Waldemar Mielecki

Immediate angioplasty versus standard therapy with rescue angioplasty after thrombolysis in the Combined Abciximab REteplase Stent Study in Acute Myocardial Infarction (CARESS-in-AMI): an open, prospective, randomised, multicentre trial

BACKGROUND Thrombolysis remains the treatment of choice in ST-segment elevation myocardial infarction (STEMI) when primary percutaneous coronary intervention (PCI) cannot be done within 90 min. However, the best subsequent management of patients after thrombolytic therapy remains unclear. To assess the best management, we randomised patients with STEMI treated by thrombolysis and abciximab at a non-interventional hospital to immediate transfer for PCI, or to standard medical therapy with transfer for rescue angioplasty. METHODS 600 patients aged 75 years or younger with one or more high-risk features (extensive ST-segment elevation, new-onset left bundle branch block, previous myocardial infarction, Killip class >2, or left ventricular ejection fraction < or =35%) in hospitals in France, Italy, and Poland were treated with half-dose reteplase, abciximab, heparin, and aspirin, and randomly assigned to immediate transfer to the nearest interventional centre for PCI, or to management in the local hospital with transfer only in case of persistent ST-segment elevation or clinical deterioration. The primary outcome was a composite of death, reinfarction, or refractory ischaemia at 30 days, and analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number 00220571. FINDINGS Of the 299 patients assigned to immediate PCI, 289 (97.0%) underwent angiography, and 255 (85.6%) received PCI. Rescue PCI was done in 91 patients (30.3%) in the standard care/rescue PCI group. The primary outcome occurred in 13 patients (4.4%) in the immediate PCI group compared with 32 (10.7%) in the standard care/rescue PCI group (hazard ratio 0.40; 95% CI 0.21-0.76, log rank p=0.004). Major bleeding was seen in ten patients in the immediate group and seven in the standard care/rescue group (3.4%vs 2.3%, p=0.47). Strokes occurred in two patients in the immediate group and four in the standard care/rescue group (0.7%vs 1.3%, p=0.50). INTERPRETATION Immediate transfer for PCI improves outcome in high-risk patients with STEMI treated at a non-interventional centre with half-dose reteplase and abciximab.

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.

Association of plasma miR-223 and platelet reactivity in patients with coronary artery disease on dual antiplatelet therapy: A preliminary report

Abstract Decreased plasma levels of microRNA-223 (miR-223), predominantly of platelet origin, were proposed as a surrogate marker of efficacy of antiplatelet therapy. However, higher on-treatment platelet reactivity was associated with lower plasma miR-223 in patients with coronary artery disease (CAD) on dual antiplatelet therapy (DAPT) including clopidogrel and aspirin. Our aim was to compare plasma miR-223 and platelet reactivity in CAD patients on DAPT with newer P2Y12 antagonists vs. clopidogrel. We studied 21 men with CAD admitted to our centre owing to a non-ST-elevation acute coronary syndrome, and with an uncomplicated hospital course. From the day of admission, the patients were receiving either clopidogrel (n = 11) or prasugrel/ticagrelor (n = 10) in addition to aspirin. Before discharge, miR-223 expression in plasma was estimated by quantitative polymerase chain reaction using the comparative Ct method relative to miR-16 as an endogenous control. Multiple electrode aggregometry was used to assess platelet aggregation in response to adenosine diphosphate (ADP). ADP-induced platelet reactivity was decreased in the patients treated with prasugrel or ticagrelor compared with those on clopidogrel (mean ± SD: 139 ± 71 vs. 313 ± 162 arbitrary units [AU]*min, p = 0.006), due to a more potent antiplatelet activity of the novel P2Y12 antagonists. Consequently, six out of seven patients in the lower tertile of the ADP-induced platelet aggregation were treated with the newer P2Y12 blockers, whereas six out of seven patients in the upper tertile were on clopidogrel. Plasma miR-223 was elevated with decreasing platelet reactivity (Spearman’s rho = –0.52; p = 0.015 for trend), being significantly higher in the lower tertile of the ADP-induced platelet aggregation (median [range]: 1.06 [0.25–2.31]) vs. the upper tertile (0.20 [0.13–2.30]) (p = 0.04). In conclusion, our preliminary results argue against the notion of low plasma miR-223 as a marker of platelet responsiveness to DAPT. On the contrary, more potent platelet inhibition associated mainly with newer P2Y12 antagonists appears to coincide with higher miR-223 relative to the subjects with attenuated responsiveness to DAPT.

More aggressive pharmacological treatment may improve clinical outcome in patients with non-ST-elevation acute coronary syndromes treated conservatively.

IntroductionIncreased adherence to guideline-recommended therapies, especially early invasive strategy introduction may improve clinical outcome in patients with non-ST-elevation acute coronary syndromes. The aim of this study was to assess the impact of more aggressive pharmacological treatment and application of current guidelines in everyday clinical practice in hospitals without on-site invasive facility, with a special focus on its influence on in-hospital mortality in non-ST-elevation acute coronary syndromes patients. MethodsWe identified 807 non-ST-elevation acute coronary syndromes patients treated conservatively in the 29 hospitals participating in the Malopolska Registry of Acute Coronary Syndromes from February to March 2005 and from December 2005 to January 2006. For all patients, pharmacotherapy index based on the use of pharmacological treatment regimen during hospital stay was assessed. Each patient received 1 point for each of the following guideline-recommended drugs used: aspirin, clopidogrel, glycoprotein IIb/IIIa inhibitor, low-molecular-weight heparin, &bgr;-blocker, angiotensin converting enzyme inhibitor/angiotensin II receptor blocker, statin – range of points from 0 to 7. ResultsThe in-hospital mortality decreased with increase of pharmacotherapy index (0 points – 80.0%, 1 point – 36.4%, 2 points – 17.4%, 3 points – 7.6%, 4 points – 5.6%, 5 points – 1.7%, 6 points – 0.0%; P<0.0001, total mortality-5.3%). Independent predictors of in-hospital death were cardiogenic shock, thrombolysis in myocardial infarction (TIMI) risk score, renal insufficiency and pharmacotherapy index. ConclusionsOur findings support the need for more aggressive pharmacological treatment of patients with non-ST-elevation acute coronary syndromes remaining in community hospitals for conservative treatment. Broader implementation of current guidelines and more frequent invasive treatment could improve the outcomes of non-ST-elevation acute coronary syndromes patients.

Transportation with very long transfer delays (> 90 min) for facilitated PCI with reduced-dose fibrinolysis in patients with ST-segment elevation myocardial infarction: The Krakow Network

BACKGROUND The majority of ST-segment elevation myocardial infarction (STEMI) patients are admitted to centers without primary percutaneous coronary intervention (PCI) facilities. Purpose of the study was to determine safety and outcomes in STEMI patients with transfer delay to PCI>90 min receiving half-dose alteplase and abciximab before PCI (facilitated PCI with reduced-dose fibrinolysis). METHODS AND RESULTS Outcomes of 669 STEMI patients (<12 h chest pain, non shock, fibrinolysis eligible, <75 years) with transfer delay to PCI>90 min who received half-dose alteplase and full-dose abciximab and were immediately transferred for PCI were compared with primary PCI effects in 1311 patients with transfer delay <90 min. Mean time from symptom-onset to PCI was longer (357 ± 145 min vs. 201 ± 177; P<0.001) in facilitated PCI with reduced-dose fibrinolysis group. In-hospital and 12-month outcomes were similar in both groups, however bleeding events were more frequent in facilitated PCI group (hemorrhagic stroke 0.9% vs. 0%; P<0.001; severe+moderate 5.5% vs. 2.3%; P<0.001). CONCLUSIONS This is the first large report showing the safety and benefits of transportation with very long transfer delay (>90 min) for facilitated PCI with reduced-dose fibrinolysis in STEMI patients. In fact, pharmacological treatment (combotherapy) was effective in overcoming the deleterious effects of long time-delay on outcome, with similar survival as compared to short-time transportation, despite higher risk of major bleeding complication.

Early abciximab administration before primary percutaneous coronary intervention improves clinical outcome in elderly patients transferred with ST-elevation myocardial infarction: Data from the EUROTRANSFER registry

BACKGROUND Limited data are available concerning benefits and risks of early abciximab (EA) administration before primary percutaneous coronary intervention (PPCI) in elderly ST-segment elevation myocardial infarction (STEMI) patients. The objective of the study was to assess the impact of EA before PPCI in elderly (>or=65 years) patients. METHODS AND RESULTS We identified 545 patients <65 years (354 with EA administration (>30 min before PPCI), 191 late abciximab (LA)), and 541 patients >or=65 years of age (373 EA, 168 LA) in the EUROTRANSFER Registry database. Elderly patients were more likely to have comorbidities, angiographic PCI complications, and bleeding events. EA promotes infarct-related artery patency before PPCI and improves myocardial reperfusion after PPCI in both age groups, but the risk of 30-day death (EA vs. LA: <65 years, 2.0% vs. 1.6%; p=0.999; >or=65 years, 5.9% vs. 14.3%; p=0.001) and 30-day death+reinfarction (EA vs. LA: <65 years, 2.5% vs. 2.1%; p=0.999; >or=65 years, 7.5% vs. 17.3%; p=0.001) was reduced in elderly patients only. There was no difference in bleedings, especially major bleedings requiring transfusion (EA vs. LA: patients <65 years, 2.3% vs. 0%, p=0.055; >or=65 years, 2.4% vs. 3%; p=0.448) between groups. CONCLUSIONS Patients >or=65 years of age have a substantially increased risk of angiographic PCI complications, death and bleeding events compared with their younger counterparts. Strategy of EA before PPCI improves reperfusion parameters and clinical outcome in elderly patients and is not associated with elevated risk of major bleeding.

ST-segment resolution assessed immediately after primary percutaneous coronary intervention correlates with infarct size and left ventricular function in cardiac magnetic resonance at 1-year follow-up

BACKGROUND Little is known about the predictive value of electrocardiographic ST-segment resolution (STR) assessed immediately after primary percutaneous coronary intervention (PCI). The aim of the study was to analyze the value of STR and maximum single-lead ST-segment elevation assessed immediately after primary PCI in prediction of infarct size and left ventricular function in cardiac magnetic resonance (CMR) at 1-year follow-up. METHODS AND RESULTS A total of 28 patients with anterior wall ST-segment elevation myocardial infarction treated with primary PCI entered the study. There was a significant correlation of STR and maximum single-lead ST-segment elevation assessed immediately after primary PCI and CMR infarct size and left ventricular function after 1 year. When analyzed according to standard optimal reperfusion cutoff (70% for STR and 1 mm for single-lead elevation), both electrocardiographic parameters were also good predictors of CMR infarct size and left ventricular function after 1 year. CONCLUSIONS ST-segment resolution and the single-lead maximum ST-segment elevation assessed immediately after primary PCI for ST-segment elevation myocardial infarction are good predictors of infarct size and left ventricular function in 1-year follow-up.

Impact of Admission Glucose Level and Presence of Diabetes Mellitus on Mortality in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome Treated Conservatively

Elevated glucose level on admission is common in patients with acute coronary syndrome (ACS) and has been shown to be a strong predictor of adverse outcome in patients both with and without diabetes. The purpose of the study was to assess the impact of admission glucose on in-hospital mortality in patients with non-ST-segment elevation ACS treated in hospitals without on-site invasive facilities. We identified 807 patients with non-ST-segment elevation ACS treated conservatively in the 29 hospitals participating in the Krakow Registry of Acute Coronary Syndromes; 763 patients with complete admission glucose data were stratified according to admission glucose level. Of these, 24.2% had admission glucose level <5, 50.6% had a level 5 to 6.9, 10.9% had a level 7 to 8.9, 6.7% had a level 9 to 10.9, and 7.6% had a level > or =11 mmol/L. In-hospital mortality was higher in patients with higher admission glucose (admission glucose <5, 5 to 6.9, 7 to 8.9, 9 to 10.9, and > or =11 mmol/L: 0.5%, 2.6%, 7.2%, 9.8%, and 24.1% respectively, p <0.0001). Similarly, significant mortality difference was observed in patient subgroups stratified by admission glucose level and presence of diabetes mellitus and cardiogenic shock. Independent predictors of in-hospital death were age, cardiogenic shock, admission glucose, chronic obstructive pulmonary disease, and renal insufficiency. In conclusion, admission glucose level is a strong predictor of in-hospital death in patients with non-ST-segment elevation ACS remaining in hospitals without on-site invasive facilities. Impact of admission glucose on mortality is independent of diabetes and cardiogenic shock presence.

Time delay in primary angioplasty: how relevant is it?

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No long‐term clinical benefit from manual aspiration thrombectomy in ST‐elevation myocardial infarction patients. Data from NRDES registry

Current STEMI guidelines recommend thrombectomy should be considered during primary PCI. Multiple data from randomized clinical trials, registries, and metanalysis have confirmed the efficacy of thrombectomy in terms of surrogate endpoints like better myocardial perfusion, less pronounced distal embolization, and conflicting results on lower all‐cause mortality. Our aim was to analyze long‐term outcome of STEMI patients treated with manual thrombectomy during primary PCI in a contemporary national registry.