The Efficacy Of Manual Thrombus Aspiration Devices In ST-segment Elevation Myocardial Infarction: A Meta-analysis Of Randomized Controlled Trials

Backgrounds:Coronary heart disease has become one of the major diseases that threaten human health, of which ST-segment elevation myocardial infarction is the most severe kind. STEMI is a kind of acute myocardial ischemic necrosis. This kind of disease makes coronary blood flow reduce or even interrupt sharply based on coronary artery lesions, thus leading to serious acute myocardial ischemia of related blood-supply area. It is mainly based on unstable coronary plaque rupture and erosion followed by thrombosis, which can lead to sustained, total occlusion of coronary artery. In the United States, the morbidity and mortality of STEMI is on the decline. But in our country, with the rapid development of economy in recent years, the change of lifestyle and the aging of the population, the morbidity and mortality of STEMI showed a trend of increase year by year and the cardiovascular diseases have been the first cause of death in China. As STEMI progresses rapidly, the most important therapeutic principle is restoring the myocardial blood perfusion as soon as possible, for saving the dying myocardia, preventing infarction from expanding or narrowing the range of myocardial ischemia. The main form of reperfusion therapy includes percutaneous coronary intervention (PCI) and thrombolysis, of which the former is more important.Although primary percutaneous coronary intervention (PPCI) has become the mainstream treatment of STEMI and PPCI can make myocardia get well reperfusion in most cases, but there are still many patients suffering from undesirable reperfusion phenomenon, showing no reflow, slow reflow, inconspicuous ST-segment resolution and so on. This kind of phenomenon is closely related to the major adverse cardiac events (MACE) including death, reinfarction, heart failure, and target vessel revascularization. The no reflow phenomenon refers to the incomplete restoration of microcirculation flow following the alleviation and even elimination of the epicardial coronary artery occlusion, excluding the basis of epicardial vascular lesions and the severe stenosis, anatomic abnormality, thrombosis and spasm in its distal end. The no reflow phenomenon begins in the phase of myocardial ischemia, deteriorates in the phase of reperfusion, with the myocardial microcirculation reperfusion disorder as the pathological core, leading to poor prognosis such as infarction area expansion, left ventricular remodeling and cardiac function reduction. So far, the mechanism of no reflow phenomenon is still not clear. It is considered that this mechanism is associated with microvascular dysfunction caused by multiple factors, and the coronary microcirculation reperfusion abnormality is recognized as the core mechanism of no reflow phenomenon. Too long coronary artery occlusion time can damage a number of distal microvascular structures, so even the reconstruction of epicardial vascular flow can also led to no reflow phenomenon.Several techniques can be applied to the diagnosis of no reflow, mainly including the electrocardiogram, coronary angiography, intracoronary Doppler blood flow and intracoronary pressure measurement, myocardial contrast echocardiography, magnetic resonance imaging, single photon emission computed tomography and serology testing methods. For the prevention of no reflow phenomenon, choosing appropriate drugs and embolic protection devices in the process of PCI could effectively reduce no reflow phenomenon, while the key is to prevent coronary microvascular thrombosis and spasm. The main measures include facilitated PCI, direct stenting, embolic protection devices, platelet GP II b/IIIa receptor antagonists, vasodilators, and statins, etc. The studies of embolic protection devices are very hot nowadays.Embolic protecting devices include distal protection devices, thrombectomy devices, thrombus ablation devices and proximal protection devices, etc., while the distal protection devices can be divided into the distal occlusion devices and the distal strainer devices. There are a lot of current studies focused on thrombectomy devices. According to whether having power system, thrombectomy devices can be divided into manual thrombus aspiration devices and mechanical thrombus aspiration devices. A large number of clinical studies for the manual thrombus aspiration devices demonstrate that the manual thrombus aspiration can significantly improve the postoperative myocardial reperfusion, but it is still controversial in clinical outcomes. The results of the studies of mechanical thrombus aspiration devices are not as optimistic as manual thrombus aspiration devices. In 2013 and 2014, the 1 month and 12 months follow-up results of the TASTE trial were announced, confirming that the manual thrombus aspiration is not able to effectively improve the clinical outcomes of short-term and long-term follow-up after PCI. As a result, in 2014 guideline on myocardial revascularization jointly issued by the European Society of Cardiology and the European Association for Cardio-Thoracic Surgery degrades the thrombus aspiration to Ⅱb, needing no routine use, only may be useful in improving the postoperative TIMI 3 flow and preventing stent thrombosis. The guideline says that the mechanical thrombus aspiration cannot bring clinical benefit. Published in 2014, the TOTAL trial protocol attracts a lot of attention. The TOTAL trial will bring into about 10700 patients, and the primary end point within 180 days includes cardiac death, reinfarction, cardiac shock and newly-presented or aggravated cardiac insufficiency which is defined as the NYHA class Ⅳ. We are looking forward to the future of the TOTAL trial results, as well as the large sample sized Meta-analysis results which will include the TOTAL trial. These results will bring us a much clearer prospect of the application of manual thrombus aspiration.Objective:Due to mechanical thrombus aspiration cannot bring clinical benefit routinely, it is necessary to make Meta-analysis focusing on the studies of manual thrombectomy devices (including TASTE trial), so as to effectively assess the value of manual thrombus aspiration in the fields of myocardial reperfusion and clinical outcomes in patients with STEMI.Methods:Retrieving RCTs in the main medical databases and the websites of international major cardiology conferences by computers till September 2014 had been finished. No language was restricted.Inclusion criteria contain the patients who had been diagnosed with STEMI, reaching to hospital to receive the PCI therapy within 12 hours from the symptom onset. All the patients were randomly allocated to manual thrombus aspiration followed by PCI group or control group (conventional PCI). The diagnosis of STEMI complied with the WHO diagnostic criteria. Exclusion criteria: 1. the lack of effective experimental data, and no reply from the author after the contact; 2. the literature which contains more comprehensive data and information would be selected when the literature was repeatedly published; 3. studies which focused on the thrombus aspiration in the transplanted great saphenous vein; 4. studies involved the use of mechanical thrombectomy devices; 5. Studies focused on the comparison of two or more different thrombectomy devices.The literatures and the data were abstracted by two independent researchers following the inclusion and exclusion criteria, and cross check was needed. The consistency between the two researchers was assessed by Kappa statistics. The inconsistent result was resolved by discussion, the third researcher was needed when necessary. The bias of the included studies was assessed by the Cochrane group’s Cochrane Handbook for Systematic Reviews of Interventions.The primary end point is the all-cause mortality. The secondary end point included infarction, TVR, stent thrombosis and stroke. As angiography and ECG results could reflect the postoperative myocardial reperfusion, including postoperative MBG grade 3, TIMI flow grade 3 and STR≥70%, so these myocardial reperfusion outcomes was also included in the secondary end point. According to the different follow-up time, the different analyses were carried out on the clinical outcomes. According to the different follow-up time in different trials, the follow-up can be divided into short-term follow-up (in hospital to 30 days), medium-term follow-up (6 to 9 months) and long-term follow-up (1 year or above). For all the clinical outcomes, intention-to-treat analysis was used. This study was performed in compliance with the quality of reporting for meta-analyses (PRISMA [Preferred Reporting Items for Systematic reviews and Meta-Analyses] statement).Since all the data used in this study are dichotomous data, the relative risk (RR) and 95% CI was used. The chi square test was needed to assess the heterogeneity between the trials included.Results:19 trials were finally included, containing a total of 10535 patients. 5270 patients were randomly assigned to the manual thrombus aspiration group, while 5265 patients were randomly assigned to conventional PCI group. The follow-up ranged from 1 month to 2 years, while 6 trials belonged to short-term follow-up (hospitalization to 1 month),8 trials belonged to the midterm follow-up (6 to 9 months),1 trial belonged to long-term follow-up (12months or above). There were 4 trials including both short-term or medium-term follow-up and the long-term follow-up.There are no significant differences between thrombus aspiration group and conventional PCI group in terms of short-term (hospitalization to 1 month) follow-up mortality (2.69%　vs 3.09%, RR= 0.87,95%　CI:0.69 to 1.10, p= 0.25) and medium-term (6 to 9 months) follow-up mortality (1.56%　vs 2.26%, RR= 0.75,95% CI:0.33 to 1.71, p= 0.50).There is a trend towards the decrease of long-term follow-up (12 months or above) mortality in thrombus aspiration group, but there is no statistical differences (5.05%　vs 5.85%, RR= 0.86,95%　CI:0.73 to 1.03, p= 0.09).There is significant difference between thrombus aspiration group and conventional PCI group in terms of short-term (hospitalization to 1 month) follow-up reinfarction rate (0.59%　vs 0.99%, RR= 0.60,95%　CI:0.38 to 0.96, p=0.03), However, there is no significant difference in terms of medium-term(6 to 9 months) follow-up reinfarction rate (3.38%　vs 5.35%, RR= 0.64,95%　CI:0.31 to 1.32, p= 0.23) and long-term follow-up (12 months or above) reinfarction rate (2.44%　vs 2.82%, RR= 0.87,95%CI:0.67 to 1.11, p= 0.26).There is no significant difference between thrombus aspiration group and conventional PCI group in terms of short-term (hospitalization to 1 month) follow-up TVR rate (2.02%　vs 2.49%, RR= 0.81,95%　CI:0.62 to 1.07, p= 0.14), In addition, there is still no significant difference in terms of medium-term(6 to 9 months) follow-up TVR rate (5.56%　vs 8.52%, RR= 0.66,95%　CI:0.38 to 1.15, p= 0.14) and long-term follow-up (12 months or above) TVR rate (5.16%　vs 5.82%, RR= 0.89, 95%CI:0.75 to 1.05, p= 0.18).As the number of RCTs related to stent thrombosis is small, we have mixed all the different follow-up trials altogether. There is no significant difference between thrombus aspiration group and conventional PCI group in terms of stent thrombosis rate (0.86%　vs 1.16%, RR= 0.74,95%　CI:0.50 to 1.11, p= 0.15).As the number of RCTs related to stroke is small, we have mixed all the different follow-up trials altogether. There is almost no difference between thrombus aspiration group and conventional PCI group in terms of stroke rate (0.57%vs 0.57%, RR= 0.99,95%　CI:0.56 to 1.75, p＝0.98).Compared with conventional PCI group, There is a significant increase in the postoperative STR≥70%　rate in thrombus aspiration group (58.23%　vs 47.00%, RR = 0.74,95%　CI:0.64 to 0.87, p= 0.0002). In addition, There is a significant increase in the postoperative TIMI flow grade 3 rate (86.00%　vs 80.19%, RR= 0.65,95%　CI: 0.48 to 0.89, p= 0.006) and postoperative MBG grade 3 rate (52.22%　vs 37.26%, RR = 0.71,95%　CI:0.58 to 0.88, p= 0.002) in thrombus aspiration group.Conclusions:The main results of this study is to find that manual thrombus aspiration devices can significantly reduce the postoperative short-term follow-up (in hospital to 1 months) of reinfarction rate, as well as reducing the postoperative long-term follow-up (12 months or above) of all-cause mortality, but did not reach statistical significance. This study also confirmed that manual thrombus aspiration devices can significantly improve the postoperative myocardial reperfusion, improving the rate of postoperative STRs≥70%, TIMI flow grade 3 and MBG grade 3 as well. However, this study proved that manual thrombus aspiration devices did not significantly influence the short-term and medium-term (6 to 9 months) follow-up of all-cause mortality, medium-term and long-term follow-up of reinfarction rate and all follow-up time of TVR rate. In addition, this study demonstrates that manual thrombus aspiration devices have little impact on the stroke rate.