SORT OUT III Substudy Hints at Differences in DES Efficacy Based on Diabetes Status

Sirolimus-eluting stents (SES) carry a lower risk of major adverse cardiovascular events (MACE) compared with zotarolimus-eluting stents (ZES) in patients with diabetes, but in nondiabetics, they increase the risk of stent thrombosis with no MACE advantage over the long term. The findings, from a substudy of the SORT OUT III trial, were published online November 10, 2014, ahead of print in the American Journal of Cardiology.

Michael Maeng, MD, PhD, of Aarhus University Hospital, Skejby (Aarhus, Denmark), and colleagues looked at the influence of diabetes status on the findings of the 2,332-patient trial, which compared Cypher Select or Cypher Select Plus SES (Cordis) with Endeavor Sprint ZES (Medtronic) at 5 Danish high-volume PCI centers; 14.5% of patients were diabetic.

In the diabetic subgroup, MACE (cardiac death, MI, and TVR) occurred at a higher rate with ZES than with SES through 5 years of follow-up, driven by a higher rate of TVR. The rate of TLR also was elevated with ZES, but there were no between-group differences for other outcomes, including MI, cardiac death, all-cause mortality, and definite stent thrombosis. In the nondiabetic subgroup, the only outcome that differed between the stent arms through 5 years was definite stent thrombosis, which occurred more frequently with SES (table 1).

Table 1. Five-Year Outcomes

Landmark analyses revealed that the relative effectiveness of the 2 stents varied according to length of follow-up for some outcomes. In the diabetic subgroup, for example, MACE was higher with ZES in the first year (OR 3.80; 95% CI 1.67-8.64) but similar between the 2 stent arms for the rest of follow-up. A similar pattern was seen for TLR and TVR.

Diabetics’ DES Response Is Different

Dr. Maeng noted in an email to TCTMD that “patients with diabetes tend to develop more neointima formation after PCI, which subsequently gives them a higher risk of restenosis” and that “Cypher reduces neointima formation and angiographic late lumen loss more efficiently than Endeavor.”

Among nondiabetics, MACE risk was elevated with ZES compared with SES in the first year (OR 1.80; 95% CI 1.20-2.71) but was lower in the final 4 years of follow-up (OR 0.74; 95% CI 0.55-1.00). Rates of TLR and TVR also showed an advantage for SES in the first year followed by an advantage for ZES thereafter. In addition, the rate of definite stent thrombosis did not become higher with SES until after the first year of follow-up, a difference most likely explained by vascular inflammation induced by [the] permanent polymer used for drug eluting by the Cypher stent,” Dr. Maeng noted.

“With almost 90% of the nondiabetic patients still alive at 5-year follow-up,” he and his colleagues write, “the significant and steady late catch-up in MACE rates in the SES group, caused primarily by very late definite stent thrombosis, is of great concern, as this indicates that less effective stents, in this case the ZES, may end up as the superior choice in low-risk populations when followed for 5 years or beyond.”

They acknowledge that the study is limited by the fact that the stents evaluated in the trial have been replaced in clinical practice by newer-generation DES.

Should Diabetes Be Considered in Stent Choice?

“Still, our findings highlight the need for a differentiated treatment strategy of patients undergoing coronary intervention in which diabetes is taken into consideration and also highlight the importance of long-term clinical evaluation of current and future DES,” they write.

The differences based on diabetes status, Dr. Maeng added, indicate that “PCI operators should pick one of the very effective drug-eluting stents when treating diabetic patients, while long-term outcomes in nondiabetic patients may be just as good when less effective stents or perhaps scaffolds are used.

Ajay J. Kirtane, MD, SM, of Columbia University Medical Center (New York, NY), drew attention to the 5-year time horizon in a telephone interview with TCTMD, saying, “It’s important to get long-term follow-up from these types of patients because it confirms observations that we may have suspected.”

He said that this exploratory analysis does not, however, indicate that the relative efficacy of the 2 stents differs based on diabetes status, pointing to the interaction P value of .05 for MACE. 

“What this suggests is that the overall results of the trial are still relatively consistent in diabetic and nondiabetic patients,” Dr. Kirtane said.


Olesen KKW, Tilsted H-H, Jensen LO, et al. Long-term outcome of sirolimus-eluting and zotarolimus-eluting coronary stent implantation in patients with and without diabetes mellitus (a SORT OUT III substudy). Am J Cardiol. 2014;Epub ahead of print.


Related Stories:

Todd Neale is the Associate News Editor for TCTMD and a Senior Medical Journalist. He got his start in journalism at …

Read Full Bio
  • Dr. Maeng makes no statement regarding conflicts of interest.
  • Dr. Kirtane reports institutional research funding to Columbia University from Abiomed, Abbott, Boston Scientific, Eli Lilly, Medtronic, St. Jude, and Vascular Dynamics.