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.

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.

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.

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.

Prehospital triage in the ambulance reduces infarct size and improves clinical outcome.

BACKGROUND: We evaluated the effect of prehospital triage (PHT) in the ambulance on infarct size and clinical outcome and studied its relationship to the distance of patient's residence to the nearest percutaneous coronary intervention (PCI) center. METHODS: All consecutive ST-segment elevation myocardial infarction patients who were transported to the Isala klinieken from 1998 to 2008 were registered in a dedicated database. Of these, 2,288 (45%) were referred via a spoke center and 2.840 (55%) via PHT. RESULTS: PHT patients were more often treated within 3 hours after symptom onset (46.2% vs 26.8%, P < .001), more often had a post-procedural thrombolysis in myocardial infarction (TIMI) 3 flow (93.0% vs 89.7%, P < .001) had a smaller infarct size (peak creatine kinase 2,188 ± 2,187 vs 2,575 ± 2,259 IU/L, P < .001) and had a lower 1-year mortality (4.9% vs 7.0%, P = .002). After multivariate analysis, PHT was independently associated with ischemic time less than 3 hours (OR 2.45, 95% CI 2.13-2.83), a peak creatine kinase less than the median value (OR 1.19, 95% CI 1.04-1.36) and a lower 1-year mortality (OR 0.67, 95% CI 0.50-0.91). The observed differences between PHT patients and the spoke group were more pronounced in the subgroup of patients living >38 km from the PCI center. CONCLUSION: PHT in the ambulance is associated with a shorter time to treatment, a smaller infarct size and a more favorable clinical outcome, especially with longer distance from the patient's residence to the nearest PCI center. Therefore, PHT in the ambulance may reduce the negative effect of living at a longer distance from the PCI center.

Facilitated reperfusion with prehospital glycoprotein IIb/IIIa inhibition: predictors of complete ST-segment resolution before primary percutaneous coronary intervention in the On-TIME 2 trial: correlates of reperfusion before primary PCI.

OBJECTIVE: The objective of this study is to evaluate the incidence, predictors, and outcome of complete ST-segment resolution (STR) during transportation after pretreatment with dual or triple antiplatelet therapy in the Ongoing Tirofiban in Myocardial Infarction Evaluation (On-TIME) 2 trial. METHODS: Patients with ST-segment elevation myocardial infarction were randomized in the ambulance to pretreatment with high-dose tirofiban (HDT) or to a control pretreatment (placebo or no HDT) on top of 600-mg clopidogrel, 500-mg aspirin, and 5000-IU unfractionated heparin. Complete STR was defined as ≥70% STR on the electrocardiogram obtained before percutaneous coronary intervention (PCI) as compared with the inclusion electrocardiogram. RESULTS: Complete STR before PCI occurred in 16.8% (n = 188/1121) and more frequently in the HDT group (19.0% vs 14.6%, P = .05). Independent predictors for complete STR before PCI were younger age (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.70-0.96, P = .01 per 10 year increase), fast diagnosis (OR, 0.97; 95% CI, 0.97-1.0, P = .004 per 15-minute increase time from symptom onset to diagnosis), longer pretreatment time (OR, 1.09; 95% CI, 1.03-1.16, P = .003 per 15-minute increase time start study medication to angiography), and randomization to HDT (OR, 1.39; 95% CI, 1.0-1.9, P = .05). Complete STR before PCI was associated with very low 30-day (0.5% vs 2.8%, P = .07) and 1-year (1.1% vs 5.0%, P = .019) mortality. CONCLUSIONS: Dual or triple antiplatelet pretreatment in the ambulance results in complete STR before PCI in 17% of patients. Fast ST-segment elevation myocardial infarction diagnosis, prehospital initiation of pretreatment early after symptom onset, and HDT independently predicted STR before PCI. Complete STR is associated with improved clinical outcome.

The golden hour of prehospital reperfusion with triple antiplatelet therapy: a sub-analysis from the Ongoing Tirofiban in Myocardial Evaluation 2 (On-TIME 2) trial early initiation of triple antiplatelet therapy.

BACKGROUND: It is known that the efficacy of thrombolytic therapy in ST-segment elevation myocardial infarction (STEMI) is highly time dependent with the best efficacy when given within the so-called golden hour. This analysis from the On-TIME 2 trial evaluated the efficacy of triple antiplatelet therapy on initial patency and ST-segment resolution (STR) in relation to time from symptom onset to first medical contact. METHODS: The On-TIME 2 trial included 1,398 consecutive STEMI patients referred for primary percutaneous coronary intervention (PCI). Patients were randomized to dual (500 mg aspirin and 600 mg clopidogrel) or triple antiplatelet (500 mg aspirin, 600 mg clopidogrel, and tirofiban 25 µg/kg bolus and 0.15 µg/kg per minute maintenance infusion for 18 hours) pretreatment in the ambulance. Primary outcome of this sub-analysis was initial patency of the infarct-related vessel and STR before PCI according to time from symptom onset to first medical contact in quartiles. In addition, the incidence of aborted myocardial infarction, defined as the absence of a rise in creatinine kinase, was assessed. RESULTS: Initial patency, STR before PCI, and the incidence of aborted myocardial infarction gradually increased with shorter time from symptom onset to first medical contact. Initial Thrombolysis in Myocardial Infarction flow was present in 21.2% in the total population and 26.2%, 21.5%, 18.1%, and 18.8% in the time quartiles, respectively (P for trend=.01). The incidence of complete STR pre-angiography was 16.6% in the total population and 23.4%, 18.2%, 14.7%, and 9.9% in the 4 quartiles, respectively (P for trend<.001). This was largely driven by the effect of triple antiplatelet therapy, which further improved initial patency and STR and led to a significantly higher incidence of aborted myocardial infarction (13.2% vs 8.7%, P=.011), especially in the patients with short duration of symptoms. CONCLUSION: Antiplatelet pretreatment before primary PCI, including a glycoprotein IIb/IIIa blocker, seems to be most effective when given shortly after symptom onset. Further studies should be performed to test this hypothesis.

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.

Impact of vessel size on distal embolization, myocardial perfusion and clinical outcome in patients undergoing primary angioplasty for ST-segment elevation myocardial infarction.

BACKGROUND: Mounting interest has emerged on the role of distal embolization as a major explanation of poor myocardial perfusion among patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary angioplasty. The aim of the current study was to evaluate the relationship between vessel size, distal embolization, myocardial perfusion and clinical outcome in patients with STEMI treated by primary angioplasty. METHODS: Our population is represented by 1969 patients with STEMI undergoing primary stenting from 1997 to 2002. All clinical, angiographic, and follow-up data were prospectively collected. RESULTS: Vessel size was linearly associated with gender, diabetes, anterior infarction location, shorter time-delay, the rate of stenting and glycoprotein IIb-IIIa inhibitors. Small vessel size was associated with poor perfusion, despite lower rates of distal embolization. These data were confirmed after correction for confounding factors. The higher risk profile and poor myocardial perfusion contribute to explain the worse outcome observed in patients with smaller vessel size. CONCLUSIONS: This study shows that in patients undergoing primary angioplasty for STEMI, small vessel size is associated with poor myocardial perfusion, despite less distal embolization, that contributes to explain the worse outcome observed among patients with small infarct related arteries.

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.

Prognostic importance of creatine kinase and creatine kinase-MB after primary percutaneous coronary intervention for ST-elevation myocardial infarction.

BACKGROUND: Although the prognostic significance of creatine kinase (CK) and creatine kinase-MB (CK-MB) after myocardial infarction has been established after thrombolysis or no reperfusion therapy, there is limited evidence of the prognostic importance after primary percutaneous coronary intervention (PCI). METHODS: In this prospective, observational study, individual data from all patients who survived at least 2 days after primary PCI between 1991 and 2004 in our hospital were recorded. The association between enzymatic infarct size (examined by peak CK and peak CK-MB levels, each divided into tertiles) and both left ventricular ejection fraction (LVEF) and 1-year mortality was evaluated. RESULTS: In the study group of 4670 patients, mean peak CK was 2327 U/L (SD 2008) and mean peak CK-MB was 244 U/L (SD 208). Both increased CK and CK-MB were associated with a lower LVEF. A total of 252 patients (5.4%) died between 2 days and 1 year after admission. Both peak CK and peak CK-MB were higher in those who died. Particularly, patients in the highest tertile of either peak CK or peak CK-MB had increased mortality, whereas the differences between the lower tertiles were not significant. In 2738 patients, after multivariable analysis including LVEF, the hazard ratio for 1-year mortality in patients in the highest CK tertile was 2.28 (95% CI 1.32-3.91) and for CK-MB, 1.91 (95% CI 1.11-3.26), compared to those in the other tertiles. CONCLUSIONS: According to this large-scale study, peak CK and peak CK-MB are comparable independent predictors of LV function and 1-year mortality in patients after primary PCI.

Comparison of usefulness of C-reactive protein versus white blood cell count to predict outcome after primary percutaneous coronary intervention for ST elevation myocardial infarction.

White blood cell (WBC) count and high-sensitive C-reactive protein (hs-CRP) are both used as markers of inflammation and prognosis after an ST elevation myocardial infarction (STEMI), but it is unknown whether they have independent prognostic value. We investigated the association and independent prognostic importance of WBC and hs-CRP after STEMI. In this subanalysis of the On-TIME trial, in 490 of 507 (97%) patients, either WBC count or CRP, and in 362 (71%) patients, both WBC count and CRP, were measured on admission before primary percutaneous coronary intervention. There was no significant correlation between WBC count and CRP (R = 0.080). Higher levels of CRP were associated with a reinfarction or death within 1 year (mean hs-CRP 14.2 +/- 20.4 vs 6.1 +/- 14.2, p = 0.006), but CRP was not associated with enzymatic infarct size (lactate dehydrogenase, LDHQ48) or left ventricular ejection fraction. A higher baseline WBC count was associated with larger LDHQ48 and lower left ventricular ejection fraction but not with 1-year reinfarction or death. In conclusion, although both WBC count and CRP are markers of inflammation and predictors of outcome after STEMI, we did not find a correlation between baseline WBC count and CRP levels in patients treated with primary percutaneous coronary intervention for STEMI. The mechanisms by which WBC counts predict outcome were related to myocardial infarct size whereas CRP were not.

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.

Mortality in patients with left ventricular ejection fraction

Decreased left ventricular (LV) function is a strong predictor of mortality. Although current guidelines recommend prophylactic implantable cardioverter-defibrillator (ICD) implantation after ST-elevation myocardial infarction and a depressed LV ejection fraction for 1 month, the prognoses of these patients may be better than those observed in randomized trials of ICDs (1-year mortality 6.8% to 19%), particularly because reperfusion treatment has improved, and the use of life-saving drugs is higher. To assess 1-year mortality in patients with depressed LV ejection fractions after primary percutaneous coronary intervention, a prospective, observational study was performed. Data from all patients who survived >/=30 days after primary percutaneous coronary intervention and had LV ejection fractions

Are patients with non-ST elevation myocardial infarction undertreated?

BACKGROUND: The worse prognosis in patients without ST-elevation (non-STEMI) as compared to ST-elevation myocardial infarction (STEMI), may be due to treatment differences. We aimed to evaluate the differences in characteristics, treatment and outcome in patients with non-STEMI versus STEMI in an unselected patient population. METHODS: Individual patient data from all patients in our hospital with a discharge diagnosis of MI between Jan 2001 and Jan 2002 were evaluated. Follow-up data were obtained until December 2004. Patients were categorized according to the presenting electrocardiogram into non-STEMI or STEMI. RESULTS: A total of 824 patients were discharged with a diagnosis of MI, 29% with non-STEMI and 71% with STEMI. Patients with non-STEMI were significantly older and had a higher cardiovascular risk profile. They underwent less frequently coronary angiography and revascularization and received less often clopidogrel and ACE-inhibitor on discharge. Long-term mortality was significantly higher in the non-STEMI patients as compared to STEMI patients, 20% vs. 12%, p = 0.006, respectively. However, multivariate analysis showed that age, diabetes, hypertension and no reperfusion therapy (but not non-STEMI presentation) were independent and significant predictors of long-term mortality. CONCLUSION: In an unselected cohort of patients discharged with MI, there were significant differences in baseline characteristics, and (invasive) treatment between STEMI and non-STEMI. Long-term mortality was also different, but this was due to differences in baseline characteristics and treatment. More aggressive treatment may improve outcome in non-STEMI patients.

Hyperglycemia is an important predictor of impaired coronary flow before reperfusion therapy in ST-segment elevation myocardial infarction.

OBJECTIVES: This study was designed to investigate whether elevated glucose is associated with impaired Thrombolysis In Myocardial Infarction (TIMI) flow before primary percutaneous coronary intervention (PCI). BACKGROUND: Reperfusion before primary PCI in patients with ST-segment elevation myocardial infarction (STEMI) is associated with an improved outcome. Hyperglycemia in patients with STEMI is associated with an adverse prognosis. Hyperglycemia may induce a pro-thrombotic state and therefore be of influence on TIMI flow before PCI. METHODS: A total of 460 consecutive patients with STEMI treated with primary PCI were included in this analysis. Hyperglycemia was defined as a glucose > or =7.8 mmol/l (140 mg/dl). RESULTS: Hyperglycemia was observed in 70% and TIMI flow grade 3 before primary PCI in 17% of the patients. Patients with hyperglycemia less often had TIMI flow grade 3 before primary PCI (12% vs. 28%, p < 0.001). After adjustment for differences in baseline variables, hyperglycemia was a strong predictor of absence of reperfusion before primary PCI (odds ratio 2.6, 95% confidence interval 1.5 to 4.5). CONCLUSIONS: Hyperglycemia in patients with STEMI is an important predictor of impaired epicardial flow before reperfusion therapy has been initiated. Investigation of methods improving coronary flow before primary PCI in these patients is warranted.

Impact of statin therapy at discharge on 1-year mortality in patients with ST-segment elevation myocardial infarction treated with primary angioplasty.

BACKGROUND: Statin therapy can reduce long-term mortality in several subgroups of patients with coronary artery disease, but the benefits after primary angioplasty for ST-segment elevation myocardial infarction (STEMI) have yet to be established. The aim of the current study was to determine whether statin therapy is associated with a reduction in mortality in patients with STEMI treated with primary angioplasty. METHODS: Our population is represented by a total of 1513 consecutive in-hospital survivors treated with primary angioplasty for STEMI between April 1997 and October 2001. Patients were divided in two groups according to statin therapy (statin group, n=893; control group, n=620) at discharge. Clinical follow-up was performed at 1 year. A propensity score, built on the basis of variables independently associated with statin prescription, was used to investigate the benefits from statin therapy in subgroups of patients that were homogeneous in terms of baseline clinical and angiographic characteristics. RESULTS: At 1-year follow-up statin therapy was associated with a significantly lower mortality (1.2% versus 7.1%, R(2) [95% CI]=0.16 [0.09-0.32], p<0.0001). These benefits were confirmed in all subgroups according to the propensity score, and at multivariate analysis (adjusted R(2) [95% CI]=0.24 [0.12-0.47], p<0.0001). CONCLUSIONS: Statin therapy at discharge was associated with a significant reduction in 1-year mortality after primary angioplasty for STEMI. Therefore, the use of statins is highly recommended in these patients.

Comparison between stenting and balloon angioplasty in patients undergoing primary angioplasty of small coronary vessels.

BACKGROUND: Primary angioplasty has been shown to improve outcomes in selected patients with ST-segment elevation myocardial infarction. However, no information has been reported so far in small vessels. In the Zwolle-6 randomized trial, consecutive patients with ST-segment elevation myocardial infarction were randomized to stenting or to balloon angioplasty without any exclusion criterion. In this study, we present data on patients with small vessels (< 3.0 mm). METHODS: From April 1997 to October 2001, 798 patients randomized to balloon angioplasty or to stenting before their initial angiogram underwent primary angioplasty of small vessels, defined according to a postprocedural reference diameter < or = 3 mm. One-year follow-up data were available from all patients. RESULTS: Three hundred eighty-seven patients were randomized to stent, whereas 411 were to balloon. The crossover rates from balloon to stent and from stent to balloon were 28% and 13.9%, respectively (P < .001). The groups were comparable in terms of postprocedural TIMI flow, myocardial blush grade, distal embolization, and ST-segment resolution. No difference was observed in 1-year mortality (7.2% vs 5.8%, P = not significant [NS]), target vessel revascularization (17.8% vs 22.1%, P = NS), and major adverse cardiac events (24.8% vs 29.0%, P = NS) between the groups. CONCLUSIONS: As compared with balloon angioplasty, routine stenting does not seem to improve clinical outcomes in patients undergoing primary angioplasty of small vessels. Future trials are certainly needed to evaluate the safety and benefits of drug-eluting stents in this high-risk subset of patients.

Impact of infarct location on left ventricular ejection fraction after correction for enzymatic infarct size in acute myocardial infarction treated with primary coronary intervention.

BACKGROUND: Left ventricular function and infarct size are strong predictors for prognosis after acute myocardial infarction (MI). Anterior MI is associated with greater reduction of left ventricular ejection fraction (LVEF) and worse prognosis. Our objective was to study whether the impact of infarct size on global LVEF is dependent of infarct location. METHODS: We analyzed 888 patients treated with primary percutaneous coronary intervention for acute MI. Enzymatic infarct size and LVEF within 1 week were measured. In 490 patients (55%), LVEF was measured a second time at 6 months. RESULTS: Every 1000 U/L of cumulative lactate dehydrogense release corresponded to a decrease of 4.7% (95% CI 4.1-5.3) in LVEF measured within 1 week post MI for left anterior descending coronary artery (LAD)-related infarcts and to a decrease of 2.4% (95% CI 1.7-3.1) in LVEF measured within 1 week post MI for non-LAD-related infarcts (P < .0001). Left ventricular ejection fraction measured 6 months post MI showed a decrease for every 1000 U/L cumulative lactate dehydrogense release of 4.8% (95% CI 4.2-5.3) for LAD and 2.4% (95% CI 1.7-3.1) for non-LAD-related infarcts (P < .0001). Multivariate correction for relevant clinical and angiographic data did not change these results. CONCLUSION: In patients with a first acute MI treated with primary percutaneous coronary intervention, LAD-related infarcts show for a similar amount of myocardial necrosis as determined by enzymatic infarct size, a lower residual LVEF when compared with non-LAD-related infarcts.