Treatment of Severe Coronary Artery Disease in a Diabetic Patient Using the Resolute Integrity Stent: A Case Study

Intro/Abstract

The Resolute Integrity drug-eluting stent (DES) (Medtronic) was approved for use in the U.S. in February 2012. The first stent to have an indication for the treatment of coronary artery disease in diabetic patients, the stent has enjoyed rapid adoption in the clinical arena. The following case study illustrates the effective use of this stent in a diabetic patient.

Case study

A 53-year-old man with a history of remote anterior wall myocardial infarction (MI) treated with stent implantation to the left anterior descending coronary artery (LAD) developed dyspnea on exertion. A nuclear stress test demonstrated significant inferior wall ischemia. The patient also had a history pertinent for insulin-dependent diabetes, paroxysmal atrial fibrillation, hypothyroidism, hypertension, and Stage III renal insufficiency. There was no history of gastrointestinal or other bleeding disorder, and there were no plans for elective major surgery in the future. The patient’s chronic medications included Humalog and Lantus insulin, spironolactone, aspirin, clopidogrel, synthroid, and amiodarone.

Cardiac catheterization was deemed to be indicated. Coronary angiography revealed a patent LAD, chronically occluded left circumflex coronary (LCX) with well-developed left-to-left collaterals, and a dominant right coronary artery with a mildly calcified 90% lesion in its proximal portion (Figure 1). Following administration of unfractionated heparin (70u/kg), the lesion was pre-dilated with a 3.0 mm x 15 mm compliant balloon at 8 atm. A 3.0 mm x 26 mm Resolute Integrity DES was then deployed at 12 atm. The stent was post-dilated with a 3.5 mm x 15 mm non-compliant balloon at 18 atm. Final angiography demonstrated a 0% residual stenosis, no dissection and brisk blood flow (Figure 2).

Results

The patient tolerated the procedure well. Routine post-procedure cardiac enzymes were not elevated and the patient was discharged to home the following day on aspirin 81 mg daily and clopidogrel 75 mg daily to be continued for 12 months.

Discussion

The Resolute Integrity drug eluting stent is constructed with three components; 1) the flexible Integrity cobalt alloy helical stent platform, 2) the tri-layer Biolinx polymer which elutes drug for up to 180 days, and 3) the rapamycin-like drug zotarolimus. To date, the Resolute DES has been studied in over 7,000 patients worldwide. Patients in the RESOLUTE US study (n = 1,402) were treated with the Resolute DES (2.25 mm - 4.0 mm diameter). Two year follow-up revealed a low incidence of target lesion failure (TLF, 7.3%) and ARC definite/probable stent thrombosis (ST, 0.2%) comparing favorably to Endeavor DES historical controls.¹ When patients receiving 2.25 mm diameter stents were excluded from analysis, two year TLF fell to 6.9% and ST to 0.1%. Notable trials comparing Resolute and Xience DES are RESOLUTE All Comers (AC) and TWENTE. RESOLUTE AC was a “real world” study with virtually no exclusion criteria. In this study patients were randomized to zotarolimus (n = 1,140) or everolimus (n = 1,152) stent implantation. At three years the incidence of TLF was 13.1% vs. 12.4% (p = NS) and ARC definite/probable very late stent thrombosis occurred with an incidence of 0.5% in both groups.² TWENTE also randomized “real world” patients (n = 1,391) to zotarolimus vs. everolimus stents. At one year, the incidence of target vessel failure (TVF) was 8.2% vs 8.1% (p = NS) and ARC definite/probable ST was 0.9% vs. 1.2 % (p = NS) for zotarolimus and everolimus stents, respectively.³ The RESOLUTE International registry included 2,349 “real world” patients. In this registry, 3,147 lesions were treated (1.6 ± 1.0 stents per patient). One year follow-up demonstrated a TLF rate of 3.4% and an incidence of ARC definite/probable ST of 0.9%.⁴

The Resolute DES has demonstrated excellent clinical efficacy in patients with diabetes. Roughly one-third of the patients who were treated in the Resolute clinical program (RESOLUTE US, RESOLUTE AC, RESOLUTE International, RESOLUTE, and RESOLUTE Japan) had diabetes. Pooled analysis of the standard risk diabetic patients in this program (n = 878) were examined and compared to the non-diabetic patients (n = 1,903). Twelve-month outcomes in these diabetic patients revealed that, despite an older population with a higher prevalence of prior PCI, CABG, and hypertension, and despite a smaller reference vessel diameter (2.66 ± 0.48 mm vs. 2.73 ± 0.49 mm) clinical results were similar in the diabetic and the non-diabetic cohorts with TLR (3.3% vs. 2.0%), TLF (6.6% vs. 4.9%), and ST (0.3% vs. 0.3%).⁵ These results compare favorably to the diabetic patients enrolled in clinical trials with previously approved DES. The SPIRIT IV trial examined the Xience DES in a population with highly restricted inclusion and exclusion criteria. Diabetics in this study had a one-year TLF rate of 6.4% and an incidence of ARC definite/probable ST of 0.8%.⁶ Due to this demonstrated efficacy, the Resolute Integrity DES is indicated for the treatment of coronary artery disease in both the U.S. and Europe. In the case described above, the utilization of the Resolute Integrity DES was felt to be appropriate due to the vessel size, lesion length, mild calcification, and presence of diabetes.

Dr. Ron Caputo can be contacted at caputo331@msn.com.

References

1. Yeung AC, Leon MB, Jain A, Tolleson TR, Spriggs DJ, Mc Laurin BT, Popma JJ, Fitzgerald PJ, Cutlip DE, Massaro JM, Mauri L; RESOLUTE US Investigators. Clinical evaluation of the Resolute zotarolimus-eluting coronary stent system in the treatment of de novo lesions in native coronary arteries: the RESOLUTE US clinical trial. J Am Coll Cardiol 2011 Apr 26;57(17):1778-1783.
2. Silber S, Windecker S, Vranckx P, Serruys PW; RESOLUTE All Comers investigators. Unrestricted randomised use of two new generation drug-eluting coronary stents: 2-year patient-related versus stent-related outcomes from the RESOLUTE All Comers trial. Lancet 2011 Apr 9;377(9773):1241-1247. 
3. von Birgelen C, Basalus MW, Tandjung K, van Houwelingen KG, Stoel MG, Louwerenburg JH, Linssen GC, Saïd SA, Kleijne MA, Sen H, Löwik MM, van der Palen J, Verhorst PM, de Man FH. A randomized controlled trial in second-generation zotarolimus-eluting Resolute stents versus everolimus-eluting Xience V stents in real-world patients: the TWENTE trial. J Am Coll Cardiol 2012 Apr 10;59(15):1350-1361.
4. Neumann FJ, Widimsky P, Belardi JA. One-year outcomes of patients with the zotarolimus-eluting coronary stent: RESOLUTE International Registry. EuroIntervention 2012 Feb;7(10):1181-1188. 
5. Lee SW. Late-breaking clinical trials. Presented at: the American Association of Clinical Endocrinologists 21st Annual Scientific and Clinical Congress Meeting; May 23-27, 2012; Philadelphia, Pennsylvania.
6. Kereiakes DJ, Cutlip DE, Applegate RJ, Wang J, Yaqub M, Sood P, Su X, Su G, Farhat N, Rizvi A, Simonton CA, Sudhir K, Stone GW. Outcomes in diabetic and nondiabetic patients treated with everolimus- or paclitaxel-eluting stents: results from the SPIRIT IV clinical trial (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System). J Am Coll Cardiol 2010 Dec 14;56(25):2084-2089.

BEHIND THE CASE

Use of the Resolute Integrity Stent at St. Joseph’s Hospital

Cath Lab Digest talks with Ronald P. Caputo, MD, FACC, FSCAI, Director of Cardiac Services, St. Joseph’s Hospital, Syracuse, New York.

Tell us about your cath lab.

We have five rooms. Two of the rooms are both coronary and peripheral rooms. Approximately 85% of our procedures are coronary, and the remainder is peripheral and structural. We do about 5,200 to 5,300 caths per year and 2,000 to 2,100 interventions per year.

What is the diabetic population at your lab?

Our data shows diabetics at around 25-28% of our patient population.

What are the challenges interventionalists face when stenting diabetic patients?

Diabetic patients are a challenge because they generally have smaller vessels and more diffuse disease. This translates into less successful acute and long-term clinical results compared to non-diabetic patients.

You have presented a case using the Medtronic Resolute stent. What do you like about this stent?

Deliverability is very high on the list of attributes that make the Resolute a nice stent to use in the lab. It is a very, very deliverable stent. I also like the stent platform, which has continuous sinusoidal mono-element configuration, rather than welded struts. Resolute is a relatively thin strut stent, and that is important as well.

Can you talk more about your decision-making process and how you choose stents for your patients?

We always have to look at the data. Deliverability and functionality are important, but ultimately, as clinical scientists, we have to pay attention to the data. The Resolute program has done an admirable job in accumulating data in the arena of well-defined, well-circumscribed patient populations such as in RESOLUTE US, for instance. The Resolute program also looked at real world patients, which is an environment where clinicians are also very interested to see device performance. Studies like RESOLUTE All-Comers, the RESOLUTE International Registry, and TWENTE took all comers, even patients with acute myocardial infarctions. It mimics what we see in our clinical practice. Having that data, from multiple centers and significant numbers of patients, is very helpful when we are sitting down and trying to analyze the clinical benefit of a particular drug-eluting stent. The Resolute stent has good numbers. It has your standard FDA approval study on patient populations, which makes it useful in comparing to other stents that have gone through the same process. It also has significant real world experience. When you look at that whole body of data, it makes a strong argument for good clinical performance with the stent.

How is the Resolute stent used in your lab?

For diabetic patients, it is the stent of choice in our lab. Resolute is the number-one implanted stent in our lab; however, we have all stents available and have the ability to choose which stent we want to use. Right now, the workhorse stent in our lab is Resolute.

What can you tell us about the outcomes in your patients who have received the Resolute stent?

Since FDA approval was in late February 2012, it has been available to us for only a short period of time. The acute performance of the stent, in terms of its deliverability, trackability, performance up front in the lab, and getting it to where it needs to be, has been very satisfying. In terms of the long-term clinical outcomes from our lab, I think it is somewhat premature to make any conclusion. Certainly there have not been any signals to arouse concern in regard to using the stent. It has performed well.

In your discussion portion of the case, you discuss target lesion failure, target vessel failure, target lesion revascularization and stent thrombosis. How can clinicians look at these different measurements?

It can be hard, because when you are comparing different studies, you often might be looking at different study populations, as well as different clinical and angiographic outcomes. It is helpful to have head-to-head device comparisons, like in RESOLUTE All-Comers and TWENTE. It is most helpful when the trial is at the same institution and in the same patient population, minimizing intergroup variability. That is the most scientific way to make a decision. In those studies, the Resolute stent performed very admirably, as did the Xience stent (Abbott Vascular).

If we compare the results we are getting in the second-generation drug-eluting stent studies to the first-generation studies, it is nice to see a trend toward better outcomes. Now, which outcome you pick matters to some extent, but every study generally looks at all the same endpoints: death, cardiac death, target vessel failure, target lesion revascularization, stent thrombosis, and major adverse cardiac events (MACE). How to prioritize them is certainly up to you. Cardiac death is obviously important, but may not be stent performance. Target vessel failure is a very good indication for how a stent is going to perform clinically. Obviously another major concern has been raised in regard to stent thrombosis, especially as it applies to real world patients who may not be as apt to adhere to their dual antiplatelet therapy. I generally look at overall MACE, target vessel failure, and stent thrombosis. Certainly if you can get data out to three years showing good numbers with the stent, it gives you confidence that these results can be translated into your patient population.

It is interesting, when you look at second-generation stents, to see how the performance is improving. It looks like there is improvement both in the acute and the long-term performance of these devices. I look forward to seeing what comes down the road in the future and hope for incremental improvement in the clinical benefits.

Dr. Ron Caputo can be contacted at caputo331@msn.com.