Abstract
Purpose
The Genous™ stent (GS) is designed to accelerate endothelization, which is potentially useful in the pro-thrombotic environment of ST-elevation acute myocardial infarction (STEMI). We aimed to evaluate the safety and effectiveness of the GS in the first year following primary percutaneous coronary intervention (PCI) and to compare our results with the few previously published studies.
Methods and Materials
All patients admitted to a single center due to STEMI that underwent primary PCI using exclusively GS, between May 2006 and January 2012, were enrolled. The primary study endpoints were major adverse cardiac events (MACEs), defined as the composite of cardiac death, acute myocardial infarction and target vessel revascularization, at one and 12 months.
Results
In the cohort of 109 patients (73.4% male, 59 ± 12 years), 24.8% were diabetic. PCI was performed in 116 lesions with angiographic success in 99.1%, using 148 GS with median diameter of 3.00 mm (2.50–4.00) and median length of 15 mm (9–33). Cumulative MACEs were 2.8% at one month and 6.4% at 12 months. Three stent thromboses (2.8%), all subacute, and one stent restenosis (0.9%) occurred. These accounted for the four target vessel revascularizations (3.7%). At 12 months, 33.9% of patients were not on dual antiplatelet therapy.
Conclusions
GS was safe and effective in the first year following primary PCI in STEMI, with an apparently safer profile comparing with the previously published data.
Summary
We report the safety and effectiveness of the Genous™ stent (GS) in the first year following primary percutaneous coronary intervention in ST-elevation acute myocardial infarction. A comprehensive review of the few studies that have been published on this subject was included and some suggest a less safe profile of the GS. Our results and the critical review included may add information and reinforce the safety and effectiveness of the GS in ST-elevation in acute myocardial infarction.
1
Introduction
The Genous™ bio-engineered R stent™ (GS) (OrbusNeich, Fort Lauderdale, Florida), is covered by monoclonal CD34 + antibodies that selectively capture the circulating endothelial progenitor cells, which accelerate the healing of the stented lesion . Usage of the GS specifically in ST-elevation acute myocardial infarction (STEMI) may offer great benefit in a highly pro-thrombotic environment, potentially reducing stent thrombosis . On the other hand, patient adherence to dual antiplatelet therapy (DAPT) following acute myocardial infarction is suboptimal and the GS could minimize the consequences of early DAPT discontinuation . Few studies have been published on the safety and effectiveness of the GS use exclusively in STEMI patients . Different results have been reported and a less safe profile of the GS has been suggested in some of these studies .
We aimed to evaluate the safety and effectiveness of the GS in the first year following primary percutaneous coronary intervention (PCI) in STEMI. We also reviewed the clinical results of the published studies on the GS usage that only included STEMI patients.
2
Methods
2.1
Patients and data collection
We conducted a cohort study of all STEMI patients admitted to our center treated with primary PCI using exclusively GS, between May 2006 and January 2012. The study protocol was approved by the hospital ethics committee and all patients signed informed consent forms before primary PCI.
In our center, the STEMI patients with barriers to prolonged dual antiplatelet therapy (DAPT) were selected to receive a Genous™ stent (GS) during the study period. The barriers included low patient adherence to the treatment regimen, the need to interrupt antiplatelet therapy due to non-cardiac invasive procedures or an increased hemorrhagic risk (mainly due to concomitant need for oral anticoagulation or recent bleeding). We analyzed the STEMI patients that received exclusively the GS.
Based on the clinical files, the following data were recorded: demographic and clinical data, including cardiovascular risk factors, previous cardiovascular events and other comorbidities; angiographic and PCI procedural data; and inhospital clinical and angiographic complications.
A clinical follow-up at one month and 12 months after discharge was carried out based on clinic visits or phone enquiry, and the following data were accounted for and verified by hospital records: death, acute myocardial infarction, target vessel revascularization (TVR), target lesion revascularization (TLR), clinical stent restenosis, stent thrombosis, angina or anginal equivalent and DAPT discontinuation.
Usage of a stent other than Genous™, rescue PCI and PCI performed after the first 12 h of the beginning of the symptoms were the exclusion criteria.
2.2
Endpoints
The primary study endpoints were major adverse cardiac events (MACEs), defined as the composite of cardiac death, acute myocardial infarction and target vessel revascularization, at one and 12 months. The incidence of stent thrombosis and clinical stent restenosis was also assessed.
2.3
Definitions
All deaths were considered a cardiac death unless otherwise documented. Acute myocardial infarction was defined according to Academic Research Consortium definition as elevation of cardiac enzymes 3 times the upper limit of normal. TVR was defined as repeat revascularization of the previously treated vessel, and TLR as repeat revascularization within 5 mm to stent edges (in-segment). Clinical stent restenosis was defined as the presence of angina or anginal equivalent, associated with > 50% stenosis in the segment covered by the stent or the adjacent 5 mm. Stent thrombosis was classified according to Academic Research Consortium definitions in which definite stent thrombosis is defined as angiographic or pathologic confirmation of acute stent thrombosis in patients with acute coronary syndromes; and probable stent thrombosis as any unexplained death in the 30 days following stent implantation or as target vessel myocardial infarction without angiographic confirmation of stent thrombosis or other identified culprit lesion. Stent thrombosis was classified as acute (first 24 h), subacute (between 24 h and 30 days) and late (after 30 days). Angiographic success was defined as residual stenosis of less than 10% and thrombolysis in myocardial infarction (TIMI) flow score 3.
2.4
Review of the published data
We searched the studies in full version indexed in the Pubmed®, between January 2005 (GS first-in-man ) and May 2013, using the keywords endothelial progenitor cell, Genous™ stent, myocardial infarction, percutaneous coronary intervention, and stent. Of the studies reporting GS usage, only those that enrolled exclusively STEMI patients were analyzed. Time of follow-up, the number of GS used, the number of patients included, intended DAPT duration, MACE, cardiac death, acute myocardial infarction, TVR, TLR, stent restenosis and stent thrombosis were analyzed.
2.5
Statistical analysis
Data were analyzed using the SPSS version 17.0 statistical software. Discrete data are presented as frequencies and percentages, whereas continuous variables are presented as means and SD or as medians and range, when appropriate.
2
Methods
2.1
Patients and data collection
We conducted a cohort study of all STEMI patients admitted to our center treated with primary PCI using exclusively GS, between May 2006 and January 2012. The study protocol was approved by the hospital ethics committee and all patients signed informed consent forms before primary PCI.
In our center, the STEMI patients with barriers to prolonged dual antiplatelet therapy (DAPT) were selected to receive a Genous™ stent (GS) during the study period. The barriers included low patient adherence to the treatment regimen, the need to interrupt antiplatelet therapy due to non-cardiac invasive procedures or an increased hemorrhagic risk (mainly due to concomitant need for oral anticoagulation or recent bleeding). We analyzed the STEMI patients that received exclusively the GS.
Based on the clinical files, the following data were recorded: demographic and clinical data, including cardiovascular risk factors, previous cardiovascular events and other comorbidities; angiographic and PCI procedural data; and inhospital clinical and angiographic complications.
A clinical follow-up at one month and 12 months after discharge was carried out based on clinic visits or phone enquiry, and the following data were accounted for and verified by hospital records: death, acute myocardial infarction, target vessel revascularization (TVR), target lesion revascularization (TLR), clinical stent restenosis, stent thrombosis, angina or anginal equivalent and DAPT discontinuation.
Usage of a stent other than Genous™, rescue PCI and PCI performed after the first 12 h of the beginning of the symptoms were the exclusion criteria.
2.2
Endpoints
The primary study endpoints were major adverse cardiac events (MACEs), defined as the composite of cardiac death, acute myocardial infarction and target vessel revascularization, at one and 12 months. The incidence of stent thrombosis and clinical stent restenosis was also assessed.
2.3
Definitions
All deaths were considered a cardiac death unless otherwise documented. Acute myocardial infarction was defined according to Academic Research Consortium definition as elevation of cardiac enzymes 3 times the upper limit of normal. TVR was defined as repeat revascularization of the previously treated vessel, and TLR as repeat revascularization within 5 mm to stent edges (in-segment). Clinical stent restenosis was defined as the presence of angina or anginal equivalent, associated with > 50% stenosis in the segment covered by the stent or the adjacent 5 mm. Stent thrombosis was classified according to Academic Research Consortium definitions in which definite stent thrombosis is defined as angiographic or pathologic confirmation of acute stent thrombosis in patients with acute coronary syndromes; and probable stent thrombosis as any unexplained death in the 30 days following stent implantation or as target vessel myocardial infarction without angiographic confirmation of stent thrombosis or other identified culprit lesion. Stent thrombosis was classified as acute (first 24 h), subacute (between 24 h and 30 days) and late (after 30 days). Angiographic success was defined as residual stenosis of less than 10% and thrombolysis in myocardial infarction (TIMI) flow score 3.
2.4
Review of the published data
We searched the studies in full version indexed in the Pubmed®, between January 2005 (GS first-in-man ) and May 2013, using the keywords endothelial progenitor cell, Genous™ stent, myocardial infarction, percutaneous coronary intervention, and stent. Of the studies reporting GS usage, only those that enrolled exclusively STEMI patients were analyzed. Time of follow-up, the number of GS used, the number of patients included, intended DAPT duration, MACE, cardiac death, acute myocardial infarction, TVR, TLR, stent restenosis and stent thrombosis were analyzed.
2.5
Statistical analysis
Data were analyzed using the SPSS version 17.0 statistical software. Discrete data are presented as frequencies and percentages, whereas continuous variables are presented as means and SD or as medians and range, when appropriate.
3
Results
Nine hundred and seventy (970) STEMI patients were treated with primary PCI in our center during the study period. Of these, 115 patients received a GS since they had barriers to prolonged DAPT, but six were excluded since they received another type of stent in addition to the GS. In our cohort of 109 patients, 80 (73.4%) were male and the mean age was 59 ± 12 years. Demographic and clinical data are presented in Table 1 . One quarter of the patients had diabetes mellitus on medication.
| N = 109 | % | |
|---|---|---|
| Male | 80 | 73.4 |
| Hypertension | 61 | 56.0 |
| Dyslipidemia | 58 | 53.2 |
| Smoking history | 58 | 53.2 |
| Diabetes mellitus | 27 | 24.8 |
| Obesity | 19 | 17.4 |
| Previous acute myocardial infarction | 7 | 6.4 |
| Previous percutaneous coronary intervention | 3 | 2.8 |
| Previous coronary artery bypass grafting | 0 | 0.0 |
| Pre-discharge depressed left ventricular ejection fraction (< 55%) | 51 | 46.8 |
Angiographic data are presented in Table 2 . In 102 (93.6%) patients only the culprit artery was treated and PCI was performed in 116 lesions. Of the intervened lesions, 49 (42.2%) were located in the left anterior descending artery, 78 (67.2%) were type B2/C and the mean stenosis was 95.6% ± 12.0%.
| N = 109 | % | |
|---|---|---|
| Multivessel disease | 37 | 33.9 |
| Lesions treated per patient | ||
| 1 | 102 | 93.6 |
| > 1 | 7 | 6.4 |
| Intervened lesion | N = 116 | % |
| Left anterior descending artery | 49 | 42.2 |
| Right coronary artery | 47 | 40.5 |
| Circumflex artery | 19 | 16.4 |
| Left main artery | 1 | 0.9 |
| Lesion risk profile | N = 116 | % |
| Lesion type B2/C | 78 | 67.2 |
| Long lesion | 34 | 29.3 |
| Bifurcation lesion | 13 | 11.2 |
| Calcified lesion | 4 | 3.4 |
| Thrombotic lesion | 69 | 59.5 |
| Previous stenting (another stent) | 2 | 1.7 |
Procedural data are presented in Table 3 . Angiographic success was achieved in 115 (99.1%) PCIs. One hundred and forty eight GSs were used with a median diameter of 3.00 mm (2.50–4.00 mm) and a median length of 15 mm (9–33 mm). Anticoagulant and antiplatelet therapy followed the standard practices and intended DAPT duration was 12 months, for all patients.
