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

• Autores: Fausto Feres, Ricardo A. Costa, Alexandre Abizaid, Martin B. Leon, J. Antonio Marin-Neto, Roberto V. Botelho, Spencer B. King III, Manuela Negoita, Minglei Liu, J. Eduardo T. de Paula, José A. Mangione, George X. Meireles, Eduardo L. Nicolela Jr, Marco A. Perin, Fernando S. Devito, André Labrunie, Décio Salvadori Jr, Marcos Gusmão, Rodolfo Staico, J. Ribamar Costa Jr, Juliana P. de Castro, Andrea S. Abizaid, Deepak L. Bhatt
• Localización: JAMA: the journal of the American Medical Association, ISSN 0098-7484, Vol. 310, Nº. 23, 2013, págs. 2510-2522
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • 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 Original recommendations for patients receiving first-generation drug-eluting stents (sirolimus- and paclitaxel-eluting stents) specified that these patients also receive 3 to 6 months of dual antiplatelet therapy with aspirin and a thienopyridine.1 However, limited trial data and retrospective analyses from real-world registries documented the occurrence of late and very late stent thrombosis and suggested that long-term (?12 months) dual antiplatelet therapy might be beneficial.2,3 Such outcomes, along with previous evidence obtained from studies of bare-metal stents, led to current guideline recommendations for prolonged dual antiplatelet therapy for all patients undergoing implantation of a drug-eluting stent.2- 6 Several observational studies showed a significant association between discontinuation of dual antiplatelet therapy and the occurrence of thrombotic events in the first 6 or 12 months after implantation of a drug-eluting stent, but not afterward.7- 10 Most recently, a few randomized trials of modest size tested different durations of dual antiplatelet therapy (3 or 6 months vs 12 or 24 months) with multiple drug-eluting stents, and results did not show benefits favoring prolonged therapy.11- 13 Moreover, many shortcomings have been identified with prolonged dual antiplatelet therapy, including bleeding and cost issues.14 At this point, even though recent trials comparing first- and second-generation drug-eluting stents have demonstrated superior safety profiles with newer devices (zotarolimus- and everolimus-eluting stents),15- 19 the optimal duration of dual antiplatelet therapy with specific types of drug-eluting stents remains unknown.20 The zotarolimus-eluting stent with a phosphorylcholine durable polymer is a second-generation drug-eluting stent that has demonstrated safety and efficacy in previous reports, despite use of dual antiplatelet therapy of relatively short duration (3 to 6 months) in most trials.21 In the OPTIMIZE (Optimized Duration of Clopidogrel Therapy Following Treatment With the Zotarolimus-Eluting Stent in Real-World Clinical Practice) trial, we sought to investigate the clinical implications of short-term (3 months) vs standard long-term (12 months) dual antiplatelet therapy in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI) solely with a zotarolimus-eluting stent in daily clinical practice and to determine whether short-term dual antiplatelet therapy would be noninferior to long-term dual antiplatelet therapy.22