Clinical Evaluation of Xience-V stent in Acute Myocardial INfArcTION - EXAMINATION

Jan 21, 2016
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Spanish Heart Foundation. Unrestricted grant from Abbott to the Spanish Heart Foundation.
Date Presented:
09/01/2015
Date Published:
10/28/2015
Date Updated:
01/21/2016
Original Posted Date:
09/26/2012
References

Description:

Numerous studies have documented the safety and efficacy of drug-eluting stent (DES) use over bare-metal stent (BMS) use in patients presenting with ST-segment elevation myocardial infarction (STEMI). However, these were all conducted with so-called “first-generation” stents, such as sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES). The current trial sought to study the safety and efficacy of one of the so-called “second-generation” stents, Xience V (everolimus-eluting stent [EES]) versus BMS in patients presenting with STEMI. It also sought to be as inclusive as possible with respect to the patient population.

Contribution to the Literature: The EXAMINATION trial showed that EES were associated with a lower MACE rate compared with BMS, including all-cause mortality and TLR at 5 years and stent thrombosis at 1 year, in patients undergoing primary PCI for STEMI.

Study Design

  • Randomized
  • Parallel

Patient Populations:

  • STEMI patients scheduled for percutaneous coronary intervention (PCI) within 48 hours of symptom onset (included primary PCI, rescue PCI, PCI after successful thrombolysis, and late comers [>12-48 hours])
  • Vessel diameter between 2.25 and 4 mm
  • Age ≥18 years


Number screened: 2,149
Number of enrollees: 1,504
Duration of follow-up: 1 year and 5 years
Mean patient age: 61.5 years (median)
Percentage female: 17%
Ejection fraction: 51%

Exclusions:

  • Pregnancy
  • Intolerance to aspirin, clopidogrel, everolimus, stainless steel, cobalt, chromium, heparin
  • Need for chronic anticoagulation with vitamin K antagonists
  • STEMI secondary to stent thrombosis
  • Inability to obtain informed consent

Primary Endpoints:

  • All-cause mortality, any MI, any revascularization

Secondary Endpoints:

  • All-cause and cardiac mortality at 1 year and yearly up to 5 years
  • Recurrent MI at 1 year and yearly up to 5 years
  • TLR and TVR at 1 year and yearly up to 5 years
  • Stent thrombosis at 1 year and yearly up to 5 years
  • Clinical device and procedure success
  • Major and minor bleeding at 1 year and yearly up to 5 years

Drug/Procedures Used:

Patients undergoing PCI for STEMI within 48 hours of onset of symptoms were randomized in a 1:1 single-blind fashion to receive either EES (Xience V) or BMS (Cobalt Chromium Multi-link Vision).

Concomitant Medications:

Unfractionated heparin (80%), bivalirudin (7%), glycoprotein IIb/IIIa inhibitors (53%), aspirin before PCI (93%), clopidogrel 600 mg load (95%). At 1 year, about 90% of patients were on dual antiplatelet therapy.

Principal Findings:

A total of 1,498 patients were randomized, 751 to EES and 747 to BMS (6 patients withdrew consent). Baseline characteristics were fairly similar between the two arms. About 17% had a history of diabetes mellitus, and 48% had hypertension. Previous PCI was noted in 4%, and previous coronary artery bypass grafting in approximately 0.7%. The majority of patients randomized (85%) were undergoing PPCI for symptoms within 12 hours; 7% were undergoing rescue PCI, 2% underwent facilitated thrombolysis, and the remainder were late presenters for STEMI. The incidence of cardiogenic shock was about 1.2%. The left anterior descending artery was the target vessel in 41% of the patients, and the right coronary artery in 44%. Single-vessel disease only was noted in approximately 87% of the patients. Approximately 65% underwent manual thrombus aspiration, and direct stenting was employed in 59% of all patients. The mean stented length was 23 mm.

The primary composite endpoint of all-cause mortality, recurrent MI, and revascularization at 1 year was similar between the EES and BMS arms (11.9% vs. 14.2%, p = 0.19). Rates of cardiac death (3.2% vs. 2.8%, p = 0.76) and recurrent MI (1.3% vs. 2.0%, p = 0.32) were similar. Both target lesion revascularization (TLR) (2.1% vs. 5.0%, p = 0.0032) and target vessel revascularization (TVR) (3.7% vs. 6.8%, p = 0.008) were significantly lower in the EES arm at 1 year. Definite and probable stent thrombosis rates were also lower with EES (0.9% vs. 2.5%, p = 0.02), as were definite stent thrombosis (0.5% vs. 1.9%, p = 0.02). A significant number of stent thrombosis events were acute (within 30 days).

5-year results: Major adverse cardiac events (MACE) for EES vs. BMS: 21.4% vs. 26.0%, p = 0.033. On landmark analysis after 1 year: 10.7% vs. 13.7%, p = 0.08. Other endpoints at 5 years included mortality: 8.8% vs. 12%, p = 0.047; recurrent MI: 5% vs. 4%, p = 0.35; TLR: 4.0% vs. 7.6%, p = 0.012; definite stent thrombosis: 1.6% vs. 2.4%, p = 0.25. On landmark analysis after 1 year, 0.6% vs. 1.2%, p = 0.27.

Interpretation:

The results of the current trial indicate that the use of EES is similar to BMS for the composite clinical endpoint at 1 year, with a significant reduction in TLR/TVR and stent thrombosis at 1 year. On long-term follow-up, EES had a lower MACE rate than BMS, including mortality and TLR; stent thrombosis rates were similar after 1 year. Numerous trials including HORIZONS-AMI, PASSION and SELECTION (PES) and STRATEGY, TYPHOON, SESAMI, and MISSION (SES) have demonstrated the safety and efficacy of DES use in STEMI patients. This is one of the first trials conducted in this population with EES, and demonstrates superior results at 5 years. This trial also had a very high rate of inclusion of all-comer STEMI patients (70%) as compared with earlier trials. The reduction in stent thrombosis at 1 year is interesting.

References:

Sabaté M, Brugaletta S, Cequier A, et al. Clinical outcomes in patients with ST-segment elevation myocardial infarction treated with everolimus-eluting stents versus bare-metal stents (EXAMINATION): 5-year results of a randomised trial. Lancet 2015;Oct 28:[Epub ahead of print].

Presented by Dr. Manel Sabate Tenas at the European Society of Cardiology Congress, London, September 1, 2015.

Sabate M, Cequier A, Iñiguez A, et al. Everolimus-Eluting Stent Versus Bare-Metal Stent in ST-Segment Elevation Myocardial Infarction (EXAMINATION): 1 Year Results of a Randomised Controlled Trial. Lancet 2012;380:1482-90.

Editorial Comment: Bhatt DL. EXAMINATION of new drug-eluting stents--top of the class! Lancet 2012;380:1453-5.

Presented by Dr. Manel Sabate at the European Society of Cardiology Congress, Paris, France, August 2011.

 

Keywords: Myocardial Infarction, Follow-Up Studies, Insurance Coverage, Cobalt, Drug-Eluting Stents, Immunosuppressive Agents, Cyclonic Storms, Sirolimus, Single-Blind Method, Percutaneous Coronary Intervention, Paclitaxel, Shock, Cardiogenic, Thrombosis, Religious Missions, Chromium, Coronary Vessels, Coronary Artery Bypass, Hypertension, Diabetes Mellitus


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