Second Generation Drug-Eluting Stent Implantation Followed by Six- Versus Twelve-Month Dual Antiplatelet Therapy - SECURITY
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.
A 6-month duration of DAPT would be noninferior to a 12-month duration following PCI with second-generation DES.
- 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%
- 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
- 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
- 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
- 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
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%).
Statins (70%), heparin (55%), glycoprotein IIb/IIIa inhibitor use (4%)
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.
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.
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.
Keywords: Myocardial Infarction, Stroke, Angina, Stable, Drug-Eluting Stents, Thrombosis, Risk Factors, Piperazines, Ticlopidine, Diabetes Mellitus, Percutaneous Coronary Intervention, Transcatheter Cardiovascular Therapeutics
< Back to Listings