High-Risk PCI with Hemodynamic Support — Impella or IABP?
High-Risk PCI with Hemodynamic Support Impella or IABP?
Abstract & Commentary
By Andrew J. Boyle, MBBS, PhD. Assistant Professor of Medicine, Interventional Cardiology, University of California, San Francisco
Source: O'Neill WW, et al. A prospective, randomized clinical trial of hemodynamic support with impella 2.5 versus intra-aortic balloon pump in patients undergoing high-risk percutaneous coronary intervention: The PROTECT II study. Circulation 2012;126:1717-1727.
In patients with severe coronary artery disease (CAD) and depressed left ventricular (LV) function, coronary artery bypass graft (CABG) surgery remains the recommended treatment. However, for some patients, CABG is not an option and high-risk percutaneous coronary intervention (PCI) is the only potential mode of revascularization. In these patients, the transient cessation of coronary artery flow during balloon inflation may result in hemodynamic compromise or even collapse. In extreme cases, this can lead to cardiac arrest. The use of hemodynamic support may improve outcomes in high-risk PCI, but there have been no direct comparisons of devices. Thus, O'Neill and colleagues performed a randomized, controlled, international multicenter trial of intra-aortic balloon pump (IABP) vs the Impella 2.5 percutaneous left ventricular support device. The Impella is an axial flow pump that is placed across the aortic valve and can pump up to 2.5 L/min from the left ventricle to the aorta. The study included a very high-risk population of patients requiring PCI and either left main disease or last remaining vessel with LV ejection fraction (EF) ≤ 35%, or triple vessel disease with LVEF ≤ 30%. Exclusion criteria were recent myocardial infarction (MI) with persistent elevation of cardiac enzymes, platelet count of < 75,000/mm3, creatinine ≥ 4 mg/dL (those on dialysis already were eligible), and severe peripheral arterial disease precluding the passage of the support devices. At 112 sites, the investigators were instructed to aim for the most complete revascularization possible in a single procedure, but details such as anticoagulation strategy, use of IIb/IIIa inhibitors, types of stents used, and use of closure devices was left to the operator's discretion.
The primary endpoint was the composite rate of major adverse events at discharge or 30-day follow-up (whichever was longer). Major adverse events included death, MI, stroke or transient ischemic attack (TIA), repeat revascularization, acute renal insufficiency, need for cardiac or vascular operation, severe intraprocedural hypotension requiring therapy or cardiopulmonary resuscitation, ventricular tachycardia, aortic regurgitation, and angiographic procedural failure. A prespecified secondary endpoint was 90-day follow rate of the primary endpoint.
The study was terminated early because of futility. Ultimately, 448 patients were randomized to support with IABP (n = 223) vs Impella 2.5 (n = 225). Baseline characteristics were similar between groups except that the Impella group had higher rates of prior CABG (38% vs 29%; P = 0.033) and heart failure (91% vs 83%; P = 0.014). This was a very high-risk cohort, with 51% diabetic, average LVEF 24 ± 6%, and an average SYNTAX score of 30 ± 15. In both groups, an average of 2.9 lesions were treated per patient. Impella provided better intra-procedural hemodynamic support than IABP. The patients in the Impella group had higher rates of rotational atherectomy, lower use of IIb/IIIa inhibitors and non-heparin anticoagulants, and required shorter durations of hemodynamic support.
The LVEF rose from 27 ± 9% to 33 ± 11% and the proportion of patients in New York Heart Association functional class III/IV improved from 62% to 26%, with no difference between groups. Intention-to-treat analysis showed no statistically significant difference in the primary composite endpoint at 30 days (35.1% Impella vs 40.1% IABP; P = 0.277). There was no difference in the components of the primary composite endpoint with the exception of a lower rate of stroke/TIA in the Impella group (0.0 vs 1.8; P = 0.043). At 90 days, the primary composite endpoint trended in favor of Impella (40.6% vs 49.3%; P = 0.066). In a per-protocol analysis (excluding those who were randomized but did not receive the treatment), the primary composite endpoint was more in favor of the Impella group, with a trend at 30 days (34.3% vs 42.2%; P = 0.092) and a significant benefit at 90 days (40.0% vs 51.0%; P = 0.023). The authors present several exploratory endpoints of interest. The Impella group appeared to have better outcomes at 90 days in those patients who did not have atherectomy, those with triple vessel disease (compared to left main disease), those with predicted mortality < 10% by Society of Thoracic Surgeons (STS) score, after excluding the first patient at each site, and after the first year of the trial. The authors conclude that the 30-day incidence of major adverse events was not different for patients with IABP or Impella 2.5 hemodynamic support. However, trends for improved outcomes were observed for Impella 2.5-supported patients at 90 days.
Commentary
This study recruited the highest risk cohort of any PCI study to date. Based on the initial feasibility study, PROTECT 1, the power calculation required 654 patients for this study to show benefit of Impella over IABP. However, at 50% enrollment, the data safety monitoring board terminated the study because the projected outcomes would not reach the primary endpoint. This effectively underpowered the study, which ultimately recruited just 69% of the projected enrollment. The authors point out that there was a learning curve with this new device, as shown by the improved results in the later years of the study and by excluding the first patient at each institution. This may have contributed to less than expected benefit with Impella early on in the study. How should we interpret these results now that we have an underpowered study with improving results over the course of the trial? First, the learning curve needs to be acknowledged and physicians and staff need to be adequately trained in the use of Impella. Second, despite a slightly higher clinical risk profile and a higher procedural risk profile, the Impella patients tended to do better than the IABP patients. This is very reassuring from a safety perspective. However, from an efficacy standpoint, because the study was underpowered and the results were trends toward better outcomes with Impella, we cannot definitely conclude for or against the use of Impella over IABP in high-risk PCI patients on the basis of these data. The exploratory endpoints are interesting and suggest that there may be subgroups who benefit from the Impella over IABP. But these must be considered hypothesis-generating and need further study. It is important to note that this study was performed in the non-emergent setting, and these results should not be extrapolated to patients with acute coronary syndromes or those in cardiogenic shock. Overall, there may be a role for Impella in the setting of high-risk elective PCI, but the results of this study are not conclusive and should form the basis of future studies of this technology.
In patients with severe coronary artery disease (CAD) and depressed left ventricular (LV) function, coronary artery bypass graft (CABG) surgery remains the recommended treatment.Subscribe Now for Access
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