Tomasz Rakowski

Early glycoprotein IIb–IIIa inhibitors in primary angioplasty (EGYPT) cooperation: an individual patient data meta-analysis

Background: Even though time-to-treatment has been shown to be a determinant of mortality in primary angioplasty, the potential benefits from early pharmacological reperfusion by glycoprotein (Gp) IIb–IIIa inhibitors are still unclear. The aim of this meta-analysis was to combine individual data from all randomised trials conducted on facilitated primary angioplasty by the use of early Gp IIb–IIIa inhibitors. Methods and results: The literature was scanned by formal searches of electronic databases (MEDLINE, EMBASE) from January 1990 to October 2007. All randomised trials on facilitation by the early administration of Gp IIb–IIIa inhibitors in ST-segment elevation myocardial infarction (STEMI) were examined. No language restrictions were enforced. Individual patient data were obtained from 11 out of 13 trials, including 1662 patients (840 patients (50.5%) randomly assigned to early and 822 patients (49.5%) to late Gp IIb–IIIa inhibitor administration). Preprocedural Thrombolysis in Myocardial Infarction Study (TIMI) grade 3 flow was more frequent with early Gp IIb–IIIa inhibitors. Postprocedural TIMI 3 flow and myocardial blush grade 3 were higher with early Gp IIb–IIIa inhibitors but did not reach statistical significance except for abciximab, whereas the rate of complete ST-segment resolution was significantly higher with early Gp IIb–IIIa inhibitors. Mortality was not significantly different between groups, although early abciximab demonstrated improved survival compared with late administration, even after adjustment for clinical and angiographic confounding factors. Conclusions: This meta-analysis shows that pharmacological facilitation with the early administration of Gp IIb–IIIa inhibitors in patients undergoing primary angioplasty for STEMI is associated with significant benefits in terms of preprocedural epicardial recanalisation and ST-segment resolution, which translated into non-significant mortality benefits except for abciximab.

Early glycoprotein IIb-IIIa inhibitors in primary angioplasty-abciximab long-term results (EGYPT-ALT) cooperation: individual patient's data meta-analysis.

Summary.  Background: Even although time to treatment has been shown to be a determinant of mortality in primary angioplasty, the potential benefits are still unclear from early pharmacological reperfusion by glycoprotein (Gp) IIb‐IIIa inhibitors. Therefore, the aim of this meta‐analysis was to combine individual data from all randomized trials conducted on upstream as compared with late peri‐procedural abciximab administration in primary angioplasty. Methods: The literature was scanned using formal searches of electronic databases (MEDLINE and EMBASE) from January 1990 to December 2010. All randomized trials on upstream abciximab administration in primary angioplasty were examined. No language restrictions were enforced. Results: We included a total of seven randomized trials enrolling 722 patients, who were randomized to early (n = 357, 49.4%) or late (n = 365, 50.6%) peri‐procedural abciximab administration. No difference in baseline characteristics was observed between the two groups. Follow‐up data were collected at a median (25th–75th percentiles) of 1095 days (720–1967). Early abciximab was associated with a significant reduction in mortality (primary endpoint) [20% vs. 24.6%; hazard ratio (HR) 95% confidence interval (CI) = 0.65 (0.42–0.98) P = 0.02, Phet = 0.6]. Furthermore, early abciximab administration was associated with a significant improvement in pre‐procedural thrombolysis in myocardial infarction (TIMI) 3 flow (21.6% vs. 10.1%, P < 0.0001), post‐procedural TIMI 3 flow (90% vs. 84.8%, P = 0.04), an improvement in myocardial perfusion as evaluated by post‐procedural myocardial blush grade (MBG) 3 (52.0% vs. 43.2%, P = 0.03) and ST‐segment resolution (58.4% vs. 43.5%, P < 0.0001) and significantly less distal embolization (10.1% vs. 16.2%, P = 0.02). No difference was observed in terms of major bleeding complications between early and late abciximab administration (3.3% vs. 2.3%, P = 0.4). Conclusions: This meta‐analysis shows that early upstream administration of abciximab in patients undergoing primary angioplasty for ST‐segment elevation myocardial infarction (STEMI) is associated with significant benefits in terms of pre‐procedural epicardial re‐canalization and ST‐segment resolution, which translates in to significant mortality benefits at long‐term follow‐up.

Impact of Multivessel Coronary Artery Disease and Noninfarct-Related Artery Revascularization on Outcome of Patients With ST-Elevation Myocardial Infarction Transferred for Primary Percutaneous Coronary Intervention (from the EUROTRANSFER Registry)

The aim of the study was to assess the impact of multivessel coronary artery disease (MVD) and noninfarct-related artery (non-IRA) revascularization during index percutaneous coronary intervention (PCI) on outcomes of patients with ST-segment elevation myocardial infarction (STEMI). Data on 1,598 of 1,650 patients with complete angiographic data, with >or=1 significantly stenosed epicardial coronary artery, and without previous coronary artery bypass grafting were retrieved from the EUROTRANSFER Registry database. Patients with 1-, 2-, and 3-vessel disease made up 48.5%, 32.0%, and 19.5% of the registry population, respectively. Patients with MVD were less likely to achieve final Thrombolysis In Myocardial Infarction grade 3 flow (1- vs 2- vs 3-vessel disease, 93.6% vs 89.3% vs 87.9%, respectively, p = 0.003) and ST-segment resolution >50% within 60 minutes after PCI (1- vs 2- vs 3-vessel disease, 80.9% vs 77.5% vs 69.3%, respectively, p <0.001). They were also at higher risk of death during 1-year follow-up (1- vs 2- vs 3-vessel disease, 4.9% vs 7.4% vs 13.5%, respectively, p <0.001), and MVD was identified as an independent predictor of 1-year death. In 70 patients (9%) non-IRA PCI was performed during index PCI. These patients were at higher risk of 30-day and 1-year death compared to patients without non-IRA PCI, but this difference in mortality was no longer significant after adjustment for covariates. In conclusion, patients with MVD have decreased epicardial and myocardial reperfusion success and had worse prognosis after primary PCI for STEMI compared to patients with 1-vessel disease. In this large multicenter registry, non-IRA PCI during the index procedure was performed in 9% of patients with MVD and it was associated with increased 1-year mortality.

Thrombus aspiration followed by direct stenting: a novel strategy of primary percutaneous coronary intervention in ST-segment elevation myocardial infarction. Results of the Polish-Italian-Hungarian RAndomized ThrombEctomy Trial (PIHRATE Trial).

BACKGROUND Previous studies with thrombectomy showed different results, mainly due to use of thrombectomy as an additional device not instead of balloon predilatation. The aim of the present study was to assess impact of aspiration thrombectomy followed by direct stenting. METHODS Patients with ST elevation myocardial infarction (STEMI) <6 hours from pain onset and occluded infarct-related artery in baseline angiography were randomized into aspiration thrombectomy followed by direct stenting (TS, n = 100) or standard balloon predilatation followed by stent implantation (n = 96). The primary end point of the study was the electrocardiographic ST-segment elevation resolution >70% (STR > 70%) 60 minutes after primary angioplasty (percutaneous coronary intervention [PCI]). Secondary end points included angiographic myocardial blush grade (MBG) after PCI, combination of STR > 70% immediately after PCI and MBG grade 3 (optimal myocardial reperfusion), Thrombolysis In Myocardial Infarction flow after PCI, angiographic complications, and in-hospital major adverse cardiac events. RESULTS Aspiration thrombectomy success rate was 91% (crossing of the lesion with thrombus reduction and flow restoration). There was no significant difference in STR ≥ 70% after 60 minutes (53.7% vs 35.1%, P = .29). STR > 70% immediately after PCI (41% vs 26%, P < .05), MBG grade 3 (76% vs 58%, P < .03), and optimal myocardial reperfusion (35.1% vs 11.8%, P < .001) were more frequent in TS. There was no difference in between the groups in 6-month mortality (4% vs 3.1%, P = .74) and reinfarction rate (1% vs 3.1%, P = .29). CONCLUSIONS Aspiration thrombectomy and direct stenting is safe and effective in STEMI patients with early presentation (<6 hours). The angiographic parameters of microcirculation reperfusion and ECG ST-segment resolution directly after PCI were significantly better in thrombectomy group despite the lack of the difference in ST-segment resolution 60 minutes after PCI.

Mesh covered stent in ST-segment elevation myocardial infarction

AIMS The MGuard stent (bare metal stent wrapped externally with a polymer mesh sleeve) is designed to prevent distal embolisation by reducing thrombus and plaque fragments released during and post percutaneous coronary intervention (PCI). The aim of this study was to confirm the clinical feasibility, safety and performance of the MGuard stent during primary PCI for ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS The present study was a multicentre, prospective, single arm study in which 60 patients with STEMI <12 hours were enrolled. Predilatation was performed in 61.7% of the cases and thrombus aspiration in 18.3%. In one (1.7%) patient the stent could not cross the lesion. Final TIMI grade 3 flow was observed in 90.0% of patients, with myocardial blush grade 3 in 73.3% of patients and complete (>70%) ST-segment resolution 60 minutes after PCI in 61.4% of patients. In 5.0% of cases distal embolisation occurred. The total major adverse cardiac events rate during the 6-month follow-up was 1.7%. CONCLUSIONS Based on this experience, the MGuard stent implantation in STEMI patients is safe and highly effective. A larger randomised trial is warranted to confirm the clinical endpoints.

Plasma asymmetric dimethylarginine is related to anticitrullinated protein antibodies in rheumatoid arthritis of short duration

We have recently demonstrated elevated plasma levels of an endogenous nitric oxide synthase inhibitor, asymmetric dimethyl-L-arginine (ADMA), and its association with carotid atherosclerosis in rheumatoid arthritis (RA). Both an elevated risk of myocardial infarction and increased levels of anticitrullinated protein antibodies (ACPAs), specific for RA, had been shown to precede the onset of clinical RA symptoms. Therefore, our aim was to verify the hypothesis that ADMA accumulation might accompany raised ACPAs titers in RA of short duration (< or = 3 years). Twenty patients (16 women, 4 men; mean age, 45 +/- 12 years; mean disease duration, 2.3 +/- 0.5 years) with active RA despite chronic disease-modifying antirheumatic medication, free of cardiovascular disease or atherosclerotic risk factors, were studied. Plasma levels of ADMA and its stereoisomer, symmetric dimethyl-L-arginine (SDMA), were assayed by liquid chromatography/tandem mass spectrometry. The ACPAs were measured by a second-generation enzyme-linked immunosorbent assay. In addition to routine biochemical assays, plasma concentrations of tumor necrosis factor alpha, monocyte chemoattractant protein-1, and vascular cell adhesion molecule-1 soluble form were analyzed with respective enzyme-linked immunosorbent assays. A significant positive correlation between levels of ACPAs and ADMA (r = .60, P = .005), but not SDMA (r = -.02, P = .9), was found. Neither ADMA nor SDMA was correlated to any of the clinical or biochemical parameters reflecting disease activity and inflammatory activation. Thus, excessive ADMA accumulation accompanies elevated ACPAs levels in patients with RA of short duration free of cardiovascular disease or risk factors.

Transradial approach in patients with ST-elevation myocardial infarction treated with abciximab results in fewer bleeding complications: data from EUROTRANSFER registry.

ObjectivesOur aim was to investigate the safety and efficacy of transradial approach, predictors of bleeding complications, and choice of radial access site in a real-life setting using a contemporary European registry of percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI). BackgroundThere is an increasing amount of data suggesting that transradial approach is associated with less bleeding at access site and other vascular complications when compared with procedures carried out through the femoral artery. MethodsConsecutive data on STEMI patients transferred for primary PCI in hospital STEMI networks between November 2005 and January 2007 from seven countries in Europe were gathered. Patients were divided into the following two groups: radial approach – with radial access site for primary PCI, and transfemoral approach (FEM) – with femoral access site. ResultsData from a total of 1650 patients were collected in the EUROTRANSFER Registry. Abciximab was administered in 1086 patients (66%), 169 patients were assigned to radial approach group, whereas 917 to FEM group. Puncture site hematomas were more frequent in the FEM group (1.2 vs. 9.4%, P<0.001). Major bleedings requiring blood transfusion occurred similarly in both the studied groups. Independent predictors of bleeding (puncture site hematoma and major bleeding requiring transfusion) included female sex, lower weight, chronic renal failure, past stroke, and femoral access site (odds ratio=3.54). ConclusionThe choice of radial access site in patients with STEMI treated with primary PCI is associated with lower local bleeding complications like puncture site hematomas and is an independent predictor of fewer bleedings.

Association between endothelial progenitor cell depletion in blood and mild-to-moderate renal insufficiency in stable angina

BACKGROUND Low blood counts of CD34/kinase-insert domain receptor double-positive cells (CD34(+)/KDR(+) cells)-a leukocytes subpopulation enriched for bone marrow-derived endothelial progenitor cells (EPC)- predict adverse outcomes in coronary artery disease (CAD). The dependence of EPC numbers on the glomerular filtration rate (GFR), another prognostic factor, has not been reported in CAD yet. Our aim was to assess CD34(+)/KDR(+) cell counts versus GFR in stable angina. METHODS We studied 102 stable angina men with severe angiographic CAD and normal left-ventricular systolic function. CD34(+)/KDR(+) cells were enumerated by flow cytometry. RESULTS With lowering GFR, CD34(+)/KDR(+) cell numbers (% of lymphocytes, median and interquartile range) decreased: 0.04 (0.03-0.06), 0.03 (0.02-0.05) and 0.02 (0.01-0.03)% for GFR >or=90, 60-89 and 30-59 ml/min/1.73 m(2), respectively (P < 0.001 for trend). CD34(+)/KDR(+) cell counts correlated with GFR (r = 0.25, P = 0.01), CAD extension score (r = -0.20, P = 0.04), soluble form of vascular cell adhesion molecule-1 (sVCAM-1) (r = -0.22, P = 0.03) and homocysteine (r = -0.20, P = 0.04) levels. A GFR <90 ml/min/1.73 m(2) was associated with insignificantly higher plasma erythropoietin concentrations (r = -0.22, P = 0.09 for trend) that correlated with haemoglobin levels (r = -0.33, P = 0.01, n = 59). The GFR-CD34(+)/KDR(+) cells relation was attenuated, yet maintained (beta = 0.19 +/- 0.09, P = 0.04) on adjustment for the remaining multivariate determinants of CD34(+)/KDR(+) cell numbers: sVCAM-1 (beta = -0.20 +/- 0.09, P = 0.03) and haemoglobin (beta = 0.18 +/- 0.09, P = 0.05). CONCLUSIONS Mild-to-moderate renal dysfunction accompanying stable angina is associated with CD34(+)/KDR(+) cell depletion, which partially depends on concomitant endothelial dysfunction and a tendency to anaemia (despite insignificantly higher erythropoietin) irrespective of an angiographic CAD extent. This may exacerbate an imbalance between endothelial injury and EPC-mediated repair, thus contributing to high cardiovascular risk in CAD coexisting with renal insufficiency.

Impact of infarct-related artery patency before primary PCI on outcome in patients with ST-segment elevation myocardial infarction: the HORIZONS-AMI trial

AIMS We assessed the impact of early infarct-related artery (IRA) recanalisation on the outcomes of patients in the recently conducted, large-scale, multicentre HORIZONS-AMI trial. METHODS AND RESULTS Of the 3,602 patients enrolled in the HORIZONS-AMI trial, 3,093 patients (85.9%) were treated with percutaneous coronary intervention (PCI) to a single artery. We analysed one-year outcomes in these patients according to the presence or absence of early IRA patency, defined as Thrombolysis in Myocardial Infarction (TIMI) 2 or 3 flow in the IRA. Baseline coronary angiography showed early IRA patency in 1,121 patients (36.2%), while 1,972 patients (63.8%) had TIMI 0 or 1 flow. The presence compared with the absence of early IRA patency was associated with better angiographic results after primary PCI with more TIMI 3 flow after PCI (93.2% vs. 82.9%, p<0.0001) and myocardial blush grade 2 or 3 (84.4% vs. 71.1%, p<0.0001). Early IRA patency was associated with lower rates of one-year mortality (2.5% vs. 3.9%, p=0.04) and definite or probable stent thrombosis (2.0% vs. 4.0%, p=0.002). In multivariable analysis, early IRA patency at baseline angiography was an independent predictor of reduced mortality at one year (HR 0.58, 95% CI: 0.36-0.98, p=0.02). CONCLUSIONS Early IRA patency in patients with STEMI undergoing primary PCI is associated with better TIMI flow and myocardial blush post PCI and is an independent predictor of lower one-year mortality. ClinicalTrials.gov identifier NCT00433966.

Out-of-hospital cardiac arrest in patients treated with primary PCI for STEMI. Long-term follow up data from EUROTRANSFER registry

OBJECTIVES Our aim was to describe long-term outcome of OHCA patients in a cohort of STEMI patients treated by primary PCI based on the EUROTRANSFER Registry data. BACKGROUND The occurrence of cardiac arrest is associated with impaired survival. There are limited number of studies reporting outcome of STEMI patients with out-of-hospital cardiac arrest (OHCA) treated by primary percutaneous coronary intervention (PCI). The recently published resuscitation guidelines of the European Resuscitation Council (ERC) support immediate angiography/PCI or fibrinolysis in these patients in order to improve survival. METHODS Consecutive data on 1650 STEMI patients, transferred for primary PCI in hospital STEMI networks between November 2005 and January 2007 from 7 countries in Europe were gathered. Patients were divided into two groups: OHCA group - 42 patients and no OHCA group - 1608 patients. RESULTS Baseline demographics, clinical characteristic on admission to cathlab and past medical history were similar in both groups. Cardiogenic shock on admission or acute heart failure defined as Killip 3+4 was more frequently observed in OHCA group. The in-hospital mortality was similar, however, 1-year mortality was 19.1% in the OHCA group vs 8.1% in no OHCA group (p=0.011) and remained significant after exclusion of patients in cardiogenic shock on admission. CONCLUSIONS STEMI patients treated with primary PCI with out-of-hospital cardiac arrest have higher long-term mortality than no OHCA patients. However, resuscitation prior to cathlab admission is not an independent predictor of long-term adverse outcome. No differences in in-hospital mortality were noticed.