Complex percutaneous transcatheter closure of incomplete surgical ligation of the left atrial appendage: a case report.

Background: Incomplete surgical left atrial appendage (LAA) closure, in the form of incompletely surgically ligated LAA (ISLL), increases thrombo-embolic risk in patients with atrial fibrillation (AF). Although its management is not standardized, the percutaneous closure of ISLL could be an alternative in patients with contraindication for anticoagulants. We present the case of a percutaneous transcatheter LAA device implantation in a patient with AF and ISLL, complicated by severe anaemia. Case summary: A 83-year-old woman, with permanent AF and a history of previous surgical LAA ligation, was referred to our hospital for fatigue and worsening dyspnoea. Laboratory tests showed severe microcytic anaemia, with a haemoglobin level of 4.9 g/dL (normal reference: 13.8-18.0 g/dL). Oesophagogastroduodenoscopy and colonoscopy excluded signs of either recent or ongoing haemorrhage. After achieving clinical improvement by haemotransfusions, we performed a transoesophageal echocardiography that showed an ISLL with a narrow neck of 5 mm. Since the patient had high thrombo-embolic and haemorrhagic risk (CHA2DS2-VASc risk score of 4 and a HAS-BLED score of 4), we decided to discontinue anticoagulant therapy and perform elective percutaneous transcatheter LAA occlusion (LAAO) with an Amplatzer Amulet device. Patient was discharged in good clinical status. After three months, the stability of haemoglobin level and the absence of device thrombosis allowed the discontinuation of antithrombotic therapy. Discussion: We described the first experience of percutaneous ISLL closure with Amulet device (Abbott Vascular, Santa Clara, CA, USA), a commercially available device for LAAO. The procedure was feasible and safe, without long-term complications.

Coronary calcification in patients presenting with acute coronary syndromes: insights from the MATRIX trial.

AIMS: The role of coronary calcification on clinical outcomes among different revascularization strategies in patients presenting with acute coronary syndromes (ACSs) has been rarely investigated. The aim of this investigation is to evaluate the role of coronary calcification, detected by coronary angiography, in the whole spectrum of patients presenting with acute ACS. METHODS AND RESULTS: The present study was a post hoc analysis of the MATRIX programme. The primary endpoint was major adverse cardiovascular events (MACE), defined as the composite of all-cause mortality, myocardial infarction (MI), or stroke up to 365 days. Among the 8404 patients randomized in the MATRIX trial, data about coronary calcification were available in 7446 (88.6%) and therefore were included in this post hoc analysis. Overall, 875 patients (11.7%) presented with severe coronary calcification, while 6571 patients (88.3%) did not present severe coronary calcification on coronary angiography. Fewer patients with severe coronary calcification underwent percutaneous coronary intervention whereas coronary artery bypass grafting or medical therapy-only was more frequent compared with patients without severe calcification. At 1-year follow-up, MACE occurred in 237 (27.1%) patients with severe calcified coronary lesions and 985 (15%) patients without severe coronary calcified lesions [hazard ratio (HR) 1.91; 95% confidence interval (CI) 1.66-2.20, P < 0.001]. All-cause mortality was 8.6% in patients presenting with and 3.7% in those without severe coronary calcification (HR 2.38, 1.84-3.09, P < 0.001). Patients with severe coronary calcification incurred higher rate of MI (20.1% vs. 11.5%, HR 1.81; 95% CI 1.53-2.1, P < 0.001) and similar rate of stroke (0.8% vs. 0.6%, HR 1.35; 95% CI 0.61-3.02, P = 0.46). CONCLUSION: Patients with ACS and severe coronary calcification, as compared to those without, are associated with worse clinical outcomes irrespective of the management strategy.

Clinical Performance of the Gore Septal Occluder in Patent Foramen Ovale Closure in Different Septal Anatomies: 1-Year Results from a Single-Center Experience.

BACKGROUND: PFO (Patent foramen ovale) is a common defect that affects about 25% of the population. Although its presence is asymptomatic in the majority of the cases, the remaining part becomes overt with different symptoms, including cryptogenic stroke. PFO closure is currently a widely available procedure in complex anatomy, with Amplatzer PFO Occluder (APO) being the most commonly used tool. However, the performance of another device, the GORE Septal Occluder (GSO), has not been completely explored with regard to different septal anatomies. METHODS: From March 2012 to June 2020, 118 consecutive patients with an indication of PFO closure were treated using the GSO system, included in a prospective analysis, and followed. After 12 months, every patient underwent transcranial Doppler ultrasound to evaluate the effectiveness of treatment. RESULTS: Of 111 patients evaluated, 107 showed effective PFO closure (96.4%), and 4 showed a residual shunt (3.6%). To better evaluate the device performance, the overall population was sorted into two clusters based on the echocardiographic characteristics. The main difference between groups was for PFO width (4.85 ± 1.8 vs. 2.9 ± 1 mm, p < 0.001) and PFO tunnel length (12.6 ± 3.8 vs. 7.2 ± 2, p < 0.001), allowing complex and simple anatomies to be identified, respectively. Regardless of the aforementioned cluster, the GSO performance required to reach an effective closure was independent of anatomy type and the chosen device size. CONCLUSION: The GSO device showed a high closure rate at 1-year follow-up in patients, with at least one anatomical factor of complexity of PFO irrespective of the level of complexity itself.

Validation of a Contemporary Acute Kidney Injury Risk Score in Patients With Acute Coronary Syndrome.

BACKGROUND: A simple, contemporary risk score for the prediction of contrast-associated acute kidney injury (CA-AKI) after percutaneous coronary intervention (PCI) was recently updated, although its external validation is lacking. OBJECTIVES: The aim of this study was to validate the updated CA-AKI risk score in a large cohort of acute coronary syndrome patients from the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of angioX) trial. METHODS: The risk score identifies 4 risk categories for CA-AKI. The primary endpoint was to appraise the receiver-operating characteristics of an 8-component and a 12-component CA-AKI model. Independent predictors of Kidney Disease Improving Global Outcomes-based acute kidney injury and the impact of CA-AKI on 1-year mortality and bleeding were also investigated. RESULTS: The MATRIX trial included 8,201 patients with complete creatinine values and no end-stage renal disease. CA-AKI occurred in 5.5% of the patients, with a stepwise increase of CA-AKI rates from the lowest to the highest of the 4 risk categories. The receiver-operating characteristic area under the curve was 0.67 (95% CI: 0.64-0.70) with model 1 and 0.71 (95% CI: 0.68-0.74) with model 2. CA-AKI risk was systematically overestimated with both models (Hosmer-Lemeshow goodness-of-fit test: P < 0.05). The 1-year risks of all-cause mortality and bleeding were higher in CA-AKI patients (HR: 7.03 [95% CI: 5.47-9.05] and HR: 3.20 [95% CI: 2.56-3.99]; respectively). There was a gradual risk increase for mortality and bleeding as a function of the CA-AKI risk category for both models. CONCLUSIONS: The updated CA-AKI risk score identifies patients at incremental risks of acute kidney injury, bleeding, and mortality. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of angioX [MATRIX]; NCT01433627).

Long-term outcomes of patients treated with sirolimus-eluting resorbable magnesium scaffolds: Insights from the SHERPA-MAGIC study.

BACKGROUND: The resorbable magnesium scaffold (RMS) is a second-generation bioresorbable scaffold (BRS) that has shown conflicting results in previous studies. These findings suggest that patient selection and implantation technique may have an impact on clinical outcomes. This study aimed to investigate the safety and long-term effectiveness of RMS in a narrowly selected population. METHODS: SHERPA-MAGIC is an investigator-driven, multicenter, prospective, single-arm study that enrolled patients undergoing BRS coronary implantation in 18 Italian centers. The present analysis considered the first 543 enrolled patients treated with RMS, with a minimum follow-up of 1 year. The study protocol included strict criteria for patient selection and standardization of RMS implantation. The primary outcome was the occurrence of the vessel-oriented composite endpoints (VOCE), including cardiac death, target vessel myocardial infarction, and ischemia-driven target vessel revascularization. RESULTS: Overall, 635 vessels were treated. The 1-year cumulative occurrence of VOCE was 22 (3.5%, 95% CI 2.2%-5.2%), which was significantly lower than the prespecified estimation (from 5.5% to 8.5%). At the median follow-up of 3.5 [2.6-4.3] years, there were 3 (0.5%) cardiac deaths, 12 (1.9%) target vessel myocardial infarctions, and 33 (5.2%) ischemia-driven target vessel revascularizations. A total of 37 (5.8%, 95%CI 4.1%-7.9%) VOCEs were detected. Scaffold thrombosis occurred in 4 (0.6%, 95%CI 0.1%-1.6%) cases. Patient-level analysis confirmed the findings of the vessel-level analysis. CONCLUSIONS: These results confirm the safety and performance of RMS technology. If confirmed in randomized controlled trials, they may rekindle interest in the use of scaffolds in daily practice.

Transient vs In-Hospital Persistent Acute Kidney Injury in Patients With Acute Coronary Syndrome.

BACKGROUND: The occurrence of acute kidney injury (AKI) among patients with acute coronary syndrome (ACS) undergoing invasive management is associated with worse outcomes. However, the prognostic implications of transient or in-hospital persistent AKI may differ. OBJECTIVES: The aim of this study was to evaluate the prognostic implications of transient or in-hospital persistent AKI in patients with ACS. METHODS: In the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial, 203 subjects were excluded because of incomplete information or end-stage renal disease, with a study population of 8,201 patients. Transient and persistent AKI were defined as renal dysfunction no longer or still fulfilling the AKI criteria (>0.5 mg/dL or a relative >25% increase in creatinine) at discharge, respectively. Thirty-day coprimary outcomes were the out-of-hospital composite of death, myocardial infarction, or stroke (major adverse cardiovascular events [MACE]) and net adverse cardiovascular events (NACE), defined as the composite of MACE or Bleeding Academic Research Consortium type 3 or 5 bleeding. RESULTS: Persistent and transient AKI occurred in 750 (9.1%) and 587 (7.2%) subjects, respectively. After multivariable adjustment, compared with patients without AKI, the risk for 30-day coprimary outcomes was higher in patients with persistent AKI (MACE: adjusted HR: 2.32; 95% CI: 1.48-3.64; P < 0.001; NACE: adjusted HR: 2.29; 95% CI: 1.48-3.52; P < 0.001), driven mainly by all-cause mortality (adjusted HR: 3.43; 95% CI: 2.03-5.82; P < 0.001), whereas transient AKI was not associated with higher rates of MACE or NACE. Results remained consistent when implementing the KDIGO (Kidney Disease Improving Global Outcomes) criteria. CONCLUSIONS: Among patients with ACS undergoing invasive management, in-hospital persistent but not transient AKI was associated with higher risk for 30-day MACE and NACE. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox [MATRIX]; NCT01433627).

Multimodality Imaging of Sudden Cardiac Death and Acute Complications in Acute Coronary Syndrome.

Sudden cardiac death (SCD) is a potentially fatal event usually caused by a cardiac arrhythmia, which is often the result of coronary artery disease (CAD). Up to 80% of patients suffering from SCD have concomitant CAD. Arrhythmic complications may occur in patients with acute coronary syndrome (ACS) before admission, during revascularization procedures, and in hospital intensive care monitoring. In addition, about 20% of patients who survive cardiac arrest develop a transmural myocardial infarction (MI). Prevention of ACS can be evaluated in selected patients using cardiac computed tomography angiography (CCTA), while diagnosis can be depicted using electrocardiography (ECG), and complications can be evaluated with cardiac magnetic resonance (CMR) and echocardiography. CCTA can evaluate plaque, burden of disease, stenosis, and adverse plaque characteristics, in patients with chest pain. ECG and echocardiography are the first-line tests for ACS and are affordable and useful for diagnosis. CMR can evaluate function and the presence of complications after ACS, such as development of ventricular thrombus and presence of myocardial tissue characterization abnormalities that can be the substrate of ventricular arrhythmias.

Impact of hemoglobin levels at admission on outcomes among elderly patients with acute coronary syndrome treated with low-dose Prasugrel or clopidogrel: A sub-study of the ELDERLY ACS 2 trial.

Hemoglobin (Hb) levels have emerged as a useful tool for risk stratification and the prediction of outcome after myocardial infarction. We aimed at evaluating the prognostic impact of this parameter among patients in advanced age, where the larger prevalence of anemia and the higher rate of comorbidities could directly impact on the cardiovascular risk. METHODS: All the patients in the ELDERLY-2 trial, were included in this analysis and stratified according to the values of hemoglobin at admission. The primary endpoint of this study was cardiovascular mortality within one year. The secondary endpoints were all-cause mortality, MI, Bleeding Academic Research Consortium (BARC) type 2-3 or 5 bleeding, any stroke, re-hospitalization for cardiovascular event or stent thrombosis (probable or definite) within 12 months after index admission. RESULTS: We included in our analysis 1364 patients, divided in quartiles of Hb values (<12.2; 12.2-13.39; 13.44-14.49; ≥ 4.5 g/dl). At a mean follow- up of 330.4 ± 99.9 days cardiovascular mortality was increased in patients with lower Hb (HR[95%CI] = 0.76 [0.59-0.97], p = 0.03). Results were no more significant after correction for baseline differences (adjusted HR[95%CI] = 1.22 [0.41-3.6], p = 0.16). Similar results were observed for overall mortality. At subgroup analysis, (according to Hb median values) a significant interaction was observed only with the type of antiplatelet therapy, but not with major high-risk subsets of patients. CONCLUSIONS: Among elderly patients with acute coronary syndrome managed invasively, lower hemoglobin at admission is associated with higher cardiovascular and all-cause mortality and major ischemic events, mainly explained by the higher risk profile.

Radial vs Femoral Access in ACS Patients Undergoing Complex PCI Is Associated With Consistent Bleeding Benefit and No Excess of Risks.

BACKGROUND: The comparative effectiveness of transradial (TRA) compared with transfemoral (TFA) access in acute coronary syndrome (ACS) patients undergoing complex percutaneous coronary intervention (PCI) remains unclear. METHODS: Among 8404 ACS patients in the Minimising Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX (MATRIX)-Access trial, 5233 underwent noncomplex (TRA: n = 2590; TFA: n = 2643) and 1491 complex (TRA: n = 777; TFA: n = 714) PCI. Co-primary outcomes were major adverse cardiovascular events (MACE, the composite of all-cause mortality, myocardial infarction, or stroke) and the composite of MACE and Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding (net adverse cardiovascular events [NACE]) at 30 days. RESULTS: Rates of 30-day MACE (HR 0.94, 95% CI 0.72-1.22) or NACE (HR 0.89, 95% CI 0.69-1.14) did not significantly differ between groups in the complex PCI group, whereas both primary end points were lower (HR 0.84, 95% CI 0.70-1.00; HR 0.83, 95% CI 0.70-0.98; respectively) with TRA among noncomplex PCI patients, with negative interaction testing (Pint = 0.473 and 0.666, respectively). Access-site BARC type 3 or 5 bleeding was lower with TRA, consistently among complex (HR 0.18, 95% CI 0.05-0.63) and noncomplex (HR 0.41, 95% CI 0.20-0.85) PCI patients, whereas the former group had a greater absolute risk reduction of 1.7% (number needed to treat: 59) owing to their higher absolute risk. CONCLUSIONS: Among ACS patients, PCI complexity did not affect the comparative efficacy and safety of TRA vs TFA, whereas the absolute risk reduction of access-site major bleeding was greater with TRA compared with TFA in complex as opposed to noncomplex PCI.

Association of statin pretreatment with presentation characteristics, infarct size and outcome in older patients with acute coronary syndrome: the Elderly ACS-2 trial.

BACKGROUND: prior statin treatment has been shown to have favourable effects on short- and long-term prognosis in patients with acute coronary syndrome (ACS). There are limited data in older patients. The aim of this study was to investigate the association of previous statin therapy and presentation characteristics, infarct size and clinical outcome in older patients, with or without atherosclerotic cardiovascular disease (ASCVD), included in the Elderly-ACS 2 trial. METHODS: data on statin use pre-admission were available for 1,192 of the 1,443 patients enrolled in the original trial. Of these, 531 (44.5%) were already taking statins. Patients were stratified based on established ASCVD and statin therapy. ACS was classified as non-ST elevation or ST elevation myocardial infarction (STEMI). Infarct size was measured by peak creatine kinase MB (CK-MB). All-cause death in-hospital and within 1 year were the major end points. RESULTS: there was a significantly lower frequency of STEMI in statin patients, in both ASCVD and No-ASCVD groups. Peak CK-MB levels were lower in statin users (10 versus 25 ng/ml, P < 0.0001). There was lower all-cause death in-hospital and within 1 year for subjects with ASCVD already on statins independent of other baseline variables. There were no differences in all-cause death for No-ASCVD patients whether or not on statins. CONCLUSIONS: statin pretreatment was associated with more favourable ACS presentation and lower myocardial damage in older ACS patients both ASCVD and No-ASCVD. The incidence of all-cause death (in-hospital and within 1 year) was significantly lower in the statin treated ASCVD patients.

[Same-day discharge after elective coronary angioplasty: a single-center initial experience]. / Dimissione in giornata dopo angioplastica coronarica elettiva: esperienza iniziale di un singolo centro.

BACKGROUND: Percutaneous coronary intervention (PCI) is usually a procedure based on patient's hospitalization. However, the increasingly widespread use of radial access, the technical evolution of the devices employed and current pharmacotherapy standards have simplified this procedure with satisfying outcomes and significantly reduced complications. It can be assumed that overnight hospitalization may not impact patient safety. The purpose of this study is to describe the experience of a single center in the same-day discharge of elective patients undergoing PCI. METHODS: A retrospective analysis of the cath-lab database was carried out for the years 2016-2019. All elective PCI patients discharged on the same day were identified. All were observed in a hospital setting for at least 6 h and then, after discharge, interviewed by telephone within 24 h and at 30 days. RESULTS: During the time interval examined, 36 patients (mean age 66 ± 10 years) who had procedural same-day discharged were identified. From 2016 to 2019, they represented 1.69%, 1.79%, 5.78% and 5.90%, respectively, of the patients electively admitted for PCI annually. All suffered from chronic coronary syndrome, were on dual antiplatelet therapy and treated with radial approach for single-vessel (88.8%) or multivessel (12.2%) PCI. Two in-hospital access site bleedings, no adverse events in the first 24 h and a new readmission, due to gastrointestinal bleeding, at 30-day follow-up were reported. CONCLUSIONS: The results of this initial experience help to confirm that the same-day discharge after a PCI is possible and safe for the patient. If this strategy could be the standard of care to increase patient satisfaction, to improve hospital performance by reducing costs and to increase efficiency without adversely affecting procedural outcomes should be confirmed in larger and unselected groups of patients.

Association of Sex with Outcome in Elderly Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Worse outcomes have been reported for women, compared with men, after an acute coronary syndrome (ACS). Whether this difference persists in elderly patients undergoing similar invasive treatment has not been studied. We investigated sex-related differences in 1-year outcome of elderly acute coronary syndrome patients treated by percutaneous coronary intervention (PCI). METHODS: Patients 75 years and older successfully treated with PCI were selected among those enrolled in 3 Italian multicenter studies. Cox regression analysis was used to assess the independent predictive value of sex on outcome at 12-month follow-up. RESULTS: A total of 2035 patients (44% women) were included. Women were older and most likely to present with ST-elevation myocardial infarction (STEMI), diabetes, hypertension, and renal dysfunction; men were more frequently overweight, with multivessel coronary disease, prior myocardial infarction, and revascularizations. Overall, no sex disparity was found about all-cause (8.3% vs 7%, P = .305) and cardiovascular mortality (5.7% vs 4.1%, P = .113). Higher cardiovascular mortality was observed in women after STEMI (8.8%) vs 5%, P = .041), but not after non ST-elevation-ACS (3.5% vs 3.7%, P = .999). A sensitivity analysis excluding patients with prior coronary events (N = 1324, 48% women) showed a significantly higher cardiovascular death in women (5.4% vs 2.9%, P = .025). After adjustment for baseline clinical variables, female sex did not predict adverse outcome. CONCLUSIONS: Elderly men and women with ACS show different clinical presentation and baseline risk profile. After successful PCI, unadjusted 1-year cardiovascular mortality was significantly higher in women with STEMI and in those with a first coronary event. However, female sex did not predict cardiovascular mortality after adjustment for the different baseline variables.

Effects of hypertension on cancer survival: A meta-analysis.

BACKGROUND: Hypertension is usually associated with increased cardiovascular mortality. Uncertainty exists about the possible role of hypertension as a poor prognostic factor for cancer-specific mortality (CSM). To assess the association between pre-existing hypertension and the risk of mortality and relapse after a diagnosis of cancer, we performed a systematic review and meta-analysis of published studies. METHODS: PubMed, Scopus, Web of Science, the Cochrane Library and EMBASE were searched from inception until May 2020, without language restrictions, for observational studies reporting the prognosis of patients with hypertension and cancer. The primary outcome of the study refers to CSM in hypertensive vs nonhypertensive patients, and secondary endpoints were overall mortality (OM) and progression- or relapse-free survival. The effect size was reported as hazard ratios (HRs) with 95% CIs. RESULTS: Mortality and relapse associated with hypertension in patients with various cancers were evaluated among 1 603 437 participants (n = 66 studies). Overall, diagnosis of cancer and hypertension was associated with an increased independent risk of OM (HR = 1.2 [95% CI, 1.13-1.27], P < .01) and CSM (HR = 1.12 [95% CI, 1.04-1.21], P < .01) but not of relapse (HR = 1.08 [95% CI, 0.98-1.19], P = .14). CONCLUSIONS: Among cancer patients, those with pre-existing hypertension have a poorer outcome, probably due to multifactorial reasons. Adequate control of lifestyle, more intensive follow-ups, monitoring for hypertension- and anticancer-related cardiovascular complications, and establishing multidisciplinary cardio-oncology units can be useful measures for reducing mortality and improving care in this setting.

Bleeding risk prediction in elderly patients managed invasively for acute coronary syndromes: External validation of the PRECISE-DAPT and PARIS scores.

BACKGROUND: We sought to assess and compare the prediction power of the PRECISE-DAPT and PARIS risk scores with regards to bleeding events in elderly patients suffering from acute coronary syndromes (ACS) and undergoing invasive management. METHODS: Our external validation cohort included 1883 patients older >74 years admitted for ACS and treated with PCI from 3 prospective, multicenter trials. RESULTS: After a median follow-up of 365 days, patients in the high-risk categories according to the PRECISE-DAPT score experienced a higher rate of BARC 3-5 bleedings (p = 0.002) while this was not observed for those in the high-risk category according to the PARIS risk score (p = 0.3). Both scores had a moderate discriminative power (c-statistics 0.70 and 0.64, respectively) and calibration was accurate for both risk scores (all χ2 > 0.05), but PARIS risk score was associated to a greater overestimation of the risk (p = 0.02). Decision curve analysis was in favor of the PRECISE-DAPT score up to a risk threshold of 2%. CONCLUSIONS: In the setting of older adults managed invasively for ACS both the PARIS and the PRECISE-DAPT scores were moderately accurate in predicting bleeding risk. However, the use of the PRECISE-DAPT is associated with better performance.

Survival of Colorectal Cancer Patients With Diabetes Mellitus: A Meta-Analysis.

OBJECTIVES: Diabetes mellitus (DM) is associated with an elevated risk of various cancers, including colorectal cancer (CRC). Similarly, pre-existing DM may also influence prognosis among patients with CRC. We performed a systematic review and meta-analysis to assess the association between DM and risk of death and relapse after a diagnosis of CRC. METHODS: PubMed, Scopus, Web of Science, The Cochrane Library and Embase were searched from inception until July 2019 for studies reporting prognosis of patients with DM and CRC. The primary outcome of the study refers to overall mortality in patients with vs without diabetes. Secondary endpoints were cancer-specific mortality and progression or relapse-free survival. The risk of death and relapse are reported as hazard ratio (HR) with 95% confidence interval (CI), and an HR >1 was associated with worst outcome in patients with diabetes compared to those without diabetes. RESULTS: Mortality and relapse associated with DM in patients with CRC were evaluated among 5,267,980 participants (total of 82 studies). Overall, concomitant diagnosis of CRC and DM were associated with an independent increased risk of overall mortality (HR, 1.21; 95% CI, 1.17 to 1.25; p<0.01) and CSM (HR, 1.11; 95% CI, 1.05 to 1.17; p<0.01). Patients were also at increased risk of relapse (HR, 1.09; 95% CI, 1.02 to 1.16; p<0.01). CONCLUSIONS: In CRC patients with DM, diabetes decreased survival and increased the risk of relapse. Adequate control of lifestyle choices, more intensive follow ups, use of some oral antidiabetics, dietary restrictions, physical activity and monitoring of diabetes-associated complications are measures for reducing mortality in this setting.

Downstream or upstream administration of P2Y12 receptor blockers in non-ST elevated acute coronary syndromes: study protocol for a randomized controlled trial.

BACKGROUND: The optimal timing to administer a P2Y12 inhibitor in patients presenting with a non-ST elevation acute coronary syndrome remains a topic of debate. Pretreatment with ticagrelor before coronary anatomy is known as a widely adopted strategy. However, there is poor evidence on how this compares with administration of a P2Y12 inhibitor after defining coronary anatomy (i.e., downstream administration). Moreover, there are limited head-to-head comparisons of the two P2Y12 inhibitors-ticagrelor and prasugrel-currently recommended by the guidelines. STUDY DESIGN: DUBIUS is a phase 4, multicenter, parallel-group, double randomized study conducted in NSTE-ACS patients designed to compare a pretreatment strategy (including only ticagrelor) versus a downstream strategy (including prasugrel or ticagrelor) and to compare downstream prasugrel with downstream ticagrelor. A total of 2520 patients will be randomly assigned to pretreatment with ticagrelor or to no pretreatment. The PCI group of the downstream arm will be further randomized to receive prasugrel or ticagrelor. The two primary hypotheses are that the downstream strategy is superior to the upstream strategy and that downstream ticagrelor is non-inferior to downstream prasugrel, both measured by the incidence of a composite efficacy and safety endpoint of death from vascular causes, non-fatal MI, or non-fatal stroke, and Bleeding Academic Research Consortium (BARC) type 3, 4, and 5 bleedings. CONCLUSIONS: The DUBIUS study will provide important evidence related to the benefits and risks of pretreatment with ticagrelor compared with a strategy of no pretreatment. Moreover, the clinical impact of using downstream ticagrelor compared with downstream prasugrel will be assessed. TRIAL REGISTRATION: ClinicalTrials.gov NCT02618837 . Registered on 1 December 2015.

Venous and arterial thromboembolic events with immune checkpoint inhibitors: A systematic review.

BACKGROUND: Venous (VTEs) and arterial thromboembolic events (ATEs) are causes of morbidity, disability, mortality, and increase in treatment costs in cancer patients. The risk associated with immune checkpoint inhibitors (ICIs) has not yet been clarified. The primary objective of this systematic review was to evaluate the incidence of VTEs and ATEs in patients treated with ICIs as single agents or in combination with other treatments. MATERIAL AND METHODS: Data from retrospective and prospective studies were selected from PubMed, EMBASE, SCOPUS, and The Cochrane Library from inception up to May up to 21st May 2020. All studies had to be in English and use human study participants. The studies were eligible if they provided a number (or rate) of VTEs and ATEs and the size of the population included. The PRISMA guidelines were followed. The data on the incidence of VTEs and ATEs were extracted for each arm, analyzed using random-effects models, and reported as weighted measures. RESULTS: A total of 20,273 patients from 68 studies were included (median follow-up ranged from a few months up to three years). Overall, there were 390 VTEs and 59 ATEs, with incidence rates of 2.7% (95%CI 1.8%-4%) and 1.1% (95%CI 0.5%-2.1%), respectively. The rate of pulmonary embolism was 1.6% (95%CI 0.7%-3.2%) and deep venous thrombosis was 2.7% (95%CI 1.4%-5.4%). In studies where ICIs were administered with chemotherapy, rates of VTEs were similar to ICI alone arms (2.8% vs 2.5%). The rate of stroke and myocardial infarction were 1.1% (95%CI 0.65%-1.45%) and 0.7% (95%CI 0.15%-1.15%), respectively. In randomized trials, compared with non-ICIs containing arms (e.g. chemotherapy), the relative risk (RR) of VTEs due to ICIs was similar (RR 1.08, 95%CI 0.6-1.9; P = .79). CONCLUSIONS: Thromboembolic events associated with ICIs are relatively rare in cancer patients with an advanced stage of the disease. However, in randomized studies, their incidence is similar to control arms, suggesting that the contributory role of ICIs to the thromboembolic risk in many cancer settings is small.

Timing of Oral P2Y12 Inhibitor Administration in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: Although oral P2Y12 inhibitors are key in the management of patients with non-ST-segment elevation acute coronary syndrome, the optimal timing of their administration is not well defined. OBJECTIVES: The purpose of this study was to compare downstream and upstream oral P2Y12 inhibitors administration strategies in patients with non-ST-segment elevation acute coronary syndrome undergoing invasive treatment. METHODS: We performed a randomized, adaptive, open-label, multicenter clinical trial. Patients were randomly assigned to receive pre-treatment with ticagrelor before angiography (upstream group) or no pre-treatment (downstream group). Patients in the downstream group undergoing percutaneous coronary intervention were further randomized to receive ticagrelor or prasugrel. The primary hypothesis was the superiority of the downstream versus the upstream strategy on the combination of efficacy and safety events (net clinical benefit). RESULTS: We randomized 1,449 patients to downstream or upstream oral P2Y12 inhibitor administration. A pre-specified stopping rule for futility at interim analysis led the trial to be stopped. The rate of the primary endpoint, a composite of death due to vascular causes; nonfatal myocardial infarction or nonfatal stroke; and Bleeding Academic Research Consortium type 3, 4, and 5 bleeding through day 30, did not differ significantly between the downstream and upstream groups (percent absolute risk reduction: -0.46; 95% repeated confidence interval: -2.90 to 1.90). These results were confirmed among patients undergoing percutaneous coronary intervention (72% of population) and regardless of the timing of coronary angiography (within or after 24 h from enrollment). CONCLUSIONS: Downstream and upstream oral P2Y12 inhibitor administration strategies were associated with low incidence of ischemic and bleeding events and minimal numeric difference of event rates between treatment groups. These findings led to premature interruption of the trial and suggest the unlikelihood of enhanced efficacy of 1 strategy over the other. (Downstream Versus Upstream Strategy for the Administration of P2Y12 Receptor Blockers In Non-ST Elevated Acute Coronary Syndromes With Initial Invasive Indication [DUBIUS]; NCT02618837).

Residual SYNTAX Score and One-Year Outcome in Elderly Patients With Acute Coronary Syndrome.

BACKGROUND: The residual burden of coronary artery disease after percutaneous coronary intervention (PCI) has been associated with worse ischemic outcome. However, data are conflicting in elderly patients. The aim of our study was to verify the incremental value of the residual Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score (rSS) over clinical variables and baseline SYNTAX score (bSS) in predicting 1-year mortality or cardiovascular events. METHODS: A post hoc analysis of data collected in the Elderly-ACS 2 multicenter randomized trial was performed. We included 630 patients aged > 75 years with multivessel coronary disease undergoing PCI for acute coronary syndrome (ACS). The primary outcome was a composite of death, recurrent myocardial infarction, and stroke at 1-year follow up. Change in c-statistic and standardized net benefit were used to evaluate the incremental value of the rSS. RESULTS: Event rates were significantly higher in patients with incomplete revascularization (rSS > 8). When the rSS was included in a core Cox regression model containing age, previous myocardial infarction, and ACS type, the hazard ratio for patients with score values > 8 was 2.47 (95% confidence interval, 1.51-4.06). However, the core model with rSS did not increase the c-statistic compared with the core model with the bSS (from 0.69 to 0.70) and gave little incremental value in the standardized net benefit. CONCLUSIONS: In elderly patients with ACS with multivessel disease undergoing PCI, incomplete revascularization was associated with worse outcome at 1-year follow-up. However, there was no clear incremental value of the rSS in the prediction of 1-year adverse outcome compared with a model including clinical variables and bSS.

CONTEXTE: Le fardeau résiduel de la coronaropathie après une intervention coronarienne percutanée (ICP) a été associé à de moins bons résultats sur le plan ischémique. Les données recueillies chez les patients âgés sont toutefois contradictoires. Cette étude avait donc pour objectif de valider la valeur ajoutée du score SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) résiduel (SSr) par rapport aux paramètres cliniques et au score SYNTAX initial (SSi) pour prédire la mortalité à 1 an et les manifestations cardiovasculaires. MÉTHODOLOGIE: Une analyse a posteriori des données de l'étude multicentrique avec répartition aléatoire Elderly-ACS 2 a été effectuée. Pour ce faire, 630 patients âgés de plus de 75 ans, atteints d'une coronaropathie multitronculaire et ayant subi une ICP pour traiter un syndrome coronarien aigu (SCA) ont été retenus. Le critère d'évaluation principal était composé du décès, de l'infarctus du myocarde récurrent et de l'accident vasculaire cérébral (AVC) au moment du suivi à 1 an. La variation de la statistique C et le bénéfice net normalisé ont servi à évaluer la valeur ajoutée du SSr. RÉSULTATS: Les manifestations étaient significativement plus fréquentes chez les patients dont la revascularisation était incomplète (SSr > 8). Lorsque le SSr a été pris en compte dans un modèle de régression de Cox de base ayant pour facteurs l'âge, les antécédents d'infarctus du myocarde et le type de SCA, le rapport des risques instantanés pour les patients ayant un score > 8 était de 2,47 (intervalle de confiance à 95 % : 1,51-4,06). L'intégration du SSr dans le modèle de base n'a toutefois pas donné lieu à une statistique C plus élevée que celle du SSi (0,70 vs 0,69) et conférait peu de valeur ajoutée sur le plan du bénéfice net normalisé. CONCLUSIONS: Chez les patients âgés présentant un SCA et une atteinte multitronculaire, et subissant une ICP, la revascularisation incomplète a été associée à de moins bons résultats au moment du suivi à 1 an. Le SSr n'a toutefois pas été clairement associé à une valeur ajoutée pour prédire une issue défavorable à 1 an comparativement à un modèle reposant sur des paramètres cliniques et le SSi.

Impact of diabetes on clinical outcome among elderly patients with acute coronary syndrome treated with percutaneous coronary intervention: insights from the ELDERLY ACS 2 trial.

BACKGROUND: Despite recent improvements in percutaneous coronary revascularization and antithrombotic therapies for the treatment of acute coronary syndromes, the outcome is still unsatisfactory in high-risk patients, such as the elderly and patients with diabetes. The aim of the current study was to investigate the prognostic impact of diabetes on clinical outcome among patients included in the Elderly-ACS 2 trial, a randomized, open-label, blinded endpoint study carried out at 32 centers in Italy. METHODS: Our population is represented by 1443 patients included in the Elderly-ACS 2 trial. Diabetes was defined as known history of diabetes at admission. The primary endpoint of this analysis was cardiovascular mortality, while secondary endpoints were all-cause death, recurrent myocardial infarction, Bleeding Academic Research Consortium type 2 or 3 bleeding, and rehospitalization for cardiovascular event or stent thrombosis within 12 months after index admission. RESULTS: Diabetes was present in 419 (29%) out of 1443 patients. Diabetic status was significantly associated with major cardiovascular risk factors and history of previous coronary disease, presentation with non-ST segment elevation myocardial infarction (P = 0.01) more extensive coronary disease (P = 0.02), more advanced Killip class at presentation (P = 0.003), use at admission of statins (P = 0.004) and diuretics at discharge (P < 0.001). Median follow-up was 367 days (interquartile range: 337-378 days). Diabetic status was associated with an absolute increase in the rate of cardiovascular mortality as compared with patients without diabetes [5.5 vs. 3.3%, hazard ratio (HR) 1.7 (0.99-2.8), P = 0.054], particularly among those treated with clopidogrel [HR (95% confidence interval (CI)) = 1.89 (0.93-3.87), P = 0.08]. However, this difference disappeared after correction for baseline differences [Adjusted HR (95% CI) 1.1(0.4-2.9), P = 0.86]. Similar findings were observed for other secondary endpoints, except for bleeding complications, significantly more frequent in diabetic patients [HR (95% CI) 2.02 (1.14-3.6), P = 0.02; adjusted HR (95% CI) = 2.1 (1.01-4.3), P = 0.05]. No significant interaction was observed between type of dual antiplatelet therapy, diabetic status and outcome. CONCLUSION: Among elderly patients with acute coronary syndromes, diabetic status was associated with higher rates of comorbidities, more severe cardiovascular risk profile and major bleeding complications fully accounting for the absolute increase in mortality. In fact, diabetes mellitus did not emerge as an independent predictor of survival in advanced age.