While rates of restenosis and major adverse cardiac events (MACEs) have both been demonstrated to be significantly reduced with the use of drug-eluting stents (DES) compared with bare-metal stents (BMS) in a broad variety of trials,1–6 the same trials could not demonstrate any difference in mortality or acute myocardial infarction (AMI) rates. Therefore, the reported clinical benefit of DES is entirely due to the highly significant reduction in the need for repeated interventions; however, concerns about late events associated with DES have recently come to light, suggesting that the indiscriminate use of DES is actually not advisable. 7–9 Moreover, subgroup analysis of such large randomised trials revealed no substantial advantage of using DES over BMS in terms of clinical outcome for short lesions and relatively large vessels (≥3.0mm). 10 Finally, in the majority of the randomised DES trials the BMS used were not the most up-to-date in terms of stent design and technology; in other studies involving last-generation BMS, lower revascularisation rates were found – approximately 7–10%.11 From the above-mentioned concepts, we hypothesised that selective use of last-generation BMS may provide satisfactory clinical results. To test this hypothesis, we designed the LEONARDO registry – cLinical Evaluation of a last generatiOn coroNAry stent in a Real worlD typical non-drug-eluting stent populatiOn – using the new Skylor™ stent (Invatec, Roncadelle, Italy; see Figure 1) in patients considered at low risk of target vessel revascularisation (TVR).
Methods
The aim of this prospective, non-randomised, single-centre study was to evaluate the safety and efficacy of the Skylor stent in patients with stable and unstable coronary artery disease (CAD). The Skylor is a balloon-expandable cobalt–chromium (Co–Cr) stent characterised by a closed cell and thin struts pre-mounted on a rapid-exchange-type balloon catheter. Skylor’s closed-cell platform is based on a uniform interconnection of monotype cells, differentiated into three families based on vessel diameters: SV (small vessels, 2.0–2.5mm), MV (medium vessels, 2.75–3.5mm) and LV (large vessels, 4.0–5.0mm). Each family features a distinct number of circumferential cells (three, four and five for SV, MV and LV, respectively) and strut thickness (70, 80 and 95μm for SV, MV and LV, respectively); this allows the stents to adapt to different vessel-size-dependent requirements. The metal-to-artery ratio has been deliberately kept on the low side for SV (12.5%) compared with MV and LV (14–15%) in order to limit metal concentration in the highly sensitive small vessels. In particular, it was the closed-cell design of the Skylor stent with its thin struts, flexibility and low profile that led us to select this stent for this non-DES clinical evaluation.
The decision to use the Skylor stent was based mainly on the clinical and angiographic baseline characteristics and risk factors of patients: the Skylor was implanted in all patients in whom DES was either contraindicated or judged not to match the requirements for optimal DES patient benefit according to commonly known and widespread criteria – i.e. large vessels, no long lesions and no complex lesions. This decision-making process is well-established in our clinical routine, and the final decision is left at the discretion of our operators.
Patients with clinical evidence of stable or unstable angina pectoris, non-ST-elevation MI (NSTEMI) or positive functional study findings suitable for percutaneous coronary intervention (PCI), and patients presenting with STEMI who underwent primary or rescue PCI, entered the study. The inclusion criteria were relatively large target vessels (reference vessel diameter ≥2.75mm) and short target lesions (lesion length ≤20mm). Patients with complex lesions (bifurcation lesions, chronic total occlusions, left main disease) and patients with in-stent restenosis were excluded from the study.
PCI was performed in accordance with the institutional standards. The lesions were pre-treated with either standard balloon angioplasty or direct stenting, according to the operator’s preference. An electrocardiogram (ECG) was obtained after the procedure or before discharge. Cardiac enzyme levels were measured eight to 16 hours after the procedure. Clinical status (including angina symptoms and adverse events) was assessed at discharge. Clinical follow-up was performed at 30 days (± five days) and at six months (±30 days) by phone contact.
Study End-points
The primary end-point was the rate of MACE at 30 days and six months. MACE was defined as a composite of cardiac death, MI (Q wave and non-Q wave) and need for repeated target lesion revascularisation (TLR).
The secondary end-points were device success, angiographic success and procedural success, according to the following definitions:
- Device success: ability to reach and cross the target lesion and deploy the stent with the same device.
- Angiographic success: achievement of a post-stent diameter residual stenosis (%DS) ≤30% with thrombolysis in MI (TIMI) three-flow.
- Procedural success: angiographic success free of in-hospital MACE.
Results
Between August 2005 and June 2006, a total of 151 consecutive patients were treated with the Skylor stent. One patient withdrew consent, implying that data from 150 patients are reported.
The baseline clinical characteristics of the population are shown in Table 1. Most of the patients (54.67%) had stable angina. Twenty-two per cent presented with AMI. Diabetes was present in a very low percentage of patients (5.33%).
The baseline lesion characteristics are shown in Table 2. Mean reference vessel diameter was 3.05mm (standard deviation (SD) 0.31mm). Mean lesion length was 15.19mm (SD 6.49 mm). Direct stent implantation was adopted in the majority of cases (107 of 184 lesions; 58.15%). Device success was achieved in 176 of 184 lesions (95.65%), angiographic success was achieved in 183 of 184 lesions (99.46%) and procedural success was achieved in 182 of 184 lesions (98.91%) (see Table 3). One patient died due to cardiac reasons one day after the procedure while recovering in the referring hospital.
Thirty-day clinical follow-up was available for 148 of the 150 patients (98.67%); 87.33% of the patients were asymptomatic. Six-month clinical follow-up was available for 149 of the 150 patients (99.33%); 82.67% of the patients presented asymptomatically. Hierarchical count at six-month follow-up showed a MACE rate of 4%. Two cardiac deaths (1.33%), one AMI (0.67%) and three clinically driven TLRs (2.00%) were reported. Detailed results of the 30-day and six-month follow-up are reported in Tables 4 and 5.
Discussion
This prospective, single-centre, non-randomised study was designed to assess the safety and efficacy of a last-generation BMS – the Skylor stent – in patients with stable and unstable CAD with coronary lesions at low to medium risk of restenosis (large vessels, no long lesions and no complex lesions) and in whom the use of DES is not indicated (patients presenting with STEMI). The Skylor stent is a closed-cell, thin-strut, Co–Cr coronary stent with a very consistent design structure and a very high flexibility, providing the benefits of high scaffolding and easy deliverability. In this registry, the Skylor stent was deployed with a high degree of procedural (98.91%) and angiographic success (99.46%). The cumulative incidence of hierarchical MACE (4%) and the rate of clinically driven TLR (2.00%) at six months were also very low.
Moreover, these results are consistent with those obtained from the two recently completed Driver registries and the Guidant Multilink Vision registry, in which two types of thin-strut, Co–Cr coronary stents were used in patients with stable and unstable CAD with de novo coronary artery lesions and a reference vessel diameter >3mm.12–14 In the Guidant Vision Multilink registry, six-month MACE rate was 6.2% and six-month TLR rate was 4.3%.12 In the first and second Driver registries, six-month MACE rates were 5.7 and 12.4%, respectively, while six-month TLR rates were 4.4 and 9.4%, respectively.13,14
In the LEONARDO registry, both the MACE and TLR rates at six-month follow-up were lower than in the two previous registries with a thin-strut Co–Cr coronary stent, mentioned above. However, we need to consider that in our study the percentage of diabetic patients (5.3%) was lower than in the other three studies (Multilink Vision: 23%; Driver: 27.6 and 15.4%), and TLRs were strictly clinically driven according to a study protocol that excluded planned angiographic follow-up.
Furthermore, a recent randomised study conducted on 104 patients comparing a thin-strut Co–Cr coronary stent (Vision) with a sirolimus-eluting stent (SES) in patients with symptomatic CAD and a target vessel diameter ≥3mm showed a significantly lower in-segment late loss in the SES group (nine months), but no any clinical difference between the two groups at 12 months.15 Another interesting factor emerging from the LEONARDO registry is the safety and efficacy of the Skylor stent in the setting of primary or rescue PCI.
In summary, although we are still in the era of DES, the very good clinical results obtained with the most recent generation of BMS – such as the Skylor Co–Cr stent – strongly support the safe and effective use of last-generation BMS in selective patients (non-diabetic patients) and in selective types of lesions (large vessels, not long lesions, not complex lesions, evidence of thrombus at lesion site).
Conclusion
In the Leonardo registry, the Invatec Skylor Co–Cr coronary stent showed optimal short- and long-term clinical results, with a low clinical MACE rate compared with historical data for contemporary BMS. Our experience confirms that selective usage of last-generation BMS is advantageous and desirable. The current registry represents a single-centre, non-randomised case series collection in a high-volume centre. Clinical follow-up was scheduled according to our centre’s policy, and therefore only symptom-driven TLRs were available for assessment.