A Randomized Comparison of Excimer LASER vs Manual Thrombus Aspiration for the Prevention of No-reflow During Primary Percutaneous Coronary Intervention of St-elevation Myocardial Infarction(LASER-AMI Study)

Acute myocardial infarction (AMI) is the leading cause of death in developed countries. In patients with AMI, prompt reopening of an occluded coronary artery is the main goal of reperfusion therapies in order to restore normal blood flow to the myocardium, thus preventing left ventricular (LV) adverse remodelling and occurrence of heart failure. Primary percutaneous coronary intervention (PPCI) represents the pivotal step in the current management of ST-segment elevation myocardial infarction (STEMI) (1). Yet, in a sizable proportion of patients, PPCI achieves epicardial coronary artery reperfusion but not myocardial reperfusion, a condition known as no-reflow (2), that increases the extent of myocardial damage. The proportion of patients who get optimal myocardial reperfusion, among those without cardiogenic shock undergoing PPCI, is about 35% (3). Thus, the prevalence of no-reflow remains extremely high. Furthermore, a series of consistent data has clearly shown that no-reflow has a strong negative impact on outcome, negating the potential benefit of PPCI (4-10). Indeed, as compared to patients without no-reflow, patients with no-reflow exhibit a higher prevalence of: 1) early post-infarction complications (arrhythmias, pericardial effusion, cardiac tamponade, early congestive heart failure); 2) LV adverse remodelling; 3) late re-hospitalizations for heart failure; 4) mortality. In man, no-reflow is caused by the variable combination of four pathogenetic mechanisms: 1) distal atherothrombotic embolization, 2) ischemic injury, 3) reperfusion injury, 4) susceptibility of coronary microcirculation to injury (3). As a consequence, appropriately designed strategies to prevent or to treat, at the right time, each of these components are expected to reduce the final number of patients with no-reflow. Manual thrombus aspiration (MTA) has been clearly shown to improve microvascular perfusion and survival in STEMI patients treated by PPCI (9,10). Accordingly, in current guidelines of the European Society of Cardiology (ESC), MTA is a 2a recommendation (1). Yet, complete ST-segment resolution (defined as >70%) is obtained in only about 50% of patients (3,6), thus suggesting that microvascular perfusion may be further improved. In such a context, Excimer laser (EL) may play an important role in order to reduce the rate of microvascular obstruction. Coronary lasers are devices emitting electromagnetic energy which, upon absorption within the atherosclerotic plaque, can debulk the target tissue (11-12). Over the past decade, a second generation of pulsed-wave lasers was introduced (13). These devices combine a brief pulse duration of light emission with a long pause interval, thus ensuring prevention of thermal injury and adverse effect on the arterial wall to be laser. The pulsed wave EL (308 nm, ultraviolet wavelength, in the UVB region of the spectrum) is an FDA and EMEA approved device for treatment of atherosclerotic coronary lesions considered "non ideal" for standard balloon angioplasty (14-16). Furthermore, continuous saline flush of saline during laser advancement has allowed to further reduce heat generation and tissue damage. Taken together device improvement and technical advancement have allowed to lower procedural complication rate and to confirm in published registries the safety of the EL assisted angioplasty (17-18). In the setting of thrombotic lesion, EL has the potential to vaporize thrombotic and plaque material, leading to particles smaller than the size of erythrocytes unlikely to plug the microcirculation (19-20), and inhibits platelet aggregation, by inducing platelets stunning (21). Furthermore, laser is able to debulk underlying thrombogenic plaque thus limiting its thrombogenicity (22). EL has been used in the setting of STEMI within registries (23-26) and in a small randomized trial vs balloon assisted PPCI (27), showing a very low rate of myocardial no-reflow, as assessed by angiography (around 5%) and electrocardiography (around 35%). These studies, however, were limited by the small sample size and for most of them by the non-randomized design. Thus, a randomized study of EL assisted PPCI has become necessary in order to evaluate the efficacy of this mechanical strategy for STEMI patients. As MTA-assisted PPCI is nowadays the recommended approach by current guidelines, the effectiveness of EL-assisted PPCI should be evaluated against MTA-assisted PPCI. The goal of this trial, which will be carried out in patients with STEMI undergoing PPCI, is to assess the superiority of EL-assisted vs MTA-assisted PPCI, having as primary end-point the rate of 90-min ST segment resolution>70% and as secondary end-points the rate of angiographic no-reflow, defined as TIMI flow3 and MBG >=2 (28), the evaluation of infarct size, as assessed by the area under the curve of cardiac markers (29) and the rate of adverse remodelling as assessed by echocardiography at 6 months follow-up

Description of LASER-AMI trial

Study design

LASER-AMI is a randomized, open-label, blind-examination (PROBE), active controlled, multinational clinical trial. Patients undergoing PPCI will be randomly assigned to 1 of 2 interventional strategies of reperfusion: MTA-assisted PPCI alone or EL-assisted PPCI alone.

Study protocol and procedure