Therapeutics
After drug-eluting stent placement, 6 months of dual antiplatelet therapy was noninferior to 12 months Clinical impact rating:
Colombo A, Chieffo A, Frasheri A, et al. Second-generation drugeluting stent implantation followed by 6- versus 12-month dual antiplatelet therapy: The SECURITY randomized clinical trial. J Am Coll Cardiol. 2014;64:2086-97.
多多多多多夞夞
Question After placement of second-generation drug-eluting stents (DESs), is 6 months of dual antiplatelet therapy (DAPT) noninferior to 12 months of DAPT?
Methods Design: Randomized, controlled, noninferiority trial (Second Generation Drug-Eluting Stent Implantation Followed by SixVersus Twelve-Month Dual Antiplatelet Therapy [SECURITY] trial). ClinicalTrials.gov NCT00944333. Allocation: Concealed.* Blinding: Blinded* ({data collectors, outcome assessors, safety committee}†, and statisticians). Follow-up period: 24 months. Trial was stopped early due to slow enrollment and minimal between-group differences in primary endpoint. Setting: {45 centers in Italy, Spain, and the Netherlands}†. Patients: 1399 patients > 18 years of age (mean age 65 y, 77% men) who had symptoms of stable angina, unstable angina, or silent ischemia and were treated with ≥ 1 second-generation DES in the previous 24 hours. Exclusion criteria included previous DES placement, bare-metal stent placement in the past 3 months, treatment for saphenous vein graft, in-stent restenosis, unprotected left main coronary artery, ST-segment elevation myocardial infarction (MI) within 48 hours of DES placement, non–ST-segment elevation MI in the past 6 months, left ventricular ejection fraction ≤ 30%, chronic kidney disease, active or risk for bleeding, or uncontrolled hypertension. Intervention: DAPT (clopidogrel, 75 mg, plus aspirin, {≥ 75 mg/ d}†) for 6 months (n = 682) or 12 months (n = 717). Patients received clopidogrel, 75 mg/d, for ≥ 3 days before stent placement or a loading dose of clopidogrel, ≥ 300 mg, if not receiving longterm clopidogrel therapy. Aspirin therapy continued indefinitely. Outcomes: Primary outcome was a composite of cardiac death, MI, stroke, definite or probable stent thrombosis, or bleeding at 12 months. Secondary outcomes included components of the primary outcome at 12 and 24 months. Patient follow-up: 90% at 12 months; 81% at 24 months (intention-to-treat analysis).
0.8%, 95% CI ⫺2.4 to 1.7; criterion for noninferiority was an upper CI < 2.0%). Groups did not differ for secondary outcomes at 24 months.
Conclusion Dual antiplatelet therapy for 6 months after second-generation stent placement was noninferior to 12 months of therapy for a composite of cardiac death, myocardial infarction, stroke, definite or probable stent thrombosis, or bleeding at 12 months. *See Glossary. †Information provided by author. Sources of funding: Fondazione Evidence; Biosensors; Medtronic; Terumo. For correspondence: Dr. Antonio Colombo, San Raffaele Scientific Institute, Milan, Italy. E-mail [email protected].
Commentary DAPT with aspirin and a P2Y12-receptor inhibitor is an important component of treatment after percutaneous coronary intervention (PCI) (1). The SECURITY trial found that a 6-month regimen of DAPT after second-generation DES implantation was noninferior to a 12-month regimen. Limitations of the trial include early stoppage, leading to lack of power; enrollment of patients with low risk; lower-than-expected event rates; and continuation of DAPT to 12 months by 34% of patients in the 6-month group. The findings, however, are consistent with several previous studies that compared shorter (3 to 6 mo) and longer (12 to 24 mo) DAPT and found no difference between durations (2-4). Recently, the DAPT trial reported that DAPT beyond 1 year after DES placement reduced stent thrombosis and major adverse cardiovascular events but increased bleeding and all-cause mortality (5). Given these conflicting results, clinicians are in a quandary regarding the optimal duration of DAPT after PCI. Based on available data, longer duration of DAPT reduces ischemic events but increases risk for bleeding. Optimal duration of DAPT after PCI is probably shorter for low-risk patients with stable ischemia than for high-risk patients with the acute coronary syndrome, and optimal DAPT duration after second- or third-generation DES placement is probably shorter than for first-generation placement. At this time, clinicians need to individualize DAPT duration based on less-than-perfect data. Debabrata Mukherjee, MD Texas Tech University, Health Sciences Center El Paso, Texas, USA
Main results The main results are in the Table. For the composite outcome, DAPT for 6 months was noninferior to DAPT for 12 months (rate difference
6- vs 12-month dual antiplatelet therapy (DAPT) after placement of second-generation drug-eluting stents‡ Outcomes
Primary composite§
Event rates
At 12 mo
6-mo DAPT
12-mo DAPT
RRI (95% CI)
4.5%
3.7%
21% (⫺27 to 99)
Cardiac death
0.7%
0.4%
75% (⫺54 to 561)
Myocardial infarction
2.3%
2.1%
12% (⫺43 to 122)
Stroke
0.9%
0.3%
215% (⫺27 to 1263)
RRR (CI) Definite or probable stent thrombosis
0.3%
0.4%
30% (⫺250 to 86)
Bleeding||
0.6%
1.1%
47% (⫺63 to 83)
‡Abbreviations defined in Glossary. RRI, RRR, and CI calculated from event rates in article. §Cardiac death, myocardial infarction, stroke, definite or probable stent thrombosis, or bleeding.
References 1. Levine GN, Bates ER, Blankenship JC, et al; American College of Cardiology Foundation. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011;58:e44-122. 2. Gwon HC, Hahn JY, Park KW, et al. Six-month versus 12-month dual antiplatelet therapy after implantation of drug-eluting stents: the Efficacy of Xience/ Promus Versus Cypher to Reduce Late Loss After Stenting (EXCELLENT) randomized, multicenter study. Circulation. 2012;125:505-13. 3. Feres F, Costa RA, Abizaid A, et al; OPTIMIZE Trial Investigators. Three vs twelve months of dual antiplatelet therapy after zotarolimus-eluting stents: the OPTIMIZE randomized trial. JAMA. 2013;310:2510-22. 4. Valgimigli M, Borghesi M, Tebaldi M, et al; PROlonging Dual antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY Investigators. Should duration of dual antiplatelet therapy depend on the type and/or potency of implanted stent? A pre-specified analysis from the PROlonging Dual antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY (PRODIGY). Eur Heart J. 2013;34:909-19. 5. Mauri L, Kereiakes DJ, Yeh RW, et al; DAPT Study Investigators. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med. 2014;371:2155-66.
||Bleeding Academic Research Consortium criteria type 3 or 5.
姝 2015 American College of Physicians
JC6
ACP Journal Club
Downloaded From: https://annals.org/ by a Tufts University User on 08/04/2017
Annals of Internal Medicine
21 April 2015
After drug-eluting stent placement, 6 months of dual antiplatelet therapy was noninferior to 12 months Clinical impact rating:
Colombo A, Chieffo A, Frasheri A, et al. Second-generation drugeluting stent implantation followed by 6- versus 12-month dual antiplatelet therapy: The SECURITY randomized clinical trial. J Am Coll Cardiol. 2014;64:2086-97.
多多多多多夞夞
Question After placement of second-generation drug-eluting stents (DESs), is 6 months of dual antiplatelet therapy (DAPT) noninferior to 12 months of DAPT?
Methods Design: Randomized, controlled, noninferiority trial (Second Generation Drug-Eluting Stent Implantation Followed by SixVersus Twelve-Month Dual Antiplatelet Therapy [SECURITY] trial). ClinicalTrials.gov NCT00944333. Allocation: Concealed.* Blinding: Blinded* ({data collectors, outcome assessors, safety committee}†, and statisticians). Follow-up period: 24 months. Trial was stopped early due to slow enrollment and minimal between-group differences in primary endpoint. Setting: {45 centers in Italy, Spain, and the Netherlands}†. Patients: 1399 patients > 18 years of age (mean age 65 y, 77% men) who had symptoms of stable angina, unstable angina, or silent ischemia and were treated with ≥ 1 second-generation DES in the previous 24 hours. Exclusion criteria included previous DES placement, bare-metal stent placement in the past 3 months, treatment for saphenous vein graft, in-stent restenosis, unprotected left main coronary artery, ST-segment elevation myocardial infarction (MI) within 48 hours of DES placement, non–ST-segment elevation MI in the past 6 months, left ventricular ejection fraction ≤ 30%, chronic kidney disease, active or risk for bleeding, or uncontrolled hypertension. Intervention: DAPT (clopidogrel, 75 mg, plus aspirin, {≥ 75 mg/ d}†) for 6 months (n = 682) or 12 months (n = 717). Patients received clopidogrel, 75 mg/d, for ≥ 3 days before stent placement or a loading dose of clopidogrel, ≥ 300 mg, if not receiving longterm clopidogrel therapy. Aspirin therapy continued indefinitely. Outcomes: Primary outcome was a composite of cardiac death, MI, stroke, definite or probable stent thrombosis, or bleeding at 12 months. Secondary outcomes included components of the primary outcome at 12 and 24 months. Patient follow-up: 90% at 12 months; 81% at 24 months (intention-to-treat analysis).
0.8%, 95% CI ⫺2.4 to 1.7; criterion for noninferiority was an upper CI < 2.0%). Groups did not differ for secondary outcomes at 24 months.
Conclusion Dual antiplatelet therapy for 6 months after second-generation stent placement was noninferior to 12 months of therapy for a composite of cardiac death, myocardial infarction, stroke, definite or probable stent thrombosis, or bleeding at 12 months. *See Glossary. †Information provided by author. Sources of funding: Fondazione Evidence; Biosensors; Medtronic; Terumo. For correspondence: Dr. Antonio Colombo, San Raffaele Scientific Institute, Milan, Italy. E-mail [email protected].
Commentary DAPT with aspirin and a P2Y12-receptor inhibitor is an important component of treatment after percutaneous coronary intervention (PCI) (1). The SECURITY trial found that a 6-month regimen of DAPT after second-generation DES implantation was noninferior to a 12-month regimen. Limitations of the trial include early stoppage, leading to lack of power; enrollment of patients with low risk; lower-than-expected event rates; and continuation of DAPT to 12 months by 34% of patients in the 6-month group. The findings, however, are consistent with several previous studies that compared shorter (3 to 6 mo) and longer (12 to 24 mo) DAPT and found no difference between durations (2-4). Recently, the DAPT trial reported that DAPT beyond 1 year after DES placement reduced stent thrombosis and major adverse cardiovascular events but increased bleeding and all-cause mortality (5). Given these conflicting results, clinicians are in a quandary regarding the optimal duration of DAPT after PCI. Based on available data, longer duration of DAPT reduces ischemic events but increases risk for bleeding. Optimal duration of DAPT after PCI is probably shorter for low-risk patients with stable ischemia than for high-risk patients with the acute coronary syndrome, and optimal DAPT duration after second- or third-generation DES placement is probably shorter than for first-generation placement. At this time, clinicians need to individualize DAPT duration based on less-than-perfect data. Debabrata Mukherjee, MD Texas Tech University, Health Sciences Center El Paso, Texas, USA
Main results The main results are in the Table. For the composite outcome, DAPT for 6 months was noninferior to DAPT for 12 months (rate difference
6- vs 12-month dual antiplatelet therapy (DAPT) after placement of second-generation drug-eluting stents‡ Outcomes
Primary composite§
Event rates
At 12 mo
6-mo DAPT
12-mo DAPT
RRI (95% CI)
4.5%
3.7%
21% (⫺27 to 99)
Cardiac death
0.7%
0.4%
75% (⫺54 to 561)
Myocardial infarction
2.3%
2.1%
12% (⫺43 to 122)
Stroke
0.9%
0.3%
215% (⫺27 to 1263)
RRR (CI) Definite or probable stent thrombosis
0.3%
0.4%
30% (⫺250 to 86)
Bleeding||
0.6%
1.1%
47% (⫺63 to 83)
‡Abbreviations defined in Glossary. RRI, RRR, and CI calculated from event rates in article. §Cardiac death, myocardial infarction, stroke, definite or probable stent thrombosis, or bleeding.
References 1. Levine GN, Bates ER, Blankenship JC, et al; American College of Cardiology Foundation. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011;58:e44-122. 2. Gwon HC, Hahn JY, Park KW, et al. Six-month versus 12-month dual antiplatelet therapy after implantation of drug-eluting stents: the Efficacy of Xience/ Promus Versus Cypher to Reduce Late Loss After Stenting (EXCELLENT) randomized, multicenter study. Circulation. 2012;125:505-13. 3. Feres F, Costa RA, Abizaid A, et al; OPTIMIZE Trial Investigators. Three vs twelve months of dual antiplatelet therapy after zotarolimus-eluting stents: the OPTIMIZE randomized trial. JAMA. 2013;310:2510-22. 4. Valgimigli M, Borghesi M, Tebaldi M, et al; PROlonging Dual antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY Investigators. Should duration of dual antiplatelet therapy depend on the type and/or potency of implanted stent? A pre-specified analysis from the PROlonging Dual antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY (PRODIGY). Eur Heart J. 2013;34:909-19. 5. Mauri L, Kereiakes DJ, Yeh RW, et al; DAPT Study Investigators. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med. 2014;371:2155-66.
||Bleeding Academic Research Consortium criteria type 3 or 5.
姝 2015 American College of Physicians
JC6
ACP Journal Club
Downloaded From: https://annals.org/ by a Tufts University User on 08/04/2017
Annals of Internal Medicine
21 April 2015
