Revisão Acesso aberto Revisado por pares

Extended Duration of Dual‐Antiplatelet Therapy After Percutaneous Coronary Intervention: How Long Is Too Long?

2019; Wiley; Volume: 8; Issue: 20 Linguagem: Inglês

10.1161/jaha.119.012639

ISSN

2047-9980

Autores

Charles E. Howard, Vijay Nambi, Hani Jneid, Umair Khalid,

Tópico(s)

Acute Myocardial Infarction Research

Resumo

HomeJournal of the American Heart AssociationVol. 8, No. 20Extended Duration of Dual‐Antiplatelet Therapy After Percutaneous Coronary Intervention: How Long Is Too Long? Open AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citations ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toOpen AccessResearch ArticlePDF/EPUBExtended Duration of Dual‐Antiplatelet Therapy After Percutaneous Coronary Intervention: How Long Is Too Long? Charles E. Howard, MD, Vijay Nambi, MD, PhD, Hani Jneid, and MD, and Umair KhalidMD Charles E. HowardCharles E. Howard *Correspondence to: Charles E. Howard, MD, 7200 Cambridge St, A10.184, BCM903, Houston, TX 77030. E‐mail: E-mail Address: [email protected] Section of Cardiology, , Department of Medicine, , Baylor College of Medicine, , Houston, , TX , Vijay NambiVijay Nambi Section of Cardiology, , Medical Care Line, , Michael E. DeBakey VA Medical Center, , Houston, , TX Section of Cardiology, , Department of Medicine, , Baylor College of Medicine, , Houston, , TX , Hani JneidHani Jneid Section of Cardiology, , Medical Care Line, , Michael E. DeBakey VA Medical Center, , Houston, , TX Section of Cardiology, , Department of Medicine, , Baylor College of Medicine, , Houston, , TX , and Umair KhalidUmair Khalid Section of Cardiology, , Medical Care Line, , Michael E. DeBakey VA Medical Center, , Houston, , TX Section of Cardiology, , Department of Medicine, , Baylor College of Medicine, , Houston, , TX Originally published2 Oct 2019https://doi.org/10.1161/JAHA.119.012639Journal of the American Heart Association. 2019;8:e012639The most recent American College of Cardiology/American Heart Association guidelines on duration of dual‐antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug‐eluting stents (DESs) give a class I recommendation to continue DAPT for at least 12 months after an acute coronary syndrome (ACS) and at least 6 months after revascularization in the setting of stable ischemic heart disease.1 These guidelines also give a class IIb recommendation for continuation of DAPT beyond 6 and 12 months in patients with stable ischemic heart disease and ACS, respectively, if these patients have tolerated DAPT without a bleeding event and are at low risk for bleeding in the future.1 However, they do not provide any guidance with respect to how long DAPT should be continued and leave it to the clinician to discuss the risks versus benefits with the patient and individualize antiplatelet therapy. Therefore, in clinical practice, we often see patients on DAPT several years after a PCI as they are instructed by their providers to never discontinue them. In fact, given how much the importance of taking DAPT in the early period after PCI is emphasized, patients at times are uncomfortable stopping the second antiplatelet agent at any time. The lack of a clear recommendation is not surprising, despite multiple recent randomized controlled trials2, 3, 4, 5 evaluating differing durations of extended DAPT given several evolving factors and the overall risk/benefits of DAPT.Guidelines commenting on DAPT duration have largely included trials using clopidogrel and early‐generation stents. The advent of more potent P2Y12 inhibitors, such as prasugrel and ticagrelor, has reduced major adverse cardiovascular events, but at the cost of increased bleeding.6, 7 On the other hand, the newer‐generation DESs, with their thinner stent struts, a more biocompatible polymer, and favorable drug‐eluting characteristics, have considerably decreased the risk of stent thrombosis, particularly late stent thrombosis.8 Although extended DAPT duration has been associated with reduction in recurrent myocardial infarction (MI) and cardiovascular death, there are statistically significant increases in major bleeding events.2, 5 With the increased recognition of bleeding events and advancements in DES technology, it has been hypothesized that shorter durations of DAPT may be more appropriate. The European and American College of Cardiology/American Heart Association guidelines have already reduced the minimum absolutely required duration of DAPT by incorporating short DAPT into their recommendations.1, 9 However, the question about the value of extended DAPT duration in selected patients still remains to be answered.To our knowledge, there are 4 randomized controlled trials that have compared the efficacy and bleeding outcomes of standard 12‐month therapy versus extended‐duration DAPT (>24 months), which are listed below: PEGASUS‐TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54) trial.2DAPT (Dual Antiplatelet Therapy) trial.5DES LATE (Optimal Duration of Clopidogrel Therapy With DES to Reduce Late Coronary Arterial Thrombotic Event) trial.4OPTIDUAL (Optimal Dual Antiplatelet Therapy) trial.3The summary of these trials can be seen in Table 1. Two of these trials, comparing >24 months of DAPT with 12 months of DAPT, showed no difference in their primary efficacy end points of cardiovascular death/MI/stroke and death/MI/stroke/major bleeding (DES‐LATE and OPTIDUAL trials), respectively.3, 4 Unlike the other 3 trials, the OPTIDUAL trial included major bleeding as part of the primary efficacy end points, which could be a reason for no statistical difference.5 The other 2 trials showed an absolute risk reduction in their primary efficacy end points by 1.6% (DAPT trial: death/MI/stroke), 1% (DAPT trial: stent thrombosis), and 1.3% (PEGASUS trial: cardiovascular death/MI/stroke) with prolonged DAPT,2, 5 although this was accompanied by a statistically significant increase in bleeding events (absolute increase in bleeding by 0.9% and 1.54% for DAPT and PEGASUS trials, respectively). However, there was no statistically significant difference in severe GUSTO or fatal bleeding.2, 5Table 1. Randomized Controlled Trials Examining Extended Duration of Dual‐Antiplatelet TherapyTrial and YearDuration Comparison, moNo. of ParticipantsPrimary Efficacy End PointPrimary Efficacy End Point ResultBleeding DefinitionBleeding End Point ResultP2Y12 InhibitorStent TypePatients With ACS, %DAPT 2014512 vs 309961Composite of death, MI, and strokeStent thrombosis.Decrease with extended DAPT for both the composite end point (4.3% vs 5.9%) and stent thrombosis (0.4% vs 1.4%)GUSTO severe or moderate bleedingaStatistically significant increase in extended DAPT (2.5% vs 1.6%), driven by moderate GUSTO bleedingClopidogrel (65%) or prasugrel (35%)Sirolimus or paclitaxel in ≈40%, zotarolimus or everolimus in ≈60%≈40DES‐LATE 2014412 vs 365045Composite of cardiovascular death, MI, and strokeNo differenceTIMI majorbNo statistical difference but trend toward increase in extended DAPTClopidogrelSirolimus or paclitaxel in ≈65%, zotarolimus or everolimus in ≈30%≈60PEGASUS 2015212 vs 3321 162Composite of cardiovascular death, MI, and strokeDecreased with extended DAPT (7.85% vs 9.04%), primarily driven by MI and stroke.TIMI majorbStatistically significant increase in extended DAPT (2.6% vs 1.1%)TicagrelorNo stenting in 20%, BMS in 41%, DES in 39%100% with ACS 1–3 y priorOPTIDUAL 2015312 vs 331385Composite of death, MI, stroke, and major bleedingNo differenceInternational Society on Thrombosis and HemostasiscNo differenceClopidogrelSirolimus or paclitaxel in ≈35%, zotarolimus or everolimus in ≈60%≈35ACS indicates acute coronary syndrome; BMS, bare metal stent; DAPT, Dual Antiplatelet Therapy; DES, drug‐eluting stent; DES‐LATE, Optimal Duration of Clopidogrel Therapy With DES to Reduce Late Coronary Arterial Thrombotic Event; MI, myocardial infarction; OPTIDUAL, Optimal Dual Antiplatelet Therapy; PEGASUS, Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin; TIMI, Thrombolysis in Myocardial Infarction.aGUSTO (Global Utilization of Streptokinase and Tpa for Occluded Arteries) severe indicates intracerebral hemorrhage or bleed, resulting in substantial hemodynamic compromise requiring treatment. GUSTO moderate indicates requiring blood transfusion but not resulting in hemodynamic compromise.bTIMI major: any intracranial bleeding (excluding microhemorrhages 24 months DAPT compared with standard 12‐month DAPT, whereas the other 2 showed no difference. The 2 studies showing a decrease in the primary end point were both larger trials, and both were driven primarily by a decrease in MI.2, 5 These 2 trials that showed a decrease in the primary efficacy end point also showed an increase in the bleeding risk. Given these differing findings, it is important to highlight some of the key differences between the trials. First, the PEGASUS trial, the largest of the randomized controlled trials, was the only extended DAPT trial to use ticagrelor.2 The 2 smaller trials, DES‐LATE and OPTIDUAL trials, used solely clopidogrel as the P2Y12 inhibitor, whereas the DAPT trial used either clopidogrel or prasugrel.3, 4, 5 In patients with ACS, both ticagrelor and prasugrel provide better cardiovascular outcomes compared with clopidogrel6, 7; hence, it is possible that the differing results may be, in part, because of the particular P2Y12 inhibitor used.Certain high‐risk conditions, such as ACS presentation, complex coronary anatomical features, diabetes mellitus, or renal failure, can influence the rate of future events. The PEGASUS trial involved only patients who experienced a prior ACS event 1 to 3 years before enrollment and had an additional high‐risk feature (aged >65 years, diabetes mellitus, a second MI, multivessel disease, or chronic renal dysfunction). This key difference, along with its larger enrollment and power, could potentially explain the more significant decrease in primary efficacy end point compared with other trials with patients at a lower risk for ischemic events. Hence, it is not surprising that the event rates in the PEGASUS trial are much higher than those in other 3 trials,2, 3, 4, 5 as seen in Table 1. The other 3 trials3, 4, 5 have a few key similar limitations. Notably, only patients who were adherent to medications and event free in the prior 12 months, without major bleeding or major adverse cardiovascular or cerebrovascular events, were eligible to continue into the extended DAPT arm, a study design that likely selects for those at lower risk for late adverse events and for bleeding. In addition, as detailed in Table 1, these trials included a variable proportion of patients receiving PCI for an ACS event to those receiving PCI without ACS.2, 3, 4, 5Patients receiving first‐generation DESs are at higher risk for in‐stent thrombosis because of delayed endothelialization, incomplete healing, and hypersensitivity.10 Although DAPT reduces this risk, first‐generation DESs had late and very late stent thrombosis, leading to development of improved second‐generation DESs, which have been safer than the first‐generation DESs.11 This is important as ≈65% of stents in the DES‐LATE trial, ≈40% in the DAPT trial, and ≈35% in the OPTIDUAL trial were older‐generation (sirolimus and paclitaxel) stents,3, 4, 5 which may, in part, contribute to some differences in the results of these trials. Of note, in the PEGASUS trial, ≈20% of participants did not receive a stent and still derived significant benefit from extended DAPT.2So, what does the future hold for extended‐duration DAPT? It is likely that adverse thrombotic and cardiac events will continue to decrease with the continuously improving polymer and stent technology, including development of ultrathin struts. Indeed, current trials, such as HOST‐IDEA (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis ‐ Coronary Intervention With Next Generation Drug‐Eluting Stent Platforms and Abbreviated Dual Antiplatelet Therapy Trial) (ClinicalTrials.gov identifier NCT02601157), are recruiting patients to compare 2 ultrathin biodegradable and polymer‐free stents with varying DAPT durations.12 Even in ACS, the pendulum is swinging toward shorter DAPT durations. A recent randomized trial assessing safety of interruption of DAPT before 12 months in patients with ST‐segment–elevation MI treated with DES reported the noninferiority of a shorter 6‐month DAPT regimen compared with the standard treatment.13A meta‐analysis by Udell et al showed that extended DAPT beyond 1 year among stabilized high‐risk patients with previous MI decreased the risk of major adverse cardiovascular events but at the cost of an increased risk of major bleeding.14 Given patients at increased risk of cardiovascular events are often also at higher risk of fatal bleeding events, determining which patients will benefit from extended DAPT can be challenging. Several clinical scores have been devised to aid clinicians in decision making of whether to continue or discontinue DAPT.15, 16 Although not perfect, the DAPT score is a validated risk score designed to identify patients for whom anticipated reduction in ischemia with continued DAPT outweighs the anticipated bleeding risk and vice versa.15 Factors that contribute to a high DAPT score include diabetes mellitus, current cigarette use, prior PCI or prior MI, congestive heart failure or left ventricular ejection fraction <30%, MI at presentation, vein graft PCI, and stent diameter <3 mm; older age contributes to a lower DAPT score. In addition to the DAPT score, procedural complexity, burden of coronary artery disease, and stent type should also be taken into consideration while deciding on the optimal DAPT duration as extended DAPT reduces events progressively in those with greater procedural complexity.17 Likewise, several subgroups from the PEGASUS trial, including those with peripheral arterial disease, diabetes mellitus, and renal dysfunction, had a particularly robust absolute risk reduction in major adverse cardiovascular events with extended DAPT.18, 19, 20Table 2 lists clinical characteristics that may benefit from more extended durations of DAPT.Table 2. Clinical Characteristics Benefiting From Extended‐Duration DAPTClinical Characteristics Benefiting From Extended‐Duration DAPTACS presentation/prior ACS eventPeripheral arterial diseaseDiabetes mellitusRenal dysfunctionCurrent cigarette useLeft ventricular ejection fraction <30%Congestive heart failureIncreased procedure complexityStent diameter <3 mmVein graft PCIHigh CAD burdenOlder‐generation stentsACS indicates acute coronary syndrome; CAD, coronary artery disease; DAPT, dual antiplatelet therapy; PCI, percutaneous coronary intervention.In summary, prolonged DAPT appears more beneficial in patients with ACS treated with ticagrelor or prasugrel, with risk factors for recurrent ischemia at a cost of increased bleeding. However, any clinician will also recognize that not all bleeding or ACS events carry the same risk. Indeed, a clinician‐patient shared decision making seems apt when discussing the optimal duration of DAPT. On the other hand, the clinician must also remember that trials evaluating DAPT over 5 years are currently lacking. Therefore, although possibly beneficial, any DAPT beyond this time period has no strong clinical evidence. With the continuous medication and stent advances, the optimal DAPT duration will likely be altered, but until then the current guidelines supporting DAPT duration of 12 months in ACS with further tailoring of therapy based on an individual risk of further ischemic or bleeding events provide an excellent framework to begin. Evolving research will help us further understand the risks and benefits of extended‐duration DAPT, especially with the newer‐generation stents.DisclosuresNone.Footnotes*Correspondence to: Charles E. Howard, MD, 7200 Cambridge St, A10.184, BCM903, Houston, TX 77030. E‐mail: charles.e.[email protected]comThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.This article was handled independently by Saket Girotra, MD, SM, as a guest editor. The editors had no role in the evaluation of the manuscript or in the decision about its acceptance.References1 Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA, Granger CB, Lange RA, Mack MJ, Mauri L, Mehran R. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: an update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease, 2013 ACCF/AHA Guideline for the Management of ST‐Elevation Myocardial Infarction, 2014 AHA/ACC Guideline for the Management of Patients With Non‐ST‐Elevation Acute Coronary Syndromes, and 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery. Circulation. 2016; 134:e123–e155.LinkGoogle Scholar2 Bonaca MP, Bhatt DL, Cohen M, Steg PG, Storey RF, Jensen EC, Magnani G, Bansilal S, Fish MP, Im K, Bengtsson O. Long‐term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015; 372:1791–1800.CrossrefMedlineGoogle Scholar3 Helft G, Steg PG, Le Feuvre C, Georges JL, Carrie D, Dreyfus X, Furber A, Leclercq F, Eltchaninoff H, Falquier JF, Henry P. Stopping or continuing clopidogrel 12 months after drug‐eluting stent placement: the OPTIDUAL randomized trial. Eur Heart J. 2016; 37:365–374.MedlineGoogle Scholar4 Lee CW, Ahn JM, Park DW, Kang SJ, Lee SW, Kim YH, Park SW, Han S, Lee SG, Seong IW, Rha SW. Optimal duration of dual antiplatelet therapy after drug‐eluting stent implantation: a randomized, controlled trial. Circulation. 2014; 129:304–312.LinkGoogle Scholar5 Mauri L, Kereiakes DJ, Yeh RW, Driscoll‐Shempp P, Cutlip DE, Steg PG, Normand SL, Braunwald E, Wiviott SD, Cohen DJ, Holmes DR. Twelve or 30 months of dual antiplatelet therapy after drug‐eluting stents. N Engl J Med. 2014; 371:2155–2166.CrossrefMedlineGoogle Scholar6 Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009; 361:1045–1057.CrossrefMedlineGoogle Scholar7 Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann FJ, Ardissino D, De Servi S, Murphy SA, Riesmeyer J. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007; 357:2001–2015.CrossrefMedlineGoogle Scholar8 Sarno G, Lagerqvist B, Fröbert O, Nilsson J, Olivecrona G, Omerovic E, Saleh N, Venetzanos D, James S. Lower risk of stent thrombosis and restenosis with unrestricted use of "new‐generation" drug‐eluting stents: a report from the nationwide Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Eur Heart J. 2012; 33:606–613.CrossrefMedlineGoogle Scholar9 Valgimigli M, Bueno H, Byrne RA, Collet JP, Costa F, Jeppsson A, Jüni P, Kastrati A, Kolh P, Mauri L, Montalescot G, Neumann FJ, Peticevic M, Roffi M, Steg PG, Windecker S, Zamorano JL. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS [in Polish]. Kardiol Pol. 2017; 75:1217–1299.MedlineGoogle Scholar10 Virmani R, Guagliumi G, Farb A, Musumeci G, Grieco N, Motta T, Mihalcsik L, Tespili M, Valsecchi O, Kolodgie FD. Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus‐eluting stent: should we be cautious?Circulation. 2004; 109:701–705.LinkGoogle Scholar11 Navarese EP, Tandjung K, Claessen B, Andreotti F, Kowalewski M, Kandzari DE, Kereiakes DJ, Waksman R, Mauri L, Meredith IT, Finn AV. Safety and efficacy outcomes of first and second generation durable polymer drug eluting stents and biodegradable polymer biolimus eluting stents in clinical practice: comprehensive network meta‐analysis. BMJ. 2013; 347:f6530.CrossrefMedlineGoogle Scholar12 Kim CH, Han JK, Yang HM, Park KW, Lee HY, Kang HJ, Koo BK, Lee N, Cha TJ, Yang TH, Jeong MH. Study protocol for a randomised controlled trial: harmonising optimal strategy for treatment of coronary artery stenosis—coronary intervention with next‐generation drug‐eluting stent platforms and abbreviated dual antiplatelet therapy (HOST‐IDEA) trial. BMJ Open. 2017; 7:e016617.CrossrefMedlineGoogle Scholar13 Kedhi E, Fabris E, Van Der Ent M, Buszman P, Von Birgelen C, Roolvink V, Zurakowski A, Schotborgh CE, Hoorntje JC, Eek CH, Cook S. Six months versus 12 months dual antiplatelet therapy after drug‐eluting stent implantation in ST‐elevation myocardial infarction (DAPT‐STEMI): randomised, multicentre, non‐inferiority trial. BMJ. 2018; 363:k3793.CrossrefMedlineGoogle Scholar14 Udell JA, Bonaca MP, Collet JP, Lincoff AM, Kereiakes DJ, Costa F, Lee CW, Mauri L, Valgimigli M, Park SJ, Montalescot G. Long‐term dual antiplatelet therapy for secondary prevention of cardiovascular events in the subgroup of patients with previous myocardial infarction: a collaborative meta‐analysis of randomized trials. Eur Heart J. 2015; 37:390–399.MedlineGoogle Scholar15 Yeh RW, Secemsky EA, Kereiakes DJ, Normand SL, Gershlick AH, Cohen DJ, Spertus JA, Steg PG, Cutlip DE, Rinaldi MJ, Camenzind E. Development and validation of a prediction rule for benefit and harm of dual antiplatelet therapy beyond 1 year after percutaneous coronary intervention. JAMA. 2016; 315:1735–1749.CrossrefMedlineGoogle Scholar16 Baber U, Mehran R, Giustino G, Cohen DJ, Henry TD, Sartori S, Ariti C, Litherland C, Dangas G, Gibson CM, Krucoff MW. Coronary thrombosis and major bleeding after PCI with drug‐eluting stents: risk scores from PARIS. J Am Coll Cardiol. 2016; 67:2224–2234.CrossrefMedlineGoogle Scholar17 Giustino G, Chieffo A, Palmerini T, Valgimigli M, Feres F, Abizaid A, Costa RA, Hong MK, Kim BK, Jang Y, Kim HS. Efficacy and safety of dual antiplatelet therapy after complex PCI. J Am Coll Cardiol. 2016; 68:1851–1864.CrossrefMedlineGoogle Scholar18 Bhatt DL, Bonaca MP, Bansilal S, Angiolillo DJ, Cohen M, Storey RF, Im K, Murphy SA, Held P, Braunwald E, Sabatine MS. Reduction in ischemic events with ticagrelor in diabetic patients with prior myocardial infarction in PEGASUS–TIMI 54. J Am Coll Cardiol. 2016; 67:2732–2740.CrossrefMedlineGoogle Scholar19 Bonaca MP, Bhatt DL, Storey RF, Steg PG, Cohen M, Kuder J, Goodrich E, Nicolau JC, Parkhomenko A, López‐Sendón J, Dellborg M. Ticagrelor for prevention of ischemic events after myocardial infarction in patients with peripheral artery disease. J Am Coll Cardiol. 2016; 67:2719–2728.CrossrefMedlineGoogle Scholar20 Magnani G, Storey RF, Steg G, Bhatt DL, Cohen M, Kuder J, Im K, Aylward P, Ardissino D, Isaza D, Parkhomenko A. Efficacy and safety of ticagrelor for long‐term secondary prevention of atherothrombotic events in relation to renal function: insights from the PEGASUS‐TIMI 54 trial. Eur Heart J. 2015; 37:400–408.MedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails October 15, 2019Vol 8, Issue 20Article InformationMetrics Download: 32,898 Copyright © 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley BlackwellThis is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.https://doi.org/10.1161/JAHA.119.012639PMID: 31576769 Originally publishedOctober 2, 2019 Keywordsguidelineacute coronary syndromedrug‐eluting stentdual‐antiplatelet therapyPDF download SubjectsTreatmentMyocardial InfarctionCardiovascular DiseaseSecondary PreventionQuality and Outcomes

Referência(s)