Primary Percutaneous Coronary Intervention and Risk of Stent Thrombosis
2011; Lippincott Williams & Wilkins; Volume: 123; Issue: 16 Linguagem: Inglês
10.1161/circulationaha.111.023366
ISSN1524-4539
AutoresLorenz Räber, Stephan Windecker,
Tópico(s)Acute Myocardial Infarction Research
ResumoHomeCirculationVol. 123, No. 16Primary Percutaneous Coronary Intervention and Risk of Stent Thrombosis Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBPrimary Percutaneous Coronary Intervention and Risk of Stent ThrombosisA Look Beyond the HORIZON Lorenz Räber, MD and Stephan Windecker, MD Lorenz RäberLorenz Räber From the Department of Cardiology and Clinical Trials Unit, Bern University Hospital, Bern, Switzerland. and Stephan WindeckerStephan Windecker From the Department of Cardiology and Clinical Trials Unit, Bern University Hospital, Bern, Switzerland. Originally published11 Apr 2011https://doi.org/10.1161/CIRCULATIONAHA.111.023366Circulation. 2011;123:1709–1712Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2011: Previous Version 1 Primary percutaneous coronary intervention (PCI) is the preferred treatment for patients with ST-segment elevation myocardial infarction (STEMI) owing to improved vessel patency, decreased infarct size, lower rates of reinfarction, and improved survival compared with pharmacological reperfusion. However, stent thrombosis (ST) remains a major concern among STEMI patients with an excess 3- to 4-fold increased risk compared with PCI in an elective setting. In the present issue of Circulation, the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial investigators provide a detailed report of the incidence, timing, and predictors of ST, specifically addressing the impact of stent type and antithrombotic regimen through 2 years.1 Definite or probable ST was common (4.4%), with little more than half of events falling into the early period ( 1 y, n (%)Definite ST Overall, n (%)Definite or Probable ST, 0 to 1 y, n (%)Definite or Probable ST, >1 y, n (%)Definite or Probable ST Overall, n (%)DEDICATIONNCT00192868313 vs 313 (DES vs BMS)3J Am Coll Cardiol. 2010;56:641–6453 (1.0) vs 7 (2.2)2 (0.6) vs 3 (1.0)5 (1.6) vs 10 (3.2)NANA9 (2.9) vs 10 (3.2)HORIZONNCT004339662238 vs 744* (PES vs BMS)3TCT, Washington DC, September 27, 201058 (2.6) vs 22 (3.0)36 (1.6) vs 6 (0.8)94 (4.2) vs 28 (3.7)70 (3.2) vs 25 (3.4)37 (1.7) vs 7 (0.9)107 (4.8) vs 32 (4.3)MISSIONISRCTN62825862158 vs 152 (SES vs BMS)3Am J Cardiol. 2010;106:4–121 (0.6) vs 1 (0.7)3 (1.9) vs 04 (2.5) vs 1 (0.7)2 (1.3) vs 3 (2.0)3 (1.9) vs 05 (3.2) vs 3 (2.0)PASSIONISRCTN65027270310 vs 309 (PES vs BMS)5JACC Cardiovasc Interv. 2011;4:24–29.3 (1.0) vs 3 (1.0)8 (2.6) vs 2 (0.6)11 (3.5) vs 5 (1.6)4 (1.3) vs 7 (2.3)8 (2.6) vs 3 (1.0)12 (3.9) vs 10 (3.2)SESAMINCT00288210160 vs 160 (SES vs BMS)3J Am Coll Cardiol. 2010;55:810–8142 (1.3) vs 1 (0.6)1 (0.6) vs 1 (0.6)3 (1.9) vs 2 (1.3)NANANAMULTI STRATEGYNCT00229515372 vs 372 (SES vs BMS)3ESC Stockholm, Sweden, August 29, 20109 (2.4) vs 11 (3.0)3 (0.8) vs 2 (0.5)13 (3.5) vs 13 (3.5)10 (2.7) vs 15 (4.0)5 (1.3) vs 2 (0.5)15 (4.0) vs 17 (4.0)TYPHOONNCT00232830355 vs 357 (SES vs BMS)4JACC Cardiovasc Interv. 2011;4:14–234 (1.6) vs 8 (3.2)5 (2.0) vs 2 (0.8)9 (3.6) vs 10 (4.0)6 (2.4) vs 9 (3.6)5 (2.0) vs 3 (1.2)11 (4.4) vs 12 (4.8)PASEONCT0075985090 vs 90 vs 90 (SES vs PES vs BMS)4Am Heart J. 2009;158:43–501 (1.1) vs 1 (1.1) vs 1 (1.1)0 vs 0 vs 01 (1.1) vs 1 (1.1) vs 1 (1.1)2 (2.2) vs 2 (2.2) vs 2 (2.2)1 (1.1) vs 2 (2.2) vs 4 (4.4)3 (3.3) vs 4 (4.4) vs 6 (6.7)STRATEGYNCT0022951588 vs 88 (SES vs BMS)5J Am Coll Cardiol. 2010;55:810–8140 vs 2 (2.2)0 vs 02 (2.2) vs 2 (2.2)1 (1.1) vs 4 (4.5)0 vs 01 (1.1) vs 4 (4.5)Not all publications reported both absolute event rates and percentages. In case only absolute event rates were available, we divided the absolute event No. by the No. of patients at risk at the time of inclusion. In case only percentages were available, we derived the absolute event numbers of events by multiplying the percentage with the No. of patients at risk at baseline.*In HORIZON, patient No. at risk for ST at baseline is different compared to the patient No. at risk for the primary outcome.ST indicates stent thrombosis; DEDICATION, Drug Elution and Distal Protection in Acute Myocardial Infarction; DES, drug-eluting stent; BMS, bare metal stent; NA, not applicable; HORIZONS, Harmonizing.Outcomes With Revascularization and Stents in Acute Myocardial Infarction; PES, paclitaxel-eluting stent; TCT, Trancatheter Cardiovascular Therapeutics Congress; MISSION, A Prospective Randomised Controlled Trial to Evaluate the Efficacy of Drug-Eluting Stents versus Bare-Metal Stents for the Treatment of Acute Myocardial Infarction; SES, siroliumus-eluting stent; PASSION, Paclitaxel-Eluting Versus Conventional Stent in Myocardial Infarction With ST-Segment Elevation; SESAMI, Sirolimus-Eluting Stent in Acute Myocardial Infarction; MULTI STRATEGY, Multicenter Evaluation of Single High-Dose Bolus Tirofiban versus Absicximab with Sirolimus-Eluting Stent or Bare-Metal Stent in Acute Myocardial Infarction Study; TYPHOON, Trial to Assess the Use of the CYPHer Sirolimus-Eluting Coronary Stent in Acute Myocardial Infarction Treated With BallOON Angioplasty; PASEO, Paclitaxel- or Sirolimus-Eluting Stent Versus Bare Metal Stent in Primary Angioplasty; and STRATEGY, Tirofiban and Sirolimus-Eluting Stent vs Abciximab and Bare-Metal Stent for Acute Myocardial Infarction.Although all studies among STEMI patients performed to date used early generation DES, newer generation DES with durable and biodegradable polymer-based drug release may provide the basis for improved biocompatibility and vascular healing. Two ongoing trials investigate newer generation DES in the setting of STEMI: Clinical Evaluation of Everolimus Eluting Coronary Stents in the Treatment of Patients With ST-segment Elevation Myocardial Infarction ( EXAMINATION; NCT 00828087) compares everolimus-eluting stents with BMS in 1504 STEMI patients, whereas Comparison of Biolimus Eluted From an Erodable Stent Coating With Bare-Metal Stents in Acute ST-Elevation Myocardial Infarction ( COMFORTABLE AMI; NCT 00962416) compares a stent releasing biolimus A9 from a biodegradable polymer with BMS in 1,159 STEMI patients. If newer generation DES maintain the early benefit compared with BMS while simultaneously eliminating the late adverse event profile, an important progress in the treatment of STEMI patients could appear on the HORIZON.Primary Percutaneous Coronary Intervention and Antithrombotic RegimenST-segment elevation myocardial infarction is mostly caused by rupture of inflamed plaques with exposure of the thrombogenic lipid-rich core, resulting in platelet aggregation and tissue factor-mediated activation of the coagulation cascade with thrombin generation. Unlike unfractionated (UFH) and low–molecular-weight heparin, direct thrombin inhibitors block not only soluble, but also clot-bound, thrombin, which is the theoretical underpinning of the more specific, and potentially more effective, profile of these agents. In this context, HORIZONS-AMI compared an antithrombotic strategy of bivalirudin monotherapy with the combined use of UFH plus a glycoprotein IIb/IIIa antagonist among STEMI patients. Although the 2-year cumulative incidence of ST was similar for both antithrombotic regimens, acute ST was more common among patients treated with bivalirudin, and bivalirudin use emerged as a strong independent predictor of acute ST. A few limitations are notable, including the open-label design, the administration of UFH before randomization in > two thirds of patients, and the variable clopidogrel loading dose. Moreover, it is arguable whether late and very late ST are in any way related to the periprocedural antithrombotic regimen. Of note, the 1.1% incremental risk of acute ST with bivalirudin monotherapy must be weighed against its benefits and overall clinical outcome. Thus, bivalirudin monotherapy compared with UFH plus glycoprotein IIb/IIIa antagonists was associated with a significant decrease in major bleeding and, more importantly, a significantly lower mortality at 30 days and 1 year, presumably because of fewer deaths from bleeding causes, rendering the excess mortality in acute ST inconsequential.Two observations emerge from the present study, which may provide guidance in the search for the most effective periprocedural antithrombotic regimen. First, prerandomization use of UFH was a strong predictor of freedom from acute ST, and lowered its risk by 73%. This finding may point to the importance of more potent and prolonged thrombin inhibition. Because of its short half-life, the antithrombotic effects of bivalirudin are quickly reversible, but may uncover residual thrombin activity, which may play a role in the genesis of recurrent ischemic events. The prolonged administration (median 7 days) of low–molecular-weight heparin was more effective than a short duration of UFH (median 2 days) in the prevention of death and MI among STEMI patients included in the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment—Thrombolysis in Myocardial Infarction 25 (ExTRACT-TIMI 25) trial.9 The difference only emerged at the time of discontinuation of UFH, suggesting that a prolonged antithrombin regimen is beneficial. One therapeutic option to mitigate the increased risk of acute ST could therefore be a prolonged infusion of bivalirudin after PCI in STEMI patients, even though this strategy may abrogate the advantage of a lower bleeding risk.Second, use of high-dose (600 mg) clopidogrel loading was a strong predictor of freedom from subacute ST. The higher loading dose affords more rapid and greater inhibition of platelet aggregation than the standard (300 mg) regimen, and reduced the risk of subacute ST by 48% in the present study. Similar findings have been observed in the Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent EveNTs/Optimal Antiplatelet Strategy for Interventions (CURRENT OASIS 7) trial,10 with a 46% lower risk of definite ST after a high- rather than a standard-dose clopidogrel regimen among patients with acute coronary syndromes undergoing PCI. Of note, the protective effect of high-dose clopidogrel to prevent ST in the present study was restricted to the subacute phase and not apparent during the acute phase, highlighting the delayed onset of action of this type of oral P2Y12 inhibitor. This shortcoming may be overcome by newer antiplatelet agents with more rapid, intense, and consistent inhibition of platelet aggregation. Compared with high loading dose clopidogrel, prasugrel as well as ticagrelor achieve a greater degree of platelet inhibition as soon as 30 minutes, which is maintained throughout 24 hours. Moreover, prasugrel and ticagrelor lowered the risk of definite ST compared with clopidogrel by 58% and 33%, respectively, in large-scale clinical trials of acute coronary syndrome patients.11,12 Accordingly, the combination of prasugrel or ticagrelor with bivalirudin may become an attractive therapeutic option, particularly among STEMI patients, as none of the antiplatelet drugs were associated with an increased risk of bleeding in this patient population.As is true of any great study, the results of HORIZONS-AMI not only contribute to the current standard of care, but also stimulate numerous important questions and hypotheses. Our blurred look of what appears on the HORIZON will be sharpened by future investigations addressing some of the hypotheses outlined above.DisclosuresDr Windecker has received consulting and lecture fees from Abbott, Boston Scientific, Biosensors, Cordis, and Medtronic. Dr Räber reports no conflicts.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Correspondence to Stephan Windecker, MD, Professor and Chief of Cardiology, Department of Cardiology, Bern University Hospital, 3010 Bern, Switzerland. E-mail stephan.[email protected]chReferences1. Dangas GD, Caixeta A, Mehran R, Parise H, Lansky AJ, Cristea E, Brodie BR, Witzenbichler B, Guagliumi G, Peruga JZ, Dudek D, Möeckel M, Stone GW. Frequency and predictors of stent thrombosis after percutaneous coronary intervention in acute myocardial infarction. Circulation. 2011; 123:1745–1756. LinkGoogle Scholar2. Brar SS, Leon MB, Stone GW, Mehran R, Moses JW, Brar SK, Dangas G. Use of drug-eluting stents in acute myocardial infarction: a systematic review and meta-analysis. J Am Coll Cardiol. 2009; 53:1677–1689. CrossrefMedlineGoogle Scholar3. Brodie B, Pokharel Y, Fleishman N, Bensimhon A, Kissling G, Hansen C, Milks S, Cooper M, McAlhany C, Stuckey T. Very late stent thrombosis after primary percutaneous coronary intervention with bare-metal and drug-eluting stents for ST-segment elevation myocardial infarction. J Am Coll Cardiol Cardiovasc Interv. 2011; 4:30–38. CrossrefGoogle Scholar4. Kukreja N, Onuma Y, Garcia-Garcia H, Daemen J, van Domburg R, Serruys PW. Primary percutaneous coronary intervention for acute myocardial infarction: long-term outcome after bare metal and drug-eluting stent implantation. Circ Cardiovasc Interv. 2008; 1:103–110. LinkGoogle Scholar5. Nakazawa G, Finn AV, Joner M, Ladich E, Kutys R, Mont EK, Gold HK, Burke AP, Kolodgie FD, Virmani R. Delayed arterial healing and increased late stent thrombosis at culprit sites after drug-eluting stent placement for acute myocardial infarction patients: an autopsy study. Circulation. 2008; 118:1138–1145. LinkGoogle Scholar6. Guo N, Maehara A, Mintz GS, He Y, Xu K, Wu X, Lansky AJ, Witzenbichler B, Guagliumi G, Brodie B, Kellett MA, Dressler O, Parise H, Mehran R, Stone GW. Incidence, mechanisms, predictors, and clinical impact of acute and late stent malapposition after primary intervention in patients with acute myocardial infarction: an intravascular ultrasound substudy of the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial. Circulation. 2010; 122:1077–1084. LinkGoogle Scholar7. Cook S, Ladich E, Nakazawa G, Eshtehardi P, Neidhart M, Vogel R, Togni M, Wenaweser P, Billinger M, Seiler C, Gay S, Meier B, Pichler WJ, Juni P, Virmani R, Windecker S. Correlation of intravascular ultrasound findings with histopathological analysis of thrombus aspirates in patients with very late drug-eluting stent thrombosis. Circulation. 2009; 120:391–399. LinkGoogle Scholar8. Guagliumi G, Costa MA, Sirbu V, Musumeci G, Bezerra HG, Suzuki N, Matiashvili A, Lortkipanidze N, Mihalcsik L, Trivisonno A, Valsecchi O, Mintz GS, Dressler O, Parise H, Maehara A, Cristea E, Lansky AJ, Mehran R, Stone GW. Strut coverage and late malapposition with paclitaxel-eluting stents compared with bare metal stents in acute myocardial infarction: optical coherence tomography substudy of the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial. Circulation. 2011; 123:274–281. LinkGoogle Scholar9. Antman EM, Morrow DA, McCabe CH, Murphy SA, Ruda M, Sadowski Z, Budaj A, Lopez-Sendon JL, Guneri S, Jiang F, White HD, Fox KA, Braunwald E. Enoxaparin versus unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction. N Engl J Med. 2006; 354:1477–1488. CrossrefMedlineGoogle Scholar10. Mehta SR, Tanguay JF, Eikelboom JW, Jolly SS, Joyner CD, Granger CB, Faxon DP, Rupprecht HJ, Budaj A, Avezum A, Widimsky P, Steg PG, Bassand JP, Montalescot G, Macaya C, Di Pasquale G, Niemela K, Ajani AE, White HD, Chrolavicius S, Gao P, Fox KA, Yusuf S. Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7). Lancet. 2010; 376:1233–1243. CrossrefMedlineGoogle Scholar11. Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann FJ, Ardissino D, De Servi S, Murphy SA, Riesmeyer J, Weerakkody G, Gibson CM, Antman EM. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007; 357:2001–2015. CrossrefMedlineGoogle Scholar12. Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA. Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes. N Engl J Med. 2009; 61:1045–1057. CrossrefGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Hu S, Wang H, Zhu J, Li M, Li H, Gao D and Zhang H (2018) Effect of intra-coronary administration of tirofiban through aspiration catheter on patients over 60 years with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention, Medicine, 10.1097/MD.0000000000010850, 97:21, (e10850), Online publication date: 1-May-2018. Xia T, Guan W, Fu J, Zou X, Han Y, Chen C, Zhou L, Zeng C and Wang W (2016) Tirofiban induces vasorelaxation of the coronary artery via an endothelium-dependent NO-cGMP signaling by activating the PI3K/Akt/eNOS pathway, Biochemical and Biophysical Research Communications, 10.1016/j.bbrc.2016.03.110, 474:3, (599-605), Online publication date: 1-Jun-2016. Medagama A, Bandara R, De Silva C and Galgomuwa M (2015) Management of acute coronary syndromes in a developing country; time for a paradigm shift? an observational study, BMC Cardiovascular Disorders, 10.1186/s12872-015-0125-y, 15:1, Online publication date: 1-Dec-2015. Alkhushail A, Kohli S, Mitchel A, Smith R and Ilsely C (2015) Prognosis of primary percutaneous coronary intervention in elderly patients with ST-elevation myocardial infarction, Journal of the Saudi Heart Association, 10.1016/j.jsha.2014.12.002, 27:2, (85-90), Online publication date: 1-Apr-2015. Backer O, Ratcovich H, Biasco L, Pedersen F, Helqvist S, Saunamaki K, Tilsted H, Clemmensen P, Olivecrona G, Kelbaek H, Jørgensen E, Engstrøm T and Holmvang L (2017) Prehospital administration of P2Y12 inhibitors and early coronary reperfusion in primary PCI: an observational comparative study, Thrombosis and Haemostasis, 10.1160/TH15-01-0026, 114:09, (623-631), . ZHANG Q, QIU J, KIRTANE A, ZHU T, ZHANG R, YANG Z, HU J, DING F, DU R and SHEN W (2014) Comparison of Biodegradable Polymer Versus Durable Polymer Sirolimus-Eluting Stenting in Patients with Acute ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: Results of the RESOLVE Study, Journal of Interventional Cardiology, 10.1111/joic.12102, 27:2, (131-141), Online publication date: 1-Apr-2014. Mrdovic I, Savic L, Lasica R, Krljanac G, Asanin M, Brdar N, Djuricic N, Marinkovic J and Perunicic J (2013) Efficacy and safety of tirofiban-supported primary percutaneous coronary intervention in patients pretreated with 600 mg clopidogrel: results of propensity analysis using the Clinical Center of Serbia STEMI Register, European Heart Journal: Acute Cardiovascular Care, 10.1177/2048872613514013, 3:1, (56-66), Online publication date: 1-Mar-2014. Mrdovic I, Savic L, Lasica R, Krljanac G, Asanin M, Brdar N, Djuricic N, Cvetinovic N, Marinkovic J and Perunicic J (2012) Usefulness of the RISK-PCI score to predict stent thrombosis in patients treated with primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: a substudy of the RISK-PCI trial, Heart and Vessels, 10.1007/s00380-012-0276-z, 28:4, (424-433), Online publication date: 1-Jul-2013. Madan V, Coppola J and Sedlis S (2013) Avoiding stent thrombosis: advances in technique, antiplatelet pharmacotherapy and stent design, Interventional Cardiology, 10.2217/ica.13.10, 5:2, (179-201), Online publication date: 1-Apr-2013. Abdel-Wahab M and Richardt G (2011) Safety of bivalirudin in patients with coronary artery disease, Expert Opinion on Drug Safety, 10.1517/14740338.2012.628312, 11:1, (141-150), Online publication date: 1-Jan-2012. de la Torre Hernández J and Windecker S (2012) Trombosis muy tardía con nuevos stents farmacoactivos: ¿ha dejado de ser un asunto relevante?, Revista Española de Cardiología, 10.1016/j.recesp.2012.01.017, 65:7, (595-598), Online publication date: 1-Jul-2012. Hofma S, Brouwer J, Velders M, van't Hof A, Smits P, Queré M, de Vries C and van Boven A (2012) Second-Generation Everolimus-Eluting Stents Versus First-Generation Sirolimus-Eluting Stents in Acute Myocardial Infarction, Journal of the American College of Cardiology, 10.1016/j.jacc.2012.01.073, 60:5, (381-387), Online publication date: 1-Jul-2012. de la Torre Hernández J and Windecker S (2012) Very Late Stent Thrombosis With Newer Drug-Eluting Stents: No Longer an Issue?, Revista Española de Cardiología (English Edition), 10.1016/j.rec.2012.01.019, 65:7, (595-598), Online publication date: 1-Jul-2012. April 26, 2011Vol 123, Issue 16 Advertisement Article InformationMetrics © 2011 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.111.023366PMID: 21482962 Originally publishedApril 11, 2011 Keywordsstentsmyocardial infarctionEditorialsthrombosisrevascularizationPDF download Advertisement SubjectsMyocardial InfarctionStent
Referência(s)