Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

PRIORITY PRESS - Canadian Cardiovascular Congress 2009

Edmonton, Alberta / October 24-28, 2009

The APPROACH (Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease) database captures all patients who present at a single provincial cardiac interventional centre in St. John’s, Newfoundland and Labrador. There had been some concern that the zotarolimus-eluting stents (ZES) appeared to be associated with a higher incidence of late lumen loss at eight months in the ENDEAVOR III trial than a sirolimus-eluting stent (SES). To that end, the Newfoundland group under lead author Dr. Jill Colbert, third-year internal medicine resident, Memorial University, identified all patients who had received a ZES between May 2006 and April 2008 at the provincial centre. A total of 454 patients received 619 ZES during their survey interval, 74% of whom were followed up either angiographically (13%) or through the Meditech database (61%). Patients who received a ZES for in-stent thrombosis were excluded and any patient who could not be identified in the Meditech database at one year post-stent were considered lost to follow-up.

“We looked at clinical end points so patients who came back with chest pain were investigated again,” Dr. Colbert stated in an interview, “so we reviewed our outcome data to compare our adverse cardiac outcome rate post-ZES insertion in Newfoundland with published randomized controlled trials (RCTs) and registry data.”

The median stent diameter in the registry cohort was 2.75 mm while the median stent length was 14.0 mm. Analyses at one year post-stent insertion indicated that only two patients out of 454 (0.4%) included in the registry developed an Academic Research Consortium (ARC) definite/probable stent thrombosis (angiographically confirmed).

Significant in-stent restenosis occurred in 3.9% or 18 patients out of the cohort while target lesion revascularization (TLR) occurred in 3.3% or 15 patients. Some 26% of the cohort did not have complete follow-up, leaving 335 patients for mortality analysis. Based on analysis of this cohort, the all-cause mortality rate was 1.8% with a cardiac death rate of 0.9%.

“We’re quite confident about our numbers for in-stent restenosis and TLR because anybody who has those types of events will come back to our cath lab,” Dr. Colbert remarked, adding that their registry data clearly demonstrated that the ZES has a low restenosis rate and comparable safety to other DES and that results are thus “absolutely reassuring.”

In September of this year, results from ENDEAVOR IV reaffirmed the favourable safety profile of the ZES compared with a paclitaxel-eluting stent (PES) with longer-term follow-up. ENDEAVOR IV was the largest DES comparative trial to date, randomizing 1548 patients with a single de novo coronary lesion to either ZES or PES, the primary end point being target vessel failure (TVF) and safety end points.

At the recent TCT meeting, Dr. Martin Leon, Columbia University Medical Center, New York, and colleagues reported that at three years’ follow-up, there was a 23% relative risk reduction in TVF in favour of the ZES arm, as well as a 49% relative risk reduction in cardiac death and myocardial infarction (MI), a difference between the two arms which was significant for both end points. There was also a significant 93% relative risk reduction in ARC definite/probable very late stent thrombosis in favour of the ZES arm.

Indeed, three-year results confirmed that the late TLR “catch-up” was much higher with the PES, which showed an 82% increase in TLR rates between years 1 and 3 vs. a 44% increase in TLR rates for the ZES arm.

Registry Experience and RCTs

Regarding an analysis of the pooled ENDEAVOR program presented at the EuroPCR 2009 in Barcelona, Spain, Dr. David Kandzari, Scripps Clinic, La Jolla, California, and multicentre colleagues reported pooled efficacy data from 2132 patients treated with a ZES in six separate clinical trials.

At a mean follow-up of 3.28 years (range, two to five years), the average annualized rate of repeat TLR from year 1 to year 4 was 0.6%—5.4% in the first year and 7.1% in year 4. The cumulative incidence of TLR at five years was 7.0%, as Dr. Kandzari reported.

At one year, the target vessel revascularization (TVR) rate in the ENDEAVOR program was 8.1% while at year 4, it was 12%. The ZES had a very low rate of ARC definite/probable stent thrombosis of 0.8% at five years, despite the fact that only 39% of patients were on dual antiplatelet therapy at one year. The ZES also had an extremely low risk (0.2%) of very late stent thrombosis after one year through to five years.

The cumulative incidence of cardiac death and MI at five years in the ENDEAVOR pooled analysis was low at 5.6%. “Treatment with the ENDEAVOR ZES is associated with a stable and durable rate of TLR through five-year follow-up,” Dr. Kandzari observed, “and the stability in annualized rates of TLR is consistent across the individual trials and is distinguished from BMS [bare-metal stents] and alternative DES comparators.” Results from the E-Five Registry presented at this year’s ACC in Orlando confirm that findings from real-world patients treated with a ZES are highly consistent with those from RCTs. The E-Five Registry is a prospective, multicentre registry originally involving some 8000 patients, from which over 2000 patients were available for follow-up at two years.

At two years, the incidence of major adverse cardiac events (MACE) was 8.5%, as reported by Prof. Martin T. Rothman, The London NHS Trust, UK, and colleagues. TLR and TVR rates at two years were similar at 5.1% and 5.9%, respectively, with TVF seen in 7.9% of registry participants. Rates of both cardiac death and MI at two years were each 1.5%.

As the authors noted, there was only a 13% increase in TLR rates between the first and second year following stent implantation. This was in contrast to a 46% increase in TLR rates between years 1 and 2 in the ARRIVE 1 registry which involved patients who received a PES. “The E-Five real-world low TLR outcome is consistent with the ENDEAVOR pooled analysis,” the authors stated, at a cumulative incidence of 5% at two years vs. 6.7% at five years in the pooled analysis. The rate of stent thrombosis was low at 0.7% and identical to that seen in the pooled analysis. Cardiac death and MI rates were also similar at 2.7% at two years among registry participants vs. 4.6% at five years in the pooled analysis.

Five-year Follow-Up

In another presentation given by Wijns et al. during EuroPCR 2009, investigators tracked clinical event rates in patients with de novo CAD who had received a ZES or a BMS in the ENDEAVOR II study now followed for at least five years. As of 2009, over 1000 patients remained in the ENDEAVOR II program. At five years, TLR rates with the ZES remained low at 7.5%, an increase of only 0.3% between year 3 and 5 following stent implantation, as the authors noted.

In contrast, TLR rates for the BMS comparator in ENDEAVOR II were 16.5% at the same follow-up point. TLR rates also tend to plateau after three years post-ZES insertion—remaining at 7.2%, 7.2% and 7.5% in years 3, 4 and 5, respectively. The same trend is not seen in several other DES trials, which show a linear increase in TLR rates from years 3 to 5 with both PES and SES.