Ralf Birkemeyer

A randomized, multicenter, single-blinded trial comparing paclitaxel-coated balloon angioplasty with plain balloon angioplasty in drug-eluting stent restenosis: the PEPCAD-DES study.

OBJECTIVES This study sought to define the impact of paclitaxel-coated balloon angioplasty for treatment of drug-eluting stent restenosis compared with uncoated balloon angioplasty alone. BACKGROUND Drug-coated balloon angioplasty is associated with favorable results for treatment of bare-metal stent restenosis. METHODS In this prospective, single-blind, multicenter, randomized trial, the authors randomly assigned 110 patients with drug-eluting stent restenoses located in a native coronary artery to paclitaxel-coated balloon angioplasty or uncoated balloon angioplasty. Dual antiplatelet therapy was prescribed for 6 months. Angiographic follow-up was scheduled at 6 months. The primary endpoint was late lumen loss. The secondary clinical endpoint was a composite of cardiac death, myocardial infarction attributed to the target vessel, or target lesion revascularization. RESULTS There was no difference in patient baseline characteristics or procedural results. Angiographic follow-up rate was 91%. Treatment with paclitaxel-coated balloon was superior to balloon angioplasty alone with a late loss of 0.43 ± 0.61 mm versus 1.03 ± 0.77 mm (p < 0.001), respectively. Restenosis rate was significantly reduced from 58.1% to 17.2% (p < 0.001), and the composite clinical endpoint was significantly reduced from 50.0% to 16.7% (p < 0.001), respectively. CONCLUSIONS Paclitaxel-coated balloon angioplasty is superior to balloon angioplasty alone for treatment of drug-eluting stent restenosis. (PEPCAD DES-Treatment of DES-In-Stent Restenosis With SeQuent® Please Paclitaxel Eluting PTCA Catheter [PEPCAD-DES]; NCT00998439).

Intracoronary versus intravenous bolus abciximab during primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction: a randomised trial.

BACKGROUND Intracoronary administration of an abciximab bolus during a primary percutaneous coronary intervention results in a high local drug concentration, improved perfusion, and reduction of infarct size compared with intravenous bolus application. However, the safety and efficacy of intracoronary versus standard intravenous bolus application in patients with ST-elevation myocardial infarction (STEMI) undergoing this intervention has not been tested in a large-scale clinical trial. METHODS The AIDA STEMI trial was a randomised, open-label, multicentre trial. Patients presenting with STEMI in the previous 12 h with no contraindications for abciximab were randomly assigned in a 1:1 ratio by a central web-based randomisation system to intracoronary versus intravenous abciximab bolus (0·25 mg/kg bodyweight) during percutaneous coronary intervention with a subsequent 12 h intravenous infusion 0·125 μg/kg per min (maximum 10 μg/min). The primary endpoint was a composite of all-cause mortality, recurrent infarction, or new congestive heart failure within 90 days of randomisation. Secondary endpoints were the time to occurrence of the primary endpoint, each individual component of that endpoint, early ST-segment resolution, thrombolysis in myocardial infarction (TIMI) flow grade, and enzymatic infarct size. A masked central committee adjudicated the primary outcome and its components. Treatment allocation was not concealed from patients and investigators. This trial is registered with ClinicalTrials.gov, NCT00712101. FINDINGS Between July, 2008, and April, 2011, 2065 patients were randomly assigned intracoronary abciximab (n=1032) or intravenous abciximab (n=1033). Intracoronary, as compared with intravenous abciximab, resulted in a similar rate of the primary composite clinical endpoint at 90 days in 1876 analysable patients (7·0%vs 7·6%; odds ratio [OR] 0·91; 95% CI 0·64-1·28; p=0·58). The incidence of death (4·5%vs 3·6%; 1·24; 0·78-1·97; p=0·36) and reinfarction (1·8%vs 1·8%; 1·0; 0·51-1·96; p=0·99) did not differ between the treatment groups, whereas less patients in the intracoronary group had new congestive heart failure (2·4%vs 4·1%; 0·57; 0·33-0·97; p=0·04). None of the secondary endpoints or safety measures differed significantly between groups. INTERPRETATION In patients with STEMI undergoing primary percutaneous coronary intervention, intracoronary as compared to intravenous abciximab did not result in a difference in the combined endpoint of death, reinfarction, or congestive heart failure. Since intracoronary abciximab bolus administration is safe and might be related to reduced rates of congestive heart failure the intracoronary route might be preferred if abciximab is indicated. FUNDING Lilly, Germany. University of Leipzig-Heart Centre. University of Leipzig, Clinical Trial Centre Leipzig, supported by the Federal Ministry of Education and Research (BMBF).

Intracoronary compared with intravenous bolus abciximab application during primary percutaneous coronary intervention in ST-segment elevation myocardial infarction: cardiac magnetic resonance substudy of the AIDA STEMI trial.

OBJECTIVES The aim of the AIDA STEMI (Abciximab i.v. Versus i.c. in ST-elevation Myocardial Infarction) cardiac magnetic resonance (CMR) substudy was to investigate potential benefits of intracoronary versus intravenous abciximab bolus administration on infarct size and reperfusion injury in ST-segment elevation myocardial infarction. BACKGROUND The AIDA STEMI trial randomized 2,065 patients to intracoronary or intravenous abciximab and found similar rates of major adverse cardiac events at 90 days with significantly less congestive heart failure in the intracoronary abciximab group. CMR can directly visualize myocardial damage and reperfusion injury, thereby providing mechanistic and pathophysiological insights. METHODS We enrolled 795 patients in the AIDA STEMI CMR substudy. CMR was completed within 1 week after ST-segment elevation myocardial infarction. Central core laboratory-masked analyses for quantified ventricular function, volumes, infarct size, microvascular obstruction, hemorrhage, and myocardial salvage were performed. RESULTS The area at risk (p = 0.97) and final infarct size (16% [interquartile range: 9% to 25%] versus 17% [interquartile range: 8% to 25%], p = 0.52) did not differ significantly between the intracoronary and the intravenous abciximab groups. Consequently, the myocardial salvage index was similar (52 [interquartile range: 35 to 69] versus 50 [interquartile range: 29 to 69], p = 0.25). There were also no differences in microvascular obstruction (p = 0.19), intramyocardial hemorrhage (p = 0.19), or ejection fraction (p = 0.95) between both treatment groups. Patients in whom major adverse cardiac events occurred had significantly larger infarcts, less myocardial salvage, and more pronounced ventricular dysfunction. CONCLUSIONS This largest multicenter CMR study in ST-segment elevation myocardial infarction patients to date demonstrates no benefit of intracoronary versus intravenous abciximab administration on myocardial damage and/or reperfusion injury. Infarct size determined by CMR was significantly associated with major adverse cardiac events.

Prospective randomised trial evaluating a paclitaxel-coated balloon in patients treated with endothelial progenitor cell capturing stents for de novo coronary artery disease

Background Percutaneous coronary intervention with stent implantation is limited by the occurrence of re-stenosis and the risk of stent thromboses. Objective To define the impact of paclitaxel-coated balloon angioplasty plus endothelial progenitor cell capturing (EPC) stent implantation in de novo coronary artery disease. This combination may reduce neointimal proliferation within the EPC stent and address the risk of stent thrombosis by facilitating rapid endothelialisation. Methods In this prospective single-blind multicentre randomised trial, 120 patients with a de novo lesion in a native coronary artery were randomly assigned to undergo treatment with paclitaxel-coated balloon plus EPC stent or EPC stent alone. Dual antiplatelet therapy was prescribed for 3 months. Angiographic follow-up was scheduled at 6 months. The primary endpoint was in-stent late lumen loss. The secondary clinical endpoint was a composite of death from a cardiac cause, myocardial infarction attributed to the target vessel or target lesion revascularisation. Results There was no difference in patient baseline characteristics or procedural results. The angiographic follow-up rate was 96%. Treatment with paclitaxel-coated balloon plus EPC stent was superior to EPC stent alone, with an in-stent late loss of 0.34±0.45 mm versus 0.88±0.48 mm (p<0.001). The re-stenosis rate was reduced from 23.2% to 5.1% (p=0.006) and the clinical endpoint was reduced from 17.2% to 4.8% (p=0.039). There was no definite or probable stent thrombosis. Conclusions Paclitaxel-coated balloon plus EPC stent implantation is superior to EPC stent implantation alone for treatment of de novo coronary artery disease. Trial registration NCT00732953.

Intracoronary compared with intravenous bolus abciximab application during primary percutaneous coronary intervention: Design and rationale of the Abciximab Intracoronary versus intravenously Drug Application in ST-Elevation Myocardial Infarction (AIDA STEMI) trial

BACKGROUND Intravenous abciximab reduces major adverse cardiac events in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Intracoronary abciximab bolus application during PCI results in high local drug concentration, improved perfusion, reduction of infarct size, and less microvascular obstruction. The hypothesis of this trial is that abciximab bolus intracoronary in comparison to standard intravenous application will improve the outcome of patients undergoing primary PCI in STEMI. STUDY DESIGN The Abciximab Intracoronary versus intravenously Drug Application in STEMI (AIDA STEMI) study is a 1,912-patient, prospective, multicenter, randomized, open-label, controlled trial. The study is designed to compare the efficacy and safety of intracoronary versus intravenous bolus abciximab administration during primary PCI with subsequent intravenous infusion for 12 hours. Patients will be randomized in a 1:1 fashion to 1 of the 2 treatments. The primary efficacy end point of AIDA STEMI is the composite of all-cause mortality, recurrent MI, or new congestive heart failure within 90 days of randomization. The primary safety outcome assessment will be major bleeding. CONCLUSIONS The AIDA STEMI study addresses important questions regarding the efficacy and safety of intracoronary abciximab bolus administration during primary PCI in patients with STEMI, potentially optimizing the route of administration of glycoprotein IIb/IIIa inhibitors in the catheterization laboratory.

Incidence and long-term follow-up of silent cerebral lesions after pulmonary vein isolation using a remote robotic navigation system as compared with manual ablation.

Background— The incidence of silent cerebral lesions (SCL) after atrial fibrillation (AF) ablation is highly variable, depending on the technology used. Recently, an increased risk for SCL has been described for a novel, nonirrigated ablation tool using multielectrode phased radiofrequency (PVAC). The aim of this prospective study was to evaluate the incidence and long-term follow-up of SCL in patients undergoing robotically assisted pulmonary vein isolation (RA-PVI) as compared with manual PVI. Methods and Results— Circumferential PVI using irrigated radiofrequency current was performed on 70 patients (41 patients with paroxysmal AF, 59%). Fifty patients underwent RA-PVI and 20 patients underwent a manual approach. Cerebral MRI was performed the day before and the day after the ablation procedure; follow-up MRI was performed on 9 of 12 (75%) patients after a follow-up period of 21 months. SCLs were found in 12 of 70 (17%) patients in this study; the incidence of SCLs was similar in patients undergoing RA-PVI as compared with manually ablated patients (n=9, 18% versus n=3, 15%; probability value=1.0). In 1 patient undergoing manual PVI (1%), an SCL with asymptomatic subarachnoid hemorrhage was detected; the bleeding completely resolved within 1 month. Transient ischemic attack occurred in 1 (1%) patient 2 days after manual PVI. After a median follow-up period of 21 months, no residual SCLs were detected. Conclusions— The incidence of SCL using the robotic navigation system was 18% in this study. Incidence and size of SCL appears to be similar after RA-PVI as compared with manual PVI. Repeat MRI showed no residual SCLs at long-term follow-up.

Intracoronary versus intravenous abciximab bolus in patients with ST-segment elevation myocardial infarction: 1-year results of the randomized AIDA STEMI trial.

To the Editor: In patients with ST-segment elevation myocardial infarction (STEMI), direct intracoronary as compared with standard intravenous bolus administration of the glycoprotein IIb/IIIa receptor antagonist abciximab acutely causes higher local drug concentrations, greater glycoprotein IIb/

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.

Do gender differences in primary PCI mortality represent a different adherence to guideline recommended therapy? a multicenter observation

BackgroundIt is uncertain whether gender differences in outcome after primary percutaneous coronary intervention (PCI) are only attributable to different baseline characteristics or additional factors.MethodsDatabases of two German myocardial infarction network registries were combined with a total of 1104 consecutive patients admitted with acute ST-elevation myocardial infarction (STEMI) and treated according to standardized protocols.ResultsApproximately 25% of patients were females. Mean age (69 vs 61 years), incidence of diabetes (28% vs 20%), hypertension (68 vs 58%) and renal insufficiency (26% vs 19%) was significantly higher compared to males. Mean prehospital delay was numerically longer in females (227 vs 209 min) as was in hospital delay (35 vs 30 min). PCI was finally performed in 92% of females and 95% of males with comparable procedural success (95% vs 97%). Use of drug eluting stents (55% vs 68%) and application of GP 2b 3a blockers (75% vs 89%) was significantly less frequent in women. At discharge, prescription of beta blockers and lipid lowering drugs was also significantly lower in females (84% vs 90% and 71% vs 84%). Unadjusted in-hospital mortality was significantly higher in females (10% vs 5%) without attenuation after 12 months. Adjusted mortality however did not differ significantly between genders.ConclusionHigher unadjusted mortality in females after primary PCI was accompanied by significant differences in baseline characteristics, interventional approach and secondary prophylaxis in spite of the same standard of care. Lower guideline adherence seems to be less gender specific but rather a manifestation of the risk-treatment paradox.

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.