PROTECT II Published: Study of Percutaneous LVAD vs. IABP Sends Mixed Signals

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A percutaneous left ventricular assist device fails to offer improvement in 30-day outcomes compared with intra-aortic balloon pump (IABP) therapy in high-risk patients requiring hemodynamic support during percutaneous coronary intervention (PCI), according to a randomized trial published online August 30, 2012, ahead of print in Circulation. But a per protocol analysis of the data found the novel technology to be superior at 90 days, suggesting that it may hold promise over the long term.

Results of the PROTECT II trial were previously presented at the 2011 American College of Cardiology Annual Scientific Session/i2 Summit in New Orleans, LA.

William W. O’Neill, MD, of the Leonard M. Miller School of Medicine (Miami, FL), and colleagues had intended to enroll 654 patients in PROTECT II, but the trial was stopped early by the Data and Safety Monitoring Board after a planned interim analysis revealed futility. In all, the researchers analyzed results of 448 patients with complex 3-vessel or unprotected left main disease and severely impaired LV function who were randomized to PCI with the Impella 2.5 (n = 225; Abiomed, Danvers, MA) or IABP (n = 223).

Primary Endpoint Not Reached

Impella provided better hemodynamic support than IABP, showing a smaller maximal decrease in cardiac power output (-0.04 ± 0.24 Watts vs. -0.14 ± 0.27 Watts; P = 0.001).

The primary endpoint of major adverse events (MAE) at 30 days in the intent-to-treat analysis did not differ between the 2 treatment arms, a similarity that persisted to 90-day follow-up. A per protocol analysis (n = 216 Impella, n = 211 IABP) showed a strong trend favoring Impella at 30 days; the disparity in MAE reached significance at 90 days, however (table 1).

Table 1. Major Adverse Events

In the intent-to-treat analysis, mortality was statistically similar between IABP and Impella at 30 days (5.9% vs. 7.6%; P= 0.473) and 90 days (8.7% vs. 12.1%; P = 0.244). The same lack of effect was seen in the per protocol analysis.

Both treatment groups showed improvements in LVEF and NYHA functional class from baseline to 90-day follow-up.

According to the paper, a prespecified analysis of the 88% of patients not treated with atherectomy provides a more homogenous population and lessens the possibility of confounding. (Rotational atherectomy, more commonly used and more vigorously performed within the Impella arm, was associated with a higher rate of periprocedural MI due to cardiac enzyme leaks.) Within the nonatherectomy subgroup, Impella reduced MAE compared with IABP when results were analyzed according to intention to treat (RR 0.75; 95% CI 0.59-0.95; 36.5% vs. 48.7%; P = 0.014).

Later Events Deserve Consideration

“These results demonstrate that high risk, symptomatic coronary artery disease patients can be revascularized using hemodynamic support and modern PCI technique with favorable safety and efficacy,” Dr. O’Neill and colleagues conclude. Overall, they say, PROTECT II supports PCI as a “reasonable revascularization strategy for this high-risk population, since it improves heart failure symptoms and the quality of life of patients with limited therapeutic options.”

But the investigators also stress that the “present report confirms that patients with severely depressed left ventricular function who undergo PCI for a stenotic left main lesion, last patent conduit, or lesions in the setting of 3-vessel disease have a markedly increased risk for mortality compared with general non-emergent PCI patients.”

With PROTECT II failing to show a difference in its primary endpoint of 30-day MAE, “analysis of 90-day events remains exploratory,” the researchers acknowledge. That being said, “[i]mportant adverse events continued to occur after 30-day follow-up, suggesting that intense medical observation is required for at least 90 days in these patients.”

Study Details

The study’s primary endpoint was the composite MAE rate (all-cause death, Q-wave or non-Q-wave MI, stroke or TIA, repeat revascularization with PCI or CABG, need for cardiac or vascular surgery, acute renal insufficiency, severe intra-procedural hypotension requiring therapy, cardiopulmonary resuscitation or ventricular tachycardia requiring cardioversion, aortic insufficiency, and angiographic failure of PCI) at discharge or 30 days, whichever was longer, based on intention to treat.

Baseline characteristics were similar between the treatment groups except for heart failure and previous CABG, both of which were higher in the Impella arm. Patients were 67 ± 11 years old, highly symptomatic (66% New York Heart Association class III or IV), and the majority had heart failure (87%). Approximately half had diabetes. Mean LVEF was 24%. Two-thirds were considered inoperable.

Note: Study coauthor Jeffrey W. Moses, MD, is a faculty member of the Cardiovascular Research Foundation, which owns and operates TCTMD.