Scandinavian Organization for Randomized Trials With Clinical Outcome - SORT OUT IV

Description:

Although second-generation stents such as everolimus-eluting stents (EES) are routinely used, very few randomized data exist that directly compare EES to first-generation stents such as sirolimus-eluting stents (SES). The SORT OUT IV trial sought to compare outcomes after EES and SES implantation in a real-world population of patients presenting with coronary artery disease (CAD).

Contribution to the Literature: In the SORT OUT IV trial all-comers population of patients with CAD, EES is superior to SES for clinical endpoints at 5 years, including very late stent thrombosis.

Study Design

  • Blinded
  • Parallel
  • Randomized

Patient Populations:

  • Age ≥18 years
  • Chronic stable CAD or acute coronary syndrome
  • Coronary artery lesion deemed to require treatment with drug-eluting stents

    Number of screened applicants: 9,385
    Number of enrollees: 2,774
    Duration of follow-up: 9 months
    Mean patient age: 64.1 years
    Percentage female: 25%

Exclusions:

  • Life expectancy <1 year
  • Allergy to aspirin, clopidogrel, sirolimus, or everolimus
  • Participation in another randomized clinical trial

Primary Endpoints:

  • MACE (composite of cardiac death, myocardial infarction [MI], definite stent thrombosis, and clinically driven target vessel revascularization [TVR]) at 9 months

Drug/Procedures Used:

Patients were randomized in a 1:1 fashion to either EES (Xience V or Promus) or SES (Cypher Select Plus).

Concomitant Medications:

  • Dual antiplatelet therapy mandated for a minimum of 12 months in both arms
  • Lipid-lowering therapy (71%)
  • Glycoprotein IIb/IIIa inhibitors (16%)

Principal Findings:

A total of 2,774 patients were randomized, 1,390 to EES and 1,384 to SES. Baseline characteristics were fairly similar between the two arms. About 14% had diabetes, and 21% had undergone prior percutaneous coronary intervention (PCI). About 45% of patients presented with acute coronary syndromes, including 10% with ST-elevation MI. The target vessel was the left anterior descending artery in 42%, right coronary artery in 31%, and left main artery in 2% of the patients. Median reference vessel diameter was 3.2 mm. The mean number of lesions per patient was 1.3, with an average of 1.6 stents used per patient. The mean stented length was about 26.5 mm. Direct stenting was utilized in 21% of the patients.

The primary endpoint of major adverse cardiac events (MACE) at 9 months was similar between the EES and SES arms, and met the predefined criteria for noninferiority (4.9% vs. 5.2%, p for noninferiority = 0.01). MI (1.1% vs. 1.4%, p = 0.48), TVR (2.8% vs. 3.5%, p = 0.32), and definite or probable stent thrombosis (0.9% vs. 0.9%, p = 0.83) were similar between the EES and SES arms. Definite stent thrombosis was lower in the EES arm (0.1% vs. 0.7%, p = 0.05).

Three-year results: MACE rates were still similar between the EES and SES arms (10.2% vs. 11.8%, p = 0.2). Other outcomes such as all-cause mortality (7.2% vs. 6.7%, p = 0.62), MI (2.2 vs. 3.3%, p = 0.08), and TVR (1.2% vs. 1.7%, p = 0.12) were similar; stent thrombosis rates were lower: definite (0.2% vs. 1.4%, p = 0.002), very late (0.1% vs. 0.8%, p = 0.021).

Five-year results: MACE is lower with EES compared with SES (14.0% vs. 17.4%, p = 0.02). Mortality: 12.0% vs. 11.8%, p = 0.84; MI: 4.1% vs. 5.6%, p = 0.07; TVR: 8.3% vs. 10.9%,  p = 0.02; definite stent thrombosis: 0.4% vs. 2.0%, p = 0.0004. On landmark analysis at 1 year, MI: 3.0% vs. 4.2%, p = 0.09; TVR: 4.5% vs. 6.9%, p = 0.009 and very late stent thrombosis: 0.2% vs. 1.4%, p = 0.003 were significantly better with EES compared with SES.

Interpretation:

The results of the SORT OUT IV trial in a real-world population of patients with CAD in Denmark indicate that EES, a second-generation DES, is superior to SES, a first-generation DES, for a reduction in MACE out to 5 years, with a significantly lower risk of stent thrombosis, including very late (>1 year) stent thrombosis. 

Endpoint assessment for this trial was done retrospectively by interrogating three national databases (Danish civil registration system, national patient registry, and Western Denmark Heart Registry). Thus, although follow-up was 100%, capture of major cardiac events such death and revascularization was likely to be more accurate and precise versus events such as freedom from angina and probable (but not definite) stent thrombosis. Similar results have been noted in the ISAR-TEST IV trial.

References:

Jensen LO, Thayssen P, Christiansen EH, et al. Safety and Efficacy of Everolimus- Versus Sirolimus-Eluting Stents: 5-Year Results From SORT OUT IV. J Am Coll Cardiol 2016;67:751-62.

Jensen LO, Thayssen P, Maeng M, et al. Three-Year Outcomes After Revascularization With Everolimus- and Sirolimus-Eluting Stents From the SORT OUT IV Trial. JACC Cardiovasc Interv 2014;7:840-8.

Presented by Dr. Lisette Okkels Jensen at the Transcatheter Cardiovascular Therapeutics Meeting (TCT 2010), Washington, DC, September 24, 2010.

Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Interventions and ACS, Interventions and Coronary Artery Disease

Keywords: Registries, Coronary Artery Disease, Myocardial Infarction, Acute Coronary Syndrome, Follow-Up Studies, Drug-Eluting Stents, Thrombosis, Immunosuppressive Agents, Sirolimus, Diabetes Mellitus, Stents, Percutaneous Coronary Intervention


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