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Original Investigation |

Three vs Twelve Months of Dual Antiplatelet Therapy After Zotarolimus-Eluting Stents:  The OPTIMIZE Randomized Trial

Fausto Feres , MD, PhD1; Ricardo A. Costa, MD, PhD1; Alexandre Abizaid, MD, PhD1; Martin B. Leon, MD2; J. Antônio Marin-Neto, MD, PhD3; Roberto V. Botelho, MD, PhD4; Spencer B. King III, MD5; Manuela Negoita, MD6; Minglei Liu, PhD6; J. Eduardo T. de Paula, MD7; José A. Mangione, MD, PhD8; George X. Meireles, MD, PhD9; Hélio J. Castello Jr, MD, MSc10; Eduardo L. Nicolela Jr, MD11; Marco A. Perin, MD, PhD12; Fernando S. Devito, MD, PhD13; André Labrunie, MD, PhD14; Décio Salvadori Jr, MD, PhD8; Marcos Gusmão, MD15; Rodolfo Staico, MD, PhD1; J. Ribamar Costa Jr, MD, PhD1; Juliana P. de Castro, PhD16; Andrea S. Abizaid, MD, PhD16; Deepak L. Bhatt, MD, MPH17; for the OPTIMIZE Trial Investigators
[+] Author Affiliations
1Instituto Dante Pazzanese de Cardiologia, São Paulo, São Paulo, Brazil
2New York Presbyterian Medical Center, Columbia University Medical Center, and the Cardiovascular Research Foundation, New York, New York
3University of São Paulo, Ribeirão Preto, São Paulo, Brazil
4Instituto do Coração do Triângulo Mineiro, Uberlândia, Minas Gerais, Brazil
5Saint Joseph’s Medical Group, Atlanta, Georgia
6Medtronic CardioVascular, Santa Rosa, California
7Unicor de Linhares, Linhares, Espírito Santo, Brazil
8Hospital Beneficência Portuguesa de São Paulo, São Paulo, São Paulo, Brazil
9Hospital Público Estadual de São Paulo, São Paulo, São Paulo, Brazil
10Hospital Bandeirantes, São Paulo, São Paulo, Brazil
11Emcor Emergências do Coração, Piracicaba, São Paulo, Brazil
12Hospital Santa Marcelina, São Paulo, Brazil
13Hospital Padre Albino–FIPA, Catanduva, São Paulo, Brazil
14Santa Casa de Misericórdia de Marilia, Marilia, São Paulo, Brazil
15Hospital Agamenon Magalhães, Recife, Pernambuco, Brazil
16Cardiovascular Research Center, São Paulo, São Paulo, Brazil
17VA Boston Healthcare System, Brigham and Women’s Hospital, and Harvard Medical School, Boston, Massachusetts
JAMA. 2013;310(23):2510-2522. doi:10.1001/jama.2013.282183.
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Importance  The current recommendation is for at least 12 months of dual antiplatelet therapy after implantation of a drug-eluting stent. However, the optimal duration of dual antiplatelet therapy with specific types of drug-eluting stents remains unknown.

Objective  To assess the clinical noninferiority of 3 months (short-term) vs 12 months (long-term) of dual antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI) with zotarolimus-eluting stents.

Design, Setting, and Patients  The OPTIMIZE trial was an open-label, active-controlled, 1:1 randomized noninferiority study including 3119 patients in 33 sites in Brazil between April 2010 and March 2012. Clinical follow-up was performed at 1, 3, 6, and 12 months. Eligible patients were those with stable coronary artery disease or history of low-risk acute coronary syndrome (ACS) undergoing PCI with zotarolimus-eluting stents.

Interventions  After PCI with zotarolimus-eluting stents, patients were prescribed aspirin (100-200 mg daily) and clopidogrel (75 mg daily) for 3 months (n = 1563) or 12 months (n = 1556), unless contraindicated because of occurrence of an end point.

Main Outcomes and Measures  The primary end point was net adverse clinical and cerebral events (NACCE; a composite of all-cause death, myocardial infarction [MI], stroke, or major bleeding); the expected event rate at 1 year was 9%, with a noninferiority margin of 2.7%. Secondary end points were major adverse cardiac events (MACE; a composite of all-cause death, MI, emergent coronary artery bypass graft surgery, or target lesion revascularization) and Academic Research Consortium definite or probable stent thrombosis.

Results  NACCE occurred in 93 patients receiving short-term and 90 patients receiving long-term therapy (6.0% vs 5.8%, respectively; risk difference, 0.17 [95% CI, −1.52 to 1.86]; P = .002 for noninferiority). Kaplan-Meier estimates demonstrated MACE rates at 1 year of 8.3% (128) in the short-term group and 7.4% (114) in the long-term group (HR, 1.12 [95% CI, 0.87-1.45]). Between 91 and 360 days, no statistically significant association was observed for NACCE (39 [2.6%] vs 38 [2.6%] for the short- and long-term groups, respectively; HR, 1.03 [95% CI, 0.66-1.60]), MACE (78 [5.3%] vs 64 [4.3%]; HR, 1.22 [95% CI, 0.88-1.70]), or stent thrombosis (4 [0.3%] vs 1 [0.1%]; HR, 3.97 [95% CI, 0.44-35.49]).

Conclusions and Relevance  In patients with stable coronary artery disease or low-risk ACS treated with zotarolimus-eluting stents, 3 months of dual antiplatelet therapy was noninferior to 12 months for NACCE, without significantly increasing the risk of stent thrombosis.

Trial Registration  clinicaltrials.gov Identifier: NCT01113372

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Figures

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Figure 1.
Study Flow

No reliable data for number of patients assessed for eligibility are available. PCI indicates percutaneous coronary intervention.

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Figure 2.
Time to Event for the Primary Composite End Point (NACCE) Among Patients Receiving Short- and Long-term Dual Antiplatelet Therapy—0-360 Days, 0-90 Days, and 91-360 Days

Numbers of events listed under the x-axes are not cumulative but rather incremental numbers of events; numbers of events listed under the x-axes on day 0 represent periprocedural events. HR indicates hazard ratio; NACCE, net adverse clinical and cerebral events (a composite of all-cause death, myocardial infarction, stroke, or major bleeding).

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Figure 3.
Time to Event for Individual Components of the Primary Composite End Point (All-Cause Death, Myocardial Infarction) Among Patients Receiving Short- and Long-term Dual Antiplatelet Therapy at 0-360 Days, 0-90 Days, and 91-360 Days

Numbers of events listed under the x-axes are not cumulative but rather incremental numbers of events; numbers of events listed under the x-axes on day 0 represent periprocedural events. HR indicates hazard ratio.

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Figure 4.
Time to Event for Individual Components of the Primary Composite End Point (Stroke, Major Bleeding) Among Patients Receiving Short- and Long-term Dual Antiplatelet Therapy at 0-360 Days, 0-90 Days, and 91-360 Days

Numbers of events listed under the x-axes are not cumulative but rather incremental numbers of events; numbers of events listed under the x-axes on day 0 represent periprocedural events. HR indicates hazard ratio.

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Figure 5.
Forest Plot for the Primary Composite End Point According to Subgroup and Duration of Antiplatelet Therapy

Primary outcome was a composite of all-cause death, myocardial infarction, stroke, or major bleeding.

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