Real-world Clinical Outcomes in Patients Receiving Zotarolimus-eluting Stents versus Non-zotarolimus-eluting Stents for Percutaneous Coronary Intervention

Current-generation polymer-based zotarolimus-eluting stents (ZES; Resolute Onyx, Medtronic) have been shown to be an effective choice for percutaneous coronary intervention (PCI), including in high bleeding risk patients as well as in left main PCI.^1,2 However, data comparing real-world clinical outcomes between ZES and other stent platforms (non-ZES) are limited and few studies exist.^3,4

Since its establishment in July 2018, our cardiac cath lab designed a registry to track the clinical outcomes of all patients who underwent PCI at our centre. Based on the data collected in the registry, this study aimed to compare real-world clinical outcomes in patients who had received current-generation ZES with those who had received non-ZES during PCI.

Methods

This was an investigator-initiated, non-randomised, non-blinded observational registry study that aimed to compare the outcomes of ZES versus non-ZES in a real-world population of patients undergoing PCI at our tertiary speciality centre in Southeast Asia. The study was conducted with the oversight of the Centralised Institutional Review Board and complied with the Declaration of Helsinki.

Recruitment

The study was carried out from January 2020 to December 2021. We included all-comers who were treated with drug-eluting stents (DES) during PCI at our centre. The type of stent implanted was at the discretion of the managing physician. Patients who received only current-generation ZES (Resolute Onyx) were recruited into the ZES arm of the registry. Patients who received only non-ZES were recruited into the control arm of the registry. Patients who received both ZES and non-ZES or drug-coated balloons were excluded. Patients were also excluded if they declined to participate in this study. Patients were only recruited after PCI was completed. Written informed consent was obtained from all participating patients.

Study Devices and Procedures

PCI and peri-procedural management were performed as per routine standard of care. The choice of devices (including stent choice) and anti-thrombotic regimens was based on the managing physician’s best judgement. Patients in the ZES arm received only durable-polymer, slow-release zotarolimus-eluting Resolute Onyx stents. Patients in the control arm received any other commercially available DES other than the Resolute Onyx platform. Study patients were followed up by their managing physician and their data were collected via electronic health records. Patients were followed up for a total of 12 months from the index procedure.

Endpoints

The primary endpoint of our study was defined as major adverse cardiac events (MACE), which was a composite of cardiac mortality, target vessel failure (TVF) and MI at 1 year. TVF was defined as follows:

• any target vessel revascularisation (TVR); or
• re-stenosis >50% by angiography in a previously treated segment; or
• new stenosis >70% by angiography in a previously untreated segment; or
• physiological significance in that territory by non-invasive or invasive testing; or
• MI in that territory as evidenced by ECG/echocardiogram parameters, e.g. ST elevation, new Q waves, new regional wall motion abnormalities on echocardiogram, correlating to the vessel territory previously treated within 365 days of stent implantation.

TVR was defined as any repeat percutaneous intervention or surgical bypass of any segment of the target vessel. The target vessel was defined as the entire major coronary vessel proximal and distal to the target lesion, which includes upstream and downstream branches and the target lesion itself. Other secondary endpoints included all-cause mortality, cardiac mortality, stroke, MI, stent thrombosis, TVR and TVF at 12 months.

Statistical Analysis

Continuous variables are expressed as mean (SD), and categorical variables as n (%). For comparisons between ZES and controls, t-test was performed for continuous variables, and Fisher’s exact test for categorical variables. To determine the effect of ZES on 1-year outcomes, such as all-cause mortality, cardiac mortality, MI, stroke, TVR, TVF, MACE and stent thrombosis, univariate Cox regression was performed. The 1-year cumulative incidence was plotted using the Kaplan–Meier method. All statistical analyses were performed using Stata 17 (StataCorp). For all analyses, a two-tailed p-value of <0.05 was considered significant.

Results

Within the study period, 526 patients underwent PCI at our centre and fulfilled the inclusion criteria. There were 218 patients in the ZES group and 308 in the control group. Characteristics and procedural data of each group are summarised in Tables 1 and 2, respectively. Patients with acute coronary syndrome accounted for 57.3% of the total cohort; the remaining 42.7% presented with stable ischaemic heart disease. Radial access was the preferred mode of access in both the ZES and the control groups (78.9% versus 78.0%). Intravascular imaging was used in 11.7% of all cases. A breakdown of all stent types used in the control group is summarised in Table 3.

Patients in our study had low rates of MACE (3.6%) at 1 year, with no significant differences between the ZES and control groups (3.2% versus 3.9%; HR 0.82; 95% CI [0.32–2.09]; p=0.68). Comparing the clinical outcomes of the ZES and control groups, there were similar rates of all-cause mortality (1.4% versus 2.3%; HR 0.60; 95% CI [0.16–2.33]; p=0.46) and MI (0.5% versus 1.0%; HR 0.47; 95% CI [0.049–4.49]; p=0.51). There were low rates of stent-related complications and no differences in rates of TVR (1.4% versus 0.7%; HR 2.12; 95% CI [0.36–12.7]; p=0.41) and TVF (1.4% versus 0.7%; HR 2.12; 95% CI [0.36–12.7]; p=0.41) between the ZES and control groups (Table 4).

There were two cases of stent thrombosis, both in the ZES group. Both were admitted for acute coronary syndrome (ST elevation MI and unstable angina) with stents implanted in the mid left anterior descending artery. Stent thrombosis occurred 4 hours after initial PCI for the first case while the other occurred 3 days later. Both cases were deemed to be due to stent under-expansion because of underlying heavy calcification and were treated with further post-dilatation with good outcomes. Both were discharged well and had no subsequent adverse events at 1 year. Clinical outcomes of each group are shown in Table 4 and Figure 1.

Discussion

Our study describes the clinical outcomes of a single centre, real-world population of patients who were treated with PCI with either current-generation ZES or non-ZES. Despite being an all-comers study with a significant proportion of patients presenting with acute coronary syndrome, our registry had very low rates of MACE in both groups. Of note, our rate of TVR and TVF with current-generation ZES were both 1.4%, which is lower than that reported in previous randomised studies.^1,5–8

Our findings contrast with a prior real-world population comparative study in South Korea using the Korea Acute Myocardial Infarction Registry, which found that biolimus-eluting stents were superior to everolimus-eluting stents (EES) or ZES in reducing total death, cardiac death, target lesion failure and MACE in patients with acute MI.⁴ The results of our study echo those of the BIONYX and ONYX ONE trials in which current-generation ZES were found to be non-inferior to other stent platforms.^1,7 The BIONYX trial found that current-generation ZES were non-inferior to Orsiro (Biotronik) stents for a combined safety and efficacy endpoint at 1 year in all-comers.⁷ The ONYX ONE trial found that, in patients with high bleeding risk who received 1 month of dual antiplatelet therapy following PCI, current-generation ZES were non-inferior to polymer-free drug-coated stents regarding the predefined safety and effectiveness composite outcomes.¹

The findings of our ZES cohort also echo the results of a real-world study in Hong Kong that examined 1 year clinical outcomes of patients receiving current-generation ZES, showing low rates of TVR at 1 year.³ Of note, current-generation ZES have been studied in left main PCI and small vessel PCI specifically and in both patient subsets, current-generation ZES has been shown to have good safety and efficacy at 1 year.^2,9

The RESOLUTE All Comers trial compared the earlier generation Resolute Integrity ZES with EES and found it to be non-inferior to EES for target lesion failure or target lesion revascularisation at 12 months.⁵ This trial had raised some concerns with ZES having a trend towards higher rates of stent thrombosis compared with EES. In our study, there were two cases of stent thrombosis (0.9%) in the ZES group and none in the control group. On a similar note, prior concerns of late luminal loss with the earlier generation ZES platform did not appear to translate into clinically significant TVR in our study.⁵

Our registry had very low rates of MACE, despite our cardiac cath lab having only been established in July 2018. One important factor was that our cardiac cath lab was established based on existing mature cardiac lab operations and protocols of our national referral centre. Our team of operators, technicians and nursing staff were relatively experienced as they had already been practising in our other centre. We feel that this approach contributed significantly to the rapid and successful establishment of our new cardiac cath lab.

Limitations

We acknowledge that our data comes from a single centre, non-randomised registry and hence has its limitations. Furthermore, our centre was in its infancy, with our cardiac cath lab having only been established in July 2018. Patients were only recruited into the registry after receiving PCI, which was also subject to patient consent. As the decision regarding stent platform was at the discretion of the operators, there may have been an element of selection bias. Nevertheless, our data demonstrated that both groups of patients were generally similar in terms of their baseline characteristics and procedural characteristics, with a low event rate. The COVID-19 pandemic coincided with our study period; however, this should have equally affected both study groups.

Conclusion

Our PCI registry demonstrated low rates of MACE at 1 year, with no significant differences in clinical outcomes between patients receiving current-generation ZES and non-ZES platforms.