Ultrasound-guided versus fluoroscopy-guided large-bore femoral access in PCI of complex coronary lesions: the international, multicentre, randomised ULTRACOLOR Trial.

BACKGROUND: Transfemoral access is often used when large-bore guide catheters are required for percutaneous coronary intervention (PCI) of complex coronary lesions, especially when large-bore transradial access is contraindicated. Whether the risk of access site complications for these procedures may be reduced by ultrasound-guided puncture is unclear. AIMS: We aimed to show the superiority of ultrasound-guided femoral puncture compared to fluoroscopy-guided access in large-bore complex PCI with regard to access site-related Bleeding Academic Research Consortium 2, 3 or 5 bleeding and/or vascular complications requiring intervention during hospitalisation. METHODS: The ULTRACOLOR Trial is an international, multicentre, randomised controlled trial investigating whether ultrasound-guided large-bore femoral access reduces clinically relevant access site complications compared to fluoroscopy-guided large-bore femoral access in PCI of complex coronary lesions. RESULTS: A total of 544 patients undergoing complex PCI mandating large-bore (≥7 Fr) transfemoral access were randomised at 10 European centres (median age 71; 76% male). Of these patients, 68% required PCI of a chronic total occlusion. The primary endpoint was met in 18.9% of PCI with fluoroscopy-guided access and 15.7% of PCI with ultrasound-guided access (p=0.32). First-pass puncture success was 92% for ultrasound-guided access versus 85% for fluoroscopy-guided access (p=0.02). The median time in the catheterisation laboratory was 102 minutes versus 105 minutes (p=0.43), and the major adverse cardiovascular event rate at 1 month was 4.1% for fluoroscopy-guided access and 2.6% for ultrasound-guided access (p=0.32). CONCLUSIONS: As compared to fluoroscopy-guided access, the routine use of ultrasound-guided access for large-bore transfemoral complex PCI did not significantly reduce clinically relevant bleeding or vascular access site complications. A significantly higher first-pass puncture success rate was demonstrated for ultrasound-guided access. CLINICALTRIALS: gov identifier: NCT04837404.

Impact of opioids on P2Y12 receptor inhibition in patients with ST-elevation myocardial infarction who are pre-treated with crushed ticagrelor: Opioids aNd crushed Ticagrelor In Myocardial infarction Evaluation (ON-TIME 3) trial.

AIMS: Platelet inhibition induced by P2Y12 receptor antagonists in patients with ST-elevation myocardial infarction (STEMI) can be affected by concomitant use of opioids. The aim of this trial was to examine the effect of intravenous (iv) acetaminophen compared with iv fentanyl on P2Y12 receptor inhibition in patients with STEMI. METHODS AND RESULTS: The Opioids aNd crushed Ticagrelor In Myocardial infarction Evaluation (ON-TIME 3) trial randomized 195 STEMI patients who were scheduled to undergo primary percutaneous coronary intervention (PCI) and were pre-treated with crushed ticagrelor to iv acetaminophen (N = 98) or iv fentanyl (N = 97) in the ambulance. The primary endpoint, consisting of the level of platelet reactivity units (PRU) measured immediately after primary PCI, was not significantly different between the study arms [median PRU 104 (IQR 37-215) vs. 175 (63-228), P = 0.18]. However, systemic levels of ticagrelor were significantly higher in the acetaminophen arm at the start of primary PCI [151 ng/mL (32-509) vs. 60 ng/mL (13-206), P = 0.007], immediately after primary PCI [326 ng/mL (94-791) vs. 115 ng/mL (38-326), P = 0.002], and at 1 h after primary PCI [488 ng/mL (281-974) vs. 372 ng/mL (95-635), P = 0.002]. Acetaminophen resulted in the same extent of pain relief when compared with fentanyl [reduction of 3 points on 10-step-pain scale before primary PCI (IQR 1-5)] in both study arms (P = 0.67) and immediately after PCI [reduction of 5 points (3-7); P = 0.96]. CONCLUSION: The iv acetaminophen in comparison with iv fentanyl was not associated with significantly lower platelet reactivity in STEMI patients but resulted in significantly higher ticagrelor plasma levels and was effective in pain relief.

Complex Large-Bore Radial percutaneous coronary intervention: rationale of the COLOR trial study protocol.

INTRODUCTION: The radial artery has become the standard access site for percutaneous coronary intervention (PCI) in stable coronary artery disease and acute coronary syndrome, because of less access site related bleeding complications. Patients with complex coronary lesions are under-represented in randomised trials comparing radial with femoral access with regard to safety and efficacy. The femoral artery is currently the most applied access site in patients with complex coronary lesions, especially when large bore guiding catheters are required. With slender technology, transradial PCI may be increasingly applied in patients with complex coronary lesions when large bore guiding catheters are mandatory and might be a safer alternative as compared with the transfemoral approach. METHODS AND ANALYSIS: A total of 388 patients undergoing complex PCI will be randomised to radial 7 French access with Terumo Glidesheath Slender (Terumo, Japan) or femoral 7 French access as comparator. The primary outcome is the incidence of the composite end point of clinically relevant access site related bleeding and/or vascular complications requiring intervention. Procedural success and major adverse cardiovascular events up to 1 month will also be compared between both groups. ETHICS AND DISSEMINATION: Ethical approval for the study was granted by the local Ethics Committee at each recruiting center ('Medisch Ethische Toetsing Commissie Isala Zwolle', 'Commissie voor medische ethiek ZNA', 'Comité Medische Ethiek Ziekenhuis Oost-Limburg', 'Comité d'éthique CHU-Charleroi-ISPPC', 'Commission cantonale d'éthique de la recherche CCER-Republique et Canton de Geneve', 'Ethik Kommission de Ärztekammer Nordrhein' and 'Riverside Research Ethics Committee'). The trial outcomes will be published in peer-reviewed journals of the concerned literature. TRIAL REGISTRATION NUMBER: NCT03846752.

Trends in cardiovascular and bleeding outcomes in acute coronary syndrome patients treated with or without proton-pump inhibitors during the introduction of novel P2Y12 inhibitors: a five-year experience from a single-centre observational registry.

AIMS: Proton-pump inhibitors (PPIs) are commonly prescribed in acute coronary syndrome (ACS) patients on antiplatelet therapy. We studied PPI prescription in ACS patients in the era of novel P2Y12 inhibitors and assessed the association between PPI use and clinical outcomes. METHODS AND RESULTS: Between 2010 and 2014, we included all consecutive ACS patients admitted to a Dutch tertiary hospital. The main outcome was PPI prescription at discharge. Additionally, we present 1-year mortality and 30-day cardiovascular and bleeding outcomes. Of 4595 ACS patients with known discharge medication, 63.9% received a PPI. PPI-treated patients were older (67.1 ± 12.5 vs. 63.0 ± 13.3, P < 0.001). PPI treatment at discharge increased from 34.7% in 2010 to 88.7% in 2014 (P < 0.001). Concurrently, ticagrelor prescription at discharge increased from 0.0% to 48.6% in 2014 (P < 0.001), while clopidogrel prescription decreased from 78.6% in 2010 to 28.7% in 2014 (P < 0.001). PPI treatment was associated with reductions in death or myocardial infarction (MI) [adjusted hazard ratio (HR) 0.27, 95% confidence interval (CI) 0.10-0.76] and death, MI or stroke (adjusted HR 0.33, 95% CI 0.14-0.81) at 30-days post-discharge. However, this association was not present in subgroup analyses of patients treated with clopidogrel or ticagrelor. CONCLUSION: In this single-centre registry, PPI prescription in ACS patients doubled between 2010 and 2014. PPI treatment at discharge was associated with a reduction in death, MI, or stroke at 30-days post-discharge, mainly driven by a reduction in MI. There were no differences gastrointestinal bleeding between patients treated with or without a PPI. PPI treatment may serve as a marker of improved therapies and outcome, rather than causing a reduction in cardiovascular events.

Paclitaxel-eluting balloon versus everolimus-eluting stent in patients with diabetes mellitus and in-stent restenosis: Insights from the randomized DARE trial.

OBJECTIVES: To investigate the relative performance of treatment with a paclitaxel-eluting balloon (PEB) compared with an everolimus-eluting stent (EES) for in-stent restenosis (ISR) in patients with diabetes mellitus (DM). BACKGROUND: ISR remains a challenge in contemporary clinical practice, particularly in patients with DM. METHODS: In the multicenter randomized DARE trial, patients with BMS or DES ISR were randomized in a 1:1 fashion to treatment with a PEB or an EES. Patients underwent angiographic follow-up after 6 months. For the purpose of this analysis, the relative performance of PEB versus EES in diabetic patients was investigated. RESULTS: Of 278 patients enrolled in DARE, 88 (32%) had DM, of whom 46 were randomized to EES and 42 to PEB treatment. Of patients with DM, 48 (55%) had DES-ISR. Angiographic follow-up was available in 30 patients (72%) in the PEB group and 36 patients (78%) in the DES group. There were no differences in terms of 6-months minimal lumen diameter in diabetic patients treated with EES (1.46 ± 0.66 mm) versus PEB (1.78 ± 0.58 mm, P = 0.15). Adverse events at one year follow-up were similar in both groups, with Major Adverse Events (MAE, death, target vessel MI, or TVR) occurring in 17.4% in the EES group versus 11.9% in the PEB group, P = 0.44. CONCLUSIONS: In patients with ISR and DM, use of a PEB resulted in similar 6-months in-segment minimal lumen diameter and comparable rates of MAE. In-segment late loss at 6 months was significantly lower in the PEB arm. Although larger trials in DM patients with ISR are necessary, PEB is a promising treatment option obviating the need for additional stent implantation.

Trends in optimal medical therapy prescription and mortality after admission for acute coronary syndrome: a 9-year experience in a real-world setting.

Aims: Optimal medical therapy (OMT) is recommended in acute coronary syndrome (ACS) patients. Few studies present temporal trends of OMT prescription and its impact on outcomes in a real-world setting. We aimed to evaluate OMT prescription in a real-world ACS population and its relation to mortality during almost a decade. Methods and results: Consecutive ST-elevation myocardial infarction and non-ST-elevation myocardial infarction (NSTEMI) patients (n = 9202) admitted to a single Dutch tertiary hospital between 2006 and 2014 were included and followed for drug prescription and mortality up to 1 year. Optimal medical therapy was defined as prescription of aspirin, P2Y12inhibitors, statin, beta-blockers, and angiotensin converting enzyme inhibitors or angiotensin receptor blockers (ACEi/ARB). Optimal medical therapy prescription was 43.7% at discharge, 46.6% at 30-days, and 25.5% at 1-year. Optimal medical therapy prescription at discharge was lower among NSTEMI patients (34.5% vs. 49.2%, P < 0.001). Optimal medical therapy prescription at discharge, 30-days and 1-year and mortality outcomes did not change during the study period. After adjustment for baseline and admission characteristics, OMT at discharge was associated with a reduction in mortality in patients who survived hospitalization for the index event [adjusted hazard ratio: 0.66, 95% confidence interval (0.46-0.93)]. Conclusions: In this single-centre observational registry with >9000 patients reflecting almost a decade of ACS care, <50% of patients were on OMT at discharge. Prescription of OMT and mortality outcomes remained stable during the study period. After adjustment, OMT prescription at discharge was associated with reduced mortality in ACS survivors. Further contemporary randomized studies are warranted to determine the role of beta-blockers and ACEi/ARBs in ACS patients with preserved left ventricular ejection fraction.

A Randomized Comparison of Paclitaxel-Eluting Balloon Versus Everolimus-Eluting Stent for the Treatment of Any In-Stent Restenosis: The DARE Trial.

OBJECTIVES: The authors sought to evaluate the relative performance of a drug-eluting balloon (DEB) and a drug-eluting stent (DES) in patients with any (bare-metal or drug-eluting stent) in-stent restenosis (ISR). BACKGROUND: The treatment of ISR remains challenging in contemporary clinical practice. METHODS: In a multicenter randomized noninferiority trial, patients with any ISR were randomly allocated in a 1:1 fashion to treatment with a DEB (SeQuent Please paclitaxel-eluting balloon, B. Braun Melsungen, Melsungen, Germany), or a DES (XIENCE everolimus-eluting stent, Abbott Vascular, Santa Clara, California). The primary endpoint was noninferiority in terms of in-segment minimal lumen diameter (MLD) at 6-month angiographic follow-up. Secondary endpoints included angiographic parameters at 6 months and clinical follow-up up to 12 months. RESULTS: A total of 278 patients, of whom 56% had DES-ISR, were randomized at 8 sites to treatment with DEB (n = 141) or DES (n = 137). As compared with DEB, DES was associated with larger MLD and lower % stenosis immediately post-procedure (1.84 ± 0.46 vs. 1.72 ± 0.35; p = 0.018; and 26 ± 10% vs. 30 ± 10%; p = 0.03). Angiographic follow up was completed at 196 ± 53 days in 79% of patients. With respect to the primary endpoint of in-segment MLD at 6 months, DEB was noninferior to DES (DEB 1.71 ± 0.51 mm vs. DES 1.74 ± 0.61 mm; p for noninferiority <0.0001). Target vessel revascularization at 12-month follow-up was similar in both groups (DES 7.1% vs. DEB 8.8%; p = 0.65). CONCLUSIONS: In patients with ISR, treatment with DEB was noninferior compared with DES in terms of 6-month MLD. There were no differences in clinical endpoints, including target vessel revascularization up to 12 months. Therefore, use of a DEB is an attractive treatment option for in-stent restenosis, withholding the need for additional stent implantation.

Randomised comparison of drug-eluting versus bare-metal stenting in patients with non-ST elevation myocardial infarction.

OBJECTIVE: The superiority of drug-eluting stents (DES) over bare-metal stents (BMS) in patients with ST elevation myocardial infarction (STEMI) is well studied; however, randomised data in patients with non-ST elevation myocardial infarction (NSTEMI) are lacking. The objective of this study was to investigate whether stenting with everolimus-eluting stents (EES) safely reduces restenosis in patients with NSTEMI as compared to BMS. METHODS: ELISA-3 patients were asked to participate in the angiographic substudy and were randomised to DE (Xience V) or BM (Vision) stenting (ELISA-3 group). The primary end point was minimal luminal diameter (MLD) at 9-month follow-up angiography. In addition, 296 patients with NSTEMI who were excluded or did not want to participate in the ELISA-3 trial (RELI group) were randomised to DE or BM stenting and underwent clinical follow-up only (major adverse cardiac events (MACE), stent thrombosis (ST)). A pooled analysis was performed to assess an effect on clinical outcome. RESULTS: 178 of 540 ELISA-3 patients participated in the angiographic substudy. MLD at 9 months angiography was 2.37±0.63 mm (DES) versus 1.84±0.62 mm (BMS), p<0.001. Binary restenosis occurred in 1.9% in the DES group versus 16.7% in the BMS group (RR 0.11, 95% CI 0.02 to 0.84, p=0.007). In the pooled analysis, the incidence of MACE, target vessel revascularisation and ST at 2 years follow-up in the DES versus BMS group was 12.5% versus 16.0% (p=0.28), 4.0% versus 10.4% (p=0.009) and 1.3% versus 3.0% (p=0.34), respectively. CONCLUSIONS: In patients with NSTEMI, use of EES is safe and decreases both angiographic and clinical restenosis as compared to BMS http://www.isrctn.com/search?q=39230163. TRIAL REGISTRATION NUMBER: 39230163; Post-results.

Fractional Flow Reserve-Guided Deferred Versus Complete Revascularization in Patients With Diabetes Mellitus.

To assess the safety and efficacy of deferred versus complete revascularization using a fractional flow reserve (FFR)-guided strategy in patients with diabetes mellitus (DM), we analyzed all DM patients who underwent FFR-guided revascularization from January 1, 2010, to December 12, 2013. Patients were divided into 2 groups: those with ≥1 remaining FFR-negative (>0.80) medically treated lesions [FFR(-)MT] and those with only FFR-positive lesions (≤0.80) who underwent complete revascularization [FFR(+)CR] and were followed until July 1, 2015. The primary end point was the incidence of major adverse cardiovascular events (MACE), a composite of death, myocardial infarction (MI), target lesion (FFR assessed) revascularization, and rehospitalization for acute coronary syndrome. A total of 294 patients, 205 (69.7%) versus 89 (30.3%) in FFR(-)MT and FFR(+)CR, respectively, were analyzed. At a mean follow-up of 32.6 ± 18.1 months, FFR(-)MT was associated with higher MACE rate 44.0% versus 26.6% (log-rank p = 0.02, Cox regression-adjusted hazard ratio [HR] 2.01, 95% confidence interval [CI] 1.21 to 3.33, p <0.01), and driven by both safety and efficacy end points: death/MI (HR 2.02, 95% CI 1.06 to 3.86, p = 0.03), rehospitalization for acute coronary syndrome (HR 2.06, 95% CI 1.03 to 4.10, p = 0.04), and target lesion revascularization (HR 3.38, 95% CI 1.19 to 9.64, p = 0.02). Previous MI was a strong effect modifier within the FFR(-)MT group (HR 1.98, 95% CI 1.26 to 3.13, p <0.01), whereas this was not the case in the FFR(+)CR group (HR 0.66, 95% CI 0.27 to 1.62, p = 0.37). Significant interaction for MACE was present between FFR groups and previous MI (p = 0.03). In conclusion, in patients with DM, particularly those with previous MI, deferred revascularization is associated with poor medium-term outcomes. Combining FFR with imaging techniques may be required to guide our treatment strategy in these patients with high-risk, fast-progressing atherosclerosis.

The influence of system delay on 30-day and on long-term mortality in patients with anterior versus non-anterior ST-segment elevation myocardial infarction: a cohort study.

AIM: To evaluate the relationship between system delay and 30-day and long-term mortality in patients with anterior versus non-anterior ST-elevation myocardial infarction (STEMI). METHODS: We conducted a prospective observational cohort study. Patients with STEMI who were transported to the Isala Hospital, Zwolle, and underwent primary percutaneous coronary intervention (pPCI) from 2005 until 2010 were included. These patients were divided into quartiles of system delay (time from first medical contact until reperfusion therapy): Q1-Q4. RESULTS: In total, 3041 patients were included in our study. 41% (n=1253) of the patients had an anterior myocardial infarction (MI) and 59% of the patients (n=1788) had a non-anterior MI. Only in patients with an anterior MI, prolonged system delay was associated with a higher mortality (30-day Q1: 2.6%, Q2: 3.1%, Q3: 6.8%, Q4: 7.4%, p=0.001; long-term Q1: 12.8%, Q2: 13.7%, Q3: 24.1%, Q4: 22.6%, p<0.001). After multivariable adjustment, prolonged system delay was associated with a higher 30-day and long-term mortality in patients with an anterior MI (30 day Q2: HR 1.18, 95% CI (0.46 to 3.00), Q3: HR 2.45, 95% CI (1.07 to 5.63), Q4: HR 2.25, 95% CI (0.97 to 5.25)); long-term Q2: HR 1.09, 95% CI (0.71 to 1.68), Q3: HR 1.68, 95% CI (1.13 to 2.49), Q4: HR 1.55, 95% CI (1.03 to 2.33)), but not in patients with a non-anterior MI. CONCLUSIONS: Prolonged system delay significantly increased short-term as well as long-term mortality in patients with an anterior MI. This effect was not demonstrated in patients with a non-anterior MI. Therefore, it is of the greatest importance to minimise system delay in patients who present with an anterior MI.

Impact of out-of-hospital cardiac arrest due to ventricular fibrillation in patients with ST-elevation myocardial infarction admitted for primary percutaneous coronary intervention: Impact of ventricular fibrillation in STEMI patients.

OBJECTIVE: Pre-hospital life-threatening ventricular tachycardia/fibrillation (VT/VF) is relatively common in the acute phase of ST-elevation myocardial infarction (STEMI). We evaluated the prognostic impact of out-of-hospital cardiac arrest (OHCA) due to VT/VF in non-selected patients with STEMI admitted for primary percutaneous coronary intervention (PCI). METHODS: Prospective hospital registry was used to collect data of consecutive STEMI patients admitted to our hospital between 2005 and 2010. Patients with OHCA were identified from this registry, and their medical records were reviewed. RESULTS: During the study period, 4653 patients were admitted with STEMI. Data regarding OHCA due to VT/VF was available in 4643 patients (99.8%). A total of 326 patients (7.0%) had OHCA due to VT/VF. Patients with OHCA were younger (60.3 ± 11.8 vs. 64.1 ± 12.9 year, p<0.001), less often had diabetes (5.2% vs. 12.4%, p<0.001) but more often presented with signs of heart failure (Killip class >1:17.5% vs. 7.7%, p<0.001) and cardiogenic shock (29.6% vs. 2.5%, p<0.001). Coronary angiography was performed in 97.5% of the patients. Coronary angiography and primary PCI were performed equally in both groups. In patients with OHCA, the left main artery (2.3% vs. 1.0%, p=0.04) and LAD (49.2% vs. 41.2%, p=0.01) were more often the culprit artery. In-hospital mortality was significantly higher among patients with OHCA (13.80% vs. 3.4%, p<0.001). However, in patients who were discharged alive from the hospital, the one-year mortality and the combined incidence of death and appropriate ICD therapy were similar in patients with and without OHCA. CONCLUSION: In a large non-selected STEMI patient population admitted for primary PCI, OHCA due to VT/VF was associated with higher in-hospital mortality but did not affect the long-term prognosis.

Direct drug-eluting stenting to reduce stent restenosis: a randomized comparison of direct stent implantation to conventional stenting with pre-dilation or provisional stenting in elective PCI patients.

OBJECTIVES: The aim was to investigate whether a strategy of direct drug-eluting stent (DES) implantation without pre-dilation is associated with a reduced incidence of restenosis compared with CS with pre-dilation or provisional stenting (PS). BACKGROUND: Previous studies were performed comparing direct stenting (DS) with conventional stenting (CS) after pre-dilation; however, none of these in the DES era. Therefore, the STRESSED (direct Stenting To reduce REStenosis in Stent Era with Drug elution) study was designed and carried out. METHODS: A total of 600 patients with angina pectoris or recent myocardial infarction were randomized to a DS, CS, or PS strategy. The primary endpoint was the mean minimal lumen diameter at 9-month follow-up angiography. Secondary endpoints were clinical procedural success defined as angiographic success without in-hospital major adverse cardiac events (MACE), and MACE at 9-month and 2-year follow-up. RESULTS: Stent implantation in the DS group was 98%, 99% in the CS group, and 77% in the PS group. Percutaneous coronary intervention success was 99% in all groups. The minimal lumen diameter at 9-month follow-up was 2.12 ± 0.58 mm (DS), 2.17 ± 0.67 mm (CS), and 1.99 ± 0.69 mm (PS), p = 0.556 for comparison of DS with CS, p = 0.073 for comparison of DS with PS. The absolute difference was -0.05 (DS to CS), 95% confidence interval: -0.19 to -0.09, p = 0.48 and 0.13 (DS to PS), confidence interval: -0.02 to -0.27, p = 0.087. Restenosis was found in 3.4% (DS), 6.7% (CS), and 11.5% (PS), p = 0.025. At 9-month and 2-year follow-up, MACE occurred in 6.8% and 11.5% (DS), 4.6% and 10.3% (CS), and 7.6% and 13.8% (PS) (p = 0.439 and 0.536), respectively. CONCLUSIONS: Direct DES implantation compared with conventional DES implantation did not reduce restenosis. Provisional stenting, however, was associated with a higher rate of restenosis. This did not translate into a difference in the rate of MACE. (STRESSED study: direct Stenting To reduce REStenosis in Stent Era with Drug elution; ISRCTN41213536).

[Resuscitation for myocardial infarction and head injury: first the heart or first the head?]. / Reanimatie bij myocardinfarct en trauma capitis: eerst het hart of eerst het hoofd?

Loss of circulation in a patient results in collapse and therefore possible head injury. After percutaneous coronary intervention (PCI) including anticoagulation, comatose patients are sedated for mild therapeutic hypothermia. Recognised or unrecognised head trauma may have dramatic clinical consequences. A 42-year-old male with unrecognised head trauma died due to a massive intracranial haemorrhage (ICH) during the hypothermia phase after being treated with PCI. A 76-year-old female, on anticoagulation for atrial fibrillation, with recognised ICH which resulted in an adjusted PCI, died after five days due to a lethal re-bleed. In a 55-year-old male with neurological abnormalities after mild head trauma, the PCI was postponed for a (negative) head CT which might have increased cardiac muscle damage. Nowadays more patients reach hospital after being resuscitated for cardiac arrest and possible head trauma should be considered in all these patients. This could lead to adjustments being made in the treatment protocol.

The effect of thrombus aspiration during primary percutaneous coronary intervention on clinical outcome in daily clinical practice.

It was the purpose of this study to assess the effect of thrombus aspiration (TA) during primary percutaneous coronary intervention (PPCI) on reperfusion and clinical outcome in a real-world STEMI population. The decision to use TA (Export catheter, Medtronic) was at the discretion of the treating cardiologist. The primary endpoint was mortality at short (in-hospital) and long term (one year) follow-up. Secondary end points were post-PCI TIMI flow, residual ST deviation and enzymatic infarct size. Cox proportional hazard models (propensity-weighted) and logistic regression analysis were used to adjust for known covariates, associated with mortality. We performed a retrospective analysis of prospectively collected data on 2,552 consecutive PPCI-treated STEMI patients between 2007 and 2010. Use of TA increased from 6.9% in 2007 to 62.2% in 2010 (p<0.001). TA was performed in 899 patients (35.2%). In-hospital and one-year mortality rates were 3.0% and 6.0%, respectively, in the TA group and 3.5% and 7.6% in the no-TA group. After multivariate analysis, TA was not significantly associated with in-hospital mortality (adjusted odds ratio [OR]: 0.70; 95% confidence interval [CI]: 0.33-1.49, p=0.36) nor one year mortality (adjusted hazard ratio [HR]: 0.75, 95%CI: 0.47-1.20, p=0.23) or cardiac mortality (HR: 0.81; 95%CI: 0.45-1.46, p=0.49). After matching on the propensity score, the HR in the TA group for one year mortality was 0.70 (95%CI: 0.41-1.20, p=0.19) and for one-year cardiac mortality 0.70 (95%CI: 0.36-1.34, p=0.28). In conclusion, no significant relationship of TA with one of the secondary end points was found. The use of TA increased over the last years but clinical outcome was similar in both groups (TA vs no-TA) in this large cohort of real-world, unselected STEMI patients.

Is the difference in outcome between men and women treated by primary percutaneous coronary intervention age dependent? Gender difference in STEMI stratified on age.

AIM: Poorer outcomes in women with ST-elevation myocardial infarction (STEMI) are often attributed to gender differences in baseline characteristics. However, these may be age dependent. We examined the importance of gender in separate age groups of patients with STEMI undergoing primary percutaneous coronary intervention (PPCI). METHODS AND RESULTS: Data of 6746 consecutive patients with STEMI admitted for PPCI between 1998 and 2008 in our hospital were evaluated. Age was stratified into two groups, <65 years (young group) and ≥65 years (elderly). Endpoints were enzymic infarct size as well as 30-day and 1 year mortality. We studied a total of 4991 (74.0%) men and 1755 (26.0%) women; 40% of women were <65 years and 60% of men were <65 years of age. In the elderly group (≥65 years), women had more frequently diabetes and hypertension while they smoked less frequently than men. Younger women smoked more often than similarly aged men and had more hypertension. At angiography, single-vessel disease and TIMI 3 flow before PPCI was more present in younger women than men, whereas these differences were not found in the older age group. Patient delay before admission was shorter in men at all ages, while women had lower creatine kinase levels. Younger women had a higher mortality after 30 days (HR 2.1, 95% CI 1.3-3.4) and at 1 year (HR 1.7, 95% CI 1.2-2.6), whereas in the older age group women mortality rates were higher at 30 days (HR 1.5, 95% CI 1.1-2.0) but not at 1 year (HR 1.2, 95% CI 0.9-1.5). After multivariate analysis, 1-year mortality remained significantly higher in women at younger age (HR 1.7, 95% CI 1.1-2.5). Patient delay before admission was shorter in men in both age groups. Creatine kinase levels were in both age groups higher in men. CONCLUSIONS: Differences in mortality between men and women with STEMI treated with PPCI are age dependent. Although young women have less obstructive coronary artery disease and more often TIMI 3 flow before PCI (suggesting a lower risk), survival was worse compared to similarly aged men. Women had a longer patient delay compared to men, but this was not related to gender-specific mortality.

Impact of ischemic time on post-infarction left ventricular function in ST-elevation myocardial infarction treated with primary percutaneous coronary intervention.

BACKGROUND: Myocardial necrosis is a time-dependent event. Nevertheless, clinical studies on association between ischemic time and left ventricle function showed inconsistent findings. Aim of current study is to evaluate the association between ischemic time and the post-infarction left ventricular function in ST-elevation myocardial infarction treated with primary PCI. METHODS: In 2529 patients treated with primary PCI, left ventricular ejection fraction (LVEF) was measured before discharge (median day 4) by radionuclide ventriculography or by echocardiography if patients had atrial fibrillation. Ischemic time was calculated from symptom onset to first balloon inflation. RESULTS: The correlation between ischemic time as continuous variable and LVEF was significant but weak (P=0.002, r=-0.062). The LVEF of patients in ischemic time intervals of >6, >3-6, and ≤3 h was 45.1±11.7%, 44.6±11.9%, and 43.2±12.2%, respectively (P=0.029). Adjusted odds ratio of the ischemic time intervals for LVEF<40% was 1.14 (95% CI 1.00-1.30). TIMI flow 0 before and TIMI flow 3 after PCI were related with both longer ischemic time and low LVEF. CONCLUSION: Ischemic time was associated with post infarction LVEF in patients treated with primary PCI, although this association was weak. Initial TIMI flow and post-PCI TIMI flow played important role in impact of the ischemic time on the LVEF.

Net clinical benefit of prehospital glycoprotein IIb/IIIa inhibitors in patients with ST-elevation myocardial infarction and high risk of bleeding: effect of tirofiban in patients at high risk of bleeding using CRUSADE bleeding score.

AIMS: The aim of this subanalysis was to assess the net clinical effect of prehospital administration of tirofiban in ST-elevation myocardial infarction (STEMI) patients with high risk of bleeding. METHODS: This is a retrospective subanalysis of the On- TIME 2 trial, a multicenter, controlled randomized trial of the effects of high bolus-dose tirofiban given in the ambulance in STEMI patients. Tirofiban was given on top of aspirin, heparin, and clopidogrel. According to CRUSADE, patients with a moderate to very high baseline risk of bleeding were defined as high risk and patients with a very low or low baseline bleeding risk were defined as low risk. Primary endpoint was net adverse clinical events (NACE) at 30 days (defined as the combined incidence of death, recurrent myocardial infarction, urgent target vessel revascularization, stroke, or non-coronary artery bypass graft [CABG]-related major bleeding). RESULTS: Of 1309 patients, a high bleeding risk was present in 291 patients (22.2%). In these high-risk bleeding patients, tirofiban significantly improved after percutaneous coronary intervention (PCI) ST-segment resolution. Administration of tirofiban in high-risk bleeding patients showed no difference in 30-day major adverse cardiac events (MACE) (9.4% vs 13.0%; P=.330; relative risk [RR], 0.72; 95% confidence interval [CI], 0.37-1.39). However, pretreatment with tirofiban was associated with a nonsignificant increase in non-CABG related bleeding (8.6% vs 3.6%; P=.082; RR, 2.38; 95% CI, 0.90-6.39). The net clinical effect (30-day NACE) of tirofiban in this group was balanced (11.5% vs 15.2%; P=.365; RR, 0.76; 95% CI, 0.41-1.38). CONCLUSION: Prehospital use of tirofiban in STEMI patients with high risk of bleeding improves post-PCI ST-segment resolution, but increases nonsignificantly the risk of non-CABG related bleeding. The net result is a balanced effect on 30-day NACE. Additional studies should clarify how use of bleeding risk scores should modify medical (antiplatelet) therapy.

The effect of pre-hospital glycoprotein IIb-IIIa inhibitors on angiographic outcome in STEMI patients who are candidates for primary PCI.

OBJECTIVES: Aim of this study was to assess the effect of early initiation of high bolus dose tirofiban on top of dual antiplatelet therapy on angiographic outcome before and after primary percutaneous coronary intervention (PCI) in ST-elevation myocardial infraction patients. BACKGROUND: Glycoprotein IIb/IIIa inhibitors are effective inhibitors of platelet aggregation, and have shown to reduce thrombotic complications in patients undergoing PCI. METHODS: This is a pre-specified angiographic analysis of the On-TIME 2 trial (N = 984) and its open label run-in phase (N = 414). All angiographic parameters, including quantitative coronary angiography (QCA) were performed in an independent angiographic core lab. RESULTS: Of the 1,398 patients, 709 patients (50.7%) were randomized to pre-hospital tirofiban. An open infarct related vessel (TIMI 2 or 3 flow) at initial angiography was more often present in the tirofiban group as compared to the no tirofiban group (58.3% vs. 49.7%, P = 0.002). Tirofiban also reduced initial thrombus burden (P for trend = 0.035) as well as thrombus grade 5 (46.9% vs. 54.3%, P = 0.016) and showed a trend toward a reduction in large thrombus burden (LTB) (69.4% vs. 74.5%, P = 0.055). After PCI, a trend towards a lower corrected TIMI frame count (cTFC) in the tirofiban group was found. A significant interaction was found with time of initiation of study drug, with highest efficacy of tirofiban when given within 76 min after symptom onset, with a significantly lower cTFC after PCI (21.9 ± 17.6 vs. 23.9 ± 18.5, P = 0.008, P for interaction P = 0.006). CONCLUSION: In patients undergoing primary PCI, pre-hospital administration of tirofiban reduces initial thrombus burden and improves initial patency of the infarct related vessel before PCI. Initiation of tirofiban seems to be most effective when given very early after the onset of symptoms; however, this finding needs confirmation in other studies. CLINICAL TRIAL REGISTRATION: The On-TIME 2 trial is registered, at http://isrctn.org, number ISRCTN06195297.