Rationale and Design of a Randomized Clinical Comparison of Everolimus-Eluting (Xience V/Promus) and Sirolimus-Eluting (Cypher Select+) Coronary Stents in Unselected Patients with Coronary Heart Disease

Abstract

Background: The sirolimus-eluting stent has demonstrated the least amount of late lumen loss among previously released drug-eluting stents, but its safety and efficacy has not been compared head-to-head with the everolimus-eluting stent. Method: The Scandinavian Organization for Randomized Trials with Clinical Outcome (SORT OUT) IV trial was designed as a prospective, multi-center, open-label, all-comer, two-arm, randomized, non-inferiority study comparing the everolimus-eluting stent with the sirolimus-eluting stent in the treatment of atherosclerotic coronary artery lesions. Based on a non-inferiority design, power calculations estimated a needed enrolment of 2,678 patients. The primary endpoint is a composite of cardiac death, myocardial infarction, and stent thrombosis or target vessel revascularization after 9 months. Data on clinical events and mortality for all randomized patients will be obtained from national databases at 9 months. No clinical follow-up examination is scheduled. Conclusion: The SORT OUT IV trial will directly compare clinically relevant differences in efficacy and safety in two drug-eluting stents: a first-generation sirolimus-eluting stent versus a second-generation everolimus-eluting stent. The study makes use of clinical endpoints routinely collected in computerized healthcare registries, allowing complete follow-up of a large, well-defined population without scheduled angiographic examinations.

Biodegradable Polymer Versus Permanent Polymer Drug-Eluting Stents and Everolimus- Versus Sirolimus-Eluting Stents in Patients With Coronary Artery Disease

“…The main finding of the ISAR-TEST 4 trial in this respect was that in a broadly inclusive patient cohort EES are associated with similar clinical outcomes in comparison with SES out to 3 years. These observations are in line with a recently published 2-year comparative analysis of both stents in large vessels (9) and also with the 9-month results from a second randomized trial (10). Furthermore, although there was no significant difference between the 2 stent platforms in terms of safety, the numerically lower rates of stent thrombosis observed with the EES seems to be a consistent feature of clinical trials with this stent.…”

Everolimus-Eluting Versus Sirolimus-Eluting Stents

“…Notably, in one of the trials-the SORT OUT IV trial-the investigators included definite stent thrombosis as part of major adverse cardiac events. 22 The investigators of SORT OUT IV trial reported 11 patients with definite stent thrombosis. 15 Because these cases of definite stent thrombosis represent only a small fraction of those with major adverse cardiac events in the SORT OUT IV trial (140 patients) and a much smaller fraction of those with major adverse cardiac events in all 5 trials (585 patients), it is unlikely for this definition characteristic to have had a relevant impact on the overall result of the present meta-analysis.…”

“…15 However, the definitions of events were reported in detail in a full publication of the study design for this trial. 22 …”

Everolimus-eluting versus sirolimus-eluting stents: an updated meta-analysis of randomized trials

“…Second, the definition of MACE-the primary endpoint of this meta-analysis-was not consistent across the trials. In particular, the SORT OUT IV trial included definite stent thrombosis as part of MACE [26]. The investigators of SORT OUT IV trial reported 11 patients with definite stent thrombosis [19].…”

“…Nevertheless, in an effort to overcome incomplete or selective data reporting, we included these data. In one case, the event adjudication rules were reported in detail in a previous paper describing study design and rationale [26].…”