Impress trial - looking at the data

IMPRESS in Severe Shock Trial: Looking Closer at the Data

April 24, 2017

For patients with cardiogenic shock (CS), intra-aortic balloon pump (IABP) had been an important tool for maintaining patients and improving survival after percutaneous coronary intervention (PCI). Randomized controlled trials, however, have found very little evidence to support the notion that IABP is helpful for reducing mortality or improving hemodynamics for patients with CS.1,2 The Impella® heart pump has become an integral mechanical circulatory support (MCS) device also used in this patient population. Research comparing survival outcomes of the IABP and Impella® device has been notoriously difficult; the IMPRESS trial highlights these challenges.3

IMPRESS was a small, exploratory study comprising a heterogeneous patient population (N=48) with severe CS complicating acute myocardial infarction. Enrolled patients were on mechanical ventilation and more than 90% suffered cardiac arrest. Researchers compared patients receiving either IABP or Impella CP®, using 30-day mortality following PCI as the primary outcome. There was a significant discrepancy in the application of the randomized therapy, however, and the definition used for CS in this study remains unclear. Patients were deemed to have CS based on operator’s assertion.

Study Design and Definitions

This randomized, open-label trial did not complete patient enrollment and was closed as an exploratory safety study. Only 48 patients were included in the final analysis and were randomized into two groups for comparison: Impella CP® (n=24) and IABP (n=24). Interestingly, there was crossover of 3 patients from IABP to Impella® device support, and exactly 3 other patients in the Impella CP® group were not appropriately assigned and received either IABP or no device. Approximately 12% of patients in each arm did not receive their assigned device, demonstrating poor adherence to the protocol.

Since this was a small European study, adherence to stringent regulations as set forth by the FDA was not mandatory.

Timing of device placement relied on operator’s decision rather than a standardized protocol. Therefore, patients may have received the Impella® device prior to, during, or following PCI. Although early support is associated with better outcomes following revascularization, researchers still failed to make timing of device placement a priority when performing this trial.4

In this small study of patients with severe CS, researchers found that 30-day mortality was similar between Impella CP® and IABP (46% vs 50%, respectively).

Limitations

Patients in this study were in severe CS, and 92% were in cardiac arrest prior to randomization (p=0.04). Essentially, this study evaluated salvage patients with cardiac arrest and CS receiving either Impella CP® or IABP. Thus, when accounting for this complicating comorbidity, it’s challenging to describe this study as a comparison of hemodynamic support devices for patients with CS only.

Illness Severity

The severely sick patient population found in IMPRESS is not typical of an FDA-regulated U.S. study. In an accompanying editorial, Kumbhani DJ expanded on the limitations associated with the patients’ illness severity.5

“One must note that this was a very critically ill population,”

said Kumbhani.

“Nearly all had experienced cardiac arrest, with a median lactate level of nearly 8 mmol/L and a pH of 7.15. The major cause of death was anoxic brain injury, suggesting that MCS may be of limited utility in this patient population overall.”

Additionally, Kumbhani also points out that this trial was statistically underpowered, leading to further limitations to the overall findings.

Impella-Best Practices Were Not Considered

Patients with CS may benefit from early MCS; however, this study failed to demonstrate the importance of timing of device placement. Contradictory to best practices for Impella® device use, patients in this study often received late device support. Considering that early MCS with the Impella® heart pump is associated with improved outcomes, it would be interesting to see the impact if all received the device prior to PCI. Data from the retrospective cVAD registry, for example, showed that patients who received the Impella® device prior to PCI had a higher survival rate of 65.1% vs 41.5% for IABP pre-PCI.4 Notably, patients treated with early MCS support prior to PCI (n=8) in the IMPRESS exploratory study had a 30-day survival-to-discharge rate of 75% vs 47% for the remaining patients in the cohort.

Bleeding Rates

Also, major bleeding rates appeared high with the use of Impella CP® vs IABP (33% vs 8%, respectively). When examining the data closely, however, the reader can see that many of these patients were already suffering from traumatic injuries when they entered the study. Also, most of the bleeding rates were attributable to non-access site-related issues. There were only 2 patients in the Impella® device group and 1 patient in the IABP group who experienced bleeding from the access site. Another limitation of this study is the non-salvageable heterogeneous patient population, of which 35% had anoxic brain injury and refractory CS.

An Underpowered Study

Another editorial by Zeymer et al in JACC also notes that the study was significantly underpowered and calls for a greater number of patients in future similar trials.6

“…IMPRESS in Shock can only be regarded as a feasibility trial,”

according to Zeymer.

“It may serve as a basis for a larger clinical trial…however, based on the absolute mortality difference of 4%, such a trial would need approximately 2500 CS patients to show a real mortality difference with a power of 80%.”

If a similar study were to be performed in the U.S., a number of modifications to the study’s design would be necessary in order to ascertain reliable conclusions. Modifications might include enlarging the size of the patient population, obtaining a clearer definition of CS, and developing stringent exclusion and inclusion criteria. Additionally, a protocol for complete revascularization and escalation may be important changes for deducing relevant and practical findings.

The Take-Home

This small exploratory study emphasizes the need for standardized protocols which include early MCS support. It does not represent the best practices for use of the Impella® device, nor does it provide any surprising information that wasn’t already available in the literature. Using this patient population, results obtained from this study were deemed predictable and supported by other data and registries. Utilization of registries, including cVAD and SHOCK, may help guide protocol design in future research. Additionally, future trials with a greater number of patients may help provide results with more relevancy to current clinical practice.

References:

  1. Prondzinsky R, Lemm H, Swyter M, et al. Intra-aortic balloon counterpulsation in patients with acute myocardial infarction complicated by cardiogenic shock: the prospective, randomized IABP SHOCK Trial for attenuation of multiorgan dysfunction syndrome. Crit Care Med. 2010;38(1):152-160.
  2. Thiele H, Zeymer U, Neumann FJ, et al. Intraaortic Balloon Support for Myocardial Infarction with Cardiogenic Shock. N Engl J Med. 2012;367(14):1287-1296.
  3. Ouweneel DM, Eriksen E, Sjauw KD, et al. Percutaneous Mechanical Circulatory Support Versus Intra-Aortic Balloon Pump in Cardiogenic Shock After Acute Myocardial Infarction. J Am Coll Cardiol. 2017;69(3):278-287.
  4. O’Neill WW, Schreiber T, Wohns DH, et al. The current use of Impella 2.5 in acute myocardial infarction complicated by cardiogenic shock: results from the USpella Registry. J Interv Cardiol. 2014;27(1):1-11.
  5. Kumbhani DJ. IMPella versus IABP Reduces mortality in STEMI patients treated with primary PCI in Severe cardiogenic SHOCK – IMPRESS. American College of Cardiology.
  6. Zeymer U, Thiele H. Mechanical Support for Cardiogenic Shock: Lost in Translation? J Am Coll Cardiol. 2017;69(3):288-290.

ICP-013-17

Impella® Device — Indication & Safety Information

INDICATIONS FOR USE

Protected PCI

The Impella 2.5® and Impella CP® Systems are temporary (≤ 6 hours) ventricular support devices indicated for use during high-risk percutaneous coronary interventions (PCI) performed in elective or urgent, hemodynamically stable patients with severe coronary artery disease, when a heart team, including a cardiac surgeon, has determined high-risk PCI is the appropriate therapeutic option. Use of the Impella 2.5 and Impella CP Systems in these patients may prevent hemodynamic instability, which can result from repeat episodes of reversible myocardial ischemia that occur during planned temporary coronary occlusions and may reduce peri- and post-procedural adverse events.

Cardiogenic Shock

The Impella 2.5®, Impella CP®, Impella 5.0®, and Impella LD® Catheters, in conjunction with the Automated Impella Controller (collectively, “Impella® System Therapy”), are temporary ventricular support devices intended for short term use (≤ 4 days for the Impella 2.5 and Impella CP, and ≤ 6 days for the Impella 5.0, and Impella LD) and indicated for the treatment of ongoing cardiogenic shock that occurs immediately (< 48 hours) following acute myocardial infarction or open heart surgery or in the setting of cardiomyopathy, including peripartum cardiomyopathy, or myocarditis as a result of isolated left ventricular failure that is not responsive to optimal medical management and conventional treatment measures (including volume loading and use of pressors and inotropes, with or without IABP). The intent of Impella System Therapy is to reduce ventricular work and to provide the circulatory support necessary to allow heart recovery and early assessment of residual myocardial function.

Important Risk Information for Impella devices

CONTRAINDICATIONS

The Impella 2.5, Impella CP, Impella 5.0 and Impella LD are contraindicated for use with patients experiencing any of the following conditions: Mural thrombus in the left ventricle; Presence of a mechanical aortic valve or heart constrictive device; Aortic valve stenosis/calcification (equivalent to an orifice area of 0.6 cm2 or less); Moderate to severe aortic insufficiency (echocardiographic assessment graded as ≥ +2); Severe peripheral arterial disease precluding placement of the Impella System; Significant right heart failure*; Combined cardiorespiratory failure*; Presence of an Atrial or Ventricular Septal Defect (including post-infarct VSD)*; Left ventricular rupture*; Cardiac tamponade*

* This condition is a contraindication for the cardiogenic shock indication only.

POTENTIAL ADVERSE EVENTS

Acute renal dysfunction, Aortic valve injury, Bleeding, Cardiogenic shock, Cerebral vascular accident/Stroke, Death, Hemolysis, Limb ischemia, Myocardial infarction, Renal failure, Thrombocytopenia and Vascular injury

In addition to the risks above, there are other WARNINGS and PRECAUTIONS associated with Impella devices. Visit http://www.abiomed.com/important-safety-information to learn more.

General Indication and Safety Information

To learn more about the Impella platform of heart pumps, including important risk and safety information associated with the use of the devices, please visit: www.protectedpci.com/indications-use-safety-information/