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Background Although oral P2Y12 inhibitors are key in the management of patients with non-ST elevation acute coronary syndrome (NSTE-ACS), the optimal timing of their administration is not well defined. Objective to compare downstream and upstream oral P2Y12 inhibitors administration strategies in NSTE-ACS patients undergoing invasive management. Methods We performed a randomized, adaptive, open-label, multi-center, 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 (PCI) were further randomized to receive ticagrelor or prasugrel. The primary hypothesis was superiority of the downstream over the upstream strategy on the combination of efficacy and safety events (net clinical benefit). Results We randomized 1449 patients to downstream or upstream oral P2Y12 inhibitor administration. A prespecified 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, non-fatal myocardial infarction or non-fatal stroke, and Bleeding Academic Research Consortium (BARC) type 3, 4 and 5 bleedings through day 30, did not differ significantly between the downstream and upstream groups (Absolute Risk Reduction (ARR%) -0.46 [-2.90; 1.90]).These results were confirmed among patients undergoing PCI (72% of population) and regardless of the timing of coronary angiography (within or after 24 hours from enrolment). Conclusions Downstream and upstream oral P2Y12 inhibitors administration strategies were associated with low incidence of ischemic and bleeding events and minimal numerical difference of event rates between treatment groups. These findings led to premature interruption of the trial and suggest the unlikelihood of enhanced efficacy of one strategy over the other. [Funded by the Italian Society of Interventional Cardiology (SICI-GISE)]

Although oral P2YThe purpose of this study was to compare downstream and upstream oral P2YWe 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).We randomized 1,449 patients to downstream or upstream oral P2YDownstream and upstream oral P2Y

Background It remains unclear whether radial access (RA), compared with femoral access (FA), mitigates the risk of acute kidney injury (AKI). Objectives The authors assessed the incidence of AKI in patients with acute coronary syndrome (ACS) enrolled in the MATRIX-Access (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial. Methods Among 8,404 patients, 194 (2.3%) were excluded due to missing creatinine values, no or an incomplete coronary angiogram, or previous dialysis. The primary AKI-MATRIX endpoint was AKI, defined as an absolute (>0.5 mg/dl) or a relative (>25%) increase in serum creatinine (sCr). Results AKI occurred in 634 patients (15.4%) with RA and 712 patients (17.4%) with FA (odds ratio [OR]: 0.87; 95% confidence interval [CI]: 0.77 to 0.98; p = 0.0181). A >25% sCr increase was noted in 633 patients (15.4%) with RA and 710 patients (17.3%) with FA (OR: 0.87; 95% CI: 0.77 to 0.98; p = 0.0195), whereas a >0.5 mg/dl absolute sCr increase occurred in 175 patients (4.3%) with RA versus 223 patients (5.4%) with FA (OR: 0.77; 95% CI: 0.63 to 0.95; p = 0.0131). By implementing the Kidney Disease Improving Global Outcomes criteria, AKI was 3-fold less prevalent and trended lower with RA (OR: 0.85; 95% CI: 0.70 to 1.03; p = 0.090), with stage 3 AKI occurring in 28 patients (0.68%) with RA versus 46 patients (1.12%) with FA (p = 0.0367). Post-intervention dialysis was needed in 6 patients (0.15%) with RA and 14 patients (0.34%) with FA (p = 0.0814). Stratified analyses suggested greater benefit with RA than FA in patients at greater risk for AKI. Conclusions In ACS patients who underwent invasive management, RA was associated with a reduced risk of AKI compared with FA. (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX [MATRIX]; NCT01433627 )

BACKGROUND The value of prolonged bivalirudin infusion after percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) patients with or without ST-segment elevation remains unclear. OBJECTIVES The purpose of this study was to assess efficacy and safety of a full or low post-PCI bivalirudin regimen in ACS patients with or without ST-segment elevation. METHODS The MATRIX program assigned bivalirudin to patients without or with a post-PCI infusion at either a full (1.75 mg/kg/h for #4 h) or reduced (0.25 mg/kg/h for #6 h) regimen at the operator's discretion. The primary endpoint was the 30-day composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events (composite of all-cause death, myocardial infarction, or stroke, or major bleeding). RESULTS Among 3,610 patients assigned to bivalirudin, 1,799 were randomized to receive and 1,811 not to receive a post-PCI bivalirudin infusion. Post-PCI full bivalirudin was administered in 612 (ST-segment elevation myocardial infarction [STEMI], n = 399; non-ST-segment elevation acute coronary syndromes [NSTE-ACS], n = 213), whereas the low-dose regimen was administered in 1,068 (STEMI, n = 519; NSTE-ACS, n = 549) patients. The primary outcome did not differ in STEMI or NSTE-ACS patients who received or did not receive post-PCI bivalirudin. However, full compared with low bivalirudin regimen remained associated with a significant reduction of the primary endpoint after multivariable (rate ratio: 0.21; 95% CI: 0.12 to 0.35; p < 0.001) or propensity score (rate ratio: 0.16; 95% CI: 0.09 to 0.26; p < 0.001) adjustment. Full post-PCI bivalirudin was associated with improved outcomes consistently across ACS types compared with the no post-PCI infusion or heparin groups. CONCLUSIONS In ACS patients with or without ST-segment elevation, the primary endpoint did not differ with or without post-PCI bivalirudin infusion but a post-PCI full dose was associated with improved outcomes when compared with no or low-dose post-PCI infusion or heparin (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX [MATRIX]; NCT01433627). (J Am Coll Cardiol 2019; 73: 758-74) (c) 2019 by the American College of Cardiology Foundation. The trial was sponsored by the Societa Italiana di Cardiologia Invasiva (GISE, a nonprofit organization), which received grant support from The Medicines Company and TERUMO. This substudy did not receive any direct or indirect funding. Dr. Gargiulo has received research grant support from the Cardiopath PhD program. Dr. Vranckx has received consulting fees from AstraZeneca and The Medicines Company during the study; and has received speaking or consulting fees from Bayer HealthCare, Terumo, and Daiichi-Sankyo outside of the submitted work. Dr. Campo has received research grants from AstraZeneca, Boston Scientific, and Abbott Vascular outside of this work. Dr. Varbella has received personal fees from AstraZeneca, Eli Lilly, and Bayer; has received other support from Biosensors; has received grants from Medtronic, Kardia SRL, and Boston Scientific outside of the submitted work; and has received lecture fees for Advisory Board participation from AstraZeneca, Daichi-Sankyo, Bayer, Pfizer, Boehringer Ingelheim, Servier, Amgen, Novartis, Sanofi, and Biotronik. Dr. Ando has received nonfinancial support from Terumo during the conduct of the study; has received personal fees from Daiichi-Sankyo, AstraZeneca, Menarini, Pfizer, Philips, and Bayer; and has received nonfinancial support from Bayer, Boehringer Ingelheim, Chiesi, and Philips outside of the submitted work. Dr. Limbruno has received personal fees from The Medicines Company, AstraZeneca, Lilly, Boston Scientific, Biotronik, and Merck outside of the submitted work. Dr. Windecker's institution has received research contracts from Abbott, Amgen, Boston Scientific, Biotronik, Medtronic, Edwards Lifesciences, St. Jude, and Terumo. Dr. Valgimigli has received grants from The Medicines Company and Terumo during the conduct of the study; has received grants and personal fees from AstraZeneca; has received nonfinancial support from The Medicines Company; and has received personal fees from The Medicines Company, Terumo, St. Jude Vascular, Alvimedica, Abbott Vascular, and Correvio outside of the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Objectives The aim of this study was to investigate whether there is a temporal pattern of ischemic events in relation to dual antiplatelet therapy in patients with unprotected left main coronary artery (ULMCA) stenosis treated with percutaneous coronary intervention (PCI). Background Identifying which periods during follow-up of patients with ULMCA stenosis treated with PCI are associated with higher risk of clinical events might help to improve therapeutic strategies. Methods We analyzed data from 15 centers involved in an observational study conducted by the Italian Society of Invasive Cardiology on patients with ULMCA stenosis treated with PCI. Eight hundred ninety-four patients were enrolled. Results At 30-day follow-up, the rate of cardiac mortality and myocardial infarction (MI) was 5.4%. In patients still taking dual antiplatelet therapy, the adjusted incidence rate ratio/10,000 patient-days of the combination of cardiac mortality and MI in the 31- to 180-day interval compared with the 181- to 360-day interval after PCI was 3.64 (p = 0.035). This risk was particularly high in patients with acute coronary syndromes. After stopping clopidogrel, the adjusted incidence rate ratio of cardiac mortality and MI in the 0- to 90-day interval compared with the 91- to 180-day interval was 4.20 (p = 0.009). Conclusions In patients with ULMCA stenosis taking dual antiplatelet therapy there is an increased hazard of cardiac mortality and MI between 31 and 180 days compared with 181 to 360 days. Furthermore, there is an increased hazard of cardiac mortality and MI in the first 90 days after stopping clopidogrel.

Whether cyclosporine A (CsA) has beneficial effects in reperfused myocardial infarction (MI) is debated.This study investigated whether CsA improved ST-segment resolution in a randomized, multicenter phase II study.The authors randomly assigned 410 patients from 31 cardiac care units, age 63 ± 12 years, with large ST-segment elevation MI within 6 h of symptom onset, Thrombolysis In Myocardial Infarction (TIMI) flow grade 0 to 1 in the infarct-related artery, and committed to primary percutaneous coronary intervention, to 2.5 mg/kg intravenous CsA (n = 207) or control (n = 203) groups. The primary endpoint was incidence of ≥70% ST-segment resolution 60 min after TIMI flow grade 3. Secondary endpoints included high-sensitivity cardiac troponin T (hs-cTnT) on day 4, left ventricular (LV) remodeling, and clinical events at 6-month follow-up.Time from symptom onset to first antegrade flow was 180 ± 67 min; a median of 5 electrocardiography leads showed ST-segment deviation (quartile [Q]1 to Q3: 4 to 6); 49.8% of MIs were anterior. ST-segment resolution ≥70% was found in 52.0% of CsA patients and 49.0% of controls (p = 0.55). Median hs-cTnT on day 4 was 2,160 (Q1 to Q3: 1,087 to 3,274) ng/l in CsA and 2,068 (1,117 to 3,690) ng/l in controls (p = 0.85). The 2 groups did not differ in LV ejection fraction on day 4 and at 6 months. Infarct site did not influence CsA efficacy. There were no acute allergic reactions or nonsignificant excesses of 6-month mortality (5.7% CsA vs. 3.2% controls, p = 0.17) or cardiogenic shock (2.4% CsA vs. 1.5% controls, p = 0.33).In the CYCLE (CYCLosporinE A in Reperfused Acute Myocardial Infarction) trial, a single intravenous CsA bolus just before primary percutaneous coronary intervention had no effect on ST-segment resolution or hs-cTnT, and did not improve clinical outcomes or LV remodeling up to 6 months. (CYCLosporinE A in Reperfused Acute Myocardial Infarction [CYCLE]; NCT01650662; EudraCT number 2011-002876-18).

OBJECTIVES We compared the clinical outcome of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in a real-world scenario. BACKGROUND In selected patients, SES has been associated with lower late luminal loss than PES. Whether this emerging biological difference could translate into different clinical efficacy in daily practice is presently unknown. METHODS This analysis included 1,676 consecutive patients with de novo coronary lesions treated solely with drug-eluting stents (SES = 992; PES = 684). All patients were enrolled in a dynamic prospective registry comprising 13 hospitals. We assessed the cumulative incidence of major adverse cardiac events (MACE), defined as death, myocardial infarction (MI), and target vessel revascularization (TVR) during follow-up. RESULTS Overall, 29% of the patients had diabetes, 23% had prior MI, and 9% had poor left ventricular function. ST-segment elevation MI was diagnosed at admission in 12%. Multivessel intervention was performed in 16%. At 1-year follow-up, SES was associated with a reduced incidence of MACE (9.2% SES vs. 14.1% PES; p = 0.007) and TVR (5.0% SES vs. 10.0% PES; p = 0.0008) compared to PES. A propensity analysis with many clinical and angiographic variables was carried out to adjust for baseline differences. In this analysis, SES was associated with a 44% risk reduction of MACE (hazard ratio 0.56, 95% confidence interval 0.39 to 0.78) and a 55% reduction of TVR (hazard ratio 0.45, 95% confidence interval 0.29 to 0.70). This result was consistent across most subgroups tested. Similar rates of death and MI were observed in the 2 treatment groups. CONCLUSIONS In this large real-world population, SES improved 1-year clinical results as compared to PES.

We compared the clinical outcome of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in a real-world scenario.In selected patients, SES has been associated with lower late luminal loss than PES. Whether this emerging biological difference could translate into different clinical efficacy in daily practice is presently unknown.This analysis included 1,676 consecutive patients with de novo coronary lesions treated solely with drug-eluting stents (SES = 992; PES = 684). All patients were enrolled in a dynamic prospective registry comprising 13 hospitals. We assessed the cumulative incidence of major adverse cardiac events (MACE), defined as death, myocardial infarction (MI), and target vessel revascularization (TVR) during follow-up.Overall, 29% of the patients had diabetes, 23% had prior MI, and 9% had poor left ventricular function. ST-segment elevation MI was diagnosed at admission in 12%. Multivessel intervention was performed in 16%. At 1-year follow-up, SES was associated with a reduced incidence of MACE (9.2% SES vs. 14.1% PES; p = 0.007) and TVR (5.0% SES vs. 10.0% PES; p = 0.0008) compared to PES. A propensity analysis with many clinical and angiographic variables was carried out to adjust for baseline differences. In this analysis, SES was associated with a 44% risk reduction of MACE (hazard ratio 0.56, 95% confidence interval 0.39 to 0.78) and a 55% reduction of TVR (hazard ratio 0.45, 95% confidence interval 0.29 to 0.70). This result was consistent across most subgroups tested. Similar rates of death and MI were observed in the 2 treatment groups.In this large real-world population, SES improved 1-year clinical results as compared to PES.