RESOLUTE: Zotarolimus-Eluting Stent Fares Well at 2 Years

CHICAGO, IL—The zotarolimus-eluting Resolute Integrity stent, approved by the US Food and Drug Administration in February, continues to promote low restenosis rates and demonstrate clinical safety at 2 years. These results were presented March 24, 2012, at the annual American College of Cardiology (ACC)/i2 Scientific Session.

The RESOLUTE All Comers trial, which demonstrated that the Resolute stent (Medtronic, Santa Rosa, CA) had similar safety and efficacy compared with the everolimus-eluting Xience V stent (Abbott Vascular, Santa Clara, CA) through 2-year follow-up, as well as the 1-year findings of RESOLUTE US, were presented April 2011 at the annual ACC meeting.

Presenting 2-year results from the RESOLUTE US trial, Laura Mauri, MD, MSc, of Brigham and Women’s Hospital (Boston, MA), explained that the Resolute DES utilizes a hydrophilic polymer that is “durable and designed for biocompatibility to release the drug for a longer period of time than the previous zotarolimus-eluting stent, Endeavor.”

Consistent Results

The prospective observational study looked at patients with de novo native coronary lesions suitable for 1- or 2-vessel treatment with stents ranging from 2.25 to 4.2 mm in diameter. Overall, 1,402 patients were enrolled, with a mean reference vessel diameter of 2.6 ± 0.5 mm and diabetes prevalence of 34.4%. Approximately 10% of patients were treated for disease in 2 vessels.

The main analysis focused on the subset of 1,001 patients implanted with 2.5- to 3.5-mm stents in single lesions. Results with RESOLUTE US were compared with those of historical controls derived from earlier trials that tested Endeavor, including ENDEAVOR II, ENDEAVOR IV, ENDEAVOR PK, and ENDEAVOR II Continued Access.

At 2-year follow-up, the primary endpoint of target lesion failure (TLF; composite of cardiac death, MI, and clinically-driven TLR) was 5.9% for Resolute and 8.1% for historical controls (P < 0.001 for noninferiority).

For the analysis of the overall cohort, 2-year follow-up was achieved in 96.9% (n = 1,359) of patients, compared to 98.9% (n = 1,386) at 1 year (table 1).

Table 1. Clinical Outcomes for All Patients

 

 

1-Year
(n = 1,386)

2-Years
(n = 1,359)

TLF

4.6%

7.3%

Death

1.3%

3.0%

MI

1.3%

1.9%

Clinically-Driven TLR

2.8%

4.3%

Clinically-Driven TVR

4.5%

7.6%

Stent Thrombosisa

 

 

    Early (≤ 30 Days)

0.1%

0.1%

    Late (> 30 to ≤ 360 Days)

0.1%

0.1%

    Very Late (> 360 Days)

-

0.1%

aAcademic Research Consortium-defined definite or probable stent thrombosis

 

Dr. Mauri said 2-year event curves for TLF in RESOLUTE US were “quite consistent” with RESOLUTE All Comers (11.2%) and RESOLUTE International (9.8%). While dual antiplatelet therapy adherence was high at 1 year (93.5%), consistent with US guidelines, it dropped significantly at 2-years (67.2%). This gives “helpful context to interpret the results of the clinical endpoints and stent thrombosis rates,” Dr. Mauri noted, adding that adherence rates were also significantly lower at 2 years for RESOLUTE trials conducted outside the United States.

The definite or probable stent thrombosis rates were “remarkably low” and also consistent with the international trials, Dr. Mauri said; however, slightly higher rates outside the United States were “most likely driven by differences in the patient population in these trials where [patients with AMI are included] and one expects to see a significantly higher stent thrombosis rate regardless of the stent type.”

Looking at the higher-risk cohorts of small-vessel (2.25 mm) patients and diabetics, “good results” were observed, with no stent thrombosis in the diabetes cohort, Dr. Mauri said (table 2).

Table 2. Two-year Clinical Outcomes of High Risk Patients

 

 

Small Vessel
(n = 147)

Diabetes
(n = 474)

TLF

8.2%

8.9%

Death

3.4%

2.1%

MI

1.4%

1.5%

Clinically-Driven TLR

4.8%

5.7%

Stent Thrombosisa

1.4%

0.0%

aAcademic Research Consortium-defined definite or probable stent thrombosis.

 

Patient Population to Blame for Inconsistencies

Panel co-chair Hector M. Garcia, MD, MSc, of the Erasmus Medical Center (Rotterdam, the Netherlands), suggested that the “trivial” rate of stent thrombosis among diabetic patients could potentially be attributed to a lack of coronary disease

While Dr. Mauri accepted that suggestion, she said the diabetic subgroups in the international RESOLUTE studies with more complex patient populations still fared well.

Because the event numbers are relatively small, Dr. Garcia expressed concern over how many patients were lost to follow-up and how that might affect event rates.

Dr. Mauri agreed. “It’s a particularly challenge in trials where there’s an imbalance lost in follow-up. This is a single-arm study and we have to rely on an estimate only from the treatment difference. In this study, ‘lost to follow-up’ meant that they didn’t present for clinical follow-up,” she said, adding that since the trial is still ongoing, there are efforts to locate patients and include these data later on. “We never give up until the study is finally closed.”

 

Source:

Mauri L. 2-year clinical outcomes from the pivotal RESOLUTE US study. Presented at: American College of Cardiology Scientific Session; March 24, 2012; Chicago, IL.

Disclosures:

Dr. Mauri reports no significant conflicts of interest.

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