Cardiovascular Topics

Transcription

1 AFRICA CARDIOVASCULAR JOURNAL OF AFRICA Advance Online Publication, November Cardiovascular Topics Intracoronary or intravenous abciximab after aspiration thrombectomy in patients with STEMI undergoing primary percutaneous coronary intervention Ali Bedjaoui, Karima Allal, Mohamed Sofiane Lounes, Chams Eddine Belhadi, Abdelmoumen Mekarnia, Saber Sediki, Maamar Kara, Adel Azaza, Jean-Jacques Monsuez, Salim Benkhedda Abstract Objectives: To test whether aspiration thrombectomy with intracoronary (IC) instead of intravenous (IV) administration of abciximab could reduce the no-reflow phenomenon in patients undergoing primary percutaneous intervention (PCI) for ST-elevation myocardial infarction (STEMI). Background: Despite recanalisation with PCI, failure to restore microvascular flow may affect the prognosis of patients with STEMI. A combination of aspiration thrombectomy with IC abciximab may improve distal perfusion. Methods: After aspiration thrombectomy during primary PCI for STEMI, 160 patients were randomly assigned to either an IV or IC abciximab bolus delivered through the aspiration catheter, both followed by a 12-hour IV abciximab infusion. Results: ST-segment resolution 70% was achieved in 36 of 78 patients with IC versus 30 of 82 patients with IV abciximab (46.1 vs 36.6%, p = 0.368), and partial resolution in 28 of 78 versus 31 of 82 patients (35.9 vs 37.8%, p = 0.368). Postprocedural myocardial blush grade (MBG) 3 was obtained in 62.8 vs 63.4% (p = 0.235) and MBG 2 in 89.7 vs 81.7% (p = 0.148) of patients given IC and respectively. Cardiology Oncology Research Collaborative Group (CORCG), Faculty of Medicine, Benyoucef Benkhedda University, Algiers, Algeria Ali Bedjaoui, MD Salim Benkhedda, MD, PhD Department of Cardiology, Hôpital Central de l Armée Ain Naadja, Algiers, Algeria Ali Bedjaoui, MD Karima Allal, MD Mohamed Sofiane Lounes, MD Chams Eddine Belhadi, MD Abdelmoumen Mekarnia, MD Department of Cardiology, Mustapha University Hospital Centre, Algiers, Algeria Saber Sediki, MD Maamar Kara, MD Adel Azaza, MD Salim Benkhedda, MD, PhD APHP Hôpital R Muret, Hôpitaux Universitaires de Paris, Seine Saint Denis, Paris, France Jean-Jacques Monsuez, MD, PhD, jean-jacques.monsuez@aphp.fr There were three deaths in each group (3.8%). Major adverse cardiac events occurred in six of 78 patients given the IC and seven of 82 patients given the IV abciximab bolus (7.6 vs 8.5%, p = 0.410). One stroke occurred in each group, and two patients in the IC and nine in the IV group developed renal failure (2.5 vs 10.9 %, p = 0.414). Conclusion: IC versus IV abciximab did not enhance myocardial reperfusion in non-selected patients with STEMI undergoing primary PCI after aspiration thrombectomy had successfully been performed. Keywords: myocardial infarction, primary percutaneous intervention, aspiration thrombectomy, abciximab Submitted 25/5/18, accepted 31/10/18 Cardiovasc J Afr 2018; 29: online publication DOI: /CVJA Rapid and sustained restoration of a thrombolysis in myocardial infarction (TIMI) 3 anterograde flow through the epicardial coronary artery, associated with a resolution of ST-segment elevation > 70% within 90 minutes are the primary goals of the current treatment of ST-segment elevation myocardial infarction (STEMI). 1-3 Despite mechanical recanalisation of the occluded artery with primary percutaneous coronary intervention (PCI) and aggressive antithrombotic therapy directed at preventing thrombus growth and mitigating distal embolisation, these goals are not reached in many instances. A major limitation of primary PCI is the possibility of distal embolisation of thrombus and failure to restore flow at the microvascular level. ST-segment elevation persists in more than 40% of cases of patients in whom a TIMI 3 flow has been achieved by primary PCI, a drawback associated with subsequent impairment of left ventricular (LV) function and a worse prognosis. 4-6 Over the past decade, several approaches have been directed to prevent or reverse the no-reflow phenomenon, including aspiration thrombectomy 7-11 and intracoronary glycoprotein IIb/ IIIa inhibitor administration, such as abciximab Abciximab, the Fab fragment of the chimeric human murine monoclonal antibody 7E3, binds to the glycoprotein IIb/IIIa receptor of

2 2 CARDIOVASCULAR JOURNAL OF AFRICA Advance Online Publication, November 2018 AFRICA human platelets and inhibits platelet aggregation. However, randomised trials of both thrombus aspiration and intracoronary (IC) versus intravenous (IV) abciximab administration have shown inconsistent results of these adjunctive methods with regard to clinical outcomes as well as to surrogate reperfusion parameters. In addition, these two approaches have been compared to each other in the INFUSE-AMI study, in which intralesional abciximab was delivered through a dedicated infusion catheter consisting of a microporous balloon (ClearWay RX). IC abciximab delivery resulted in a modest but statistically significant reduction in infarct size compared with aspiration thrombectomy. However, in this trial, there was no control group of patients receiving IV abciximab. 18 Therefore, whether IC or IV abciximab delivery would be more effective after removal of IC thrombotic and atherosclerotic materials has not been tested. This study was intended to compare the effects of IC versus IV administration of abciximab in patients with STEMI undergoing primary PCI with aspiration thrombectomy. Intracoronary abciximab was administered through the distal part of the same catheter (Export catheter) after aspiration thrombectomy was completed. Methods This was a two-centre, open-label, controlled, single-blind, randomised study. The study was performed at the Department of Cardiology of the Military Hospital (Hôpital Central de l Armée) and at the Department of Cardiology A2 of the Mustapha Pacha University Hospital, in collaboration with the Cardiology Oncology Collaborative Research Group (COCRG). Patients were recruited in this prospective, randomised, blind study from 1 October 2013 to 31 October Inclusion criteria were a chest pain suggestive of acute myocardial infarction (AMI) evolving for 30 minutes and less than 12 hours, resistant to nitroglycerin administration, and ST-segment elevation recorded 1 mm from standard and 2 mm from precordial leads. Exclusion criteria were cardiogenic shock, high blood pressure, not controlled by treatment, after measuring twice (systolic BP 240 mmhg, diastolic BP 120 mmhg, or both), left bundle branch block, pregnancy, thrombocytopaenia, severe kidney or liver failure, major surgery lasting for less than one month, gastrointestinal haemorrhage in the past year, coagulation disorders, including coagulation factors and platelet disorders, ischaemic stroke lasting for less than one month, current staging or treatment of cancer, oral anticoagulant therapy, administration of a thrombolytic treatment during the seven days preceding the study, and allergy/hypersensitivity to aspirin, heparin or abciximab. During the study period, 160 patients were consecutively included. The study was approved by the ethics committee of the institution and patients gave informed consent at admission to the catheterisation laboratory. Patients were randomly assigned on a 1:1 basis to either an IV or IC abciximab bolus (ReoPro 10 mg/5 ml, Eli Lilly, Indianapolis, IN), delivered over one minute through the aspiration thrombectomy catheter at the site of coronary occlusion, after anterograde flow had recovered. Intracoronary or IV bolus administration was followed by a 12-hour IV infusion of abciximab at µg/kg/min. Coronary angiography was performed after introduction of a 6F catheter though the femoral or radial artery. Two-orthogonal-axis coronary artery imaging was performed to assess baseline and post-procedural TIMI flow grade and myocardial blush grade (MBG). TIMI flow grade was defined according to the TIMI study group. 19 In brief, TIMI 0 denotes no perfusion (no anterograde flow beyond the point of occlusion); TIMI 1: penetration without perfusion (faint anterograde coronary flow beyond the occlusion with incomplete filling of the distal coronary bed); TIMI 2: partial perfusion (delayed or sluggish anterograde flow with complete filling of the distal territory); TIMI 3: complete perfusion (normal flow with complete filling of the distal territory). 19 Myocardial blush grade 0 denotes no contrast density or persistent blush or staining in the territory supplied by the infarct artery; MBG 1: minimal contrast density; MBG 2: moderate contrast density but less than that obtained during angiography of a contralateral or ipsilateral non-infarct-related coronary artery; and MBG 3: normal contrast density, comparable with that obtained during angiography of a contralateral or ipsilateral non-infarct-related coronary artery. 20 Before PCI, patients were treated with aspirin (bolus of 250 mg), intravenous heparin (60-IU/kg bolus) and clopidogrel (loading dose of 600 mg). Adjunctive therapy included 1 mg IC nitroglycerin during the procedure. After completion of primary PCI, patients received 150 mg clopidogrel daily p.o. for one month, then 75 mg p.o. daily for one year, together with a statin, beta-blocker, angiotensin converting enzyme inhibitor or angiotensin receptor antagonist, and 75 mg aspirin. Aspiration thrombectomy was performed using an Export catheter (Medtronic, Minneapolis, Minnesota). IC abciximab was administered through the distal part of the same catheter after aspiration thrombectomy was completed. Additional or post-balloon predilatation as well as stenting remained at the discretion of the interventional cardiologist. The primary efficacy endpoint was assessed by ST-segment resolution. ST-segment elevation was measured to the nearest 0.1 mv, 40 ms after the end of the QRS using the TP segment as baseline. According to previous reports, 5-6 ST-segment resolution was defined as successful if 70% of the sum of ST-elevation present on the baseline ECG had resolved by 60 minutes after primary PCI (complete ST-segment resolution). Partial ST-segment resolution was defined if 50% but < 70% of the sum of ST-elevation present on the baseline ECG had resolved by 60 minutes after primary PCI. 5,6,21,22 Secondary efficacy endpoints consisted of (1) major adverse cardiovascular events (MACE), including cardiovascular death, stent thrombosis, target-vessel revascularisation, and recurrent myocardial infarction at 30 days and six months; and (2) achievement of MBG 2 to 3 after completion of primary PCI. Recurrent AMI was defined as recurrent symptoms or ST-elevation or increase in troponin levels. 23 Target vessel revascularisation was defined as any repeat revascularisation procedure on the infarct-related coronary artery. Safety endpoints consisted of major and minor bleeding during hospital stay. Major haemorrhage was defined as retroperitoneal or intracranial bleeding, bleeding resulting in a 15% absolute decrease in haematocrit or a decrease in haemoglobin level > 5 g/dl. 20 Minor haemorrhage consisted of

3 AFRICA CARDIOVASCULAR JOURNAL OF AFRICA Advance Online Publication, November clinical or echo/ct scan-documented bleeding associated with a decrease in blood haemoglobin level > 3 g/dl and < 5 g/dl or a decrease in haematocrit > 9% and < 15%. 24 Statistical analysis This study was powered for a ST-segment resolution rate of 56% at 60 minutes. 7 Evaluating two groups of 72 patients would provide 90% power to demonstrate a relative 25% difference in ST-segment resolution rate between the IC and IV groups. Assuming approximately 10% lost to follow up, 160 patients were randomised. All statistical analyses were performed using the SPSS statistical software (graduate pack for Windows, version 20). For categorical variables, the frequencies and percentages were calculated. Continuous variables are presented as means ± SD and were compared using the Student s t-test or the Mann Whitney U-test as appropriate. Categorical variables are presented as proportions and were compared with the χ² or Fisher s exact test. A p-value < 0.05 was considered significant. Results The study flow chart is described in Fig. 1. Baseline characteristics of patients are summarised in Table 1. Patients randomised to IC administration were younger (58.8 ± 14.8 vs 60.6 ± 12.2 years) and less frequently hypertensive (36 vs 53%). An increased waist circumference was less frequently observed (6.4 vs 22.2%, p < 0.05). There was no significant difference with regard to the patients past history between the groups, including prior coronary artery Patients admitted with STEMI <12 h, n = 172 Excluded for exclusion criteria, n = 12 Patients included to , Patients randomised to IV abciximab bolus, Aspiration thrombectomy: 68 patients ECG criteria: available for 82 patients Angiographic criteria: available for 82 patients MACE at 1 month: available for 79 patients MACE at 6 months: available for 71 patients Patients randomised to IC abciximab bolus, n = 78 Aspiration thrombectomy: 62 patients ECG criteria: available for 78 patients Angiographic criteria: available for 78 patients MACE at 1 month: available for 75 patients MACE at 6 months: available for 70 patients Fig. 1. Study flow chart. MACE: major cardiac events. Table 1. Baseline characteristics of patients All patients, Patients Age, years 59.7 ± ± ± Men, n (%) 137 (85.6) 72 (87.8) 65 (83.3) Cardiovascular risk factors Diabetes, n (%) 54 (33.8) 30 (36.6) 24 (30.8) Hypertension, n (%) 72 (45) 44 (53.7) 28 (35.9) Smokers, n (%) 67 (41.9) 29 (35.4) 38 (48.7) Dyslipidaemia, n (%) 30 (18.8) 16 (19.5) 14 (17.9) 0.8 Obesity, n (%) 23 (14.4) 18 (22.2) 5 (6.4) Heredity, n (%) 9(5.6) 4 (4.9) 5 (6.4) Past history Stroke, n (%) 6 (3.8) 5 (6.1) 1 (1.3) Peripheral artery 4 (2.5) 3 (3.7) 1 (1.3) disease, n (%) Previous MI, n (%) 20 (12.5) 16 (19.5) 4 (5.1) Previous PCI, n (%) 10 (6.3) 8 (8.9) 2 (2.6) 0.06 Clinical findings Heart rate, bpm 86.2 ± ± ± Mean systolic blood ± ± ± pressure, mmhg Killip class, n (%): (93.1) 75 (91.5) 74 (94.9) (1.3) 5 (6.1) (5.6) 2 (2.4) 4 (5.1) Delay from symptom onset to cathlab, min ± ± ± LVEF, % 52.6 ± ± ± LVEF: left ventricular ejection fraction; MI: myocardial infarction; PCI: percutaneous coronary intervention. bypass graft (CABG), PCI, stroke and peripheral artery disease. Previous AMI was less frequent among patients with IC versus IV abciximab (5.1 vs 19.5%, p = 0.05). There was no significant difference between the two groups with regard to delay from symptom onset to balloon, heart rate, systolic and diastolic blood pressure, heart failure signs and left ventricular ejection fraction (LVEF) at admission. Pre-procedural features of the target vessel lesions and coronary angiography findings are summarised in Table 2. The infarct-related coronary artery was the left anterior descending coronary artery (LAD) in 62% of patients with IC and 61% with IV administration (p = 0.470). Single-vessel disease was observed in 70.5 vs 57% in patients with IC vs IV administration (p = 0.127). There was no difference with regard to pre-pci TIMI flow between the two groups. A TIMI flow of 0 (occlusion) was Table 2. Target-vessel characteristics n = 78 All patients, p-value Anterior MI, n (%) 104 (65) 53 (64.6) 51 (65.4) Posterior/inferior MI, n (%) 56 (35) 29 (35.4) 27 (34.6) Single vessel, n (%) 102 (63.8) 47 (57.3) 55 (70.5) vessels, n (%) 40 (25) 26 (31.7) 14 (17.9) 3 vessels, n (%) 18 (11.3) 9 (11) 9 (11.5) TIMI flow: 0, n (%) 111 (69.4) 59 (72) 52 (66.7) , n (%) 11 (6.9) 6 (7.3) 5 (6.4) 2, n (%) 21 (13.1) 10 (12.2) 11 (14.1) 3, n (%) 17 (10.6) 7 (8.5) 10 (12.8) TIMI: thrombolysis in myocardial infarction.

4 4 CARDIOVASCULAR JOURNAL OF AFRICA Advance Online Publication, November 2018 AFRICA Table 3. Procedural characteristics All patients, Radial access, n (%) 116 (72.5) 57 (69.5) 59 (75.6) Aspiration thrombectomy, n (%) 130 (81.3) 68 (82.9) 62 (79.5) Predilatation, n (%) 49 (30.6) 29 (35.4) 20 (25.6) Direct stenting, n (%) 83 (51.9) 44 (53.7) 39 (50) Delayed stenting, n (%) 58 (36.3) 28 (34.1) 30 (38.5) UFH IU, n (%) 135 (84.4) 75 (91.5) 60 (76.9) UFH IU, n (%) 25 (15.6) 7 (8.5) 18 (23.1) Clopidogrel 300 mg, n (%) 13 (18.1) 6 (7.3) 7 (9) Clopidogrel 600 mg, n (%) 147 (91.9) 76 (92.7) 71 (91) Abciximab IV perfusion, n (%) 112 (70) 64 (78) 48 (61.5) UFH: unfractioned heparin. observed in 67% with IC compared to 72% of those with IV administration (p = 0.799). Procedural characteristics of the two groups are shown in Table 3. There was no difference between the two groups with regard to radial catheterisation, aspiration thrombectomy and stenting rates. Manual aspiration thrombectomy was systematically performed before angioplasty or stenting. No serious complications, such as flow-limiting dissection or air embolisation occurred after angiography. Direct stenting (stenting after thrombus aspiration without balloon pre-dilatation) was performed in 51.9% of the patients with IC administration and in 53.7% of those treated with IV administration (p = 0.851). Angiographic outcome is presented in Table 4. Post-procedural TIMI flow grade was similar in both groups, with achievement of a TIMI 3 flow grade in 89.7% of patients with IC and in 89% of those with IV administration (p = 0.747). Post-procedural MBG 3 was obtained in 62.8% of patients with IC and in 63.4% of those with IV administration (p = 0.235). An MBG 2 was more frequently obtained with IC versus IV administration (89.7 vs 81.7%), but this did not reach statistical significance (p = 0.148). There was no difference between patients randomised to IC and IV abciximab with regard to ST-segment resolution rate. ST-segment resolution 70% was achieved in 36 of 78 patients with IC versus 30 of 82 patients with IV abciximab bolus (46.1 vs 36.6%, p = 0.368). Partial ST-segment resolution was achieved in 28 of 78 versus 31 of 82 patients (35.9 vs 37.8%, p = 0.368). No resolution was observed in 14 of 78 versus 21 of 82 patients Table 4. Angiographic outcomes All patients, Post-procedural TIMI flow: 0, n (%) 3 (1.9) 1 (1.2) 2 (2.6) , n (%) 14 (8.8) 8 (9.8) 6 (7.7) 3, n (%) 143 (89.4) 73 (89) 70 (89.7) Post-procedural MBG: 0, n (%) 8 (5) 4 (4.9) 4 (5.1) 1, n (%) 15 (9.4) 11 (13.4) 4 (5.1) , n (%) 36 (22.5) 15 (18.3) 21 (26.9) 3, n (%) 101 (63.1) 52 (63.4) 49 (62.8) MBG 0/1, n (%) 23 ( (18.3) 8 (10.3) MBG 2/3, n (%) 137 (85.6) 67 (81.7) 70 (89.7) TIMI: thrombolysis in myocardial infarction; MBG: myocardial blush grade. Table 5. Major cardiac events Events Heart failure, n (%) 4 (4.9) 3 (3.8) Cardiac death, n (%) 2 (2.4) 3 (3.8) Non-cardiac death, n (%) 1 (1.2) 0 (0) Major cardiac events, n (%) 7 (8.5) 6 (7.6) (17.9 vs 25.6%, p = 0.368) with IC and IV abciximab bolus, respectively. In-hospital outcome: major cardiac events are listed in Table 5. Occurrence of death, recurrent myocardial infarction and target revascularisation rates within 30 days were similar in the two groups. There were three deaths in each group (mortality rate: 3.8%). MACE occurred in six of 78 patients given the IC, and seven of 82 patients given the IV abciximab bolus (7.6 vs 8.5%, p = 0.410). One stroke occurred in each group, and two patients in the IC and nine in the IV group developed renal failure (2.5 vs 10.9 %, p = 0.414). Major bleeding complications occurred in one patient in the IC group and none in the IV group. Minor bleeding complications occurred in seven of 78 patients given IC versus eight of 82 patients given the IV abciximab bolus (9.3 vs 9.9%, p = 0.578). Thrombocytopenia occurred in five of 78 patients with IC versus three of 82 patients with IV abciximab (6.4 vs 3.7%, p = 0.414). Short-term clinical outcome: after the one-month follow up, there was only one cardiac death in each group, one stent thrombosis in the IC group, and similar rates of MACE in both groups (2.66 vs 2.53%, p = 0.588). Also, there was no difference in mortality rate (one death in the IV group), stent thrombosis (one in the IC group) and MACE (5.9 vs 8.8%, p = 0.714) after six months of follow up. Discussion This study was intended to assess the potential benefit of IC over IV abciximab administration after manual thrombus aspiration in patients undergoing primary PCI for STEMI. It showed that distal, intralesional IC administration of abciximab through the aspiration catheter following aspiration thrombectomy did not provide additional benefit over IV administration of the drug. Among 160 patients randomised to either IC or IV abciximab bolus, no significant difference between the two groups was observed. Baseline clinical characteristics of patients, symptom-to-balloon time, which impacts on MBG, 25 coronary angiography findings, infarct-related coronary artery, target vessel and procedural characteristics were similar in the two groups. Reperfusion parameters including the primary outcome endpoint, ST-segment resolution, and the secondary endpoint, achievement of MBG grade 2, did not differ between the groups. Also, no difference was observed with regard to the rate of MACE and major bleeding. Over the past decade, several approaches have been used to prevent or reverse the no-reflow phenomenon. This included aspiration thrombectomy and intralesional administration of glycoprotein IIb/IIIa inhibitors via dedicated perfusion catheters to achieve higher concentration of the drug at the coronary vascular bed in order to improve myocardial reperfusion and to reduce infarct size.

5 AFRICA CARDIOVASCULAR JOURNAL OF AFRICA Advance Online Publication, November Initial results from the Thrombus Aspiration during Percutaneous Coronary Intervention in Acute Myocardial Infarction (TAPAS) trial suggested that aspiration thrombectomy could be effective in improving revascularisation at the microvascular level. 7 Also, a meta-analysis of randomised trials, including patients, showed improved myocardial perfusion, as assessed by ST-segment resolution and MBG. 8 However, aspiration thrombectomy was subsequently challenged by the results of two trials, Thrombus Aspiration in ST-elevation Myocardial Infarction in Scandinavia (TASTE) and Trial of Routine Aspiration Thrombectomy with PCI versus PCI alone in Patients with STEMI (TOTAL), which both failed to show substantial clinical and perfusion benefit in patients despite successful aspiration of clotting material Coronary thrombus material triggers thrombotic, inflammatory, vasoconstrictor and other pathways, and evacuating a portion of the thrombus and plaque material addresses only a part of the pathophysiological problem. Pharmacologically disrupting thrombus formation may be more effective. Abciximab, a potent inhibitor of platelet aggregation, disrupts fresh thrombus at high local drug concentrations, such as those delivered by IC administration, and also exhibits antiinflammatory effects by inhibiting smooth muscle cell migration and proliferation, thereby suppressing platelets, white blood cells and endothelial-mediated mechanisms. 26 Adjunctive abciximab administration has been demonstrated to reduce the rate of mortality and re-infarction in patients with STEMI referred for invasive management. 12 The standard abciximab regimen consists of an IV bolus followed by a 12-hour IV infusion. Intracoronary administration has been suggested to optimise myocardial perfusion beyond recanalisation, since antiglycoprotein IIb/IIIa concentration has been reported as much as 280-fold higher with local compared with IV delivery. 12 Initial studies, in which abciximab bolus was delivered through the guiding catheter after wiring the infarct-related artery, were followed by the use of new application systems such as infusion catheters. These systems consist of a perfusion balloon that occludes anterograde blood flow while drugs are infused through a microporous surface, thereby allowing achievement of high drug concentrations and prolonged focal dwelling times at the site of coronary thrombus. Delivery of abciximab through such dedicated catheters (ClearWay Rx, Atrium Medical Hudson, New Hampshire) was associated with a significant reduction in thrombotic burden, improved microcirculatory flow, and lower rates of one-year adverse events, compared with conventional intracoronary drug administration through the guiding catheter in the small, randomised COCTAIL-II trial. 13 Also, a meta-analysis of eight randomised trials to assess the clinical efficacy and safety of intracoronary versus IV abciximab in STEMI patients undergoing primary PCI showed that intracoronary administration was associated with significant benefits in myocardial perfusion, but not in clinical outcome at short-term follow up. 14 Another meta-analysis of 14 randomised trials of IC versus IV glycoprotein IIb/IIIa inhibitors with a total of patients undergoing primary PCI showed no statistically significant difference between the IC and the IV groups for the primary outcome of MACE. Subgroup analysis showed however that the IC group was superior to the IV group in short-term MACE rate, TIMI 3 flow, MBG 2 to 3 rates, improvement of LVEF, and ST-segment resolution, compared to the IV group, with a trend towards less stent thrombosis. 15 Among diabetic patients, IC versus IV abciximab bolus was associated with a significantly reduced risk of death and stent thrombosis and increased myocardial salvage. 16,17 In addition, in the INFUSE-AMI study, randomisation to intralesional abciximab through a ClearWay Rx catheter resulted in a modest but statistically significant reduction in infarct size compared with aspiration thrombectomy, but not with IV abciximab administration. However, in this trial, there was no control group of patients receiving IV abciximab. 18 Uncertainties regarding the use of IC abciximab are due, in part, to mixed results observed across studies. Indeed, although initial, small-sized investigations found an improvement in surrogate endpoints with the AIDA STEMI trial, which was powered to assess clinical outcomes, failed to demonstrate a reduction in the primary endpoint of all-cause mortality, recurrent infarction, or new incidence of congestive heart failure among patients randomised to IC compared to IV abciximab bolus. 27 In the study by Piccolo et al. in diabetic patients, aspiration thrombectomy was performed in fewer than 20% of patients, while IC abciximab resulted in significant improvement of the effectiveness of PCI, including an increased myocardial salvage index and a reduced risk of death (5.8 vs 11.2%, p = 0.043). 17 The effectiveness of IC abciximab administration is also supported by the Intracoronary Abciximab Infusion and Aspiration Thrombectomy in Patients Undergoing Percutaneous Coronary Intervention for Anterior ST-segment Elevation Myocardial Infarction (INFUSE-AMI) trial, in which an IC bolus of the glycoprotein IIb/IIIa inhibitor abciximab was effective in reducing the infarct size, whereas thrombectomy by means of manual aspiration was not. 18 In the INFUSE-AMI trial, which did not include an IV abciximab administration control group, the beneficial effects of intralesional abciximab and thrombus aspiration were not additional. Nonetheless, although debated, the question of potential benefits of IC abciximab has recently been re-opened A recent meta-analysis of 14 trials of IC versus IV glycoprotein IIb/IIIa inhibitors in patients with STEMI undergoing primary PCI also showed improved ST-segment resolution rates and superior angiographic results with IC glycoprotein IIb/IIIa inhibitors, evidenced by improved achievement of post-procedural TIMI 3 flow and MBG 2 to 3, compared with the IV group. 15 Overall, these observations suggest that adjuvant therapy with aspiration thrombectomy or IC abciximab administration, even in combination, are not required in all patients undergoing PCI. They should rather be considered for selected patients only, including those at increased risk of microvascular obstruction, such as diabetics and patients with a large thrombotic burden or severe distal coronary embolisation. 11,15,17,28-30 Trials to evaluate the effectiveness of such approaches in these selected patients remain to be undertaken. Study limitation A major limitation pertains to the selection of patients. Patients with STEMI were included for primary PCI after a rather long delay from symptom onset to catheterisation laboratory of about 300 minutes. This was due to the specific area where the study was

6 6 CARDIOVASCULAR JOURNAL OF AFRICA Advance Online Publication, November 2018 AFRICA carried out, namely northern Africa. However, similar symptomto-door and symptom-to-balloon times have been reported in registries from Egypt, 25 Tunisia 31 and Morocco. 32 Despite this delay, primary PCI was performed instead of thrombolysis in our study, as it was done in about 35% of patients included in northern African registries. 25,31-33 We acknowledge that this delay is not optimal to assess the efficacy of an IC delivery of abciximab, an approach expected to improve distal perfusion after recanalisation of the occluded coronary artery. Therefore we cannot exclude any beneficial effect resulting from a shorter delay before primary PCI. Conclusion These data further compliment the overall INFUSE-AMI trial results. Because the patients who received IC and IV abciximab combined with aspiration thrombectomy had similar rates of ST-segment resolution and MBG, we concluded that IC instead of IV abciximab did not enhance myocardial reperfusion in non-selected patients with STEMI undergoing primary PCI, even after aspiration thrombectomy had successfully been performed. Funding was provided by the Cardiology Oncology Research Collaborative Group (CORCG), Department of Cardiology, CHU Mustapha, Faculty of Medicine, Benyoucef Benkhedda University, Algiers, Algeria. There was no financial relationship with industry. References 1. Windecker S, Kohl P, Alfonso F, et al ESC/EACTS guidelines on myocardial revascularization. Eur Heart J 2014; 35: Ibanez B, James S, Agewall S, et al ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2018; 39(2): Levine GN, Bates ER, Blankenship JC, et al ACC/AHA/SCAI focused update on primary percutaneous coronary intervention for patients with ST-elevation myocardial infarction: an update of the 2011 ACC/AHA/SCAI guideline for percutaneous coronary intervention and the 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction. J Am Coll Cardiol 2016; 67: Nijveldt R, Beck AM, Hirsch A, et al. Functional recovery after acute myocardial infarction: comparison between angiography, electrocardiography, and cardiovascular magnetic resonance measures of microvascular injury. J Am Coll Cardiol 2008; 52: Schröder R. Extent of early ST-segment elevation resolution: a strong predictor of outcome in patients with acute myocardial infarction and a sensitive measure to compare thrombolytic regimens. A substudy of the International Joint Efficacy Comparison of Thrombolytics (INJECT) trial. J Am Coll Cardiol 1995; 26: Schröder R, Dissmann R, Brüggemann T, et al. Extent of early ST-segment elevation resolution: a simple but strong predictor of outcome in patients with acute myocardial infarction. J Am Coll Cardiol 1994; 24: Vlaar PJ, Svilaas T, van der Horst IC, et al. Cardiac death and re-infarction after 1 year in the Thrombus Aspiration during Percutaneous Coronary Intervention in Acute Myocardial Infarction Study (TAPAS). Lancet 2008; 371: Kumbhani DJ, Bavry AA, Desai MY, et al. Role of aspiration and mechanical thrombectomy in patients with acute myocardial infarction undergoing primary angioplasty. J Am Coll Cardiol 2013; 62: Lagerqvist B, Fröbert O, Olivecrona GK, et al. Outcomes 1 year after thrombus aspiration for myocardial infarction. N Engl J Med 2014; 371: Jolly SS, Cairns JA, Yusuf S, et al. Outcomes after thrombus aspiration for ST elevation myocardial infarction: 1-year follow up of the prospective randomized TOTAL trial. Lancet 2016; 387: Jolly SS, James S, Dzavik V, et al. Thrombus aspiration in ST-segment elevation myocardial infarction: an individual patient meta-analysis: Thrombectomy Trialists Collaboration. Circulation 2017; 135: Romagnoli E, Burzotta F, Trani C, et al. Angiographic evaluation of the effect of intracoronary abciximab administration in patients undergoing urgent PCI. Int J Cardiol 2005; 105: Prati F, Capodanno D, Pawmowski T, et al. Local delivery versus intracoronary infusion of abciximab in patients with acute coronary syndromes. J Am Coll Cardiol Cardiovasc Interv 2010; 3: De Luca G, Verdoia M, Suryapranata H. Benefits from intracoronary as compared to intravenous abciximab administration for STEMI patients undergoing primary angioplasty: a meta-analysis of 8 randomized trials. Atherosclerosis 2012; 222: Elbadawi A, Elgendy IY, Megaly M, et al. Meta-analysis of randomized trials of intracoronary versus intravenous glycoprotein IIb/IIIa inhibitors in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Am J Cardiol 2017; 120: Piccolo R, Eitel I, Galasso G, et al. One-year outcomes with intracoronary abciximab in diabetic patients undergoing primary percutaneous coronary intervention. J Am Coll Cardiol 2016; 68: Piccolo R, Eitel I, Galasso G, et al. Intracoronary abciximab in diabetic patients with ST-segment elevation myocardial infarction undergoing primary percutaneous intervention. Vasc Pharmacol 2015; 73: Stone GW, Maehara A, Witzenbichler B, et al. Intracoronary abciximab and aspiration thrombectomy in patients with large anterior myocardial infarction: the INFUSE-AMI randomized trial. J Am Med Assoc 2012; 3017: TIMI Study group. The Thrombolysis in Myocardial Infarction (TIMI) trial, phase I findings. N Engl J Med 1985; 312: Van t Hof AWJ, Liem A, Suryapranata H. Angiographic assessment of myocardial reperfusion in patients treated with primary angioplasty for acute myocardial infarction: myocardial blush grade. Circulation 1998; 97: Aitmokhtar O, Paganelli F, Benamara S, et al. Impact of platelet inhibition level on subsequent no-reflow in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Arch Cardiovasc Dis 2017; 110(11): Bouleti C, Mewton M, Germain S. The no-reflow phenomenon: state of the art. Arch Cardiovasc Dis 2015; 108: Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. Eur Heart J 2012; 33: Rao AK, Pratt C, Berke A, et al. Thrombolysis in Myocardial Infarction (TIMI) trial phase I: hemorrhagic manifestations and changes in plasma fibrinogen and the fibrinolytic system in patients treated with recombinant tissue plasminogen activator and streptokinase. J Am Coll Cardiol 1988; 11: Faragh EM, Al-Daydamony MM. Symptom-to-balloon time and myocardial blush grade are predictors of left ventricular remodeling after successful primary percutaneous intervention. Cardiovasc J Afr 2017; 28:

7 AFRICA CARDIOVASCULAR JOURNAL OF AFRICA Advance Online Publication, November Dominguez- Rodriguez A, Avanzas P, et al. Intracoronary abciximab and local anti-inflammatory effects. Int J Cardiol 2013; 168: Thiele H, Wohrle J, Hambrecht R, et al. Intracoronary versus intravenous bolus abciximab administration during primary percutaneous intervention in patients with acute ST-elevation myocardial infarction: a randomized trial. Lancet 2012; 379: De Rosa S, Caiazzo G, Torella D, et al. Intracoronary abciximab reduces death and major adverse cardiovascular events in acute coronary syndromes: a meta-analysis of clinical trials. Int J Cardiol 2013; 168: De Rosa S, Caiazzo G, Torella D, et al. What accounts for the higher clinical efficacy of intracoronary abciximab? Int J Cardiol 2013; 168: Zimarino M, Radico F, Dalby K, et al. Intracoronary vs intravenous abciximab in interventional cardiology: a reopened question? Vasc Pharmacol 2015; 73: Addad F, Gouider J, Boughzela E, et al. Management of patients treated for acute ST-elevation myocardial infarction in Tunisia. Ann Cardiol Angeiol 2015; 64: Akoukad H, El Khorb N, Sekkali N, et al. Acute myocardial infarction in Morocco: FES-AMI registry data. Ann Cardiol Angeiol 2015; 64: Delport R. Toward developing guidelines and systems of care to facilitate early reperfusion for ST-elevation myocardial infarction in Africa. Cardiovasc J Afr 2014; 25: