Empagliflozin in acute myocardial infarction: the EMMY trial.

AIMS: Sodium-glucose co-transporter 2 inhibition reduces the risk of hospitalization for heart failure and for death in patients with symptomatic heart failure. However, trials investigating the effects of this drug class in patients following acute myocardial infarction are lacking. METHODS AND RESULTS: In this academic, multicentre, double-blind trial, patients (n = 476) with acute myocardial infarction accompanied by a large creatine kinase elevation (>800 IU/L) were randomly assigned to empagliflozin 10 mg or matching placebo once daily within 72 h of percutaneous coronary intervention. The primary outcome was the N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP) change over 26 weeks. Secondary outcomes included changes in echocardiographic parameters. Baseline median (interquartile range) NT-proBNP was 1294 (757-2246) pg/mL. NT-proBNP reduction was significantly greater in the empagliflozin group, compared with placebo, being 15% lower [95% confidence interval (CI) -4.4% to -23.6%] after adjusting for baseline NT-proBNP, sex, and diabetes status (P = 0.026). Absolute left-ventricular ejection fraction improvement was significantly greater (1.5%, 95% CI 0.2-2.9%, P = 0.029), mean E/e' reduction was 6.8% (95% CI 1.3-11.3%, P = 0.015) greater, and left-ventricular end-systolic and end-diastolic volumes were lower by 7.5 mL (95% CI 3.4-11.5 mL, P = 0.0003) and 9.7 mL (95% CI 3.7-15.7 mL, P = 0.0015), respectively, in the empagliflozin group, compared with placebo. Seven patients were hospitalized for heart failure (three in the empagliflozin group). Other predefined serious adverse events were rare and did not differ significantly between groups. CONCLUSION: In patients with a recent myocardial infarction, empagliflozin was associated with a significantly greater NT-proBNP reduction over 26 weeks, accompanied by a significant improvement in echocardiographic functional and structural parameters. CLINICALTRIALS.GOV REGISTRATION: NCT03087773.

Ertugliflozin to reduce arrhythmic burden in ICD/CRT patients (ERASe-trial) - A phase III study.

Sodium glucose cotransporter 2 (SGLT2) have proven profound positive effects in heart failure with reduced ejection fraction (HFrEF). These effects are independent from the presence of diabetes. Metabolic effects, antiinflammatory, and antifibrotic properties are discussed as underlying mechanisms. Despite a strong correlation of ventricular arrhythmias with HFrEF, the impact of ertugliflozin on the ventricular arrhythmic burden has not been investigated, yet. Therefore, the Ertugliflozin to Reduce Arrhythmic burden in ICD ± CRT patientS (ERASe) trial was designed to investigate the efficacy and safety of ertugliflozin in patients with reduced and midrange ejection fraction (EF) with or without diabetes. METHODS: Within a multicentre, national, randomized, double-blind, placebo-controlled, phase 3b trial we aim to enrol a total of 402 patients across Austria. Patients with reduced or midrange EF and ICD ± CRT therapy >3 months and previous ventricular tachycardia (at least 10 documented VT episodes within the last 12 months) are randomized in a 1:1 ratio to ertugliflozin (5 mg once daily orally administered) or matching placebo. The primary endpoint of the ERASe trial is to investigate the impact of ertugliflozin on total burden of ventricular arrhythmias. Further objectives will include number of therapeutic interventions of implanted devices, atrial fibrillation and heart failure biomarkers. CONCLUSION: The ERASe trial will be the first trial to test ertugliflozin in heart failure patients with nonpreserved ejection fraction and ongoing ICD ± CRT therapy regardless of their diabetic status. The ERASe trial may therefore extend the concept of SGLT2 inhibition to improve cardiac remodelling, including reduced arrhythmic burden. Trial registration Identifier EudraCT Nr. 2020-002581-14 / ClinicalTrials.gov Identifier: NCT04600921.

Risk prediction models for discrete ordinal outcomes: Calibration and the impact of the proportional odds assumption.

Calibration is a vital aspect of the performance of risk prediction models, but research in the context of ordinal outcomes is scarce. This study compared calibration measures for risk models predicting a discrete ordinal outcome, and investigated the impact of the proportional odds assumption on calibration and overfitting. We studied the multinomial, cumulative, adjacent category, continuation ratio, and stereotype logit/logistic models. To assess calibration, we investigated calibration intercepts and slopes, calibration plots, and the estimated calibration index. Using large sample simulations, we studied the performance of models for risk estimation under various conditions, assuming that the true model has either a multinomial logistic form or a cumulative logit proportional odds form. Small sample simulations were used to compare the tendency for overfitting between models. As a case study, we developed models to diagnose the degree of coronary artery disease (five categories) in symptomatic patients. When the true model was multinomial logistic, proportional odds models often yielded poor risk estimates, with calibration slopes deviating considerably from unity even on large model development datasets. The stereotype logistic model improved the calibration slope, but still provided biased risk estimates for individual patients. When the true model had a cumulative logit proportional odds form, multinomial logistic regression provided biased risk estimates, although these biases were modest. Nonproportional odds models require more parameters to be estimated from the data, and hence suffered more from overfitting. Despite larger sample size requirements, we generally recommend multinomial logistic regression for risk prediction modeling of discrete ordinal outcomes.

The prevalence of cirrhotic cardiomyopathy according to different diagnostic criteria.

BACKGROUND AND AIMS: Recently published criteria by 2019 Cirrhotic Cardiomyopathy Consortium set a lower threshold for reduced ejection fraction to diagnose systolic dysfunction in cirrhotic patients, and stress testing was replaced by echocardiography strain imaging. The criteria to diagnose diastolic dysfunction are in general concordant with the 2016 ASE/EACVI guidelines and differ considerably from the 2005 Montreal recommendations. We aimed to assess the prevalence of cirrhotic cardiomyopathy according to different diagnostic criteria. METHODS: Cirrhotic patients without another structural heart disease, arterial hypertension, portal vein thrombosis, HCC outside Milan criteria and presence of TIPS were enrolled. Speckle-tracking echocardiography was performed by EACVI certified investigators. RESULTS: A total of 122 patients with cirrhosis fulfilled the inclusion criteria. Overall prevalence of cirrhotic cardiomyopathy was similar for 2005 Montreal and 2019 CCC: 67.2% vs 55.7% (P = .09); and significantly higher compared to 2009 ASE/EACVI criteria: 67.2% vs 35.2% (P < .0001) and 55.7% vs 35.2% (P = .002) respectively. Significantly more patients had diastolic dysfunction according to the 2005 Montreal compared to the 2009 ASE/EACVI and 2019 CCC criteria: 64.8% vs 32.8% (P < .0001) and 64.8% vs 7.4% (P < .0001). Systolic dysfunction was more frequently diagnosed according to 2019 CCC criteria compared to 2005 Montreal (53.3% vs 16.4%,P < .0001) or ASE/EACVI criteria (53.3% vs 4.9%,P < .0001). CONCLUSION: Cirrhotic cardiomyopathy was present in around 60% of cirrhotic patients when applying the hepatological criteria. A considerably higher prevalence of systolic dysfunction according to the 2019 CCC criteria was observed. Long-term follow-up studies are needed to establish the validity of these criteria to predict clinically relevant outcomes.

Impact of EMpagliflozin on cardiac function and biomarkers of heart failure in patients with acute MYocardial infarction-The EMMY trial.

BACKGROUND: Sodium glucose cotransporter 2 (SGLT2) inhibitors are established antidiabetic drugs with proven cardiovascular benefit. Although growing evidence suggests beneficial effects on myocardial remodeling, fluid balance and cardiac function, the impact of empagliflozin initiated early after acute myocardial infarction (AMI) has not been investigated yet. Therefore, the impact of EMpagliflozin on cardiac function and biomarkers of heart failure in patients with acute MYocardial infarction (EMMY) trial was designed to investigate the efficacy and safety of empagliflozin in diabetic and non-diabetic patients after severe AMI. METHODS: Within a multicenter, randomized, double-blind, placebo-controlled, phase 3b trial we will enroll patients with AMI and characteristics suggestive of severe myocardial necrosis are randomized in a 1:1 ratio to empagliflozin (10 mg once daily) or matching placebo. The primary endpoint is the impact of empagliflozin on changes in NT-proBNP within 6 months after AMI. Secondary endpoints include changes in echocardiographic parameters, levels of ketone body concentrations, HbA1c levels and body weight, respectively. Hospitalization rate due to heart failure or other causes, the duration of hospital stay and all-cause mortality will be assessed as exploratory secondary endpoints. DISCUSSION: The EMMY trial will test empagliflozin in patients with AMI regardless of their diabetic status. The EMMY trial may therefore underpin the concept of SGLT2 inhibition to improve cardiac remodeling, pre-and afterload reduction and cardiac metabolism regardless of its antidiabetic effects. Results will provide the rationale for the conduct of a cardiovascular outcome trial to test the effect of empagliflozin in patients with AMI.

[Secondary prevention with antiplatelet therapy in cardiac rehabilitation]. / Sekundärpräventive Antiplättchentherapie in der kardiologischen Rehabilitation.

The long-term increased cardiovascular risk of patients with an acute coronary syndrome (ACS) is a challenging and common clinical problem. Recent evidence demonstrated an ischemic benefit for a prolonged dual antiplatelet therapy beyond the initial 12 months at the cost of an increased bleeding risk. Individual, careful and repeated risk-benefit analyses are essential for an optimized patient management in which cardiovascular rehabilitation providers may play a central role.

Long-term efficacy and safety of biodegradable-polymer biolimus-eluting stents: main results of the Basel Stent Kosten-Effektivitäts Trial-PROspective Validation Examination II (BASKET-PROVE II), a randomized, controlled noninferiority 2-year outcome trial.

BACKGROUND: Biodegradable-polymer drug-eluting stents (BP-DES) were developed to be as effective as second-generation durable-polymer drug-eluting stents (DP-DES) and as safe >1 year as bare-metal stents (BMS). Thus, very late stent thrombosis (VLST) attributable to durable polymers should no longer appear. METHODS AND RESULTS: To address these early and late aspects, 2291 patients presenting with acute or stable coronary disease needing stents ≥3.0 mm in diameter between April 2010 and May 2012 were randomly assigned to biolimus-A9-eluting BP-DES, second-generation everolimus-eluting DP-DES, or thin-strut silicon-carbide-coated BMS in 8 European centers. All patients were treated with aspirin and risk-adjusted doses of prasugrel. The primary end point was combined cardiac death, myocardial infarction, and clinically indicated target-vessel revascularization within 2 years. The combined secondary safety end point was a composite of VLST, myocardial infarction, and cardiac death. The cumulative incidence of the primary end point was 7.6% with BP-DES, 6.8% with DP-DES, and 12.7% with BMS. By intention-to-treat BP-DES were noninferior (predefined margin, 3.80%) compared with DP-DES (absolute risk difference, 0.78%; -1.93% to 3.50%; P for noninferiority 0.042; per protocol P=0.09) and superior to BMS (absolute risk difference, -5.16; -8.32 to -2.01; P=0.0011). The 3 stent groups did not differ in the combined safety end point, with no decrease in events >1 year, particularly VLST with BP-DES. CONCLUSIONS: In large vessel stenting, BP-DES appeared barely noninferior compared with DP-DES and more effective than thin-strut BMS, but without evidence for better safety nor lower VLST rates >1 year. Findings challenge the concept that durable polymers are key in VLST formation. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01166685.

Improved outcomes of elderly patients treated with drug-eluting versus bare metal stents in large coronary arteries: results from the BAsel Stent Kosten-Effektivitäts Trial PROspective Validation Examination randomized trial.

BACKGROUND: Drug-eluting stents (DES) improve outcomes in elderly patients with small coronary artery disease compared with bare-metal stents (BMS), but randomized data in elderly patients in need of large coronary stents are not available. METHODS: Planned secondary analysis of patients ≥75 years recruited to the "BASKET-PROVE" trial, in which 2,314 patients undergoing percutaneous coronary intervention for large (≥3.0 mm) native vessel disease were randomized 2:1 to DES (everolimus- vs sirolimus-eluting stents 1:1) versus BMS. All patients received 12 months of dual antiplatelet therapy. The primary end point was a composite of cardiac death or nonfatal myocardial infarction at 2 years. RESULTS: Comparison of DES versus BMS among 405 patients ≥75 years showed significantly lower rates of the primary end point for DES (5.0% vs 11.6%; hazard ration (HR) 0.64 [0.44-0.91]; P = .014). Rates of nonfatal myocardial infarction (1.2% vs 5.5%, hazard ration (HR) 0.44 [0.21-0.83]; P = .009), all-cause death (7.4% vs 14.4%; HR 0.7 [0.51-0.95]; P = .02), and target vessel revascularization (TVR) (2.3% vs 6.2%; HR 0.59 [0.34-0.99]; P = .046) were also lower, whereas stent thrombosis and bleeding rates were similar. In contrast, among patients <75 years (n = 1,909), the only significant benefit of DES was a reduced rate of TVR (4.0% vs 8.7%, HR 0.66 [0.55-0.80]; P < .0001). CONCLUSIONS: In patients ≥75 years requiring large (≥3.0 mm) coronary stents, use of DES was beneficial compared with BMS and reduced the rate of ischemic events, mortality, and TVR. These data suggest that DES should be preferred over BMS in elderly patients.

CYP2C19 Phenoconversion by Routinely Prescribed Proton Pump Inhibitors Omeprazole and Esomeprazole: Clinical Implications for Personalized Medicine.

The phenotype pantoprazole-(13)C breath test (Ptz-BT) was used to evaluate the extent of phenoconversion of CYP2C19 enzyme activity caused by commonly prescribed proton pump inhibitors (PPI) omeprazole and esomprazole. The Ptz-BT was administered to 26 healthy volunteers and 8 stable cardiovascular patients twice at baseline and after 28 days of PPI therapy to evaluate reproducibility of the Ptz-BT and changes in CYP2C19 enzyme activity (phenoconversion) after PPI therapy. The average intrapatient interday variability in CYP2C19 phenotype (n = 31) determined by Ptz-BT was considerably low (coefficient of variation, 17%). Phenotype conversion resulted in 25 of 26 (96%) nonpoor metabolizer (non-PM) volunteers/patients as measured by the Ptz-BT at baseline and after PPI therapy. The incidence of PM status by phenotype following administration of omeprazole/esomeprazole (known inhibitors of CYP2C19) was 10-fold higher than those who are genetically PMs in the general population, which could have critical clinical implications for personalizing medications primarily metabolized by CYP2C19, such as clopidogrel, PPI, cyclophosphamide, thalidomide, citalopram, clonazepam, diazepam, phenytoin, etc. The Ptz-BT can rapidly (30 minutes) evaluate CYP2C19 phenotype and, more importantly, can identify patients with phenoconversion in CYP2C19 enzyme activity caused by nongenetic factors such as concomitant drugs.

Tradeoff between bleeding and stent thrombosis in different dual antiplatelet therapy regimes: Importance of case fatality rates and effective treatment durations.

BACKGROUND: The tradeoff between stent thrombosis (ST) and major bleeding (MB) of 12- versus 6-month dual antiplatelet therapy (DAPT) after coronary stent implantation has not been clearly defined. METHODS: Definite/probable ST and MB (TIMI major and Bleeding Academic Research Consortium (BARC) ≥ 3) were compared in 2 subsequent trials with similar inclusion criteria but different DAPT duration, that is, BASKET (6 months; n = 557) and BASKET-PROVE (12 months; n = 2,314), between months 0 to 6 (DAPT in both trials), 7 to 12 (DAPT in BASKET-PROVE only), and 13 to 24 (aspirin in both trials) using propensity score-adjusted, time-stratified Cox proportional hazard models. RESULTS: Overall, event rates were low with fewer ST but similar MB in prolonged DAPT. Analysis of the 3 periods showed a uniform pattern for ST (interaction DAPT/period; P = .145) but an inconsistent pattern for MB (interaction DAPT/period; P < .001 for TIMI major and P = .046 for BARC ≥ 3), with more MB occurring during months 7 to 12 with prolonged DAPT. Considering observed case fatality rates of 31% with ST and 11% with MB, the extrapolated prevention of 27 ST deaths and the excess of 5 MB deaths resulted in an expected benefit of 22 survivors/10,000 patients treated over 2 years with prolonged DAPT. CONCLUSION: Despite overall low event rates, prolonged DAPT was associated with more MB during months 7 to 12 according to the interaction DAPT/period. Given the higher observed case fatality rates of ST versus MB, 12- versus 6-month DAPT was associated with an extrapolated reduction in mortality. Effective treatment periods and case fatality rates seem important in the analysis of different DAPT durations, specifically with regard to ongoing trials.

Same-day discharge after percutaneous coronary procedures-Structured review and comprehensive meta-analysis.

INTRODUCTION: Percutaneous coronary intervention is a well-established revascularization strategy for patients with coronary artery disease. The safety and feasibility of performing these procedures on a same-day discharge basis for selected patients has been studied in a large number of mostly nonrandomized trials. An up to date literature review should focus on trials with radial access, representing the current standard for coronary procedures in Austria and other European countries. METHODS: The aim of this consensus statement is to review the most recent evidence for the safety and feasibility of performing same-day discharge procedures in selected patients. A structured literature search was performed using prespecified search criteria, focusing on trials with radial access procedures. RESULTS: A total of 44 clinical trials and 4 large meta-analyses were retrieved, spanning 21 years of clinical evidence from 2001 to 2022. The outcome data from a wide range of clinical settings were unanimous in showing no negative effect on early (24 h) or late (30 day) major adverse events after same-day discharge coronary procedures. Based on nine prospective trials a comprehensive meta-analysis was compiled. Using 1­month major adverse events data the pooled odds ratio of same-day discharge versus overnight stay procedures was 0.66 (95% confidence interval, CI 0.35-01.24; p = 0.19; I2 0%), indicating a noninferiority in carefully selected patients. CONCLUSION: Outcome data from same-day discharge coronary intervention trials with radial access confirm the robust safety profile showing no increase in the risk of major adverse events compared to overnight stay.

Same-day discharge after percutaneous coronary procedures-Consensus statement of the working group of interventional cardiology (AGIK) of the Austrian Society of Cardiology.

INTRODUCTION: Percutaneous coronary intervention is a well-established revascularization strategy for patients with coronary artery disease. Recent technical advances such as radial access, third generation drug-eluting stents and highly effective antiplatelet therapy have substantially improved the safety profile of coronary procedures. Despite several practice guidelines and a clear patient preference of early hospital discharge, the percentage of coronary procedures performed in an outpatient setting in Austria remains low, mostly due to safety concerns. METHODS: The aim of this consensus statement is to provide a practical framework for the safe and effective implementation of coronary outpatient clinics in Austria. Based on a structured literature review and an in-depth analysis of available practice guidelines a consensus statement was developed and peer-reviewed within the working group of interventional cardiology (AGIK) of the Austrian Society of Cardiology. RESULTS: Based on the available literature same-day discharge coronary procedures show a favorable safety profile with no increase in the risk of major adverse events compared to an overnight stay. This document provides a detailed consensus in various clinical settings. The most important prerequisite for same-day discharge is, however, adequate selection of suitable patients and a structured peri-interventional and postinterventional management plan. CONCLUSION: Based on the data analysis this consensus document provides detailed practice guidelines for the safe operation of daycare cathlab programs in Austria.

Drug-eluting versus bare-metal stents in large coronary arteries.

BACKGROUND: Recent data have suggested that patients with coronary disease in large arteries are at increased risk for late cardiac events after percutaneous intervention with first-generation drug-eluting stents, as compared with bare-metal stents. We sought to confirm this observation and to assess whether this increase in risk was also seen with second-generation drug-eluting stents. METHODS: We randomly assigned 2314 patients needing stents that were 3.0 mm or more in diameter to receive sirolimus-eluting, everolimus-eluting, or bare-metal stents. The primary end point was the composite of death from cardiac causes or nonfatal myocardial infarction at 2 years. Late events (occurring during months 7 to 24) and target-vessel revascularization were the main secondary end points. RESULTS: The rates of the primary end point were 2.6% among patients receiving sirolimus-eluting stents, 3.2% among those receiving everolimus-eluting stents, and 4.8% among those receiving bare-metal stents, with no significant differences between patients receiving either drug-eluting stent and those receiving bare-metal stents. There were also no significant between-group differences in the rate of late events or in the rate of death, myocardial infarction, or stent thrombosis. Rates of target-vessel revascularization for reasons unrelated to myocardial infarction were 3.7% among patients receiving sirolimus-eluting stents, 3.1% among those receiving everolimus-eluting stents, and 8.9% among those receiving bare-metal stents. The rate of target-vessel revascularization was significantly reduced among patients receiving either drug-eluting stent, as compared with a bare-metal stent, with no significant difference between the two types of drug-eluting stents. CONCLUSIONS: In patients requiring stenting of large coronary arteries, no significant differences were found among sirolimus-eluting, everolimus-eluting, and bare-metal stents with respect to the rate of death or myocardial infarction. With the two drug-eluting stents, similar reductions in rates of target-vessel revascularization were seen. (Funded by the Basel Cardiovascular Research Foundation and the Swiss National Foundation for Research; Current Controlled Trials number, ISRCTN72444640.).

Simulation of bempedoic acid and ezetimibe in the lipid-lowering treatment pathway in Austria using the contemporary SANTORINI cohort of high and very high risk patients.

OBJECTIVE: The low-density lipoprotein cholesterol goals in the 2019 European Society of Cardiology/European Atherosclerosis Society dyslipidaemia guidelines necessitate greater use of combination therapies. We describe a real-world cohort of patients in Austria and simulate the addition of oral bempedoic acid and ezetimibe to estimate the proportion of patients reaching goals. METHODS: Patients at high or very high cardiovascular risk on lipid-lowering treatments (excluding proprotein convertase subtilisin/kexin type 9 inhibitors) from the Austrian cohort of the observational SANTORINI study were included using specific criteria. For patients not at their risk-based goals at baseline, addition of ezetimibe (if not already received) and subsequently bempedoic acid was simulated using a Monte Carlo simulation. RESULTS: A cohort of patients (N = 144) with a mean low-density lipoprotein cholesterol of 76.4 mg/dL, with 94% (n = 135) on statins and 24% (n = 35) on ezetimibe monotherapy or in combination, were used in the simulation. Only 36% of patients were at goal (n = 52). Sequential simulation of ezetimibe (where applicable) and bempedoic acid increased the proportion of patients at goal to 69% (n = 100), with a decrease in the mean low-density lipoprotein cholesterol from 76.4 mg/dL at baseline to 57.7 mg/dL overall. CONCLUSIONS: The SANTORINI real-world data in Austria suggest that a proportion of high and very high-risk patients remain below the guideline-recommended low-density lipoprotein cholesterol goals. Optimising use of oral ezetimibe and bempedoic acid after statins in the lipid-lowering pathway could result in substantially more patients attaining low-density lipoprotein cholesterol goals, likely with additional health benefits.

Conservative versus Invasive Strategy in Elderly Patients with Non-ST-Elevation Myocardial Infarction: Insights from the International POPular Age Registry.

This registry assessed the impact of conservative and invasive strategies on major adverse clinical events (MACE) in elderly patients with non-ST-elevation myocardial infarction (NSTEMI). Patients aged ≥75 years with NSTEMI were prospectively registered from European centers and followed up for one year. Outcomes were compared between conservative and invasive groups in the overall population and a propensity score-matched (PSM) cohort. MACE included cardiovascular death, acute coronary syndrome, and stroke. The study included 1190 patients (median age 80 years, 43% female). CAG was performed in 67% (N = 798), with two-thirds undergoing revascularization. Conservatively treated patients had higher baseline risk. After propensity score matching, 319 patient pairs were successfully matched. MACE occurred more frequently in the conservative group (total population 20% vs. 12%, adjHR 0.53, 95% CI 0.37-0.77, p = 0.001), remaining significant in the PSM cohort (18% vs. 12%, adjHR 0.50, 95% CI 0.31-0.81, p = 0.004). In conclusion, an early invasive strategy was associated with benefits over conservative management in elderly patients with NSTEMI. Risk factors associated with ischemia and bleeding should guide strategy selection rather than solely relying on age.

Second internal thoracic artery versus radial artery in coronary artery bypass grafting: a long-term, propensity score-matched follow-up study.

BACKGROUND: The best second arterial conduit for multiple arterial revascularization (MAR) is still a matter of debate. Previous studies on the benefit of either using the radial artery (RA) or the right internal thoracic artery (RITA) in coronary artery bypass grafting are not conclusive. The aim of our study was to compare the perioperative and long-term outcome of either RA or RITA grafts as second conduits for MAR. METHODS AND RESULTS: A consecutive series of 1001 patients undergoing first nonemergent coronary artery bypass grafting receiving either RA or RITA as second graft for MAR between 2001 and 2010 were studied. There were 277 patients receiving a RITA and 724 patients receiving a RA in addition to a left internal thoracic artery (LITA). Concomitant saphenous vein grafts (SVG) were grafted in addition as necessary. Propensity score-matched analysis was performed to compare the 2 groups, bilateral ITA±SVG (BITA±SVG group) and the LITA+RA±SVG group relative to overall survival and major adverse cardiac and cerebrovascular events-free survival. Hazard ratios and their 95% confidence intervals were estimated by COX regression stratified on matched pairs. The incidence of perioperative major adverse cardiac and cerebrovascular events was significantly lower in the BITA±SVG group (1.4% versus 7.6%, P<0.001). Overall survival (hazard ratio 0.23; 95% confidence interval 0.066-0.81; P=0.022) and major adverse cardiac and cerebrovascular events-free survival (hazard ratio 0.18; 95% confidence interval 0.08-0.42; P<0.001) were significantly better in the BITA±SVG group compared to the LITA+RA±SVG group. CONCLUSIONS: The results of our study provide strong evidence for the superiority of a RITA graft compared to RA as a second conduit in MAR.

Newest-generation drug-eluting and bare-metal stents combined with prasugrel-based antiplatelet therapy in large coronary arteries: the BAsel Stent Kosten Effektivitäts Trial PROspective Validation Examination part II (BASKET-PROVE II) trial design.

BACKGROUND: In the BAsel Stent Kosten Effektivitäts Trial PROspective Validation Examination (BASKET-PROVE), drug-eluting stents (DESs) had similar 2-year rates of death and myocardial infarction but lower rates of target vessel revascularization and major adverse cardiac events compared with bare-metal stents (BMSs). However, comparative clinical effects of newest-generation DES with biodegradable polymers vs second-generation DES or newest-generation BMS with biocompatible coatings, all combined with a prasugrel-based antiplatelet therapy, on 2-year outcomes are not known. METHODS: In BASKET-PROVE II, 2,400 patients with de novo lesions in native vessels ≥3 mm in diameter are randomized 1:1:1 to receive a conventional DES, a DES with a biodegradable polymer, or a BMS with biocompatible coating. In addition to aspirin, stable patients with BMS will receive prasugrel for 1 month, whereas all others will receive prasugrel for 12 months. The primary end point will be combined cardiac death, nonfatal myocardial infarction, and target vessel revascularization up to 2 years. Secondary end points include stent thrombosis and major bleeding. The primary aim is to test (1) the noninferiority of a biodegradable-polymer DES to a conventional DES and (2) the superiority of both DESs to BMS. A secondary aim is to compare the outcomes with those of BASKET-PROVE regarding the effects of prasugrel-based vs clopidogrel-based antiplatelet therapy. RESULTS: By the end of 2010, 878 patients (37% of those planned) were enrolled. CONCLUSIONS: This study will test the comparative long-term safety and efficacy of newest-generation stents on the background of contemporary antiplatelet therapy in a large all-comer population undergoing large native coronary artery stenting.

Clopidogrel pre-treatment is associated with reduced in-hospital mortality in primary percutaneous coronary intervention for acute ST-elevation myocardial infarction.

AIMS Pre-treatment with clopidogrel results in a reduction of ischaemic events in non-ST-elevation acute coronary syndromes. Data on upstream clopidogrel in the setting of primary percutaneous coronary intervention (PCI) are limited. The aim of this study was to investigate whether clopidogrel loading before arrival at the PCI centre may result in an improved outcome of primary PCI for ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS In a multicentre registry of acute PCI, 5955 patients undergoing primary PCI in Austria between January 2005 and December 2009 were prospectively enrolled. The patients consisted of two groups, a clopidogrel pre-treatment group (n = 1635 patients) receiving clopidogrel before arrival at the PCI centre and a peri-interventional clopidogrel group (n = 4320 patients) receiving clopidogrel at a later stage. Multiple logistic regression analysis including major confounding factors stratified by the participating centres was applied to investigate the effect of pre-treatment with clopidogrel on the in-hospital mortality. Additionally, two subgroups, with or without the use of GP IIb/IIIa antagonist therapy in the catheterization laboratory, were analysed. On univariate analysis, clopidogrel pre-treatment was associated with a reduced in-hospital mortality (3.4 vs. 6.1%, P< 0.01) after primary PCI. On multivariate analysis, clopidogrel pre-treatment remained an independent predictor of in-hospital mortality [odds ratio (OR) = 0.60, 95% confidence interval (CI) 0.35-0.99; P =0.048], especially in patients receiving additional GP IIb/IIIa antagonist therapy in the catheterization laboratory (OR = 0.40, 95% CI 0.19-0.83; P =0.01). CONCLUSION Clopidogrel pre-treatment before arrival at the PCI centre is associated with reduced mortality in a real world setting of primary PCI. These results strongly support the recommendation of clopidogrel treatment 'as soon as possible' in patients with STEMI undergoing pimary PCI.

Dutogliptin in Combination with Filgrastim in Early Recovery Post-Myocardial Infarction-The REC-DUT-002 Trial.

Patients with acute myocardial infarction are at high risk for developing heart failure due to scar development. Although regenerative approaches are evolving, consistent clinical benefits have not yet been reported. Treatment with dutogliptin, a second-generation DPP-4 inhibitor, in co-administration with filgrastim (G-CSF) has been shown to enhance endogenous repair mechanisms in experimental models. The REC-DUT-002 trial was a phase 2, multicenter, double-blind placebo-controlled trial which explored the safety, tolerability, and efficacy of dutogliptin and filgrastim in patients with ST-elevation Myocardial Infarction (STEMI). Patients (n = 47, 56.1 ± 10.7 years, 29% female) with STEMI, reduced left ventricular ejection fraction (EF ≤ 45%) and successful revascularization following primary PCI were randomized to receive either study treatment or matching placebo. Cardiac magnetic resonance imaging (cMRI) was performed within 72 h post-PCI and repeated after 3 months. The study was closed out early due to the SARS-CoV-2 pandemic. There was no statistically significant difference between the groups with respect to serious adverse events (SAE). Predefined mean changes within cMRI-derived functional and structural parameters from baseline to 90 days did not differ between placebo and treatment (left ventricular end-diastolic volume: +13.7 mL vs. +15.7 mL; LV-EF: +5.7% vs. +5.9%). Improvement in cardiac tissue health over time was noted in both groups: full-width at half-maximum late gadolinium enhancement (FWHM LGE) mass (placebo: -12.7 g, treatment: -19.9 g; p = 0.23). Concomitant treatment was well tolerated, and no safety issues were detected. Based on the results, the FDA and EMA have already approved an adequately powered large outcome trial.