Second Generation Drug-Eluting Stent Implantation Followed by Six- Versus Twelve-Month Dual Antiplatelet Therapy - SECURITY

Description:

The optimal duration of dual antiplatelet therapy (DAPT) following drug-eluting stent (DES) percutaneous coronary intervention (PCI) remains unclear. The current trial sought to investigate the utility of a short duration of DAPT (6 months) versus 12 months following PCI with a second-generation DES.

Hypothesis:

A 6-month duration of DAPT would be noninferior to a 12-month duration following PCI with second-generation DES.

Study Design

  • Randomized
  • Parallel

Patient Populations:

  • Stable angina, as defined by Canadian Cardiovascular Society classification, or unstable angina, as defined by Braunwald classification, or patients with documented silent ischemia, treated with at least one second-generation DES implanted in the target lesion within 24 hours
  • One or more de novo stenosis ≥70% in a native coronary artery
  • Patient age over 18 years
  • No other DES implanted before the target procedure
  • No bare-metal stent implanted in the 3 months before the target procedure

    Number of screened applicants: 1,399
    Number of enrollees: 100
    Duration of follow-up: 24 months
    Mean patient age: 65 years
    Percentage female: 23%

Exclusions:

  • Lesion in saphenous vein graft
  • In-stent restenosis
  • Unprotected left main PCI
  • ST-segment elevation MI (STEMI) in the 48 hours prior to the procedure
  • Non–STEMI in the previous 6 months
  • Left ventricular ejection fraction ≤30%
  • Known hypersensitivity to aspirin, thienopyridines, heparin, limus analogues, cobalt, chromium, nickel, molybdenum, or contrast media
  • History of significant thrombocytopenia with aspirin or thienopyridines
  • Chronic kidney disease (creatinine >2 mg/dl)
  • Women during pregnancy or during lactation
  • Active bleeding or significant risk of bleeding
  • Uncontrolled hypertension
  • Life expectancy of <24 months and any medical condition that could preclude follow-up, as defined in the protocol

Primary Endpoints:

  • Composite of cardiac death, MI, stroke, definite or probable stent thrombosis, or bleeding academic consortium criteria (BARC) type 3 or 5 bleeding at 12 months

Secondary Endpoints:

  • Composite of cardiac death, spontaneous MI, stroke, definite or probable stent thrombosis, or BARC type 2, 3, or 5 bleeding at 12 and 24 months
  • Cumulative incidence of the individual components of the primary endpoint at 12 and 24 months
  • MI
  • Urgent target vessel revascularization (coronary artery bypass surgery or PCI because of acute cardiac ischemia)
  • All-bleeding events
  • All-cause mortality at 30 days; 6, 12, and 24 months

Drug/Procedures Used:

Patients were randomized in a 1:1 ratio to receive either 6 or 12 months of DAPT. Clopidogrel 75 mg per day for at least 3 days before the procedure or a preprocedural loading dose of a minimum of 300 mg of clopidogrel was administered in patients not on chronic clopidogrel therapy.

In the post-procedure period, 75 mg of clopidogrel for 6 or 12 months, according to randomization allocation, was administered. Following the introduction on the market of new antiplatelet compounds, prasugrel and ticagrelor were also allowed in a protocol amendment, but were utilized in <1% of patients. Post-procedure use of aspirin was prescribed indefinitely. PCI was performed with either Endeavor Resolute (41%), Xience (9%), Promus (11%), Nobori (26%), or the Biomatrix (7%).

Concomitant Medications:

Statins (70%), heparin (55%), glycoprotein IIb/IIIa inhibitor use (4%)

Principal Findings:

The trial was terminated prematurely due to slow enrollment. At this time, a total of 1,399 patients had been randomized, 682 to 6-month DAPT and 717 to 12-month DAPT. Baseline characteristics were fairly similar between the two arms. Approximately 30% had diabetes, 22% were current smokers, and 18% had undergone prior PCI. Nearly two thirds of the patients were recruited for stable angina. About 31% had two-vessel disease and 11% had three-vessel disease, with the target vessel being left anterior descending (LAD) in 44%. Approximately 14% were bifurcation lesions, with a median lesion length of 18 mm and a median reference vessel diameter of 2.9 mm. An average of 1.62 stents were implanted per patient, with multivessel PCI performed in 28%.

At 12 months, 34% and 96% were taking DAPT in the two arms, respectively; the majority of patients in the short-duration arm were taking aspirin alone. The incidence of the primary endpoint was similar between the 6-month and 12-month DAPT arms (4.5% vs. 3.7%, p for noninferiority < 0.05, p for superiority = 0.47). Other endpoints at 12 months including cardiac mortality (0.7% vs. 0.4%, p = 0.44), myocardial infarction (MI) (2.3% vs. 2.1%, p = 0.75), stroke (0.9% vs. 0.3%, p = 0.14), and bleeding (0.6% vs. 1.1%, p = 0.28) were similar between the two arms. Definite or probable stent thrombosis were similar at 12 months (0.3% vs. 0.4%, p = 0.69) and 24 months (0.4% vs. 0.4%, p = 0.95). At 12 months, significant predictors of the primary endpoint were age, use of Endeavor stent, longer stent length, higher number of stents, and mean stent size.

Interpretation:

The results of the SECURITY trial indicate that a 6-month duration of DAPT may be noninferior for ischemic and bleeding outcomes to a 12-month duration in low-risk patients undergoing PCI with a second-generation DES. The trial was initially powered to detect a difference in stent thrombosis, and then modified to accommodate a composite endpoint to lower the sample size. Despite this, the trial was prematurely terminated due to slow recruitment, and <50% of the anticipated sample size was enrolled.

A number of other trials including EXCELLENT, OPTIMIZE, and PRODIGY have attempted to address a similar question regarding the optimal duration of DAPT following DES PCI. There is no conclusive evidence yet, but the totality of data suggests that a shorter duration may be possible in low-risk patients undergoing a second-generation DES implantation. Interestingly, while the OPTIMIZE trial used all Endeavor stents, in the current trial, use of the Endeavor stent was actually a risk factor for a higher risk of the primary outcome. The results of the large DAPT trial are eagerly awaited. Current American College of Cardiology/American Heart Association guidelines still recommend 12 months of DAPT following DES PCI.

References:

Colombo A, Chieffo A, Frasheri A, et al. Second Generation Drug-Eluting Stent Implantation Followed by Six- Versus Twelve-Month - Dual Antiplatelet Therapy - The SECURITY Randomized Clinical Trial. J Am Coll Cardiol 2014;Sep 15:[Epub ahead of print].

Editorial: Holmes DR. Art and Science. J Am Coll Cardiol 2014;Sep 15:[Epub ahead of print].

Presented by Dr. Antonio Colombo at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2014), Washington, DC, September 15, 2014.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, Chronic Angina

Keywords: Myocardial Infarction, Stroke, Angina, Stable, Drug-Eluting Stents, Thrombosis, Risk Factors, Piperazines, Ticlopidine, Diabetes Mellitus, Percutaneous Coronary Intervention, Transcatheter Cardiovascular Therapeutics


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