study level meta-analysis and a review of randomized trials selected using PubMed, Embase, EBSCO, Cochrane database of systematic reviews, Web of Science, and abstract from major cardiology congresses. Six randomized trials with 12,156 patients evaluating the strategy of DT vs. TT in patients treated with PCI with indication for long-term OAT were included., Results: Patients treated with DT demonstrated a 45% relative reduction in the risk of TIMI major bleeding (1.71% vs. 2.99%; OR 0.55, 95% CI 0.41-0.71; P<0.0001) and TIMI minor bleeding compared to TT arm (4.67% vs 7.83%, OR 0.55 95% CI 0.39-0.78, P = 0.0007). All-cause mortality was similar in two arms (3.95% vs 3.77%, P = 0.92), as well as cardiovascular mortality (2.21% vs 2.19%, P = 0.97). DT was associated with a borderline increase of ST (1.02% vs 0.67%, P = 0.07). No significant differences were observed in occurrence of MI and stroke., Conclusions: Our findings suggest that DT is safer than TT with regard to occurrence of major bleeding. DT with a direct oral anticoagulant plus clopidogrel at discharge could be effective in most patients, maintaining aspirin in periprocedural phase and as longer "tailored" treatment for patients at higher ischemic risk., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Diabetes mellitus is an important risk factor for a first cardiovascular event and for worse outcomes after a cardiovascular event has occurred. This situation might be caused, at least in part, by the prothrombotic status observed in patients with diabetes. Therefore, contemporary antithrombotic strategies, including more potent agents or drug combinations, might provide greater clinical benefit in patients with diabetes than in those without diabetes. In this Consensus Statement, our Working Group explores the mechanisms of platelet and coagulation activity, the current debate on antiplatelet therapy in primary cardiovascular disease prevention, and the benefit of various antithrombotic approaches in secondary prevention of cardiovascular disease in patients with diabetes. While acknowledging that current data are often derived from underpowered, observational studies or subgroup analyses of larger trials, we propose antithrombotic strategies for patients with diabetes in various cardiovascular settings (primary prevention, stable coronary artery disease, acute coronary syndromes, ischaemic stroke and transient ischaemic attack, peripheral artery disease, atrial fibrillation, and venous thromboembolism). Finally, we summarize the improvements in cardiovascular outcomes observed with the latest glucose-lowering drugs, and on the basis of the available evidence, we expand and integrate current guideline recommendations on antithrombotic strategies in patients with diabetes for both primary and secondary prevention of cardiovascular disease.

The prognostic role of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with stable coronary artery disease (CAD) is still unclear. We enrolled 500 patients undergoing elective percutaneous coronary intervention (PCI). Blood samples were drawn prior to PCI for NLR and PLR calculation. Major adverse clinical events (MACE), which included death, myocardial infarction (MI), and target vessel revascularization (TVR), were recorded up to 5 years. Patients in the higher tertile of NLR presented higher Kaplan-Meier estimates of MACE (26.0% vs. 16.9% in tertile 2 vs. 14.3% in tertile 1; p = 0.042) and death (12.0% vs 6.9% in tertile 2 vs. 4.6% in tertile 1; p = 0.040), whereas there were no significant differences in the estimates of MI and TVR. NLR in the higher tertile was an independent predictor of MACE (HR 1.65, 95% CI 1.07-2.55, p = 0.024). No significant difference was observed across tertiles of PLR. Unlike PLR, elevated pre-procedural NLR is associated with an increased risk of 5-year clinical adverse events.

The hybrid strategy allows for a complete myocardial revascularization in patients with multivessel coronary artery disease and a high frailty index. These patients, due to their old age and multi-comorbidities, are evaluated with inadequate tools for their clinical complexity and destined to an incomplete revascularization for increased surgical or procedural risk. Hybrid revascularization enables to use the best techniques resulting from the surgical and percutaneous approach defining a tailored strategy for the patient. In the frail patient, this strategy is associated with favorable outcomes and a lower exposure to periprocedural complications.

Diabetes mellitus represents a major risk factor for the development of coronary artery disease and other vascular complications. Glycated haemoglobin, fructosamine, and fasting blood glucose levels are partial parameters to exhaustively describe patient dysglycemic status. Thus, recently the new concept of glycemic variability has emerged, including information about two major aspects: the magnitude of blood glucose excursions (from nadir to peak, thus lower and higher spikes) and the time intervals in which these fluctuations occur. Despite the lack of consensus regarding the most appropriate definition and tools for its assessment, glycemic variability seems to have more deleterious effects than sustained hyperglycemia in the pathogenesis of diabetic cardiovascular complications. This manuscript aimed to review the most recent evidence on glycemic variability and its potential use in everyday clinical practice to identify diabetic patients at higher risk of cardiovascular complications and thus needing stricter monitoring and treatment., (© 2018 John Wiley & Sons, Ltd.)

Atherosclerotic cardiovascular (CV) disease represents one of leading cause of mortality and morbidity in Western countries. An increased risk of CV events was identified in patients with peripheral arterial diseases (PADs), which include all arterial diseases, other than coronary arteries and the aorta. In particular, lower extremity artery disease (LEAD) and/or carotid artery disease present growing incidence in general population and a consequent increase in mortality and morbidity. Medical treatment, including antiplatelet therapy, is a cornerstone in management of these patients, even when they are treated with endovascular or surgical procedures. Despite their clinical relevance, data on optimal antiplatelet treatment in this clinical setting are lacking and often derived from clinical trials on coronary artery disease and by subgroups analysis. The purpose of this review is to examine the available data from registries, randomized trials and meta-analysis on antiplatelet treatment in patients with LEAD and carotid stenosis with the aim to provide evidence to support clinical decision making., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Chronic renal failure (CRF) impairs prognosis in patients with acute coronary syndromes (ACS); the differential impact of CRF on ischemic and bleeding events in the setting of ACS is unclear. We explored the predictive role of CRF, identified by different equations for the glomerular filtration rate estimation, on the occurrence of the composite end point, including both ischemic cardiovascular and major bleeding (major adverse cardiovascular and bleeding events [MACBE]) at 1 year, and its components. We accessed each patients data from 718 participants in the prospective, multicenter, and START ANTIPLATELET registry, performed on patients with ACS. The ability to predict the risk of MACBE was modest and similar for Cockcroft-Gault, MDRD, and CKD-EPI equations (area under the curves: 0.55, 95% confidence interval [CI] 0.47 to 0.63; 0.53, 95% CI 0.45 to 0.61; 0.54, 95% CI 0.46 to 0.62; respectively, overall p = 0.63). The incidence of MACBE in patients with CRF was 12.6 versus 7.4 per 100 patients/year in those with preserved renal function (adjusted odds ratio [OR] 1.80, 1.02 to 3.20, p = 0.045); the absolute excess in events rate due to CRF was higher for ischemic events (3.5%) than for major bleeding (2.6%). The increased occurrence of MACBE was even greater in patients with CRF and concomitant anemia (OR 2.16) and in patients with severe CRF (OR 2.78). In conclusion, our study indicates that, in patients with ACS, CRF impairs the clinical outcome at 1 year, especially when severe and when is concomitant with anemia. CRF is associated with greater absolute increase of ischemic events than major bleeding., (Copyright © 2018. Published by Elsevier Inc.)

No comprehensive data are available on the role of platelet indexes (PI) in the periprocedural risk stratification of patients who underwent percutaneous coronary intervention (PCI). The aim of this study was to investigate the relation of PI to platelet reactivity (PR) and periprocedural myocardial infarction (PMI) in patients receiving PCI. A total of 502 PCI patients had preprocedural measurement of PI and PR, the latter assessed by VerifyNow P2Y12 assay. Study end points were incidence of PMI and high platelet reactivity (HPR) according to tertiles of PI and evaluation of PI in HPR patients. Incidence of PMI in the overall population was 6.6%. Rates of PMI were not different in PI tertiles: platelet count (I: 6.0%, II: 7.1%, III: 6.5%; p = 0.74), mean platelet volume (MPV, I: 6.6%, II: 7.3%, III: 5.8%;p = 0.86), platelet distribution width (I: 7.2%, II: 7.2%, III: 5.8%;p = 0.74), and MPV/P ratio (I: 6.6%, II: 6.0%, III: 7.1%; p = 0.91). The occurrence of PMI was significantly different in PR tertiles (I: 3%, II: 5.4%, III: 11.4%; p = 0.006). Platelet count and MPV/P ratio were significantly different in patients with and without HPR (221.8 ± 58.6 × 103/µL vs207 ± 59.4 × 103/µL, p = 0.008; 51.73 ± 15.17 vs 56.7 ± 18.3, p = 0.002).In conclusion, this study showed no relation between PI and PMI in PCI patients but confirms the association of HPR with increased incidence of PMI; thus, PI seem to be not able to identify patients at higher periprocedural risk, but monitoring PR by a bedside assay remains a useful tool for risk stratification., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We investigated the impact of suboptimal platelet reactivity on clinical outcomes after percutaneous coronary intervention (PCI). We enrolled 500 patients with stable coronary artery disease undergoing elective PCI. Platelet reactivity was measured before PCI using the VerifyNow P2Y12 assay. Primary endpoint was the incidence of ischemic or bleeding events at 1 month and 5 years. Patients with high platelet reactivity (HPR) showed significantly higher rates of ischemic events both during the 1st month after PCI (HR 2.06, 95% CI 1.02-4.06), and beyond 1 month compared with patients without HPR (HR 1.73, 95% CI 1.02-2.95). Conversely, compared with patients without low platelet reactivity (LPR), patients with LPR presented significantly higher rates of bleeding only during the 1st month (HR 3.67, 95% CI 1.68-8.02). In conclusion, pre-procedural HPR is associated with ischemic events even beyond the 1st month after PCI. The association of LPR with bleeding events seems to be confined to the periprocedural period.

There are limited real-world data on prevalence and predictors of dual antiplatelet therapy (DAPT) prolongation beyond one year after acute coronary syndrome (ACS). We have explored such issue in the START ANTIPLATELET Registry, which is a prospective, observational, multicenter, Italian registry performed in seven Italian cardiology institutions including patients admitted for ACS and followed up to one year. Out of a total population of 840 ACS patients, 596 patients had completed 12-month follow-up being on DAPT. Decision to prolong DAPT beyond one year was taken in 79 patients (13%), whereas in 517 patients DAPT was stopped. The strongest predictors of DAPT continuation were a new cardiovascular events after the index admission event (OR 3.3, 95% CI 1.4-7.7), no bleeding complications (OR 3.2, 95% CI 1.2-8.3) and no anemia during one-year follow-up (OR 2.6, 95% CI 1.1-5.9); other independent predictors were renal failure (OR 2.5, 95% CI 1.3-5.0) and peripheral artery disease (OR 1.8, 95% CI 1.1-3.0). The choice of DAPT prolongation was not correlated with younger ager, presence of diabetes mellitus, coronary angioplasty as initial treatment strategy or type of implanted stent (drug-eluting vs bare metal). In conclusion, this study provides a real-world snapshot on the factors influencing the option to continue DAPT beyond one year after ACS; a low bleeding risk seems to influence the choice to prolong DAPT more than a high ischemic risk.

The left atrial appendage (LAA) is the main source of thromboembolism in patients with non-valvular atrial fibrillation (AF). As such, the LAA can be the target of specific occluding device therapies. Optimal management of patients with AF includes a comprehensive knowledge of the many aspects related to LAA structure and thrombosis. Here we provide baseline notions on the anatomy and function of the LAA, and then focus on current imaging tools for the identification of anatomical varieties. We also describe pathogenetic mechanisms of LAA thrombosis in AF patients, and examine the available evidence on treatment strategies for LAA thrombosis, including the use of non-vitamin K antagonist oral anticoagulants and interventional approaches., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Background: Diabetes is a known risk predictor for thromboembolic events in patients with atrial fibrillation (AF), but no study has explored the prognostic weight of insulin in this setting., Objectives: This study evaluated the differential role of insulin versus no insulin therapy on thromboembolic risk in patients with diabetes and AF., Methods: We accessed individual patient data from the prospective, real-world, multicenter, PREFER in AF (European Prevention of thromboembolic events-European Registry in Atrial Fibrillation). We compared the rates of stroke/systemic embolism at 1 year according to diabetes status (no diabetes, diabetes without insulin therapy, diabetes on insulin therapy)., Results: In an overall population of 5,717 patients, 1,288 had diabetes, 22.4% of whom were on insulin. For patients with diabetes who were on insulin, there was a significantly increased risk of stroke/systemic embolism at 1 year versus either no diabetes (5.2% vs. 1.9%; hazard ratio: 2.89; 95% confidence interval: 1.67 to 5.02; p = 0.0002) or diabetes without insulin treatment (5.2% vs. 1.8%; hazard ratio: 2.96; 95% confidence interval: 1.49 to 5.87; p = 0.0019). Notably, rates of stroke/embolism were similar in patients with diabetes not receiving insulin versus patients without diabetes (hazard ratio: 0.97; 95% confidence interval: 0.58 to 1.61; p = 0.90). The selective predictive role of insulin-requiring diabetes was independent of potential confounders, including diabetes duration, and was maintained in various subpopulations, including the subgroup receiving anticoagulant therapy., Conclusions: In this cohort of anticoagulated patients with AF, the sole presence of diabetes not requiring insulin did not imply an increased thromboembolic risk. Conversely, insulin-requiring diabetes contributed most, if not exclusively, to the overall increase of thromboembolic risk in AF., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Data from experimental studies suggest that the f current-inhibitor ivabradine may reduce oxidative stress and improve endothelial function. We aimed to evaluate the effect of ivabradine on endothelial function in patients with coronary artery disease (CAD) after complete revascularization with percutaneous coronary angioplasty (PCI)., Methods and Results: At least 30 days after PCI, 70 patients were randomized (T0) to receive ivabradine 5 mg twice daily (ivabradine group, n = 36) or to continue with standard medical therapy (control group, n = 34). After 4 weeks (T1), ivabradine dose was adjusted up to 7.5 mg twice daily in patients with heart rate (HR) at rest >60 bpm, and thereafter continued for additional 4 weeks (T2). At all timings, brachial artery reactivity was assessed by flow-mediated dilatation (FMD) and nitroglycerin-mediated dilatation (NMD). No significant differences were observed at T0 between ivabradine and control groups in terms of HR (68.0 ± 6.4 vs. 67.6 ± 6.4 bpm; p = 0.803), FMD (8.7 ± 4.9 vs. 8.0 ± 5.5 %; p = 0.577) and NMD (12.7 ± 6.7 vs. 13.3 ± 6.2 %; p = 0.715). Over the study period, a significant reduction of HR (65.2 ± 5.9 bpm at T1, 62.2 ± 5.7 bpm at T2; p < 0.001), and improvement of FMD (12.2 ± 6.2 % at T1, 15.0 ± 7.7 % at T2; p < 0.001) and NMD (16.6 ± 10.4 % at T1, 17.7 ± 10.8 at T2; p < 0.001) were observed in the ivabradine group, while no significant changes were observed in the control group. In the ivabradine group, a moderate negative correlation was observed between the HR variation and FMD variation from T1 to T3 (r = -0.448; p = 0.006)., Conclusions: In patients with CAD undergoing complete revascularization with PCI, addition of ivabradine to the standard medical therapy produces a significant improvement in endothelial function. This effect seems to be related to HR reduction. ClinicalTrials.gov number, NCT02681978.

Neutrophil to lymphocyte ratio (NLR) has been proposed as a marker of cardiovascular risk. The potential relation between NLR and periprocedural myocardial damage after percutaneous coronary intervention (PCI) is unclear. We enrolled 502 consecutive patients with stable coronary artery disease undergoing elective PCI. Blood samples were drawn in all patients at baseline, 6 hours, and 24 hours after PCI for complete blood cell count and cardiac biomarkers (creatine kinase-MB and troponin T [Tn-T]) assessment. NLR was calculated as the ratio between the absolute number of neutrophil over the absolute number of lymphocyte. Periprocedural myocardial infarction (PMI) was defined according to the 2012 universal definition of myocardial infarction. In the overall population, a significant postprocedural increase in NLR was observed (3.255 [2.763 to 3.995] at baseline, 4.430 [3.390 to 6.020] at 6 hours, 4.720 [3.940 to 5.750] at 24 hours, p <0.0001). PMI occurred in 33 patients (6.6%). Baseline NLR was similar in patients with and without PMI (3.250 [2.820 to 3.885] vs 3.260 [2.750 to 4.000], p = 0.898); however, patients who developed PMI showed significantly higher NLR both at 6 hours (5.750 [4.360 to 9.095] vs 4.370 [3.370 to 5.950], p <0.001) and 24 hours (5.180 [4.440 to 8.065] vs 4.670 [3.920 to 5.710], p = 0.003). Among patients who developed PMI, periprocedural NLR increase showed a moderate positive correlation with both creatine kinase-MB (rho = 0.377, p = 0.031) and troponin T increase (rho = 0.506, p = 0.003). In conclusion, preprocedural NLR values do not impact on the occurrence of PMI during elective PCI; however, PCI procedures induce a significant increase in NLR that seems to be proportional to the magnitude of periprocedural myocardial damage., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: There is poor evidence on clinical outcome of switching from clopidogrel to prasugrel in patients undergoing percutaneous coronary intervention., Objectives: Data on the topic are limited and we performed a study-level meta-analysis to assess safety and efficacy of such strategy., Methods: A total of 15 studies and 3974 patients were included. The following comparisons were performed: prasugrel switching versus prasugrel only therapy; and prasugrel switching versus clopidogrel only therapy. Outcome measures were overall bleeding, major bleeding, and major adverse cardiac events (MACE)., Results: There was no statistically significant increased bleeding risk in the prasugrel switching versus prasugrel only group [overall bleeding: OR 1.07, 95% confidence interval (CI), 0.69-1.66; P = 0.77; major bleeding: OR 0.69, 95% CI, 0.32-1.49; P = 0.34]; MACE rates were also comparable. Incidence of safety end points was similar in the prasugrel switching and clopidogrel only groups (overall bleeding: OR 1.27, 95% CI, 0.75-2.15; P = 0.37; major bleeding: OR 0.70, 95% CI, 0.29-1.68; P = 0.42); occurrence of MACE was 3.8% in the prasugrel switching versus 8.3% in the clopidogrel only group (P = 0.23). No statistically significant difference in the safety outcomes was present stratifying by clinical presentation., Conclusions: Switching from clopidogrel to prasugrel does not increase bleeding complications during follow-up of patients undergoing percutaneous coronary intervention; however, the strength of the data is not sufficient to make definitive clinical recommendations.

Endothelial progenitor cells (EPCs) may concur to endogenous vascular repair. Previous studies have reported that statin treatment increases EPC levels. We investigated whether this occurs in patients on long-term statin treatment who underwent percutaneous coronary interventions (PCIs). In a phase A study, 53 patients (atorvastatin reload [AR] 80 mg 12 hours before + 40 mg 2 hours before PCI, n = 27; placebo [P], n = 26) were evaluated for EPC mobilization as CD45dim/CD34+/CD133+/KDR+ cell number by flow cytometry. Assays were run at randomization (12 hours before PCI, R), immediately before PCI (T0) at 8 (T8) and 24 hours (T24). In phase B study, 50 patients (AR, n = 25; P, n = 25) were evaluated for early colony formation by Hill colony forming unit (CFU) assay, with sampling at randomization and 24 hours later. In phase A, EPCs levels were similar at randomization between 2 arms (0.23% [0.14 to 0.54] of total events in AR vs 0.22% [0.04 to 0.37] in P group; p = 0.33). At PCI, EPC levels were higher in AR arm (0.42% [0.06 to 0.30] vs 0.19% [0.06 to 030]; p = 0.009). Higher EPC levels in AR group were also found at 8 and 24 hours. In phase B, EPC CFUs/well numbers at randomization were similar in the 2 arms (8 [6 to 12] in AR vs 12 [6 to 20] in P group, p = 0.109). EPC CFU/well at 24 hours became significantly higher in AR arm (17 [10 to 23] vs 5 [2 to 13], p = 0.002). In conclusion, high-dose AR before PCI in patients on long-term statin therapy promptly increases EPCs mobilization, which are capable of early colony formation and may contribute to cardioprotection., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Limited data are available on long-term efficacy and safety of drug-eluting stents (DES) in elderly patients who underwent PCI. A total of 635 consecutive patients aged ≥75 years who underwent PCI were enrolled at 2 European centers. Of these, 170 patients received at least 1 DES, whereas 465 patients received bare metal stent (BMS) only. Primary end point was the incidence of net adverse clinical events (NACE), defined as the occurrence of ischemic events or bleeding events, and was compared at a median follow-up of 31.2 months. Clinical follow-up information was available in 593 patients (93.4%). The duration of dual antiplatelet therapy was 12.3±5.1 months in the DES group and 3.8±7.4 months in the BMS group. The Kaplan-Meier estimate of NACE at 5 years was significantly lower in DES-treated patients (40.5%) than in BMS-treated patients (55.7%; p=0.009). This benefit was driven by a significant reduction in myocardial infarction (8.6% vs 16.6%; p=0.038) and target vessel revascularization rates (7.9% vs 21.9%; p=0.003) in the DES group, with no significant increase in the incidence of bleeding events (13.8% vs 12.2%; p=0.882). These results were confirmed at propensity score-adjusted Cox proportional hazard analysis. In conclusion, in patients≥75 years, the use of DES compared with BMS seems to reduce myocardial infarction and repeat revascularization rates at long-term follow-up, without an increase in bleeding despite longer duration of dual antiplatelet therapy. This net clinical benefit, resulting from persistent efficacy and safety over time, may support the use of DES as a reasonable option in patients≥75 years., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Growing evidence suggests that platelet reactivity (PR) may predict bleeding. We investigate the incremental value of PR in predicting bleeding after percutaneous coronary intervention (PCI) via the femoral approach over a validated bleeding risk score (BRS) of clinical and procedural variables., Methods and Results: A total of 800 patients undergoing elective PCI via the femoral approach were included. PR was measured before PCI with the VerifyNow P2Y12 assay and low PR was defined as a P2Y12 reaction unit value ≤ 178. Calculation of the BRS included the following: age, sex, intra-aortic balloon pump, glycoprotein IIb/IIIa inhibitors, chronic kidney disease, anemia, and low-molecular-weight heparin within 48-hour pre-PCI. A new risk score including low PR (BRS-PR) was developed and validated in an independent cohort of patients (n = 310). Bleeding events at 30 days after PCI were defined according to the thrombolysis in myocardial infarction, Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2, and Bleeding Academic Research Consortium criteria. Both BRS and PR showed high discriminatory power for bleeding (area under the curve [AUC] > 0.7 for all definitions). Discriminatory power of BRS-PR (AUC = 0.809 for thrombolysis in myocardial infarction bleeding; AUC = 0.814 for Bleeding Academic Research Consortium class ≥ 2 bleeding; AUC = 0.708 for Bleeding Academic Research Consortium class ≥ 3 bleeding; and AUC = 0.813 for REPLACE-2 bleeding) was significantly higher than that of BRS alone (P < 0.001 for all bleeding definitions). In the validation set, BRS-PR showed higher discriminatory power for thrombolysis in myocardial infarction bleeding than BRS alone (AUC = 0.788 versus 0.709; P = 0.036)., Conclusions: PR has incremental predictive value on bleeding events after elective PCI via the femoral approach over a validated risk score of clinical and procedural variables. A risk score including PR yields significantly better prognostic performance compared with the original BRS., (© 2015 American Heart Association, Inc.)

Despite dual antiplatelet treatment with aspirin and clopidogrel, patients with acute coronary syndromes (ACSs) remain at risk for recurrent cardiovascular events. This may be due, at least in part, to an incomplete response to clopidogrel, which is more frequent in ACS patients compared to stable patients because of massive platelet activation and increased platelet turnover. Currently, numerous laboratory-based methods and point-of-care tests are available to assess platelet reactivity. Several studies have tried to establish a standardized definition of high on-treatment platelet reactivity and to evaluate a correlation between this aggregometric phenomenon and clinical outcomes. Indeed a strong relationship between high on-treatment platelet reactivity and ischemic events was found, especially in high-risk ACS patients undergoing percutaneous coronary revascularization. Therefore, evaluation of platelet reactivity in this subset of patients may guide physicians to choose the best antiplatelet regimen for the individual patient avoiding both ischemic and bleeding complications. This was the rationale for tailored antiplatelet therapy pursued by utilization of different clopidogrel regimens, more potent P2Y12 receptor antagonists, or more extensive administration of glycoprotein IIb/IIIa inhibitors. To date, data from randomized studies addressing the concept of tailored antiplatelet therapy did not show any clinical benefit from a strategy based on platelet reactivity monitoring. However, as predominantly elective and stable patients were included into the latter studies, these results cannot be completely transferred into an ACS setting. This review summarizes current evidence about the potential role of platelet reactivity in the therapeutic management of patients with ACS.