The PASEO (PaclitAxel or Sirolimus-Eluting Stent Versus Bare Metal Stent in Primary Angioplasty) Randomized Trial

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1 JACC: CARDIOVASCULAR INTERVENTIONS VOL. 2, NO. 6, BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION ISSN /09/$36.00 PUBLISHED BY ELSEVIER INC. DOI: /j.jcin The PASEO (PaclitAxel or Sirolimus-Eluting Stent Versus Bare Metal Stent in Primary Angioplasty) Randomized Trial Emilio Di Lorenzo, MD, PHD,* Giuseppe De Luca, MD, PHD, Rosario Sauro, MD,* Attilio Varricchio, MD, PHD,* Michele Capasso, MD,* Tonino Lanzillo, MD,* Fiore Manganelli, MD,* Ciro Mariello, MD,* Francesco Siano, MD,* Maria Rosaria Pagliuca, MD,* Giovanni Stanco, MD,* Giuseppe Rosato, MD* Avellino and Novara, Italy Objectives The aim of this study was to evaluate the benefits of sirolimus-eluting stents (SES) and paclitaxeleluting stents (PES) as compared with bare-metal stents (BMS) in patients undergoing primary angioplasty. Background Recent concerns have emerged on the potential higher risk of stent thrombosis after drugeluting stent implantation, especially among ST-segment elevation myocardial infarction (STEMI) patients. Methods We randomly assigned STEMI patients admitted within 12 h of symptom onset undergoing primary angioplasty and stent implantation to BMS, PES, or SES. The primary study end point was target lesion revascularization at 1-year follow-up. All patients were reviewed at our outpatient clinic or by telephone interview at 6, 12, and 24 months. Results From October 2003 to December 2005, 270 STEMI patients undergoing primary angioplasty were randomized to BMS (n 90), PES (n 90), or SES (n 90). No patient was lost to follow-up. As compared with BMS (14.4%), both PES (4.4%, p 0.023) and SES (3.3%, p 0.016) were associated with a significant reduction in target lesion revascularization at 1-year follow-up. At 2-year follow-up no difference was observed in terms of death, reinfarction, and combined death and/or reinfarction, but as compared with BMS, both PES and SES were associated with significant benefits in major adverse cardiac events (PES: 16.7%, p 0.015; SES: 15.6%, p 0.009, respectively). Conclusions This study shows that among STEMI patients undergoing primary angioplasty, both SES and PES are safe and associated with significant benefits in terms of target lesion revascularization up to the 2-year follow-up. Thus, until the results of further large randomized trials with longterm follow-up become available, drug-eluting stents may be considered for STEMI patients undergoing primary angioplasty. (PaclitAxel or Sirolimus-Eluting Stent versus Bare Metal Stent in Primary Angioplasty [PASEO] Randomized Trial; NCT ) (J Am Coll Cardiol Intv 2009;2:515 23) 2009 by the American College of Cardiology Foundation From the *Division of Cardiology, Ospedale S.G. Moscati, Avellino, Italy; Division of Cardiology, Ospedale Maggiore della Carità, and Centro di Biotecnologie per la Ricerca Medica Applicata (BRMA), Eastern Piedmont University, Novara, Italy. Drs. Di Lorenzo and De Luca contributed equally to this study. Manuscript received February 12, 2009, accepted March 17, 2009.

2 516 JACC: CARDIOVASCULAR INTERVENTIONS, VOL. 2, NO. 6, 2009 Abbreviations and Acronyms BMS bare-metal stent(s) DES drug-eluting stent(s) PCI percutaneous coronary intervention PES paclitaxel-eluting stent(s) SES sirolimus-eluting stent(s) STEMI ST-segment elevation myocardial infarction TLR target lesion revascularization TVR target vessel revascularization Primary percutaneous coronary intervention (PCI), when performed expeditiously and expertly, has been shown to be superior to thrombolytic therapy in the treatment of patients with ST-segment elevation myocardial infarction (STEMI) (1). Although, as compared with balloon angioplasty, stent implantation has reduced the occurrence of restenosis in selected STEMI patients (2,3), the outcome of bare-metal stents (BMS) seem to be worse in unselected patients with a rate of target vessel revascularization (TVR) up to 20% (4,5). Several randomized trials have shown that drugeluting stents (DES), compared with BMS, are associated with a significant reduction in restenosis and TVR in elective patients (6 10). However, recent concerns have emerged on the potential higher risk of stent thrombosis with DES (11 14) that might be even more pronounced among STEMI patients, as suggested by a prospective registry (15). The aim of the current study was to evaluate the benefits of sirolimus-eluting stents (SES) and paclitaxeleluting stents (PES) as compared with the benefits of BMS in patients undergoing primary angioplasty for STEMI. Methods The PASEO (PaclitAxel or Sirolimus-Eluting Stent versus Bare Metal Stent in Primary Angioplasty) trial was a prospective, single-center, randomized trial evaluating the benefits of SES or PES as compared with BMS implantation in patients undergoing primary angioplasty for acute STEMI. Individuals eligible for enrollment were patients presenting with STEMI who fulfilled all the following inclusion criteria: 1) chest pain for more than 30 min; 2) ST-segment elevation of 1 mm or more in 2 or more contiguous electrocardiograph leads or with presumably new left bundle branch block; 3) hospital admission within 12 h from symptoms onset. Exclusion criteria included: 1) active internal bleeding or a history of bleeding diathesis within the previous 30 days; 2) history of intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation or aneurysm; 3) known allergy to sirolimus, paclitaxel, heparin, aspirin, or clopidogrel; 4) history of stroke within 30 days or any history of hemorrhagic stroke; 5) major surgical procedure or severe physical trauma within the previous month; 6) history, symptoms, or findings suggestive of aortic dissection; 7) thrombolytic/fibrinolytic therapy within 24 h; 8) history of thrombocytopenia; 9) hemorrhagic retinopathy; 10) patients on warfarin or acenocoumarol with international normalized ratio 2; and 11) pregnancy. Previous gastrointestinal ulcer or gastrointestinal bleeding were not exclusion criteria. A vessel size 2.25 mm was the only angiographic exclusion criteria. The institutional review board of the Ospedale S.G. Moscati (Avellino, Italy) approved the protocol in 2003, and all patients gave written informed consent. Open-label randomization was performed in the catheterization laboratory after initial angiography by the treating physician when eligibility criteria were met. A 1:1:1 computer-generated random sequence, without blocking or stratification, was used. Sealed envelopes indicated the treatment group to which the patients were assigned: SES, PES, or BMS. Medications. In the coronary care unit, all patients received 70 U/kg intravenous bolus of unfractionated heparin plus 1000 U/h infusion (to maintain an activated clotting time of at least 200 s), aspirin intravenously (500 mg), and clopidogrel (300-mg loading dose). All patients received upstream glycoprotein IIb/IIIa inhibitors as a routine adjunctive therapy before primary PCI. Post-interventional antiplatelet therapy for all patients included in the 3 study groups consisted of aspirin (100 mg) indefinitely and clopidogrel (75 mg for 6 months). Angioplasty procedure. Stenting procedures were performed according to standard techniques. The number, size, and length of stents (based on online quantitative angiographic analyses), and the type of BMS to be implanted, were left to the operator s discretion. In cases of DES implantation, it was recommended to cover the entire length of the lesion with additional coverage of 5 mm proximal and distal to the lesion. The use of intravascular ultrasound, adjunctive thrombectomy devices, distal protection devices, and intra-aortic balloon pump were left to the operator s discretion. Angiographic analysis. Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 coronary flow in the treated vessel and a residual stenosis less than 30% were the criteria used to define a successful PCI. Offline quantitative coronary angiography (Integris Allura, Philips, Best, the Netherlands) were performed by 2 experienced technicians who were unaware of treatment assignment with the averaging scores if they were not in agreement. The target lesion was defined as the stented segment plus the 5-mm segments immediately proximal and distal to the stent. Data collection and follow-up. All patients were reviewed at our outpatient clinic or by telephone interview at 6, 12, and 24 months. A stress test was performed at 6 to 8 months and subsequently yearly. For patients who died during followup, hospital records and necropsy data were reviewed when possible. No patient was lost to follow-up. Study end points and definitions. The primary end point was target lesion revascularization (TLR) at 1-year follow-up. Secondary end points were: 1) cumulative combined incidence of death and/or recurrent MI at 2-year follow-up; 2)

3 JACC: CARDIOVASCULAR INTERVENTIONS, VOL. 2, NO. 6, Figure 1. Study Flow Chart The figure shows how patients were assigned to specific stent treatment groups. BMS bare-metal stent(s); PES paclitaxel-eluting stent(s); pts patients; SES sirolimus-eluting stent(s); STEMI ST-segment elevation myocardial infarction. cumulative incidence of in-stent thrombosis (assessed according to Academic Research Consortium s definition [16]) at 2-year follow-up; and 3) major adverse cardiac events (combined death and/or recurrent MI and/or TLR) at 2-year follow-up. All deaths were considered cardiac unless an unequivocal noncardiac cause could be identified. Recurrent MI was defined as recurrence of anginal symptoms with typical electrocardiographic changes and increase above the upper limit of normal of creatine kinase-myocardial band or troponin. The indication for a second intervention had to be substantiated by symptoms or by electrocardiographic or scintigraphic evidence of ischemia at rest or during exercise. Subsequent revascularization of other coronary arteries did not constitute an end point. All events were reviewed by 2 cardiologists blinded to treatment assignment. Statistical analysis. Statistical analysis was performed using SPSS version 15.0 (SPSS Inc., Chicago, Illinois). Continuous data were expressed as mean (SD) and categorical data as percentages. Data were analyzed according to intentionto-treat analysis (SES vs. BMS and PES vs. BMS). The analysis of variance or the Mann-Whitney U test were appropriately used for continuous variables. (Normal distribution was assessed by the Kolmogorov-Smirnov test.) The chi-square test or Fisher exact test was used for categorical variables The difference in event rates between groups during the follow-up period was assessed by the Kaplan- Meier method with the log-rank test. A probability value of p (with Bonferroni correction) was considered significant. SAMPLE SIZE CALCULATION. According to recent reports (4,5), we estimated a rate of TLR at 1 year of 20% in the BMS group. With an anticipated 2-sided test for differences in independent binomial proportions at the 2.5% significance level (with Bonferroni correction) with a power of 80%, 89 patients were necessary to detect a reduction in a primary end point of 80% (from 20% to 4%) with DES (PES and SES, respectively). The number of patients was extended to 90 per group. Results Patient population. From October 1, 2003, to December 31, 2005, 270 patients with STEMI undergoing primary angioplasty and stent implantation were randomized to BMS (n 90), PES (n 90), or SES (n 90) treatment. A trial flow diagram is shown in Figure 1. As reported in Tables 1 and 2, no difference was observed in terms of baseline demographic, clinical, and angiographic characteristics among the groups. Procedural results. As shown in Table 2, no difference was observed in terms of angiographic and procedural characteristics. Almost 50% of patients underwent PCI of left anterior descending artery. All patients received upstream glycoprotein IIb/IIIa inhibitors. Procedural success was obtained in 93% to 95% of patients. A direct stenting strategy was adopted in 24% to 29% of patients. In the PES group, we observed a higher number of stents per patient ( vs , p 0.036). Clinical outcome at 1-year follow-up. Follow-up data were available for all patients. Almost all patients stopped clopidogrel therapy at 6-month follow-up (Table 3). As reported in Table 4, at 1-year follow-up, no difference was observed in terms of death (6 deaths in BMS patients due to: heart failure [n 3], sudden death [n 1], reinfarction [n 1], cardiac surgery [n 1]; 4 deaths in PES patients due to: sudden death [n 2], reinfarction [n 2]; 3 deaths in SES patients due to: sudden death [n 2], reinfarction [n 1]), reinfarction, and combined death and/or reinfarction. One stent thrombosis was documented in both the BMS (1.1%) and PES (1.1%) groups, both of them within 30 days from primary PCI, whereas no case of stent thrombosis was observed after 30 days. As compared with BMS (14.4%),

4 518 JACC: CARDIOVASCULAR INTERVENTIONS, VOL. 2, NO. 6, 2009 Table 1. Baseline Demographic and Clinical Characteristics of the 3 Groups of Patients Variable BMS (n 90) PES (n 90) p Value SES (n 90) p Value Age, yrs Male, % Hypertension, % Diabetes, % IDDM NIDDM Smoking, % Previous MI, % Previous CABG, % Previous PCI, % Cardiogenic shock, % Anterior MI, % Ejection fraction 40%, % Ischemia time, min Door-to-balloon time, min BMS bare-metal stent(s); CABG coronary artery bypass graft; IDDM insulin-dependent diabetes mellitus; MI myocardial infarction; NIDDM noninsulin-dependent diabetes mellitus; PES paclitaxel-eluting stent(s); PCI percutaneous coronary intervention; SES sirolimus-eluting stent(s). both PES (4.4%, hazard ratio [HR] [95% confidence interval (CI)]: 0.29 [0.095 to 0.89], p 0.023) and SES (3.3%, HR [95% CI]: 0.21 [0.06 to 0.75], p 0.016) were associated with a significant reduction in TLR (primary study end point). Finally, as compared with BMS (24.4%), both PES and SES were associated with significant benefits Table 2. Angiographic and Procedural Characteristics of the 3 Groups of Patients Variable BMS (n 90) PES (n 90) p Value SES (n 90) p Value IRA, % LAD LCX RCA Pre-procedural TIMI flow grade, % Post-procedural TIMI flow grade, % RD, mm % stenosis before % stenosis after Stent diameter, mm Max stent diameter, mm Total stent length, mm Number of stents stent, % Direct stenting, % Maximal balloon inflation, atm Procedural success, % GP IIb/IIIa inhibitors, % Thrombectomy devices, % GP glycoprotein; IRA infarct-related artery; LAD left anterior descending artery; LCX left circumflex artery; RCA right coronary artery; RD reference diameter; TIMI Thrombolysis In Myocardial Infarction; other abbreviations as in Table 1.

5 JACC: CARDIOVASCULAR INTERVENTIONS, VOL. 2, NO. 6, Table 3. Medical Therapy of the 3 Groups of Patients Variable BMS (n 90) PES (n 90) p Value SES (n 90) p Value Aspirin, % Beta-blockers, % ACE inhibitors, % Statins, % Clopidogrel at discharge, % Clopidogrel administration, days Clopidogrel at 30 days, % months, % ACE angiotensin-converting enzyme; other abbreviations as in Table 1. in major adverse cardiac events (PES: 11.1%, HR [95% CI]: 0.42 [0.2 to 0.9], p 0.02; SES: 11.1%, HR [95% CI]: 0.42 [0.2 to 0.89], p 0.02). Clinical outcome at 2-year follow-up. Follow-up data were available in all patients. As reported in Table 4, at 2-year follow-up, no difference was observed in terms of death (Fig. 2) (9 deaths in BMS patients due to: heart failure [n 4], sudden death [n 2], cardiac surgery [n 1], reinfarction [n 2]; 6 deaths in PES patients due to: sudden death [n 2], reinfarction [n 2]; cardiogenic shock [n 2]; 5 deaths in SES patients due to: sudden death [n 2], reinfarction [n 2], noncardiac death [n 1]), reinfarction (Fig. 3), and combined death and/or reinfarction (secondary study end point) (PES: 12.2%, HR [95% CI]: 0.63 [0.29 to 1.34], p 0.17; SES: 11.1%, HR [95% CI]: 0.57 [0.26 to 1.23], p 0.27), as compared with BMS (18.3%) (Fig. 4). No additional case of in-stent thrombosis was observed up to 2-year follow-up. As compared with BMS (17.8%), both PES (5.6%, HR [95% CI]: 0.29 [0.11 to 0.8], p 0.01) and SES (4.4%, HR [95% CI]: 0.23 [0.076 to 0.68], p 0.004) were associated with a significant reduction in TLR (Fig. 5). Finally, as compared with BMS (32.2%), both PES and SES were associated with significant benefits in overall MACE (secondary study end point) (PES: 16.7%, HR [95% CI]: 0.47 [0.25 to 0.88], p 0.015; SES: 15.6%, HR [95% CI]: 0.44 [0.23 to 0.83], p 0.005) (Fig. 6). Table 4. Clinical Outcome at 1-Year Follow-Up Variable BMS (n 90) PES (n 90) p Value PES vs. BMS HR [95% CI] SES (n 90) p Value SES vs. BMS HR [95% CI] 1-year outcome Death, % [ ] [ ] remi, % [ ] [ ] Death and/or remi, % [ ] [ ] TLR, % [ ] [ ] Definite IST, % [ ] [ ] Early ( 30 days) [ ] [ ] Late ( 30 days) Total IST,* % [ ] [ ] MACE, % [ ] [ ] 2-year outcome Death [ ] [ ] ReMI, % [ ] [ ] Death and/or remi, % [ ] [ ] TLR, % [ ] [ ] Definite IST, % [ ] [ ] Very late IST ( 1 year) Total IST* [ ] [ ] MACE, % [ ] [ ] *Definite, probable, and possible in-stent thrombosis. CI confidence interval; HR hazard ratio; IST angiographic in-stent thrombosis; MACE major adverse cardiac events; remi reinfarction; TLR target lesion revascularization; other abbreviations as in Table 1.

6 520 JACC: CARDIOVASCULAR INTERVENTIONS, VOL. 2, NO. 6, 2009 Figure 2. Kaplan-Meier Survival Curves for Death Comparing BMS, PES, and SES Kaplan-Meier survival curves comparing BMS with PES (p 0.84) and SES (p 0.52). Abbreviations as in Figure 1. prospective multicenter primary angioplasty registry (PRE- MIER [Prospective Registry Evaluating Myocardial Infarction Events and Recovery]), the use of DES rather than BMS was associated with higher risk of mortality within the first 6 months (presumably due to higher stent thrombosis), particularly in the case of early discontinuation of double oral antiplatelet therapy (18). In fact, unlike with elective patients, it may be difficult to forecast future long-term patients compliance at the time of intervention among STEMI patients (18). Several randomized trials have been conducted so far in STEMI (19 35). Valgimigli et al. (19) compared SES plus tirofiban with the bare-metal Bx Velocity (Cordis Corp., Bridgewater, New Jersey) plus abciximab in 175 STEMI patients. At 8-month follow-up, SES was associated with a significant reduction in TVR (7% vs. 20%, p 0.01), with a similar outcome in terms of death (2% vs. 3%, p NS), reinfarction (1% vs. 3%, p NS), and stent thrombosis (0% vs. 2%, p NS). Similar benefits have been observed in the larger MULTISTRATEGY (Multicentre Evaluation of Single High-Dose Bolus Tirofiban versus Abciximab with Sirolimus-Eluting Stent or Bare Metal Stent in Acute Myocardial Infarction Study) trial (32). The benefits from SES in terms of reducing clinical and angiographic restenosis without an increase in death or MI have been confirmed in subsequent moderate-sized randomized trials Discussion To the best of our knowledge, this is the first randomized study evaluating the benefits and safety of both PES and SES versus BMS in patients undergoing primary angioplasty for STEMI at long-term follow-up (2 years). The main finding of the current study is that PES and SES are safer and more effective than BMS, mainly due to a reduction in TLR. After the initial safety concerns, numerous studies and randomized trials have demonstrated the safety and efficacy of stenting in the setting of STEMI (3). A recent comprehensive meta-analysis in patients undergoing primary PCI has shown the benefits of stenting compared with balloon angioplasty alone in terms of reducing TVR, though no definite affect on death and reinfarction was present (3). However, restenosis rates after BMS in STEMI patients are still high, especially in unselected patients with complex lesion morphology (4,5). Several randomized trials have shown that, among elective patients, DES are associated with a significant reduction in restenosis and TVR (6 10). However, recent concerns have emerged regarding an increased risk of late thrombosis stent associated with DES (12 15). As most episodes of stent thrombosis result in MI, this increase with DES may impact mortality, particularly after primary angioplasty, as reinfarction is a major determinant of survival (17). In a recent Figure 3. Kaplan-Meier Event-Free Survival Curves for Reinfarction Comparing BMS, PES, and SES Kaplan-Meier event-free survival curves for reinfarction comparing BMS with PES (p 0.34) and SES (p 0.58). Abbreviations as in Figure 1.

7 JACC: CARDIOVASCULAR INTERVENTIONS, VOL. 2, NO. 6, Figure 4. Kaplan-Meier Event-Free Survival Curves (for Death and/or Reinfarction) Comparing BMS, PES, and SES Kaplan-Meier event-free survival curves (for death and/or reinfarction) comparing BMS with PES (p 0.44) and SES (p 0.29). Abbreviations as in Figure 1. Acute Myocardial Infarction) trial (32), including more than 3,000 STEMI patients, that have shown significant benefits in terms of TLR with Taxus (Boston Scientific) stents as compared with BMS (4.5% vs. 7.5%, respectively), with similar outcome in terms of death and reinfarction. However, almost all currently available trials have provided relatively short-term follow-up data (not longer than 12 months), whereas late stent thrombosis has been described up to 1 to 2 years after clopidogrel discontinuation. The STRATEGY (Single High-Dose Bolus Tirofiban and Sirolimus-Eluting Stent vs. Abciximab and Bare-Metal Stent in Myocardial Infarction) trial is the only trial published so far with 2-year follow-up data, showing long-term safety and benefits of SES as compared with BMS (33). In our study, including a larger population, we demonstrated the long-term safety and benefits of both SES and PES as compared with BMS. Of relevance, unlike the vast majority of randomized trials so far conducted, in our trial, the superiority of SES and PES was observed without use of routine angiographic follow-up. Large randomized trials, with longer follow-up data are certainly needed to further investigate the long-term safety of DES in primary angioplasty. In this regard, important information is expected to be derived from the HORIZONS- AMI trial (34). such as the TYPHOON (Trial to Assess the Use of the Cypher Stent in Acute Myocardial Infarction Treated with Angioplasty), SESAMI (Sirolimus-Eluting Stent Versus Bare-Metal Stent in Acute Myocardial Infarction), and MISSION trials (21,22,27). In the PASSION (Paclitaxel-Eluting Stent versus Conventional Stent in ST-Segment Elevation Myocardial Infarction ) trial (20), Laarman et al. compared PES versus Express (Boston Scientific, Natick, Massachusetts) stents in 619 STEMI patients. Despite the safety of PES in terms of death (4.6% vs. 6.5%, p NS) and stent thrombosis (1% vs. 1%, p NS) at 1-year follow-up, as compared with BMS, only a weak trend was present toward a reduction in TLR (5.3% vs. 7.8%, p NS). The relatively less favorable outcomes of PES in this trial compared with the outcomes of SES in the previous trials may relate either to the less marked reduction of neointimal hyperplasia with paclitaxel versus sirolimus, or a better outcome with the control stents in the PASSION trial compared with the Bx Velocity stents in the SES trials. Also of note, routine angiographic follow-up was not performed in the PASSION trial. In fact, several reports have demonstrated that routine angiographic follow-up is associated with a larger rate of TVR, even in the era of DES (36). Similar findings have been observed in the recently conducted large HORIZONS AMI (Harmonizing Outcomes with Revascularization and Stents in Figure 5. Kaplan-Meier Event-Free Survival Curves for TLR Comparing BMS, PES, and SES Kaplan-Meier event-free survival curves for target lesion revascularization (TLR) comparing BMS with PES (p 0.02) and SES (p 0.008). Abbreviations as in Figure 1.

8 522 JACC: CARDIOVASCULAR INTERVENTIONS, VOL. 2, NO. 6, 2009 Reprint requests and correspondence: Dr. Emilio Di Lorenzo, Division of Cardiology, Laboratory of Cardiac Catheterization and Interventional Cardiology, S.G. Moscati Hospital, Via Otranto, Avellino, Italy. REFERENCES Figure 6. Kaplan-Meier Event-Free Survival Curves for MACE Comparing BMS, PES, and SES Kaplan-Meier event-free survival curves for major adverse cardiac events (MACE) comparing BMS with PES (p 0.03) and SES (p 0.018). Abbreviations as in Figure 1. Study limitations. Due to a relatively late randomization strategy (after initial angiography), patients have for the most part been selected, and thus the conclusion of this trial cannot be extended to all patients undergoing primary angioplasty for STEMI. Even though small vessels (2.25 to 2.5 mm) were not excluded, our patient population had a relatively larger (3.1 mm) mean reference diameters than were included in previous randomized trials. Furthermore, to avoid any bias due to length of clopidogrel prescription, we preferred to prescribe clopidogrel up to 6 months in BMS patients as well. Despite long-term follow-up data, due to the relatively small sample size, this trial cannot provide definite conclusions on DES safety in terms of death and reinfarction that will be hopefully provided by large randomized trials. Conclusions This study shows that among STEMI patients undergoing primary angioplasty, both SES and PES are safe and associated with significant benefits in terms of TLR up to 2-year follow-up. Thus, until the results of further large randomized trials with long-term follow-up become available, DES may be considered for use for STEMI patients undergoing primary angioplasty. 1. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. 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