Results from the SORT OUT III trial presented at ACC 2010 surprised delegates by showing that the Cypher stent was associated with significantly lower rates of major adverse cardiac events (MACE), all-cause mortality, myocardial infarction (MI) and target lesion revascularisation (TLR).
The trial was conducted by researchers from the university hospitals in Denmark under the auspices of the Danish Organization for Randomized Trials with Clinical Outcomes (SORT OUT). The SORT OUT III trial randomised patients with coronary artery disease to either the Endeavor (1,162 patients) or the Cypher (1,170 patients) stent. Both stents are drug-eluting, but the Endeavor is a second-generation zotarolimus-eluting stent, while the Cypher is a first-generation sirolimus-eluting stent.
The investigators said that the results represent real-world experience due to the methodology of SORT-OUT III. There was no angiographic or clinical follow-up scheduled to reflect routine clinical practice, patient-driven event detection was attained via a personal identification number and tracked through the Danish Civil Registry system, the National Patient Registry and the Danish Heart Registries. Clinical event tracking included cardiac and non-cardiac death, myocardial infarction and repeat interventions due to in-stent restenosis or definite stent thrombosis. This unique system of tracking allows for high-quality monitoring and query resolution, the investigators claimed.
The researchers found that after 18 months, significantly more patients with the Endeavor experienced the primary composite endpoint of cardiac death, heart attack or target vessel revascularisation than patients with the Cypher stent, at 9.7% and 4.5%, respectively. Patients with the Endeavor also experienced the secondary endpoints more frequently than those with the Cypher, including heart attack (2.1% versus 0.9%); target vessel revascularisation (7.9% versus 3.3%); and all-cause death (4.4% versus 2.7%).
“Based on the Endeavor III trial findings showing that the Endeavor stent had a more uniform layer of neointimal coverage, we and many others believed it would provide strong protection against general stent thrombosis and heart attack, but we found there is a high risk of early stent thrombosis and early heart attack in the Endeavor, which may be related to the faster elution of the drug,” said Michael Maeng, Department of Cardiology at Aarhus University Hospital in Denmark and the lead researcher. “If you have to compare the two stents, the Cypher stent is a better stent.”
Maeng pointed to the fact that two main characteristics of the SORT OUT III trial could have caused the difference: the SORT OUT trial was an all-comer trial that accepted nearly all patients receiving a drug-eluting stent, and it was powered to assess clinical endpoints. “If you want to assess clinically relevant differences between the various drug-eluting stents, you have to compare the stents in routine clinical care patients,” Maeng noted. “As an example the ENDEAVOR III was performed in 436 low-risk patients with a single non-complex lesion and was only powered to assess an angiographic endpoint. SORT OUT III randomised 2,332 all-comers and was powered to assess a clinical endpoint.” Another characteristic of the SORT-OUT III trial was the use of Danish health registries to detect clinical events during follow-up. “This means that only clinical events which were seriously enough to bring the patient in contact with the health care system were detected and thereby bringing the results more in line with what is seen in daily clinical practice. Furthermore, the results were unaffected by biases since there were no direct patient contact and no angiographic follow up during the study”, Maeng stated.