Καπλάνης Ιωάννης Καρδιολόγος Γ.Ν.Α. Η Ελπίς

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1 Καπλάνης Ιωάννης Καρδιολόγος Γ.Ν.Α. Η Ελπίς

2 Early Cutlip DE e al. Circulation 2007; 115:

3 Παρουσίαση περιστατικού Άνδρας, 77 ετών Α.Α.: χρόνια κολπική µαρµαρυγή (υπό sintrom) πρόσθιο STEMI προ 14 µηνών, για το οποίο είχε υποβληθεί σε primary PCI Παρούσα Νόσος: Προκάρδιο άλγος µε αντανάκλαση στη ράχη, όµοιο µε το άλγος του προηγηθέντος εµφράγµατος (ΤΕΠ Περιφερειακού Νοσοκοµείου) ΗΚΓ: ST elevation V2-V4, Avr INR: 3 ΔΙΑΚΟΜΙΔΗ ΓΙΑ PRIMARY PCI Aντικ. Εξέταση: ΑΠ: mmhg, 99bmp S1,S2, άρρυθµος Υγροί στις βάσεις Οµότιµα ψηλαφητές περιφερικές σφύξεις ΑΙΜΟΔΥΝΑΜΙΚΟ ΕΡΓΑΣΤΗΡΙΟ Λόγω του υψηλού αιµορραγικού κινδύνου αποφασίστηκε η διακερκιδική προσπέλαση από την αριστερή κερκιδική αρτηρία (δύο περιφερικοί φλεβοκαθετήρες στο δεξί άνω άκρο) Κλοπιδογρέλη (φόρτιση)

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22 DATA FROM THE LITERATURE:! In the BMS era, ST usually presented acutely or subacutely (<1%)! In randomized trial comparing BSM with DES, rates of early ST under DAPT were similar for both stent types! Registry (8146 patiens who received DES): a persistent excess ST risk of 0.6%/year for DES compared with historical control subjects who received BMS! Meta-analysis of 14 RCTs, 6675 patients randomized to SES or PES vs BMS: 0.5% excess risk of very late ST with DES Stone GW et al N Engl J Med 220 Mauri L et al N Engl J Med 2007 Daemen J et al Lancet 2007 Bavry AA et al Am J Med 2206 o Registry of 6906 patients, BMS vs DES: No difference in clinical outcomes or ST rate over 1year of FOLLOW-UP o Meta-analysis of 8 trials, 4545 patients randomized to SES or PES vs BMS: No difference in rates of ST over 4 years follow-up Mauri L t al N Engl J Med 2007 Williams D et al Circulation 2006

23 " Data regarding risk factors for DES thrombosis are derived from non-randomized registries and randomized clinical trials " Evidence for increased long-term risk for ST with DES is primarily from patient registries and not from RCTs, suggesting that part of the incremental risk is associated with treatment of complex coronary lesions in real-world patients Jaffe and Strauss JACC 2007

24 Response of the vessel to DES " Late hypersensitivity reactions to DES:! IVUS evidence of vessel enlargement with absence of neointimal formation Autopsy evidence of aneurysmal dilation of the stented segments, with severe localized hypersensitivity reaction (predominantly T lymphocytes and eosinophils), 18 months after 2 SES (sirolimus is minimally present in vessel wall after 60 days effect of nonerodable polymer;) (Virmani R et al Circulation 2004) (Τsimikas S JACC 2006)! Delayed healing of vessel wall, fibrin deposition, delayed endothelization (Joner M et al JACC 2006)! 17 cases of hypersensitivity reaction to DES (14 SES, 3 PES) up to 210 days post-implantation (4 autopsy data: intra-stent eosinophilic inflammation, thrombosis, lack of intimal healing) (Nebeker JR et al JACC 2006 RADAR Project) Jaffe and Strauss JACC 2007

25 62% 31% Stent malapposition: the separation of 1stent strut from the intimal surface of the coronary arterial wall (without involvement of side branches) 356 lesions " The presence of plaque/thrombus protrusion within the stent body was a predictor of late-acquired stent malappostion (later thrombus resolution as a pathogenetic mechanism) 16% " Clinical events (cardiovascular death, MI, stent thrombosis) did not occur during 28.6±10.3 months follow-up " 77% new-generation DES 175±60 days after stent implantation Circ Cardiovasc Interv 2014;7:88-96

26 " Growth of neo-intimal atherosclerosis inside a previously implanted coronary stent " Reported in both BMS and DES, BUT at an earlier time-point after DESimplantation " Multifactorial underlying mechanisms! Lack of functional endothelialized luminal surface within stented segment! Infiltration of foamy macrophage clusters within the neointima! Thin-cap fibroatheroma with neointimal rupture and thrombus formation OCT is able to detect neointimal hyperplasia, thin-cap fibroatheroma, plaque rupture and thrombus protruding into lumen Assessment of the pathological basis and mechanisms of VLST and the choice of appropriated management (?) Definite treatment of VLST due to neo-atherosclerosisi is still under debate Mamary AA et al J Saudi Heart Assoc 2014

27 Focal PLT-rich luminal thrombus with uncovered struts, transmural inflammation and extensive malapposition of stent struts with fibrin deposition = hypersensitivity reaction ACS 15 months after LAD PCI: OCT shows evaginations, red thrombus and uncovered stent struts Scand Cardiovasc J 2014

28 ! The largest case-control study of late/very late stent thrombosis (LVLST)! Retrospective study! 21 international sites Aim: to provide clinical, procedural & angiographic correlates of LVLST, as well as to determine the clinical outcomes of these events Sirolimus-eluting stents: 50.2% Paclitaxel-eluting stents: 40.3% Everolimus-eluting stents: 7% Zotarolimus-eluting stents: 1.8% 90% 1 st -generation DES Walksman R et al. JACC 2014

29 35% VLST: >3years post-implantation Occurred as long as 7.3 years (Bern Rotterdam group: 0.6% per year, continued hazard ratio up to 5 years Wenawesser P et al JACC 2008) Clinical presentation: STEMI: 66.7% Non-STEMI: 22% Cardiogenic shock: 4.7% Visual thrombus: 98.8% TIMI Flow 0: 74.6% Off-line QCA: Total occlusion 73% Diffuse thrombosis 14.1% Focal thrombosis 9.2% Stent edge thrombosis 3.2% Stent Malapposition: 5.9% by CAA 4.7% by IVUS (9.9% underwent IVUS) Walksman R et al. JACC 2014

30 30% of patients on DAPT at time of ST % DAPT cessation according to time of ST: " ST(30days- 1year):49.1% " ST >1year: 78.3% Walksman R et al. JACC 2014

31 taking DAPT is not a magic bullet for preventing late ST and other nonantiplatelet-related mechanisms may contribute to the late ST phenomenon. Among these are late restenosis with progression of narrowing of the stent lumen and neoatherosclerosis as a result of local inflammation of the polymer that may result in rupture of a new form of atherosclerotic plaque. The DESERT does not support the idea that a longer duration of DAPT beyond 1 year will further reduce very late ST. Walksman R et al. JACC 2014

32 " NS for primary endpoint (death, MI, stent thrombosis, stroke, urgent revascularization) " NS for secondary endpoint (stent thrombosis, any urgent revascularization) " Safety endpoint: major and minor STEEPLE bleedings Our finding suggests no apparent benefit but instead harm with extension of DAPT beyond 1 year after ste nting with DES when no event has occurred within the first year after stenting. No conclusion can be drawn for high-risk patients who could not be randomised. The consistency between findings from all trials of such interruption suggests the need for a reappraisal of guidelines for DAPT after coronary stenting towards shorter duration of treatment Lancet 2014 Nov 1;384(9954):

33 Lesion characteristics at time of DES implantation & angiographic correlates of LVLST Pre-implantation: " LAD location " SVG lesion " Complex B2/C lesions " Pre-diameter stenosis " Lesion length " Visual thrombus " TIMI flow 0/1 " In-stent restenosis Post-procedure: " Greater residual in-stent diameter stenosis " Longer stented segments " Stent overlap " No of stents per lesion Not independent correlates: o In-stent restenosis o bifurcation Walksman R et al. JACC 2014

34 Clinical correlates " Younger age " Active smoking " Multivessel disease " African-Americans Walksman R et al. JACC 2014

35 LATE/VERY LATE ST TREATMENT AND OUTCOMES " Thrombus aspiration: 47% " Balloon angioplasty: 78.1% " DES implantation: 30.8% " BMS implantation: 20.6% ICU admission: 72.4% Median ICU length of stay: 5 days! In-hospital mortality: 3.7%! Reinfarction (STEMI): 0.8%! CABG: 2.9%! Repeat PCI: 2.2%! Acute renal failure: 4.1%! Stroke (ischemic/hemorrhagic): 0.4%! Recurrent ST within the same hospitalization: 0.6% All-cause out-of-hospital mortality rate at 12 months: 2.87% (lower compared with acute/subacute ST) Overall major adverse cardiac event rate: 16.4% Walksman R et al. JACC 2014

36 the investigators suggest that the lower mortality rate seen in late and VLST compared with historically higher mortality rates in acute and subacute ST is due to a different pathological mechanism for this phenomenon In the case of LVLST or neoatherosclerosis within the stent, the event is not as abrupt as with subacute DES thrombosis, and the patient may experience preconditioning ischemia or collaterals may even develop that mitigate the adverse clinical outcome of the ST event. Walksman R et al. JACC 2014

37 STUDY LIMITATIONS " 90% of patients had 1 st generation DES- different correlates may apply for 2 nd generation DES or biodegradable polymers and scaffolds " The prognostic impact of LVLST may have been underestimated by excluding patients whose initial presentation was SCD Walksman R et al. JACC 2014

38 Lee JM et al Am J Cardiol 2014! The rate of very late definite or probable ST was very low and comparable between the 2 stents ( 0.1%)! In multivariate analysis, chronic renal failure and off-label indication were the strongest predictors of target lesion failure at 3 years! Both stents showed comparable safety and efficacy at 3-year follow-up in this robust realworld registry

39 JACC 2014 n= 2770 patients At 3 year follow-up, the MACE rate did not differ significantly between EES- and SES-treated patients. A significant reduction of overall (0.2% vs 1.4%) and very late definite (0.1% vs 0.8%) stent thrombosis was found in the EES group

40 ! Mortality not influenced by lower ST: may be due to a general lack of statistical power due to an overall low number of definite stent thrombosis! With the promising development of new DESs with biodegradeable polymers, will the incidence of adverse outcomes be reduced even further in the future? Nature Reviews Cardiology 2014

41 656 patients with definite ST (angiographically) " 20% early ST / 21% Late ST / 59% VLST " 76% of VLST >2years Stent thrombosis timing was significantly associated with 30-day mortality risk VLST had significantly lower 30-day mortality (HR 0.38: 95% ci, ) vs early ST Am Heart Journal 2014

42 Δήλι άναξ, πανδερκές έχων φαεσίµβροτον όµµα Ευχαριστώ πολύ για την προσοχή σας!!!

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47 JACC Cardiovasc Interv Jan;7(1): doi: /j.jcin Epub 2013 Oct 16. A next-generation bioresorbable coronary scaffold system: from bench to first clinical evaluation: 6- and 12-month clinical and multimodality imaging results. Verheye S 1, Ormiston JA 2, Stewart J 2, Webster M 3, Sanidas E 4, Costa R 5, Costa JR Jr 5, Chamie D 5, Abizaid AS 5, Pinto I 5, Morrison L 6, Toyloy S 6, Bhat V 6, Yan J 6, Abizaid A 5. Author information Abstract OBJECTIVES: This study sought to perform clinical and imaging assessments of the DESolve Bioresorbable Coronary Scaffold (BCS). BACKGROUND: BCS, which is drug eluting, may have potential advantages compared with conventional metallic drug-eluting stents. The DESolve system, designed to provide vessel support and neointimal suppression, combines a poly-l-lactic acid-based scaffold with the antiproliferative myolimus. METHODS: The DESolve First-in-Man (a non-randomized, consecutive enrollment evaluation of the DESolve myolimus eluting bioresorbable coronary stent in the treatment of patients with de novo native coronary artery lesions) trial was a prospective multicenter study enrolling 16 patients eligible for treatment. The principal safety endpoint was a composite of cardiac death, myocardial infarction, and clinically indicated target lesion revascularization. The principal imaging endpoint was in-scaffold late lumen loss (LLL) assessed by quantitative coronary angiography (QCA) at 6 months. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) imaging was performed at baseline and 6 months; multislice computed tomography (MSCT) was performed at 12 months. RESULTS: Acute procedural success was achieved in 15 of 15 patients receiving a study scaffold. At 12 months, there was no scaffold thrombosisand no major adverse cardiac events directly attributable to the scaffold. At 6 months, in-scaffold LLL (by QCA) was 0.19 ± 0.19 mm; neointimal volume (by IVUS) was 7.19 ± 3.56%, with no evidence of scaffold recoil or late malapposition. Findings were confirmed with OCT and showed uniform, thin neointimal coverage (0.12 ± 0.04 mm). At 12 months, MSCT demonstrated excellent vessel patency. CONCLUSIONS: This study demonstrated the feasibility and efficacy of the DESolve BCS. Results showing low in-scaffold LLL, low % neointimal volume at 6 months, no chronic recoil, and maintenance of lumen patency at 12 months prompt further study. (DESolve First-in-Man; EudraCT number ).

48 Polymer-free, bioabsorbable, or coated with monoclonal antibodies that bind circulating endothelial progenitor cells Serruys PW JACC 2006

49 Response of the vessel to DES " DES expose the vessel wall to antiproliferative drugs with variable effects on endothelial regeneration and function " Malapposition of the stent to the vessel wall, apart from procedural, may be acquired :! drug-induced inhibition of neointimal formation! delayed reparative events that usually enable the vessel wall to incorporate the stent! Drug-induced positive remodeling of the vessel wall Hoffma SH et al Eur Heart J 2006, Serruys PW et al Circulation 2002, Ako J et al JACC 2005, Tanabe K et al Circulation 2005, Jaffe and Strauss JACC 2007

50 New Engl J Med 2014

51 Διπλή αντιαιµοπεταλιακή αγωγή πέραν του ενός έτους από την αγγειοπλαστική µε drug-eluting stents (ARCTIC-Interruption). Αποτελέσµατα Διενεργήθηκε τυχαιοποιηµένη µελέτη σε περίπου 1300 ασθενείς, που υποβλήθηκαν σε αγγειοπλαστική µε τοποθέτηση drug-eluting stents όσον αφορά την αποτελεσµατικότητα και την ασφάλεια της χορήγησης αντιαιµοπεταλιακής αγωγής πέραν των καθιερωµένων οδηγιών για ένα έτος. Πρωτογενές καταληκτικό σηµείο αποτέλεσε ο συνδυασµός θνητότητας, µυοκαρδιακού εµφράγµατος, θρόµβωσης του stent, αγγειακού εγκεφαλικού επεισοδίου και επείγουσας επαναγγείωσης. Σύµφωνα µε τα αποτελέσµατα διάµεσης παρακολούθησης 17 µηνών δεν υπήρχε διαφορά στο καταληκτικό σηµείο µεταξύ των οµάδων της συνέχισης και της διακοπής της διπλής αντιαιµοπεταλιακής αγωγής στο πρώτο έτος, ενώ παρατηρήθηκε αυξηµένη επίπτωση ελάσσονων και µείζονων αιµορραγιών στην οµάδα της συνέχισης της αγωγής. Τα τελευταία ευρήµατα συγκλίνουν στη µη αποτελεσµατικότητα και τον αυξηµένο κίνδυνο χορήγησης διπλής αντιαιµοπεταλιακής αγωγής πέραν του έτους, µετά από αγγειοπλαστική µε drug-eluting stents, τουλάχιστον σε µη υψηλού κινδύνου ασθενείς. Lancet [Epub ahead of print] Έξι έναντι δώδεκα µήνες διπλής αντιαιµοπεταλιακής αγωγής σε αγγειοπλαστική µε τα νεότερα-δεύτερης γενιάς Drug- Eluting Stents(SECURITY Clinical Trial) Διενεργήθηκε τυχαιοποιηµένη, πολυκεντρική µελέτη για τη διερεύνηση µη-κατωτερότητας, όσον αφορά την εξάµηνη, έναντι της ετήσιας διπλής αντιαιµοπεταλιακής αγωγής, σε 1400 ασθενείς που υποβλήθηκαν σε αγγειοπλασική µε τα νεότερα-δεύτερης γενιάς Drug-Eluting Stents. Πρωτογενές καταληκτικό σηµείο αποτέλεσε ο συνδυασµός καρδιακής θνητότητας, µυοκαρδιακού εµφράγµατος, θρόµβωσης του stent, αγγειακού εγκεφαλικού επεισοδίου και αιµορραγίας στους 12 µήνες της παρακολούθησης. Σύµφωνα µε τα αποτελέσµατα της µελέτης, το πρωτογενές συνδυαστικό καταληκτικό σηµείο είχε την ίδια συχνότητα στις δύο οµάδες των ασθενών. Η υπόθεση της µη-κατωτερότητας ως προς την αποτελεσµατικότητα και την ασφάλεια, όσον αφορά τη µικρότερη του έτους διάρκεια χορήγησης διπλής αντιαιµοπεταλιακής αγωγής, τουλάχιστον σε ασθενείς χαµηλού κινδύνου που λαµβάνουν τα νεότερα stents, ενισχύθηκε από τα αποτελέσµατα της ανωτέρω µελέτης. J Am Coll Cardiol [Epub ahead of print]

52 Lancet Nov 1;384(9954): doi: /S (14) Epub 2014 Jul 15. Dual-antiplatelet treatment beyond 1 year after drug-eluting stent implantation (ARCTIC-Interruption): a randomised trial. Collet JP 1, Silvain J 1, Barthélémy O 1, Rangé G 2, Cayla G 3, Van Belle E 4, Cuisset T 5, Elhadad S 6, Schiele F 7, Lhoest N 8, Ohlmann P 9, Carrié D 10, Rousseau H 11, Aubry P 12, Monségu J 13, Sabouret P 1, O'Connor SA 1, Abtan J 1, Kerneis M 1, Saint-Etienne C 14, Beygui F 15, Vicaut E 16, Montalescot G 17 ; ARCTIC investigators. Author information 1 ACTION Study Group, Institut de Cardiologie Hôpital Pitié-Salpêtrière (APHP), Université Paris 6, INSERM, Paris, France.. Abstract BACKGROUND: Optimum duration of dual antiplatelet treatment (DAPT) after coronary stenting remains uncertain, with an unknown efficacy to safety ratio of extended treatment leading to discrepancies between international guidelines and clinical practice. We assessed whether DAPT continuation beyond 1 year after coronary stenting is beneficial. METHODS: This analysis was a planned extension of the previously published ARCTIC-Monitoring trial, in which we randomly allocated 2440 patients to a strategy of platelet function testing with antiplatelet treatment adjustment or a conventional strategy after coronary stenting with drug-eluting stent (DES). We recruited patients (aged 18 years or older) scheduled for planned DES implantation at 38 centres in France. After 1 year of follow-up, patients without contraindication to interruption of DAPT were eligible for a second randomisation to this second phase of the study (ARCTIC-Interruption). Using a computer-generated randomisation sequence (1:1; stratified by centre), we allocated patients to a strategy of interruption of DAPT where the thienopyridine was interrupted and single aspirin antiplatelet treatment was maintained (interruption group) or a strategy of DAPT continuation for 6-18 months (continuation group). The primary endpoint was the composite of death, myocardial infarction, stentthrombosis, stroke, or urgent revascularisation, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT FINDINGS: Between Jan 4, 2011, and March 3, 2012, 1259 eligible patients were randomly allocated to treatment in ARCTIC-Interruption: 624 to the interruption group and 635 to the continuation group. After a median follow-up of 17 months (IQR 15-18), the primary endpoint occurred in 27 (4%) patients in the interruption group and 24 (4%) patients in the continuation group (hazard ratio [HR] 1 17 [95% CI ]; p=0 58). STEEPLE major bleeding events occurred more often in the continuation group (seven [1%] patients) compared with the interruption group (one [<0 5%] patient; HR 0 15 [ ]; p=0 073). Major or minor bleedings were also more common in the continuation group compared with the interruption group (12 [2%] patients vs three [1%] patients; HR 0 26 [ ]; p=0 04). INTERPRETATION: Our finding suggests no apparent benefit but instead harm with extension of DAPT beyond 1 year after stenting with DES when no event has occurred within the first year after stenting. No conclusion can be drawn for high-risk patients who could not be randomised. The consistency between findings from all trials of such interruption suggests the need for a reappraisal of guidelines for DAPT after coronary stenting towards shorter duration of treatment.

53 Lancet Nov 1;384(9954): doi: /S (14) Epub 2014 Jul 15 Dual-antiplatelet treatment beyond 1 year after drug-eluting stent implantation (ARCTIC- Interruption): a randomised trial Collet JP, Silvain J, Barthélémy O, Rangé G, Cayla G, Van Belle E, Cuisset T, Elhadad S, Schiele F, Lhoest N, Ohlmann P, Carrié D Rousseau H, Aubry P, Monségu J, Sabouret P, O'Connor SA, Abtan J, Kerneis M, Saint-Etienne C, Beygui F, Vicaut E, Montalescot G; ARCTIC investigators ACTION Study Group, Institut de Cardiologie Hôpital Pitié-Salpêtrière (APHP), Université Paris 6, INSERM, Paris, France BACKGROUND: Optimum duration of dual antiplatelet treatment (DAPT) after coronary stenting remains uncertain, with an unknown efficacy to safety ratio of extended treatment leading to discrepancies between international guidelines and clinical practice. We assessed whether DAPT continuation beyond 1 year after coronary stenting is beneficial. METHODS: This analysis was a planned extension of the previously published ARCTIC-Monitoring trial, in which we randomly allocated 2440 patients to a strategy of platelet function testing with antiplatelet treatment adjustment or a conventional strategy after coronary stenting with drug-eluting stent (DES). We recruited patients (aged 18 years or older) scheduled for planned DES implantation at 38 centres in France. After 1 year of follow-up, patients without contraindication to interruption of DAPT were eligible for a second randomisation to this second phase of the study (ARCTIC-Interruption). Using a computer-generated randomisation sequence (1:1; stratified by centre), we allocated patients to a strategy of interruption of DAPT where the thienopyridine was interrupted and single aspirin antiplatelet treatment was maintained (interruption group) or a strategy of DAPT continuation for 6-18 months (continuation group). The primary endpoint was the composite of death, myocardial infarction, stentthrombosis, stroke, or urgent revascularisation, analysed by intention to treat. FINDINGS: Between Jan 4, 2011, and March 3, 2012, 1259 eligible patients were randomly allocated to treatment in ARCTIC-Interruption: 624 to the interruption group and 635 to the continuation group. After a median follow-up of 17 months (IQR 15-18), the primary endpoint occurred in 27 (4%) patients in the interruption group and 24 (4%) patients in the continuation group (hazard ratio [HR] 1 17 [95% CI ]; p=0 58). STEEPLE major bleeding events occurred more often in the continuation group (seven [1%] patients) compared with the interruption group (one [<0 5%] patient; HR 0 15 [ ]; p=0 073). Major or minor bleedings were also more common in the continuation group compared with the interruption group (12 [2%] patients vs three [1%] patients; HR 0 26 [ ]; p=0 04) INTERPRETATION: Our finding suggests no apparent benefit but instead harm with extension of DAPT beyond 1 year after stenting with DES INTERPRETATION: Our finding suggests no apparent benefit but instead harm with extension of DAPT beyond 1 year after stenting with DES when no event has occurred within the when no event has occurred within the first year after stenting. No conclusion can be drawn for high-risk patients who first year after stenting. No conclusion can be drawn for high-risk patients who could not be randomised. The consistency between findings from all trials of such interruption suggests could the not need be for randomised. a reappraisal of guidelines The consistency for DAPT after between coronary stenting findings towards from shorter all duration trials of of treatment. such interruption suggests the need for a reappraisal of guidelines for DAPT after coronary stenting towards shorter duration of treatment

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56 Lee JM et al Am J Cardiol 2014