3 Clinical evidence

Summary of clinical evidence

3.1 The main clinical outcomes for treatment of in-stent restenosis with SeQuent Please balloon catheter are successful revascularisation, the occurrence of restenosis, and the avoidance of major adverse cardiac events, including death, myocardial infarction and stroke. Further restenosis is assessed angiographically by measuring late lumen loss at the site of intervention or by the presence of coronary stenosis greater than 50% (binary restenosis), and by determining target lesion revascularisation or target vessel revascularisation. Full details of all clinical outcomes considered by the Committee are available in the assessment report.

3.2 The PEPCAD II trial was a randomised controlled trial (RCT) of 131 patients with a single restenosis in a bare metal stent treated by SeQuent Please balloon catheter or paclitaxel-eluting stent. PEPCAD II reported binary in-stent restenosis rates of 7% (4/66) with SeQuent Please balloon catheter and 17% (10/65) with paclitaxel-eluting stent at 12-month follow-up (p = 0.17). The ISR I and II trials included 108 patients with a single restenotic lesion in a bare metal stent or drug-eluting stent treated by SeQuent Please balloon catheter or an uncoated balloon catheter. This RCT showed a significant difference in binary in-stent restenosis rates of 6% (3/54) with SeQuent Please balloon catheter and 49% (24/54) with uncoated balloon catheter at 6-month follow-up (p = 0.001). In the PEPCAD I trial, a non-randomised controlled study of 118 patients with a single de novo lesion in a native small calibre coronary artery, the binary restenosis rate (in-lesion) was 6% (4/82) for patients treated with SeQuent Please balloon catheter and 41% (12/32) in patients treated by SeQuent Please balloon catheter plus bare metal stent implantation at 12-month follow-up.

3.3 The PEPCAD II trial has reported in-stent late lumen loss of 0.19 ± 0.39 mm for SeQuent Please balloon catheter compared with 0.45 ± 0.68 mm for paclitaxel-eluting stent at 6 months (p = 0.01). The ISR I and II trials reported combined in-stent late lumen loss of 0.14 ± 0.46 mm for SeQuent Please balloon catheter and 0.81 ± 0.79 mm for uncoated balloon catheter at 6 months (p = 0.001). The PEPCAD I trial reported in-lesion late lumen loss of 0.18 ± 0.38 mm for SeQuent Please balloon catheter and 0.73 ± 0.74 mm for SeQuent Please balloon catheter plus bare metal stent implantation at 6-month follow-up (p < 0.0001).

3.4 The ISR I and II trials reported target lesion revascularisation rates of 6% (3/54) for SeQuent Please balloon catheter and 37% (20/54) for uncoated balloon catheter at 24-month follow-up (p = 0.001). The PEPCAD II trial reported target lesion revascularisation rates of 6% (4/66) for SeQuent Please balloon catheter and 15% (10/65) for paclitaxel-eluting stent at 12-month follow-up (p = 0.15). For patients with bifurcation lesions, the PEPCAD V study reported a target lesion revascularisation rate of 4% (1/28) at 9 months. The mean target lesion revascularisation rate for all 118 patients with small coronary arteries in the PEPCAD I trial was 12% (14/118) at 12-month follow-up. In this study, target lesion revascularisation rate was reported in 5% (4/82) of patients treated with SeQuent Please balloon catheter and 28% (9/32) of patients treated with SeQuent Please balloon catheter plus additional bare metal stent at 12-month follow-up (p < 0.0001; as-treated analysis).

3.5 The rate of major adverse coronary events was significantly lower at 24 months for patients treated with SeQuent Please balloon catheter compared with patients treated with the uncoated balloon catheter (11% [6/54] vs 46% [25/54]) in ISR I and II (p = 0.001). Major adverse coronary events at 12-month follow-up in the PEPCAD II trial were 8% in patients treated with SeQuent Please balloon catheter compared with 17% after treatment by drug-eluting stent (p = 0.17) (intention-to-treat analysis). Major adverse coronary events rates at 6-month follow-up were reported as 6% for patients treated with SeQuent Please balloon catheter and 38% for patients treated with SeQuent Please plus bare metal stent in the PEPCAD I trial (p ≤ 0.0001). The PEPCAD V study had an associated major adverse coronary event rate of 11% at 9 months. A lower major adverse coronary event rate was associated with SeQuent Please balloon catheter use compared with the uncoated balloon catheter at 24 months in ISR I and II, although the reductions were not statistically significant. PEPCAD II reported death in 3% (2) of patients treated with SeQuent Please balloon catheter and 5% (3) of patients treated with paclitaxel-eluting stent at 12-month follow-up. Among these patients, non-cardiac death occurred in 1 and 3 patients respectively and there was one cardiac death in the SeQuent Please balloon catheter group, compared with no deaths in the drug-eluting stent group. Myocardial infarction was reported in 1 patient in the drug-eluting stent treatment group. At 12 months, the PEPCAD I trial reported no deaths in either patient group, with myocardial infarction rates of 1.3% for the SeQuent Please balloon catheter group and 3.1% for the SeQuent Please balloon catheter plus bare metal stent group. The PEPCAD V trial reported no deaths at 9-month follow-up.

Committee considerations

3.6 The Committee considered that the available evidence, although limited in quantity and relatively short term, supported a lower incidence of restenosis after treatment of in-stent restenosis by SeQuent Please balloon catheter compared with paclitaxel-eluting stents and uncoated balloon catheters, and that there was a consistent trend towards a reduced need for re-treatment and major adverse cardiac events. The Committee noted that an important aspect of the clinical utility of the technology was the effective treatment of in-stent restenosis when the passage and delivery of another stent is not technically possible. It was noted that in the PEPCAD II trial, an RCT of 131 patients with a single restenosis in a bare metal stent treated by SeQuent Please balloon catheter or paclitaxel-eluting stent, inserting a paclitaxel-eluting stent was not possible in five patients. Of these five patients, four were successfully treated with SeQuent Please balloon catheter.

3.7 The Committee recognised that the majority of evidence was on in-stent restenosis within a bare metal stent and not a drug-eluting stent. The Committee judged that the evidence was insufficient to recommend SeQuent Please balloon catheter for in-stent restenosis within drug-eluting stent at the present time. This is reflected in the guidance recommendation 1.2.

3.8 The recommended duration of clopidogrel therapy after using SeQuent Please is 3 months compared with 12 months after using a drug-eluting stent. One study protocol specified that patients treated with SeQuent Please balloon catheter would receive 3 months of clopidogrel therapy and two study protocols specified 1 month of clopidogrel therapy after treatment with SeQuent Please balloon catheter. The Committee was advised that reducing the duration of clopidogrel therapy may have clinical advantages in terms of safety, where there are special concerns about an increased risk of bleeding or need for surgical intervention. This is reflected in the guidance recommendation 1.3.

3.9 The Committee was advised that other indications for SeQuent Please balloon catheter might include stenoses in small coronary arteries and complex coronary disease (for example, stenoses at vessel bifurcations). Indications might also include situations where using stents is difficult or undesirable, for example in calcified or tortuous vessels, or in people with diabetes. The Committee concluded that data on these subgroups would be useful (see section 1.4).

3.10 The Committee noted that none of the trial data were from the UK and it debated the generalisability of the evidence to the UK NHS. The Committee was advised that the restrictions of a trial environment meant that the data could not be assumed to apply to the generality of UK cardiology practice.

3.11 The Committee noted that there are ongoing trials of SeQuent Please balloon catheter in other countries.

3.12 The Committee considered that there was no evidence to suggest that SeQuent Please balloon catheter is harmful. Because no permanent scaffold or polymer is left in the vessel and the overall dose of paclitaxel delivered by the SeQuent Please balloon catheter is less than with the paclitaxel-eluting stent, the Committee considered that theoretical concerns about long-term safety were unlikely to exceed those for drug-eluting stent implantation, although longer-term data would be useful.

  • National Institute for Health and Care Excellence (NICE)