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W2116794265 abstract "HomeCirculationVol. 128, No. 25Management of Antiplatelet Therapy in Patients With Coronary Artery Disease Requiring Cardiac and Noncardiac Surgery Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBManagement of Antiplatelet Therapy in Patients With Coronary Artery Disease Requiring Cardiac and Noncardiac Surgery Davide Capodanno, MD, PhD and Dominick J. Angiolillo, MD, PhD Davide CapodannoDavide Capodanno From the Ferrarotto Hospital, University of Catania, Catania, Italy (D.C.); and University of Florida College of Medicine-Jacksonville, Jacksonville, FL (D.C., D.J.A.). Search for more papers by this author and Dominick J. AngiolilloDominick J. Angiolillo From the Ferrarotto Hospital, University of Catania, Catania, Italy (D.C.); and University of Florida College of Medicine-Jacksonville, Jacksonville, FL (D.C., D.J.A.). Search for more papers by this author Originally published24 Dec 2013https://doi.org/10.1161/CIRCULATIONAHA.113.003675Circulation. 2013;128:2785–2798Approximately 5% to 15% of patients undergoing coronary stent implantation are estimated to undergo a surgical procedure within 2 years.1–7 In the largest (N=126 773) cohort study to date describing the incidence and timing of noncardiac surgery after coronary stent placement, 12% of patients who received bare metal stents (BMSs) and 47% of patients who received drug-eluting stents (DESs) had early surgery, defined as surgical procedures occurring within 6 weeks in patients treated with BMSs or within 12 months in those treated with DESs.8 Although the majority were minor procedures, major surgical procedures were more likely to occur within 12 months of stent placement in comparison with 12 to 24 months. Interestingly, a decline in surgical procedures was noted after publication of the American College of Cardiology/American Heart Association Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery in 2007 (preguidelines 25% versus postguidelines 13%, P=0.001).8 Stented patients undergoing surgery are likely to discontinue dual-antiplatelet therapy (DAPT), composed of aspirin and a P2Y12 receptor antagonist (mostly clopidogrel, but may also include prasugrel or ticagrelor), thereby being exposed to a withdrawal of protection with subsequent risk for stent thrombosis or other ischemic events. In a survey of 1358 consecutive patients treated with DESs and discharged on aspirin and clopidogrel, surgery was identified as the second cause of early discontinuation within 1 year (21%) and the first cause of late discontinuation thereafter (49%).9Defining the fine balance between ischemic and bleeding risk remains a challenge in stented patients undergoing surgery treated with antiplatelet therapy. Understanding whether an antithrombotic drug should or should not be discontinued and tailoring treatment strategies based on the type of intervention are key to balancing the safety and efficacy profiles of antithrombotic medications in this particular scenario. Importantly, such a healthcare problem is relevant not only to the interventional cardiology community, but also to general cardiologists, surgeons, anesthesiologists, and primary care physicians. This article provides an overview of the currently available evidence on the perioperative management of antiplatelet therapy in patients with coronary artery disease (CAD), especially those treated with stents, undergoing surgery. In particular, a description of thrombosis and bleeding profiles that characterize CAD patients undergoing surgery, considerations for the use of antithrombotic agents, and a review of current recommendations and future perspectives are provided.Ischemic and Bleeding Risk in CAD Patients Requiring SurgeryIschemic RiskAntiplatelet therapy is a mainstay in the management of patients with CAD. This includes not only patients who have undergone stent implantation, but also those with an acute coronary syndrome (ACS) who are medically treated, in whom the clustering of adverse thrombotic events has been described in the early period after interruption of oral antiplatelet agents.10–12 The risk of a recurrent ischemic event for patients discontinuing or not adhering to aspirin treatment has been suggested to increase 3-fold, with similar estimates of risk in patients with an ACS, on secondary prevention for CAD and those undergoing coronary artery bypass grafting (CABG), and higher risk in patients treated with DESs.13 Importantly, stent thrombosis is a serious complication that is known to commonly present with death or a large nonfatal myocardial infarction, usually with ST elevation.14–16Rebound platelet reactivity after discontinuation of antithrombotic therapy has been advocated to lead the increased thrombotic risk in stented patients undergoing surgery.10,12 However, this hypothesis was not supported by 2 specifically designed randomized studies that used multiple time points, assays, agonists, and agonist concentrations.17,18 Differences in response profiles to aspirin after clopidogrel withdrawal have been suggested as a mechanism for differences in individual propensity to develop thrombotic complications.19 An alternative explanation for the reported clustering of ischemic events after discontinuation of clopidogrel is the recovery of platelet reactivity to pretreatment levels, and therefore more appropriately considered as “withdrawal of protection.”17,18 This may assume clinical relevance in specific settings such as surgery, which is inherently associated with an increased prothrombotic and inflammatory environment, including increased cytokines, neuroendocrine inflammatory mediator release, platelet adhesiveness, persistently high platelet counts, and decreased or impaired fibrinolysis.20–22 Adding to the withdrawal of protection with DAPT discontinuation, in case of early surgery following percutaneous coronary intervention (PCI), these factors characterize a unique prothrombotic state that typically occurs in the vulnerable period in which stents are not fully endothelialized.The first alarming report of adverse perioperative outcomes in BMS patients was published in 2000,23 followed by several additional reports of severe cardiac complications and death when surgical operations were performed within 3 to 7 weeks from BMS implantation.24–27 These studies, in general, are inherently biased in that patients who require surgery more rapidly are likely to be sicker. However, because BMS thrombosis is more frequent in the first 2 weeks after stent placement and rare more than 4 weeks after, when endothelialization of the stent has generally occurred, current guidelines recommend delaying surgery 4 to 6 weeks after BMS placement to allow proper thienopyridine use to reduce the risk of coronary stent thrombosis.28 This recommendation is presently given a IIa class with level of evidence B, reflecting the limited and sometimes conflicting evidence mostly coming from nonrandomized studies. In a recent large-cohort registry from Wijeysundera et al,29 the incidence of 30-day ischemic events in patients with BMSs was 2.6% when the interval between stent insertion and major elective cardiac surgery was 45 to 180 days and 6.7% when the interval was <45 days.Data on the risk of surgery after DES placement generally relates to small series with mixed results.30–36 DES thrombosis may occur late and has been reported up to 5.5 years after implantation, but particularly in the context of discontinuation of antiplatelet agents before noncardiac surgery.30–37 Although the risk of death, myocardial infarction, or stent thrombosis decreases significantly for the increasing interval between PCI and surgery, the intermediate-term risk extending at least 2 to 3 years remains ≈1%.38 In the Evaluation of Drug-Eluting Stents and Ischemic Events (EVENT) registry, among 206 patients who received ≥1 DESs and underwent major noncardiac surgery at a median of 6 months after PCI, the risk of cardiac death, myocardial infarction, or stent thrombosis was increased 27-fold in the week following noncardiac surgery in comparison with any other week after stent implantation, but data on how aspirin and clopidogrel were managed were not collected in such a way that it could be determined which patients were on antiplatelet therapy during the surgical procedure and those who were not.1 Wijeysundera et al29 reported a high (20%) 30-day incidence of adverse ischemic events in 905 patients with DESs when the interval between stent insertion and surgery was <45 days, whereas the event rate was only 1.2% once the interval exceeded 180 days. In aggregate, these findings support the understanding that early surgery and antiplatelet therapy discontinuation are risk factors for cardiac events at the time of noncardiac surgery after DES placement, although some relative risk persists at longer term. It should be noted that the available studies are generally poorly informative on whether the risk of thrombotic events in the surgical period is mainly linked to discontinuation of thienopyridines, or both aspirin and thienopyridines. Consistently, current guidelines recommend withholding elective noncardiac surgery for at least 12 months after DES implantation in patients in whom thienopyridine therapy, or aspirin and thienopyridine therapy, will need to be discontinued perioperatively.28,39Bleeding RiskWhen facing the problem of perioperative bleeding, it should be important to distinguish bleedings related to the surgical procedure itself from those that occur in patients on antithrombotic therapy, especially when anticoagulant and antiplatelet drugs are administered in proximity to surgery. In fact, certain procedures are not typically associated with postoperative bleeding in patients not on antithrombotic medications but may be if antithrombotics are given in proximity to the procedure. Interestingly, when surgeons are not aware if aspirin was used or not, they often cannot distinguish, based on the type of bleeding, patients on aspirin from those who have discontinued.40 The American College of Chest Physicians guidelines for the perioperative management of antithrombotic therapy have identified a group of surgeries and procedures that appear to be associated with a high risk for bleeding in the context of perioperative anticoagulant and antiplatelet drug use.41 An alternative approach coming from a joint national consensus defined the interventions at greater risk of bleeding within an array of different surgeries or invasive procedures (Table 1).42 CABG differs from other major surgeries in that it includes specific risk factors for bleeding, including full heparinization therapy, platelet dysfunction from the pump, and altered fibrinolysis.43Table 1. Interventions at High Bleeding Risk in Multiple Surgical and Invasive ScenariosType of surgeryCardiac surgeryReintervention, endocarditis, coronary artery bypass grafting after failed percutaneous coronary intervention, aortic dissectionGeneral surgeryHepatic resection, pancreaticoduodenectomyMaxillofacial surgeryRadical and reconstructive surgery for cancer of the head and neck, open reduction of orbital-zygomatic fracture, submandibular sialoadenectomyPlastic surgeryFunctional treatment of trauma outcomes, treatment of conspicuous postdemolitive loss of substance, large liposuction, surgical treatment of burns >15%, treatment of leg ulcers (American Society of Anesthesiology class III–IV), large lipofilling, postbariatric surgeryThoracic surgeryEsophagectomy, pleuropneumectomy, pulmonary decorticationVascular surgeryOpen surgery of the thoracic and thoracoabdominal aortaDigestive endoscopyDilation for achalasia, mucosectomy, submucosal resection, fine-needle aspiration biopsy of pancreatic cystic lesions, Vater ampulla ampullectomyGynecological surgeryLaparoscopic or laparotomic hysterectomy for large uterus, laparoscopic or laparotomic myomectomy, laparoscopic or laparotomic surgery for severe/deep endometriosis, debulking of ovarian cancer, radical surgery for carcinoma of the cervix and endometrium, pelvic/lombo-aortic lymphadenectomy, pelvic eviscerationNeurosurgeryRemoval of intradural lesions (intracerebral masses, intraparenchymal hemorrhages)PneumologyTransbronchial and lung biopsies, operative bronchoscopy with a rigid bronchoscopeDentistryNoneOphthalmologyNoneOrthopedic surgeryMajor prosthetic surgery (hip, knee), major traumatology (pelvis, long bones), fractures of the proximal femur in elderly patientsUrologyTotal and partial nephrectomy, percutaneous nephrostomy, percutaneous lithotripsy, radical cystectomy and prostatectomy, prostatic endoscopic resection, endoscopic bladder interventions, penectomy, partial orchiectomyAdapted from Rossini et al42 with permission of the publisher. Copyright © 2012, Il Pensiero Scientifico Editore. Authorization for this adaptation has been obtained both from the owner of the copyright in the original work and from the owner of copyright in the translation or adaptation.Antiplatelet agents that irreversibly inhibit platelet function, thereby requiring 7 to 10 days for an entire platelet pool to be replaced regardless of their half-lives,44,45 are aspirin, ticlopidine, clopidogrel, and prasugrel. Most of the studies of aspirin use in the preoperative setting are not randomized; and, consequently, the maintenance of aspirin therapy may be a marker of increased comorbidity and, hence, also a marker of increased bleeding risk. Two randomized clinical trials conducted on the comparative effectiveness and safety of low-dose aspirin versus placebo in patients undergoing noncardiac surgery were prematurely stopped and are therefore underpowered for assessing bleeding and ischemic end points.46,47 Taking these limitations into account, both trials showed no significant differences between patients on aspirin and those on placebo in terms of bleeding events within 30 days from surgery,46,47 and one suggested the potential for a significant risk reduction in postoperative major adverse cardiac events.46 In a meta-analysis of 49 590 patients, the frequency of bleeding complications while on aspirin in patients undergoing noncardiac surgery varied between 0 (skin lesion excision, cataract surgery) and 75% (transrectal prostate biopsy).48 Aspirin was found to be associated with a 1.5-fold increased risk of bleeding complications, but it did not increase the level of the severity of bleeding complications and acted only quantitatively on hemorrhages, with the exception of intracranial surgery and transurethral prostatectomy. As far as CABG is concerned, a meta-analysis of randomized and observational studies comparing preoperative aspirin with no aspirin/placebo showed that aspirin is likely to increase postoperative bleeding, but this may be avoided by the use of doses <325 mg/d.49 However, the importance of aspirin therapy on graft patency should also be noted, particularly during the first postoperative year.50,51The first major evidence on the impact of P2Y12-inhibiting therapy on surgical bleeding derives from the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial comparing clopidogrel versus placebo, on top of aspirin, in ACS patients.52 In CURE, a total of 2072 patients (16.5% of study population) underwent CABG at any time after randomization. Among these, the risk of CURE major bleeding occurred in 9.6% and 7.5% in the clopidogrel and placebo arms, respectively (relative risk, 1.27; 95% confidence interval [CI], 0.96–1.69; P=0.095).53 However, the bleeding hazards varied markedly according to whether clopidogrel was stopped for ≤5 days before surgery in comparison with >5 days before surgery. Whereas no excess in any bleeding was observed for those stopping the drug for >5 days before surgery (clopidogrel 4.4% versus placebo 5.3%), a 53% relative increase in major bleeding was seen for those who continued the drug within 5 days of surgery (clopidogrel 9.6% versus placebo 6.3%). Other studies, mainly retrospective in nature, reported on the perioperative continuation of clopidogrel, suggesting increased rates of bleeding with perioperative or periprocedural clopidogrel continuation in noncardiac surgery.24,26,54 In a study of 4330 patients undergoing CABG, those on clopidogrel plus aspirin within 5 and 2 days before surgery, respectively, were found to experience higher blood loss and reoperation for bleeding.55 This finding seems consistent irrespective of whether surgery is performed on- or off-pump56,57 and is likely to be sensitive to the loading dose administered.58 A systematic review of post hoc analyses from 3 prospective randomized studies and 17 observational studies yielded mixed results.59 In fact, contrary to the findings from the meta-analysis of randomized trials, the combination of observational studies showed that recent exposure to clopidogrel before CABG is associated with increased risk of postoperative death, reoperations for bleeding, blood loss, and need of blood transfusions. Another meta-analysis of 34 studies (29 observational) questioned that, although mortality is increased in clopidogrel-treated versus non–clopidogrel-treated patients at the time of CABG (odds ratio, 1.6; 95% CI, 1.30–1.96; P<0.00001), this is mainly influenced by the ACS status and case urgency, implying that ACS patients requiring urgent CABG should proceed with surgery without delay for a clopidogrel-free period,60,61 as also noted elsewhere.62Prasugrel is a third-generation thienopyridine with more potent antiplatelet effects than clopidogrel, which was extensively evaluated in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis In Myocardial Infarction 38 (TRITON–TIMI 38) trial in the setting of ACS patients undergoing PCI.63 Because this was a trial intended for PCI, there were only 368 patients (2.7%) who underwent CABG during the study period, which however provided very informative results. Among patients undergoing CABG, the rate of TIMI major bleeding was greater with prasugrel than with clopidogrel (13.4% versus 3.2%, P<0.001).63 The difference in CABG-related TIMI major or minor bleeding between prasugrel and clopidogrel was remarkable when the time from the last dose of the study drug was ≤3 days pre-CABG (26.7% versus 5.0%, P<0.001), but also when the drug was discontinued within 4 to 7 days (11.3% versus 3.4%, P<0.001). Consistently, a significantly higher mean 12-hour chest tube blood loss was observed with prasugrel in comparison with clopidogrel, without significant differences in red blood cell transfusion.11 These findings led to the package insert recommendation that, when possible, prasugrel should be discontinued at least 7 days before any surgery, including CABG.64,65 The pharmacodynamic basis for this recommendation has been recently reinforced by 2 pharmacodynamic studies.66,67Antiplatelet agents that reversibly inhibit platelet function are dipyridamole, cilostazol, nonsteroidal anti-inflammatory drugs and ticagrelor. These agents have self-limiting effects depending on their half-lives (ie, ≈10 hours for dipyridamole and cilostazol, 2–20 hours for different nonsteroidal anti-inflammatory drugs, and 8–12 hours for ticagrelor and its metabolites). Ticagrelor is a novel generation P2Y12 receptor inhibitor, a first in class cyclopentyltriazolopyrimidine, with more potent antiplatelet effects than clopidogrel, but faster speed of offset, comparable residual platelet inhibition at 24 hours and 3 days after the last dose, and return to baseline platelet reactivity at day 5 similar to clopidogrel on day 7.68 In the Platelet Inhibition and Patient Outcomes (PLATO) trial, comparing ticagrelor versus clopidogrel in ACS patients treated with an invasive or noninvasive strategy, 1899 (10.2% of study population) patients underwent CABG at any time after randomization, and 6.8% had CABG within 7 days after discontinuation of study treatment.69 TIMI major bleeding occurred in 59.3% versus 57.6% (hazard ratio, 1.03; 95% CI, 0.89–1.19; P=0.68) and TIMI minor bleeding in 21.1% versus 21.6% (hazard ratio, 0.97; 95% CI, 0.77–1.24; P=0.82) in the ticagrelor and clopidogrel groups, respectively. None of the various bleeding definition rates, including fatal CABG-related bleeding, differed between the ticagrelor group and the clopidogrel group. Importantly, there was no difference in major/fatal/life-threatening CABG-related bleeding and blood loss between ticagrelor and clopidogrel, with respect to time from last intake of study drug before CABG, including when the drug was stopped 1 day before surgery. A further analysis investigating differences in specific causes of post-CABG deaths in the PLATO trial showed that the mortality reduction with ticagrelor versus clopidogrel was associated with fewer deaths from cardiovascular, bleeding, and infection complications.70 The Food and Drug Administration–approved package insert of ticagrelor recommends to discontinue ticagrelor at least 5 days before any surgery, including CABG, while the European Medicines Agency package insert recommends discontinuation for at least 7 days.71,72Although current guidelines recommend delaying elective CABG for ≥5 days after the last dose of clopidogrel and ticagrelor and 7 days after the last dose of prasugrel, if possible,73 concerns exist because this delay comes at the expense of increased risk of ischemic events while awaiting surgery.74,75 Indeed, an increase in residual antiplatelet effect was shown to be associated with a significant reduction of mortality in patients treated with prasugrel (adjusted odds ratio, 0.26; 95% CI, 0.08–0.85; P=0.025) and ticagrelor (hazard ratio, 0.49; 95% CI, 0.32–0.77; P<0.01) in comparison with clopidogrel in subanalyses of the TRITON TIMI 38 and PLATO trials.11,69,70 The survival benefit with these drugs was noted primarily in the first 30 days, suggesting that surgery-related perioperative outcomes are decreased by residual and continued antiplatelet therapy. Adding to similar findings described with clopidogrel and abciximab in patients undergoing CABG,76,77 these analyses coming from more contemporary trials investigating potent antiplatelet agents corroborate the understanding that platelet P2Y12 inhibition does ultimately have a benefit in patients who undergo CABG, including less mortality, although at the price of an increase in bleeding and transfusion.Practical Recommendations and Future DirectionsAvoiding Unnecessary Revascularization or Stent PlacementUnrestricted use of noninvasive stress testing and coronary angiography may be a driver of unnecessary prophylactic revascularizations in patients with CAD referred to noncardiac surgery. Based on guidelines, noninvasive stress testing should be restricted to patients with ≥3 clinical risk factors (including history of ischemic heart disease, history of compensated or previous heart failure, history of cerebrovascular disease, diabetes mellitus, and renal insufficiency) and poor functional capacity who require vascular surgery.28 These patients may also benefit from β-blocker and statin use in the perioperative period.28Adding to the overemphasis on preoperative diagnostic assessment in patients with risk factors for CAD, the actual need for effective prophylactic coronary revascularization in patients with established stable CAD undergoing surgery is also debatable. In the Coronary Artery Revascularization Prophylaxis (CARP) trial, 510 patients with stable CAD at increased risk for perioperative cardiac complications were randomly assigned to undergo either revascularization (percutaneous or surgical) or no revascularization, before elective major vascular surgery.78 Preoperative coronary revascularization was not found to decrease the incidence of postoperative myocardial infarction (8.4% versus 8.4%, P=0.99) or long-term mortality (22% versus 23%, P=0.92) in comparison with no revascularization. Consistently, in a subsequent small randomized study targeting patients undergoing vascular surgery with extensive CAD assessed by dobutamine echocardiography or stress nuclear imaging, revascularization did not improve the composite of all-cause death or myocardial infarction at 30 days in comparison with no revascularization (43% versus 33%, P=0.30).79 In addition, no benefit of revascularization was observed at 1 year (49% versus 44%, P=0.48).The results of these 2 studies therefore suggest that, at least in patients with stable CAD, the adoption of a systematic prophylactic coronary revascularization strategy is not indicated. However, this statement may not be applicable to patients with ACS or those with severe ischemia on noninvasive testing at a blood pressure and heart rate that could be overcome in the perioperative period. Although there are no adequate clinical trials on which to base firm recommendations, American College of Cardiology/American Heart Association guidelines suggest that, in patients with active cardiac conditions such as acute (≤7 days) or recent (>7 days but ≤1 month) myocardial infarction with evidence of important ischemic risk by clinical symptoms or noninvasive study, it is reasonable to wait 4 to 6 weeks before performing elective surgery.28 If PCI is necessary, a careful balance between the urgency of noncardiac surgery and the risk of bleeding need to be considered.28 After an ACS, a strategy of plain old balloon angioplasty only without stent implantation may be safer than stent placement if a good angiography result is achieved.80–82 However, in patients revascularized by balloon angioplasty, surgery should not be postponed beyond 6 to 8 weeks to prevent restenosis. On the other side, delaying surgery for at least a week after balloon angioplasty allows for healing of the vessel injury and decreases the risk of acute or subacute closure.In both stable and ACS patients, current American College of Cardiology/American Heart Association guidelines underline that, in case of low risk of bleeding or if the noncardiac surgery can be postponed 12 months or more, PCI with DES and prolonged DAPT may be considered.28 If the noncardiac surgery cannot be postponed and is likely to be performed within 1 to 12 months, then placement of a BMS and 4 to 6 weeks of DAPT is considered appropriate. However, at least in the stable CAD setting, these recommendations do not take into account emerging data that suggest a lower risk of late stent thrombosis with second-generation DES, with no need for prolonged DAPT.Optimal Duration of DAPT and Stent SelectionAlthough practice guidelines advocate for prolonged use of DAPT after DES implantation and thus ideally postponing noncardiac surgery for 12 months, the optimal duration of DAPT remains unknown. This in turn is the basis for the conundrums surrounding optimal timing of surgery. Although an overview on the impact of DAPT duration goes beyond the scope of this article, observational studies have thus far yielded conflicting findings; some studies have suggested that shorter durations of treatment after DES implant (eg, 6 months) may be adequate for the prevention of thrombotic recurrences, whereas others have suggested that this should be even more prolonged (>12 months).30,83–88 However, in randomized clinical trials there appears to be some evidence of a more favorable risk-benefit ratio linked to shorter duration, likely attributed to the increased bleeding risk that occurs with longer duration of DAPT.89–94 Several trials will further address this topic (Figure 1). The ongoing Dual Anti Platelet Study (DAPT, NCT00977938) is randomly assigning >20 000 patients treated with BMS or DES free from events at 12 months to placebo versus additional 18 months of thienopirydine (clopidogrel or prasugrel) treatment. The Safety and efficacy of Six-month dual antiplatelet therapy after drug-eluting stenting (ISAR-SAFE, NCT00661206) will compare the efficacy of the 6- and 12-month DAPT strategies in reducing the rate of death, myocardial infarction, stroke, and major bleeding at 15 months in 6000 6-month event-free patients. These trials, in particular, will shed more light on the benefit of prolonging DAPT beyond 6 or 12 months, in addition to the evolving data on the bleeding risk with long-term P2Y12-inhibiting therapy. Indeed, these studies will provide insights on patients who may require surgery during participation in the trial, and how outcomes may be affected by stent type, as well.Download figureDownload PowerPointFigure 1. Randomized clinical trials on the duration of dual-antiplatelet therapy after stent implantation. Solid lines identify available or ongoing comparisons between different regimes of dual-antiplatelet therapy duration. Dotted lines identify theoretical comparisons that have not yet been the object of specific investigation. Studies whose results are available at the date of publication of this article89–94 are shown in black. Ongoing studies or studies whose results are not available are shown in gray. ARCTIC indicates Double Randomization of a Monitoring Adjusted Antiplatelet Treatment Versus a Common Antiplatelet Treatment for DES Implantation, and a Interruption Versus Continuation of Double Antiplatelet Therapy, One Year After Stenting94; DAPT, The Dual Antiplatelet Therapy Study; DES-LATE, Duration of Dual Antiplatelet Therapy After Implantation of Drug-Eluting Stents; EXCELLENT, Efficacy of Xience/Promus Versus Cypher in Reducing Late Loss After stenting; ISAR-SAFE, Safety and Efficacy of Six Months Dual Antiplatelet Therapy After Drug-Eluting Stenting; ITALIC, Is There A LIfe for Drug-eluting Stents After Discontinuation of Clopidogrel; OPTIDUAL, Optimal Duration" @default.
W2116794265 created "2016-06-24" @default.
W2116794265 creator A5040418600 @default.
W2116794265 creator A5087550320 @default.
W2116794265 date "2013-12-01" @default.
W2116794265 modified "2023-10-07" @default.
W2116794265 title "Management of Antiplatelet Therapy in Patients With Coronary Artery Disease Requiring Cardiac and Noncardiac Surgery" @default.
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