3 Clinical evidence

3 Clinical evidence

Summary of clinical evidence

3.1 Full details of all clinical outcomes considered by the Committee are available in the assessment report overview.

3.2 The key clinical outcomes for the E‑vita open plus presented in the decision problem were:

  • completion and success of technical procedure(s)

  • mortality

  • major complications, for example stroke, paraplegia, renal failure, myocardial infarction and other events that may delay discharge

  • length of intensive care unit stay

  • total length of hospital stay

  • freedom from further interventions

  • long-term survival rates

  • incidence of junctional endoleak

  • device-related adverse events.

3.3 The sponsor identified 13 papers relevant to the E‑vita open plus. Most of these were derived from the International E‑vita Open Registry, which is reported to contain data on 70–80% of patients in 11 European centres who have received the E‑vita open or open plus devices to treat their complex aortic disease. The sponsor excluded 10 (of the 13) papers from further consideration, either because the data were already included in a more recent report on the entire register dataset at the time of publication (Jakob et al. 2011), or because they reported on small numbers of patients or on animal studies. The External Assessment Centre excluded a further 2 papers from its evaluation: a small study with limited follow-up, and a study using the same data as the paper by Jakob et al. (2011). The External Assessment Centre judged that the principal clinical evidence for the E‑vita open plus was presented in the observational study on the International E‑vita Open Registry by Jakob et al. (2011).

3.4 Jakob et al. (2011) reported observational data, gathered between January 2005 and December 2010, for 274 patients with complex aortic disease enrolled in the International E‑vita Open Registry from, at the time, 8 European centres. This comprised the entire dataset at the time of publication. Details of the 274 patients treated, in terms of condition and interventions, are shown in table 1. Outcomes were presented as proportions and survival analysis was carried out using the Kaplan–Meier technique. Stent-graft deployment and arch replacement were carried out under selective antegrade cerebral perfusion during a mean time of 75 minutes. Median length of hospital stay was 19 days (range 12–29). Adverse events are shown in table 2. For patients with dissections the false lumen was assessed postoperatively and at a median time of 59 months (range 28–99) after surgery. The false lumen thrombosed fully in 83% (62/75) of patients with acute aortic dissection, and 72% (68/94) of patients with chronic aortic dissection. After follow-up these figures rose to 93% and 92% respectively. For patients with aneurysms, complete exclusion of the aneurysm was achieved in 77% of cases (61/79). The overall 5‑year survival rate was 74%. Of the 233 patients surviving the procedure initially, secondary endovascular intervention was needed in 13% (29) and surgery downstream was needed in 3% (6) of cases.

Table 1 Conditions and interventions for patients enrolled in the International E‑vita Open Registry (Jakob et al. 2011)

Included patients (n=274)

Emergency surgery

Previous proximal repair

Presenting condition needing treatment

Acute aortic dissection

88 (32%)

77 (88%)

-

Chronic aortic dissection

102 (37%)

-

71 (70%)

Thoracic aortic aneurysm

84 (31%)

-

-

Underlying condition

Marfan's syndrome

12 (5%)

-

-

Interventions received during treatment with the E‑vita open plus

Arch replacement with E‑vita open plus

151 (55%)

-

-

Arch replacement with other prosthesis

123 (45%)

-

-

Additional coronary artery bypass graft

43 (16%)

-

-

3.5 The sponsor presented limited evidence on clinical outcomes for 2-stage procedures to allow comparison with those for the E‑vita open plus. The External Assessment Centre therefore carried out a systematic review and meta-analysis of available data for the comparator procedures. The review identified 10 papers and the meta‑analysis provided pooled estimates of outcome rates with 95% confidence intervals forin-hospital and 30 day mortality, stroke, bleeding, paraplegia and renal failure, which were the main complications reported in the literature. The External Assessment Centre was unable to calculate single outcome estimates for the combined 2-stage procedures because of a lack of data. It judged that direct comparisons between the E‑vita open plus and the comparators would therefore be complex and that the figures did not take into account factors such as survival from stage 1 to 2 or the impact of the combined outcomes for each procedure. Long-term survival rates could not be included in the meta-analysis because no confidence intervals were reported and individual patient data were not available. The pooled estimate data for the comparators are shown in table 2.

Table 2 Adverse events for the E‑vita open plus, as reported in Jakob et al. (2011), and comparators

Stage

E‑vita open plus

(Jakob et al. 2011)

(n; %; 95% confidence interval)

2-stage open surgical repair with vascular graft placement

(%; 95% confidence interval

2-stage repair with endovascular stent graft placement

Open surgical 'debranching' with endoluminal stent graft placement (2-stage procedure)

In-hospital mortality

1

41 (15.0%: 11.0 to 19.7%)

8.5% (6.4 to 11.1%)

8.9% (3.4 to 21.4%)

13.5% (4.5 to 28.8%)

2

-

8.0% (5.6 to 11.2%)

9.6% (4.4 to 19.8%)

3.7% (0.1 to 19.0%)

30 day mortality

1

33 (12.0%: 8.4 to 16.5%)

7.5% (5.4 to 10.5%)

-

-

2

-

5.9% (1.6 to 19.0%)

3.2% (0.08 to 16.7%)

-

Re-exploration for bleeding

1

38 (13.9%: 10.0 to 18.5%)

4.6% (2.8 to 7.4%)

4.2% (0.1 to 21.1%)

8.1% (1.7 to 21.9%)

2

-

3.7% (1.7 to 7.8%)

5.6% (0.1 to 27.3%)

-

Stroke

1

16 (5.8%: 3.4 to 9.3%)

3.4% (2.3 to 4.9%)

7.4% (3.3 to 16.1%)

8.1% (1.7 to 21.9%)

2

-

3.9% (1.1 to 13.0%)

-

3.7% (0.1 to 19.0%)

Paraplegia

1

22 (8.0%: 5.1 to 11.9%)

-

4.2% (0.1 to 21.1%)

-

2

-

4.1% (1.6 to 9.8%)

7.8% (3.0 to 19.1%)

-

Renal failure (permanent)

1

10 (3.6%: 1.8 to 6.6%)

8.5% (3.4 to 19.6%)

12.5% (2.7 to 32.4%)

-

2

-

6.0% (1.1 to 27.6%)

-

-

95% confidence intervals were calculated by the External Assessment Centre, and pooled outcome estimates for the comparator technologies were taken from the External Assessment Centre's meta-analysis.

3.6 During consultation, an additional clinical report was identified that presented more recent data from the International E‑vita Open Registry (Jakob and Tsagakis, 2013). The paper reported outcomes for in-hospital mortality, stroke, paraplegia and 5-year survival rates for a total of 416 patients from 11 international centres. No outcomes were reported for 30-day mortality, bleeding or renal failure. Figures for 5-year survival rates were reported for 3 subgroups but no overall figure was reported or could be calculated from the data presented. The External Assessment Centre determined that, overall, there was insufficient information available, in terms of completeness or long-term follow-up, to provide additional reliable estimates of outcome rates beyond those derived from the Jakob et al. (2011) study (see section 3.4).

Committee considerations

3.7 The Committee considered that the clinical evidence was limited because it was restricted to observational studies. However, it considered that the evidence was sufficient, when taken together with clinical expert advice, to conclude that the E‑vita open plus is effective for use in a selected group of people (see 3.10–3.11).

3.8 The Committee considered that the pooled estimates of outcomes for the comparators produced by the External Assessment Centre indicated that more bleeding would be likely to occur with the E‑vita open plus (13.9%) than with the comparators (ranging from 4.2% to 8.1% at stage 1, and from 3.7% to 5.6% at stage 2). The Committee was advised that bleeding was a complication experienced with both the E‑vita open plus and the comparators and that excess bleeding with the E‑vita open plus may have reflected incorrect choice of device size during early experiences of its use. It was mindful that bleeding is a complication which is normally controlled at the time of surgery, without patients experiencing long-lasting adverse consequences, in contrast to the other major adverse events (stroke, paraplegia and renal failure) which may have serious consequences for patients in the long term.

3.9 The Committee was advised that patient selection would be important in realising the claimed benefits of the E‑vita open plus. The Committee heard expert clinical advice that the E‑vita open plus is primarily suitable for people needing aortic arch repair and that the device enables repair to the arch to be completed more rapidly than by other techniques. Expert advice also confirmed that in people whose aortic disease extends less than 10 cm into the descending aorta (based on the size of the stent graft portion of the device), the E‑vita open plus would allow a complex repair in a single procedure.

3.10 The Committee concluded that in people with aneurysms or acute aortic dissections needing repair of the aortic arch and ascending aorta, if the disease extends less than 10 cm into the descending aorta, the E‑vita open plus would be a suitable treatment. The Committee recognised that the E‑vita open plus might be suitable for use in other people with more extensive disease in the descending aorta that would need multiple stent grafts. However, it decided that the potential benefits of the technology for these people were not clear, based on the evidence presented. The Committee therefore considered that making a recommendation for use of the technology in those with more extensive disease in the descending thoracic aorta was not possible.

3.11 The Committee was advised that many people for whom treatment with the E‑vita open plus would be suitable have progressive aortic disease that would need further interventions, regardless of whether the repair was carried out in a single or 2-stage procedure. It was advised that this is significantly more likely in people with connective tissue disorders such as Marfan's syndrome than in those with atherosclerotic disease.

3.12 The Committee judged that the main advantage of the E‑vita open plus is the avoidance of a second procedure with its associated serious risks, which include stroke, renal failure, paraplegia and bleeding. The Committee was advised by clinical experts that some people decide not to return for a second procedure because of negative experiences from the first operation. The Committee considered that the opportunity to repair the aorta in a single procedure would confer significant benefits to these people.

3.13 The Committee was advised by clinical experts that the estimate in the scope for the number of people in England (50–100 per year) eligible for treatment was reasonable.

3.14 The Committee considered the paper by Jakob and Tsagakis (2013), but judged that the outcomes it reported did not add to the evidence base for the E‑vita open plus: no data for 30-day mortality, bleeding or renal failure were reported. It considered that the included outcome data did not differ significantly from those reported by Jakob et al. (2011) and would not alter the outcomes from the External Assessment Centre's cost analysis.

  • National Institute for Health and Care Excellence (NICE)