Antiplatelet therapy in myocardial infarction and coronary stent thrombosis Heestermans, Antonius Adrianus Cornelius Maria

Transcription

1 University of Groningen Antiplatelet therapy in myocardial infarction and coronary stent thrombosis Heestermans, Antonius Adrianus Cornelius Maria IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2010 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Heestermans, A. A. C. M. (2010). Antiplatelet therapy in myocardial infarction and coronary stent thrombosis Groningen: s.n. Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date:

2 8 Long-term clinical outcome after a first angiographically confirmed coronary stent thrombosis: an analysis of 431 cases J.W. van Werkum, A.A.C.M. Heestermans, F.I. de Korte, J.C. Kelder, M.J. Suttorp, B.J.W.M. Rensing, B. Zwart, B.R.G. Brueren, J.J. Koolen, J-H.E. Dambrink, A.W.J. van t Hof, F.W.A. Verheugt, J.M. ten Berg Circulation. 2009;119:828-34

3 Chapter 8 Abstract Background: There are limited data on the long-term clinical outcome after an angiographically confirmed ( definite ) stent thrombosis (ST). Methods and Results: Four hundred-thirty-one consecutive patients with a definite ST were enrolled in this multicenter registry. The primary endpoint was the composite of cardiac death and definite recurrent ST. The secondary endpoints were all cause death, cardiac death, definite recurrent ST, definite and probable recurrent ST, any myocardial infarction and any target-vessel revascularization. The primary endpoint occurred in 111 patients after a median follow-up of 27.1 months. The estimated cumulative event rates at 30 days, 1, 2 and 3 years were 18.0%, 23.6%, 25.2% and 27.9%, respectively. The cumulative incidence rates of definite recurrent ST, definite or probable recurrent ST, any myocardial infarction and any target-vessel revascularization were 18.8%, 20.1%, 21.3% and 32.0%, respectively at the longest available follow-up. Independent predictors for the primary endpoint were diabetes mellitus, total stent length, severe calcification, ACC/AHA B2-C lesions, TIMI flow<3 post-pci and left ventricular ejection fraction < 45%. The implantation of an additional coronary stent during the first ST was also associated with unfavorable outcome. Clinical outcome was not affected by the type of previously implanted stent (DES or BMS) or the category of ST (early versus late). Conclusions: The long-term clinical outcome after a first definite ST is unfavorable with a high mortality and recurrence rate. Diabetes mellitus, left ventricular ejection fraction < 45%, long total stent length, complex coronary lesions, TIMI flow <3 post-pci and the implantation of an additional coronary stent during the emergent PCI for the ST were associated with this unfavorable outcome. 116

4 Coronary stent thrombosis Introduction Stent thrombosis is a serious complication after percutaneous coronary intervention (PCI) manifesting as a myocardial infarction or even as cardiac death [1-6]. Emergent PCI is the current treatment strategy to (re)establish vessel patency in patients with stent thrombosis. Previous studies, however, have provided limited information on the occurrence of major-adverse cardiac events after suffering from a stent thrombosis because the follow-up was censored upon end point achievement. We conducted a multicenter registry including all consecutive patients who presented with a definite first stent thrombosis with the specific purpose to examine the incidence of major-adverse cardiac events after stent thrombosis and to identify determinants that are associated with these major-adverse cardiac events. Methods Study design and patient population The Dutch stent thrombosis registry is a multi-centre study conducted in three highvolume centers in the Netherlands. All consecutive patients with an angiographically confirmed stent thrombosis presenting from January 2004 to February 2007 were enrolled. The study was conducted according to the principles of the Declaration of Helsinki. Patients gave informed consent for the inclusion of data in the registry. Stent thrombosis was defined according to the Academic Research Consortium (ARC) definite definition [7]. Stent thrombosis was categorized according to the timing of the event as acute (occurrence within the first 24 h after the index-procedure), subacute (from 24 h to 30 days), late (from 30 days to 1 year) and very late (>1 year after the index procedure). Detailed data on patient characteristics, the index PCI-procedure and the emergent PCI procedure for the first stent thrombosis were collected. Coronary angiograms of both the index procedure as well as of the stent thrombosis were reviewed independently by two experienced interventional cardiologists. In case of disagreement, a consensus was established between the two reviewers or a third interventional cardiologist was consulted. Patients with stable angina pectoris who underwent a scheduled PCI were adequately pretreated with a 300 mg clopidogrel loading dose at least 48 hours prior to the PCI procedure. Patients presenting with an acute-coronary syndrome that required an urgent PCI were loaded at the time of intervention with a 600 mg loading dose of clopidogrel. All patients were re-loaded with a 600 mg loading dose of clopidogrel at the time of 117

5 Chapter 8 the stent thrombosis. The use of glycoprotein IIb/IIIa therapy during index PCI as well as at the time of the stent thrombosis was left to the discretion of the interventional cardiologist. Clinical follow-up Clinical follow-up information was obtained from telephonic interviews with the patients, their relatives, their general practitioners, pharmacies and from hospital records. Information regarding the development of major adverse cardiac events, pre-defined as death, recurrent stent thrombosis, any myocardial infarction and any coronary revascularization (either PCI or coronary-artery bypass grafting (CABG)) was collected. Study end points and definitions The pre-defined primary end point of the present study was a composite of cardiac death and definite recurrent stent thrombosis (according to the ARC-criteria )[1]. The secondary end points were all-cause mortality, cardiac mortality, recurrent definite stent thrombosis, recurrent definite or probable stent thrombosis, myocardial infarction (target-vessel and non-target vessel related), and any ischemia-driven target-vessel revascularization (TVR). Deaths were classified as cardiac or non-cardiac on the basis of the information obtained from hospital records and telephone contact with relatives of the patient or attending physician. Recurrent stent thrombosis was defined according to the ARC definite and probable definitions. The diagnosis of myocardial infarction required an elevation of creatine-kinase levels to twice the upper limit of normal, together with a rise in creatine kinase-mb fraction. TVR was defined as ischemia-driven PCI performed in the same vessel as the index PCI with or without implantation of a stent or coronary-artery bypass grafting. Statistical analysis Statistical analysis was performed using SAS, version 9.1 (SAS Institute Inc., Cary, North Carolina). Continuous data are expressed as mean ± SD or as median and the interquartile range. Categorical data are presented as percentages. Predictors of cardiac death and recurrent stent thrombosis were assessed using a stepwise Cox proportional hazards model. First, an univariate analysis was performed. Then, variables with a p-value <0.10 were entered into the multivariate model. Kaplan- Meier survival analyses were used to show the cumulative incidence of the primary and secondary endpoint(s). Kaplan-Meier survival analyses were used to show the cumulative incidence of the primary and secondary endpoint(s). When death was not 118

6 Coronary stent thrombosis part of the end point used in the analysis at hand, we censored patients when none of the events of interest had occurred; non-fatal events not part of an end point were no reason for censoring. All authors had full access to and take full responsibility for the integrity of the data. All authors have read and agree to the manuscript as written. Results Characteristics of the patients During the study period 437 patients with a definite stent thrombosis were enrolled. Of these, 6 patients were excluded from analysis because they had suffered from a previous stent thrombosis before the start of the inclusion period. The timing of the definite first stent thrombosis in the remaining 431 patients was acute in 140 (total group 32.5%; 33% for BMS, 30% for DES), subacute in 177 (total group 41.1%; 42% for BMS, 40% for DES), late in 57 (total group 13.2%; 12% for BMS, 16% for DES) and very late in 57 (total group 13.2%; 12% for BMS, 15% for DES). No significant differences between DES and BMS were observed according to the timing of the ST (p=0.51). Clinical, angiographic and index-procedural characteristics are shown in Tables 1, 2 and 3. The stent thrombosis was related to a drug-eluting stent (DES) in 150 (34.8%) patients and to a bare-metal stent (BMS) in 265 (61.5%) patients. In the remaining 16 patients (3.7%), a thrombus was visualized in a segment in which both a DES and BMS were placed. One-hundred thirty-four patients (31.1%) were not on clopidogrel therapy at the time of the first stent thrombosis and 56 (13.0%) patients did not use aspirin. Treatment of the first stent thrombosis The characteristics of the emergent PCI for stent thrombosis are also listed in Table 1. The thrombosis was limited to one or multiple stents in 1 coronary vessel in 417 patients (96.8%), however, a thrombosis was diagnosed in multiple stents in different coronary arteries in 14 patients (3.2%). The vast majority of the patients (n=421; 97.7%) underwent emergent PCI upon presentation with stent thrombosis. Of these, 203 patients (46.1%) were treated with balloon angioplasty, 214 patients (49.7%) underwent balloon angioplasty followed by the implantation of an additional stent (113 BMS; 100 DES) and 4 patients were treated with thrombus aspiration only. Fifty-one patients (12.8%) underwent thrombus aspiration for the ST prior to the emergent PCI. In 6 patients, the emergent angioplasty for the stent thrombosis was not successful. Two patients underwent emergent CABG after urgent coronary angiography. Thirteen patients (3%) underwent CABG in a later stage of the hospitalization after balloon angioplasty in the acute phase of the stent thrombosis. This was mainly due to an imperfect procedural success (TIMI<3) or residual coronary vessel disease. 119

7 Chapter 8 Table 1: Clinical Patient Characteristics Overall n=431 Event free n=320 With event n=111 P-value Male sex no.(%) 323 (74.9%) 233 (72.8%) 90 (81.1%) 0.09 Age yr 61.1± ± ± BMI kg/m ± ± ± History no.(%) Diabetes mellitus 100 (23.2%) 64 (20%) 36 (32.4%) Hypercholesterolemia 229 (53.1%) 166 (51.8%) 63 (56.8%) 0.41 Hypertension 202 (46.9%) 146 (45.6%) 56 (50.5%) 0.38 Renal failure (MDRDeGFR<60) 73 (16.9%) 49 (15.3%) 24 (21.6%) 0.11 Family history of CAD 213(49.4%) 156 (48.8%) 57 (51.4%) 0.71 Myocardial infarction 128 (29.7%) 81 (25.3%) 47 (42.3%) PCI 102 (23.7%) 67 (20.9%) 35 (31.5%) 0.03 CABG 21 (4.9%) 16 (5.0%) 5 (4.5%) 0.81 Current smoking no.(%) 280 (65.0%) 211(65.9%) 69 (62.2%) 0.39 LVEF at the time of index procedure - % < 30% 45 (10.4%) 27 (8.4%) 18 (16.2%) % 72 (16.7%) 55 (17.2%) 17 (15.3%) 0.07 > 45% 314 (72.9%) 238 (74.4%) 76 (68.5%) ref. Abbreviations: BMI, body mass index; CABG, coronary-artery bypass grafting; CAD, coronary artery disease; LVEF, left ventricular ejection fraction; MDRDeGFR, Modification of Diet in Renal Disease Study Equation for Estimating Glomerular Filtration Rate; PCI, percutaneous coronary intervention; Follow-up The median follow-up time for the 431 patients was 27.1 months [interquartile range 17.4 months to 37.1 months]. Clinical follow-up was available in 416 (96.5%) patients. The vital status could not be ascertained in 15 patients (of which 10 moved abroad) and the last available follow-up was used. Primary endpoint In-hospital During the hospitalization for the first stent thrombosis, 26 patients died of a cardiac cause and 44 patients experienced a definite recurrent stent thrombosis (the timing was acute in 12 patients and subacute in 32 patients; median: 4 days after the emergent PCI for the first stent thrombosis). 120

8 Coronary stent thrombosis Table 2: Procedural and angiographic characteristics of the patients Overall n=431 Event free With event P-value n=320 n=111 PCI-treated vessel no.(%) LAD 269 (62.4%) 194 (60.6%) 75 (67.6%) ref. RCA 127 (29.5%) 92 (28.8%) 35 (31.5%) 0.93 RCX 65 (15.1%) 55 (17.2%) 10 (9.0%) 0.06 Venegraft 4 (0.9%) 3 (0.9%) 1 (0.9%) 0.99 Bifurcation-lesion ( 2 mm Ø) no.(%) 223 (51.7%) 167 (52.2%) 56 (50.5%) 0.83 ACC/AHA classification no.(%) B2/C 330 (76.6%) 256 (80.0%) 74 (66.7%) Severe calcification no.(%) 85 (19.7%) 54 (16.9%) 31 (27.9%) 0.08 Lesion in coronary ostium no.(%) 10 (2.3%) 8 (2.5%) 2 (1.8%) 0.64 Severe tortuosity no.(%) 11 (2.6%) 7(2.2%) 4 (3.6%) 0.45 Chronic total occlusion no.(%) 11 (2.6%) 6 (1.9%) 5 (4.5%) 0.09 Indication for the index PCI no.(%) ACS (NSTEMI/STEMI) 321 (74.5%) 240 (75.0%) 81 (73.0%) 0.66 Administration of GP IIb/IIIa therapy no.(%) 135 (31.3%) 99 (30.9%) 36 (32.4%) 0.74 Type of coronary stent no.(%) BMS only 265 (61.5%) 201 (62.8%) 64 (57.7%) 0.17 DES only 150 (34.8%) 110 (34.4%) 40 (36.0%) 0.22 BMS+DES 16 (3.7%) 9 (2.8%) 7 (6.3%) 0.50 Number of stents per patient 1.54± ± ± Total stent length mm 27.85± ± ± Diameter of the stent mm 2.99± ± ± Balloon pressure atm ± ± ± Post-procedural TIMI flow no.(%) TIMI-flow grade (2.8%) 9 (2.8%) 3 (2.7%) ref. TIMI-flow grade 2 60 (13.9%) 42 (13.1%) 18 (16.2%) 0.54 TIMI-flow grade (83.3%) 267 (83.4%) 92 (82.9%) 0.68 Abbreviations: ACS, acute-coronary syndrome; BMS, bare-metal stent; DES, drug-eluting stent; GP, Glycoprotein; LAD, left anterior descending artery; NSTEMI, non ST-elevated myocardial infarction; PCI, percutaneous coronary intervention; RCA, right coronary artery; RCX, circumflex artery; STEMI, ST-elevated myocardial infarction;timi, Thrombolysis in Myocardial Infarction 121

9 Chapter 8 Table 3: Details of the first ST Overall n=431 Event free n=320 With event n=111 P-value Category of the 1 st stent thrombosis at time of inclusion no.(%) Acute stent thrombosis 140 (32.5 %) 114 (35.6%) 26 (23.4%) ref. Subacute stent thrombosis 177 (41.0%) 124 (38.8%) 53 (47.7%) 0.02 Late Stent thrombosis 57 (13.2%) 41 (12.8%) 16 (14.4%) 0.12 Very late Stent thrombosis 57 (13.2%) 41 (12.8%) 16 (14.4%) 0.16 Double-Trouble - stent thrombosis no.(%) 14 (3.2%) 10 (3.1%) 4 (3.6%) 0.71 In-hospital occurrence of the 1 st stent 240 (55.7%) 181 (56.6%) 59 (53.2%) 0.95 thrombosis no.(%) Use of aspirin at the time of the 1 st stent thrombosis no.(%) 375 (87.0%) 284 (88.8%) 91 (82.0%) 0.06 Use of clopidogrel at the time of the 1 st stent 297 (68.9%) 217 (67.8%) 80 (72.1%) 0.35 thrombosis no.(%) Use of oral anticoagulation therapy at the 47 (10.9%) 33 (10.3%) 14 (12.6%) 0.53 time of the 1 st stent thrombosis no.(%) Treatment of the 1 st stent thrombosis no.(%) Aspiration 55 (12.8%) 39 (12.2%) 16 (14.4%) 0.74 Balloon angioplasty 203 (47.1%) 159 (49.7%) 42 (37.8%) 0.03 PCI with additional stent implantation 214 (49.7%) 148 (46.3%) 66 (59.5%) ref. Emergent CABG 2 (0.5%) 2 (0.6%) 0 (0%) 0.98 Administration of GP IIb/IIIa therapy no.(%) 352 (81.7%) 263 (82.2%) 89 (80.2%) 0.48 Postprocedural TIMI flow no.(%) TIMI-flow grade (5.3%) 16 (5.0%) 7 (6.3%) ref. TIMI-flow grade 2 34 (7.9 %) 17 (5.3%) 17 (15.3%) 0.13 TIMI-flow grade (86.8%) 288 (90%) 86 (77.5%) 0.96 LVEF after the 1 st stent thrombosis - % <30% 92 (21.4%) 70 (21.9%) 22 (19.8%) % 96 (22.3%) 59 (18.4%) 37 (33.3%) 0.04 >45% 243 (56.4%) 191 (59.7%) 52 (46.8%) ref. Abbreviations: CABG, coronary-artery bypass grafting; LVEF, left ventricular ejection fraction; PCI, percutaneous coronary intervention; TIMI, Thrombolysis in Myocardial Infarction Long-term outcome At the longest available follow-up, the primary endpoint (cardiac death and definite recurrent stent thrombosis) occurred in 111 patients. The estimated cumulative event rates at 30 days, 1, 2 and 3 year were 18.0%, 23.6%, 25.2% and 27.9%, respectively (Figure 1A). 122

10 Coronary stent thrombosis Secondary endpoints In-hospital Twenty-seven patients died during hospitalization including 26 cardiac deaths. Fortyfour cases of angiographically confirmed recurrent stent thrombosis were observed and stent thrombosis could not be excluded in 6 patients who died suddenly during hospitalization ( probable recurrent stent thrombosis). A total of 53 patients underwent TVR: 45 repeated PCI s (including 44 emergent PCI s for definite recurrent stent thrombosis) and 13 CABG (5 of these patients also suffered a recurrent stent thrombosis). Long-term outcome At the longest available follow-up, 45 out of 56 (80.4%) deaths were defined as cardiac deaths. The cumulative incidences of all-cause mortality and cardiac mortality were 7.7% and 7.3%, at 30 days, 10.7% and 9.5% at 1 year, 12.0% and 10.0% at 2 years and 15.4% and 12.3% at the end of the available follow up, respectively (Figure 1A and 1B). A total of 75 patients had experienced at least one episode of a definite recurrent stent thrombosis. Of these patients, 62 suffered one recurrent stent thrombosis, 11 patients had two episodes of recurrent stent thrombosis and 2 patients suffered 3 episodes of recurrent stent thrombosis. The timing of the first definite recurrent stent thrombosis was acute in 14 patients, subacute in 40 patients, late in 15 patients and very late in 6 patients. Definite or probable stent thrombosis occurred in 81 patients (18.8%). The cumulative incidences of definite or probable recurrent stent thrombosis at 30 days, 1, 2, and 3 years were 14.4%, 18.2%, 19.6% and 20.1% respectively (Figure 1B) Except for recurrent stent thrombosis, myocardial infarction did not occur frequently and the cumulative incidences at 30 days, 1, 2, and 3 years are shown in figure 1B. At the longest available follow-up, target vessel revascularization (including the emergent PCI for definite recurrent stent thrombosis) was performed in 124 patients: 87 TVR s were related to a bare-metal stent (BMS) and 37 TVR s were related to a drugeluting stent (DES). After excluding all emergent PCI s for definite recurrent stent thrombosis, the cumulative incidence of target vessel revascularization remained relatively high (22% for BMS and 15% for DES). Although not statistically significant, there was a trend towards a lower TVR rate in DES as compared to BMS (Figure 1C). Predictors for the combined endpoint of cardiac mortality and definite recurrent stent thrombosis After adjustment in the stepwise Cox-proportional-hazard model, diabetes mellitus, left ventricular ejection fraction < 45%, severe calcification of the target vessel and the implantation of an additional stent during the emergent PCI for the first stent thrombosis 123

11 Chapter 8 were independent predictors of the primary endpoint (Table 4). This observation was not influenced by the type of coronary stent (either DES or BMS). Importantly, the type of coronary stent (DES or BMS) that was implanted during the index PCI and the timing of the stent thrombosis (either acute, subacute, late or very late) were not independently associated with the primary endpoint (hazard ratio (HR) 1.12, 95% CI 0.75 to 1.69, P=0.58 for stent type and HR: 1.18, 95% CI 0.60 to 2.3, P=0.64 for timing of stent thrombosis (Figure 1D)). Of note, the independent correlates in the Cox-proportional-hazard model did not change substantially when the combined primary end point was replaced by one of its single components (either cardiac death or definite recurrent stent thrombosis) or when the composite endpoint of cardiac death and definite recurrent stent thrombosis was replaced by a composite of cardiac death and any myocardial infarction (data not shown). Table 4: Multivariate Cox proportional Hazard analysis of the predictors for the combined endpoint cardiac death and definite recurrent stent thrombosis Hazard Ratio (95%-CI) p-value Clinical Characteristics Diabetes Mellitus 1.97 ( ) Male gender 1.64 ( ) 0.06 LVEF after the 1 st stent thrombosis <45% 1.72 ( ) 0.02 Angiographic Characteristics Severe Calcification 1.69 ( ) ACC/AHA B2-C lesion 2.65 ( ) < Stent in LAD 2.33 ( ) 0.02 Total stent length (per mm) ( ) Characteristics of the emergent PCI for the 1 st stent thrombosis Additional stent implantation during ST 1.73 ( ) <0.001 TIMI-flow post emergent PCI < ( ) 0.05 Abbreviations: LAD, left anterior descending artery; LVEF, left ventricular ejection fraction; PCI, percutaneous coronary intervention; ST, stent thrombosis 124

12 Coronary stent thrombosis (A) Primary Endpoint and its components 50 Cumulative incidence of the primary endpoint and its single components Primary Endpoint Definite RST Cardiac death 0 No. at risk Primary EP Definite RST CV death Time (B) Secondary Endpoints 25 Cumulative incidence of the secondary endpoints Any myocardial infarction Def/Prob RST Definite RST All cause death Cardiac death Time No. at risk Any MI Def/Prob RST Definite RST All cause death CV death

13 Chapter 8 (C) TVR (influence of BMS and DES) Cumulative incidence of TVR BMS and mixed stents Any TVR Des only BMS and mixed stents Non RST related TVR Des only P=0.16 P= No. at risk Any TVR BMS + mixed 281 Any DES 150 Non-recurrent stent thrombosis related TVR BMS + mixed 281 Any DES Time (D) Timing of ST and clinical outcome Cumulative incidence of the primary endpoint acute ST subacute ST late ST very late ST 0 Log-rank test for Acute ST versus subacute ST/late ST/very late ST: p-value = Time No. at risk Acute ST Subacute ST Late ST Very late ST

14 Coronary stent thrombosis Figure 1: Panel A: cumulative incidence of the primary endpoint and its single components cardiac death and definite recurrent stent thrombosis. Panel B: cumulative incidence of the secondary endpoints including all-cause death (all cause and cardiac), recurrent stent thrombosis ( definite and definite or probable ) and myocardial infarction. Panel C: cumulative incidence of target vessel revascularization related to a BMS or a DES in- or excluding the emergent PCI for recurrent stent thrombosis. Panel D: cumulative incidence of the primary endpoint stratified according to the timing of stent thrombosis (either acute, subacute, late and very late). Abbreviations: BMS, bare-metal stent; DES, drug-eluting stent; EP, endpoint; CV, cardiovascular; MI, myocardial infarction; RST, recurrent stent thrombosis; TVR, target vessel revascularization. Discussion Although case-reports, registries and meta-analyses have identified several correlates that are associated with an increased risk for stent thrombosis [1-3;6;8], limited information to date is available about the long-term clinical outcome after a first definite stent thrombosis in the real world of mixed BMS and DES use [6;9]. The present multicenter observational study comprises the largest cohort of patients with stent thrombosis thus far and demonstrates that the clinical outcome in patients who suffer from a first definite stent thrombosis is unfavorable. Although the presented mortality rates are lower than reported by others [2;3], the high incidence rate of recurrent stent thrombosis is remarkable: nearly 1 in 5 patients with a first definite stent thrombosis experience another definite recurrent stent thrombosis. Moreover, more than one recurrences of stent thrombosis are not uncommon in the studied population. Target-vessel revascularization rates (after exclusion of the emergent PCI for recurrent stent thrombosis) were also high in our study population. This might be a reflection of the complexity of the coronary lesions in these patients. Although not reaching statistical significance, the advantage of drug-eluting stents in reducing restenosis is also notable [10;11]. There are a number of possible explanations for the difference in mortality rates between the results of the present study (15.4%) and those of previous studies (up to 40%). First, we used a very conservative definition of stent thrombosis at the time of inclusion (only patients with a definite stent thrombosis). As a result, patients with a previous implanted coronary stent who died prior to hospital presentation ( probable or even possible stent thrombosis) were not included. Second, the present study 127

15 Chapter 8 was performed in the settings of the well-organized Dutch ambulance system with a very effective pre-hospital triage, short call-to-balloon times and national guidelines that support primary PCI in every patient with a ST-elevated myocardial infarction. In a setting of longer transfer distances and the unavailability of interventional centers, mortality rates are probably higher. Third, only high volume PCI centers participated in the presented study and it is commonly known that mortality rates are considerably lower in these centers as compared to centers with a lower procedure volume [12]. Examining the factors that are associated with an unfavorable clinical outcome can improve patient selection criteria for coronary stenting and/or optimize the current adopted treatment for stent thrombosis. In the present study, the presence of diabetes mellitus, male gender and an impaired left ventricular ejection fraction were identified as important clinical predictors of poor outcome. These findings are consistent with previous studies [4;5] and are surprisingly similar to the reported determinants that are associated with an increased risk for stent thrombosis [2;3;8]. Severely calcified and complex lesions (ACC/AHA B2-C) as well as a long total stent length were also important angiographic and procedural predictors for an unfavorable outcome. This strongly suggests that the index PCI was performed for more complex lesion characteristics and it has been known for almost two decades that these patients experience higher event rates including death. Another important observation in our study is that clinical outcome was neither affected by the type of the previous implanted stent (DES or BMS) nor by the category of stent thrombosis (early versus late). Given the observational nature of the present registry, the optimal treatment strategy for stent thrombosis cannot be determined. Nonetheless, our data do offer certain guidance on the management of patients with stent thrombosis. It is worth noting that patients who were treated with an additional coronary stent during the first stent thrombosis faired less well. Randomized trials are urgently needed to determine the optimal treatment strategy in patients with stent thrombosis. In conclusion, longterm clinical outcome after a first definite stent thrombosis is unfavorable with a high mortality and recurrence stent thrombosis rate. Diabetes mellitus, left ventricular ejection fraction < 45%, long stent length, complex coronary lesions, post-procedural TIMI flow <3 and the implantation of an additional coronary stent during the emergent PCI for the stent thrombosis were associated with an unfavorable outcome Acknowledgements This study was presented as a late-breaking clinical trial at the ACC-SCAI Scientific Sessions; March 29-April ; Chicago. 128

16 Coronary stent thrombosis References 1. Cutlip DE, Baim DS, Ho KKet al.: Stent thrombosis in the modern era: a pooled analysis of multicenter coronary stent clinical trials. Circulation 103(15), (2001). 2. Iakovou I, Schmidt T, Bonizzoni Eet al.: Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 293(17), (2005). 3. Kuchulakanti PK, Chu WW, Torguson Ret al.: Correlates and long-term outcomes of angiographically proven stent thrombosis with sirolimus- and paclitaxel-eluting stents. Circulation 113(8), (2006). 4. de la Torre-Hernandez JM, Alfonso F, Hernandez Fet al.: Drug-eluting stent thrombosis: results from the multicenter Spanish registry ESTROFA (Estudio ESpanol sobre TROmbosis de stents FArmacoactivos). J. Am. Coll. Cardiol. 51(10), (2008). 5. Wenaweser P, Rey C, Eberli FRet al.: Stent thrombosis following bare-metal stent implantation: success of emergency percutaneous coronary intervention and predictors of adverse outcome. Eur. Heart J. 26(12), (2005). 6. Airoldi F, Colombo A, Morici Net al.: Incidence and predictors of drug-eluting stent thrombosis during and after discontinuation of thienopyridine treatment. Circulation 116(7), (2007). 7. Cutlip DE, Windecker S, Mehran Ret al.: Clinical end points in coronary stent trials: a case for standardized definitions. Circulation 115(17), (2007). 8. Park DW, Park SW, Park KHet al.: Frequency of and risk factors for stent thrombosis after drug-eluting stent implantation during long-term follow-up. Am. J. Cardiol. 98(3), (2006). 9. Mauri L, Hsieh WH, Massaro JM, Ho KK, D Agostino R, Cutlip DE: Stent thrombosis in randomized clinical trials of drug-eluting stents. N. Engl. J Med. 356(10), (2007). 10. Morice MC, Serruys PW, Sousa JEet al.: A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N. Engl. J. Med. 346(23), (2002). 11. Stone GW, Ellis SG, Cox DAet al.: A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease. N. Engl. J. Med. 350(3), (2004). 12. Canto JG, Every NR, Magid DJet al.: The volume of primary angioplasty procedures and survival after acute myocardial infarction. National Registry of Myocardial Infarction 2 Investigators. N. Engl. J. Med. 342(21), (2000). 129

17 Chapter 8 130