Clinical and technical evidence

A literature search was carried out for this briefing in accordance with the published process and methods statement. This briefing includes the most relevant and best publicly available evidence relating to the clinical and cost effectiveness of the technology. The literature search strategy, evidence selection methods and detailed data extraction tables are available on request by contacting

Published evidence

This briefing summarises 5 studies: 1 meta-analysis (Briasoulis et al. 2016), 1 randomised controlled trial (PROTECT II, O'Neill et al. 2012), 2 registry studies (USpella, Maini et al. 2012; Europella, Sjauw et al. 2009) and 1 retrospective, comparative, single-arm study using registry (USpella) and trial (PROTECT II) data (Cohen et al. 2015). These studies include a total of 1,586 patients excluding overlapping cohorts.

Table 2 summarises the clinical evidence as well as its strengths and limitations.

Strengths and limitations of the evidence

The main limitation of the meta‑analysis and observational studies is that they were descriptive and do not provide comparative data. One study from the meta‑analysis that could not be identified (Schreiber et al. 2016) is likely to be unpublished data; however, the results are consistent with other studies.

The PROTECT II randomised controlled trial (O'Neill et al. 2012) was a high quality study that provides comparative data with clear, prospectively defined primary and secondary end points. However, after review of the interim data (n=327), the data safety monitoring board recommended early discontinuation of the study for futility. An extra 125 patients had been enrolled by the time the executive committee accepted the recommendation and study enrolment ceased, but the trial had not enrolled the number of patients for which it was powered. Therefore, definitive statements concerning the primary end point are speculative. However, the authors did report that they observed a notable learning curve in the trial, with marked improvement in safety for patients who had Impella in the last half of the trial.

The retrospective study by Cohen et al. (2015), which compared data from the PROTECT II trial with registry data, suggests the results are generalisable to real‑life clinical practice.

Two of the studies had funding from the manufacturer (O'Neill et al. 2012, Sjauw et al. 2009) and the authors of a third study had affiliations with and institutional research support from the manufacturer (Cohen et al. 2015).

Table 2 Summary of the selected studies


Details of intervention [and comparator]


Strengths and limitations

Briasoulis et al. (2016)


Meta-analysis (11 cohort and registry studies, and the Impella arm of the PROTECT II trial)

Impella 2.5 assisted PCI (no control arm).

The pooled cohort analysis for 30‑day mortality, 30‑day MI, clinical major bleeding and vascular complication rates were 3.5%, 3.3%, 7.1% and 4.9% respectively.

Significant heterogeneity between studies was observed for pooled 30‑day MI rate, pooled clinical major bleeding rate and pooled vascular complication rate, but not for pooled clinical 30‑day mortality rate.

After exclusion of low quality studies, the rates of 30‑day mortality, major bleeding, and MI did not change substantially. However, in the group of low risk of bias studies, the vascular complication rate was higher.

One study used in the meta-analysis for Impella was not referenced and could not be identified.

The meta-analyses were based on single-armed data and were descriptive rather than analytic.

There was heterogeneity between studies in terms of patient baseline characteristics and outcomes.

Individual studies were critically appraised using appropriate methodology.

O'Neill et al. (2012)

n=448 patients indicated for high-risk PCI

Randomised controlled trial – PROTECT II

Multinational – 112 sites

US, Canada and Europe

Impella 2.5 assisted PCI (intervention group; n=225) compared with IABP assisted PCI (control group; n=223).

There was no significant difference in the primary outcome (occurrence of MAEs at 30 days) between the Impella group compared with the IABP group.

Fewer MAEs were reported at 90‑day follow‑up when using Impella 2.5. These were statistically significant using the per protocol analysis but not for the intention-to-treat analysis.

After hospital discharge, there were significantly fewer irreversible MAEs involving death, stroke, MI or repeat vascularisation events in the Impella 2.5 group in comparison with the IABP group.

Patient cardiac function and functional status improved significantly after revascularisation in the Impella 2.5 group.

Impella 2.5 provided better haemodynamic support than IABP during the high-risk procedures based on maximal drop in cardiac power output from baseline.

Patients with STS morbidity risk scores of <10 had better 90‑day outcomes with Impella 2.5 than with IABP.

The study was terminated early after interim futility analysis indicated the primary outcome was unlikely to be achieved.

Therefore insufficient patients were enrolled to adequately power the study to detect a treatment difference of 10% between Impella 2.5 and IABP (relative reduction in major adverse events of 33%).

Blinding was not possible because of study nature and may have introduced potential changes leading to performance bias. Median rotational atherectomy time per lesion was significantly higher in the Impella arm.

Patient characteristics at baseline were comparable.

The authors also used an intention-to-treat analysis which allowed for a more pragmatic evaluation of the benefit of the treatment change.

Maini et al. (2012)

n=175 patients indicated for elective or urgent PCI

Retrospective single-arm cohort study – based on prospectively collected registry data (USpella)

Multicentre – 18 centres

North America

Impella 2.5 assisted high-risk PCI (single-arm study).

Overall, angiographic revascularisation was successful in 99% of patients and in 90% of those with multi-vessel revascularisation.

Systolic and diastolic blood pressures improved significantly while on support. Overall, there was a significant reduction of the mean SYNTAX score (grade for severity of coronary artery disease).

There was an improvement of the functional status by one or more NYHA classes at discharge.

Major vascular complications, haematomas (>4 cm), renal failure and bleeding requiring transfusion were reported in 4.0, 8.6, 2.8 and 9.7% of patients respectively.

All deaths were considered cardiac and not directly related to the Impella 2.5 device.

Provides real-world data on the safety profile and clinical outcomes of the Impella 2.5.

The single-armed design of the registry did not provide comparative data for Impella 2.5 with standard care or a no-device approach.

Main outcomes were related to the effectiveness of PCI rather than Impella.

This was the only study to investigate follow-up at 12 months.

Consecutive patients were analysed reducing the likelihood of selection bias.

Sjauw et al. (2009)

n=144 consecutive patients having elective high-risk PCI

Retrospective single-arm cohort study – based on prospectively collected registry data (Europella Registry)

Multicentre – 10 tertiary PCI centres across Europe

Cardiac support with Impella 2.5 (single-arm study).

Successful passage through the femoral artery and implantation of the Impella 2.5 into the LV was achieved in all 144 patients.

Both implantation and removal of the Impella were considered easy or suitable in >99% of the cases.

Mortality at 30 days was 5.5%.

Rates of MI, stroke, bleeding requiring transfusion/surgery, and vascular complications at 30 days were 0%, 0.7%, 6.2% and 4.0% respectively.

All adverse events were based on clinical diagnoses by the patient's physician.

However, events were entered in a prospectively developed case report form and centrally adjudicated by an independent clinician.

Consecutive patients were analysed reducing the likelihood of selection bias.

Cohen et al. (2015)

n=637 patients having high-risk PCI (USpella registry)

n=216 (PROTECT II trial)

Retrospective comparative single-arm study – using registry (USpella) and trial (PROTECT II) data

USpella – multicentre (49 centres: US and Canada)

PROTECT II – multinational (112 centres, US, Canada and Europe)

Cardiac support with Impella 2.5 – comparison of real-world registry data with clinical trial data.

A subset of patients (n=339) included in the USpella registry were identified that would have met eligibility for the PROTECT II trial and defined as PROTECT II-like patients.

The baseline risk of the PROTECT II-'like' patients was comparable to the clinical trial data. However, they were considered at higher risk of mortality in terms of age, renal insufficiency, coronary heart failure and LVEF.

At hospital discharge, registry patients experienced a similar reduction in NYHA class III to IV symptoms compared to trial patients.

There was a significantly lower rate of post-procedural MI and repeat revascularisation in USpella PROTECT II-'like' patients compared with the PROTECT II Impella arm patients.

Registry patients had a trend toward lower in-hospital mortality.

Despite the higher risk profile of registry patients, clinical outcomes appeared to be favourable and consistent compared with those in the randomised trial.

No propensity matching was performed. As data were collected retrospectively, only the major exclusion criteria from the PROTECT II trial could be assessed, which makes the interpretation of the results somewhat limited.

Results within the abstract do not correspond with those within the table of the study.

Abbreviations: IABP, intra‑aortic balloon pump; LV, left ventricle; LVEF, left ventricular ejection fraction; MI, myocardial infarction; MAE, major adverse event; NYHA, New York Heart Association; PCI, percutaneous coronary intervention; STS, Society for Thoracic Surgery.

Recent and ongoing studies

One in‑development trial on Impella 2.5 was identified in the preparation of this briefing:

  • NCT02468778: Coronary Interventions in High‑Risk Patients Using a Novel Percutaneous Left Ventricular Support Device (SHIELD II) – currently recruiting patients to evaluate the use of HeartMate PHP with Impella 2.5 as the active comparator for both the elective and urgent indications.