FDA Approval of New Lengths of the Resolute Integrity Stent: An Interview With Ronald Caputo, MD

In February 2013, the US Food and Drug Administration (FDA) approved longer lengths of Medtronic’s Resolute Integrity drug-eluting  stent (DES). The 34 mm and 38 mm lengths of the stent in diameters of 3.0 mm, 3.5 mm, and 4.0 mm were approved with an indication for patients with diabetes. These longer lengths enable the treatment of long coronary lesions. Approval of the stents was based on data from the global RESOLUTE clinical program, specifically an analysis of 1-year outcomes in patients with long coronary lesions who participated in the RESOLUTE US and RESOLUTE Asia studies.

Vascular Disease Management interviewed Ronald Caputo, MD, who was a principal investigator for the RESOLUTE US study, about the study and the approval of the new stent lengths.

Q: Please describe your involvement with the RESOLUTE studies.

A: I was privileged to be a part of the RESOLUTE US study as a principal investigator at St. Joseph’s Hospital in Syracuse. I am also the national principal investigator for the ongoing RESOLUTE US postmarket registry study. Recently, I examined the performance of the Resolute DES in small vessels.

Q: Could you give an overview of the significant findings of the studies of the Resolute stent?

A: There has now been significant data gathered regarding the Resolute DES, inclusive of a broad range of patients. Relatively long-term follow-up (up to 5 years) is also available.  RESOLUTE US examined on-label performance of the Resolute DES and revealed 2-year rates of target lesion failure (TLF) at 7.3% and stent thrombosis (ST) at 0.2%. Importantly, significant data regarding the real-world performance of this stent has been gathered in large all-comers studies such as TWENTE, RESOLUTE All Comers, and RESOLUTE International.  In these studies, the ST rates were less than 2% and TLF was less than 12% at 2 years. 

 Q: Is this stent the first FDA-approved long-length DES with a specific indication for diabetic patients? Please explain the evolution of this stent’s FDA approval. 

A: Yes, the Resolute Integrity DES is the first and only DES with an indication to treat diabetic patients, and this indication is applicable across all sizes. Before the longer lengths were approved, pooled data from 5 studies involving nearly 900 standard risk diabetic patients demonstrated very low TLF rates at 1 year comparing favorably to nondiabetic patients (6.6% vs 4.9%).  

When compared to a prespecified performance standard that was derived from a cohort of 1,300 standard risk diabetic patients treated with a DES pooled from prior studies, there was a significant benefit regarding target vessel failure (TVF) at 1 year (7.8% vs 14.5%). Medtronic has worked with the FDA with this innovative approach to data analysis prior to completion of the RESOLUTE US trial. This approach was innovative in that a prespecified analysis of data derived from similar patients enrolled in several different studies was used for examination by the FDA.

Diabetic patients tend to have more diffuse coronary artery disease and longer lesions. The recent approval of the 34-mm and 38-mm Resolute Integrity stent lengths may allow for more optimal treatment of these types of lesions and help to avoid the need for stent overlap and repeat inflations while reducing procedure time. 

Importantly, these patients often have concomitant renal insufficiency. Positioning multiple stents may also require significant contrast,  and the use of a long stent like Resolute Integrity may help reduce this need.   

Q: What are the current limitations of this device, in terms of either its indication or its physical structure? 

A: The limitations of this device remain similar to the broad limitations for all currently used DES.  In my opinion, the biggest limitation is the continued requirement for extended dual antiplatelet therapy, although that appears to be changing in Europe. 

Q: What are the other options available for treatment of long lesions in diabetic patients, and how does this stent compare to those other options? 

A: When treating complex multivessel disease, coronary artery bypass grafting (CABG) is often considered. For many patients, especially diabetics with a high Syntax score, CABG may be the optimal method of revascularization, which was recently underscored by the results of the FREEDOM trial.  However, it must be remembered that roughly 33,000 patients were screened for inclusion of 1,900 study patients, which is perhaps a testimony to the individualized treatment decisions made in these complex patients.  

In general, when compared to first-generation stents, newer-generation DES show improved clinical results.  For example, pooled data from a RESOLUTE clinical program showed that non-insulin dependent diabetic patients demonstrated a target lesion revascularization rate of only 4.3% at 2 years.  This may translate into improved outcomes in complex patient and lesion subgroups.  The recent approval of the longer Resolute Integrity DES lengths may also prove beneficial in treating these patients with diffuse disease.

Q: In your opinion, what do you consider to be the most exciting features of this stent, or most important results of the studies?

A: Interventional cardiologists are always concerned with deliverability. The Resolute Integrity DES platform and delivery system have performed very well in our lab. Combining excellent deliverability with the excellent clinical results demonstrated in real-world patients from RESOLUTE All Comers (3-year TLF 13.1%), RESOLUTE International (3-year TLF 11.4%), and TWENTE (2-year TVF 10.9%) is very exciting. 

Q: What is the benefit to patients and vascular specialists of using this drug-eluting stent? 

A: The benefit of the Resolute Integrity DES for vascular specialists is the confident ability to use a well-studied device in a broad range of patients. This can help streamline the decision process in the lab. Ease of use is also a benefit.  Superior clinical results with a newer generation DES like Resolute Integrity are also obviously a benefit for patients.  Let’s not forget that patients also benefit from deliverability and longer stent sizes with shorter procedure times, fluoroscopy times, and less contrast. 

Ronald Caputo, MD, FACC, FSCAI, is director of cardiac services and cardiology research at St. Joseph’s Hospital in Syracuse, New York. Dr. Caputo reports consultancy to Boston Scientific and Medtronic.