Cardiovasc Interv and Ther DOI 10.1007/s12928-016-0445-6
Left main crossover stenting in a patient with severe thrombocytopenia due to aplastic anemia Marie Nishikawa1 • Jun Shiraishi1 • Muneo Ohshiro2 • Masaki Yashige1 Masayuki Hyogo1 • Takahisa Sawada1
Received: 25 June 2016 / Accepted: 15 November 2016 Ó Japanese Association of Cardiovascular Intervention and Therapeutics 2016
Abstract A 76-year-old man with aplastic anemia presented with recurrent acute myocardial infarction (AMI) with heart failure. After the initial appearance of AMI approximately 2 months earlier, he had received conservative treatment/transfusion alone because of severe thrombocytopenia and anemia (platelet 11 9 103/lL, hemoglobin 6.4 g/dL). Refractory heart failure persisted despite repeated conservative treatment/transfusion for the second AMI, and therefore, we performed transradial coronary angiography and left main crossover stenting with a bare metal stent. His critical condition markedly improved; however, soon after discharge, he complicated with subdural hematoma. He has since been free of cardiovascular/hemorrhagic events for 7 months without antiplatelet/anticoagulant therapy.
arterial thrombosis, such as acute myocardial infarction (AMI). Indeed, there are few reports of AMI in cases with aplastic anemia, in which anabolic steroids or platelet transfusion might play a significant role in the pathogenesis of coronary or stent thrombosis, respectively [1, 2]. Here, we describe our experience in an unusual serious case of AMI complicated with aplastic anemia-induced severe thrombocytopenia, heart failure, and 3-vessel disease, including the culprit lesion in the just proximal left anterior descending coronary artery (LAD). Left main crossover stenting was successfully achieved under single antiplatelet therapy with aspirin and intravenous infusion of unfractionated heparin, leading to stabilization of hemodynamics; however, subdural hematoma after discharge required surgical treatment and cessation of aspirin.
Keywords Percutaneous coronary intervention Bare metal stent Complications Subdural hematoma
Case report Introduction Aplastic anemia is a form of anemia characterized by bone-marrow hypoplasia and peripheral pancytopenia. Patients with severe thrombocytopenia due to this hematological disorder have a higher frequency of bleeding complications, but a lower frequency of an & Jun Shiraishi [email protected] 1
Department of Cardiology, Kyoto First Red Cross Hospital, Honmachi, Higashiyama-ku, Kyoto 605-0981, Japan
Department of Hematology, Kyoto First Red Cross Hospital, Honmachi, Higashiyama-ku, Kyoto 605-0981, Japan
A 76-year-old man with aplastic anemia was admitted to our hospital due to general fatigue and appetite loss. His coronary risk factors included hypertension, which had been pointed out at the age of 25, but left almost without medication until the onset of previous angina. He had experienced angina on effort and undergone percutaneous coronary intervention (PCI) using a bare metal stent (BMS) for an intermediate branch and balloon dilation alone for mid-distal segments of the left circumflex coronary artery (LCx) 17 years earlier. Since then, he had taken aspirin; however, aspirin was stopped because of thrombocytopenia (platelet 23 9 103/lL) 4 months before admission. Two months before admission, a bone-marrow immunohistochemical study for thrombocytopenia confirmed the diagnosis of aplastic anemia, and immunosuppressive therapy
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with cyclosporine A was started. After this therapy, the platelet count still remained at around 13 9 103/lL. At admission, an electrocardiogram (ECG) showed STsegment elevation in III and aVF, in addition to ST-segment depression in I, aVL, and V4–6 leads, and a chest radiograph revealed cardiomegaly with lung congestion. Subsequent transthoracic echocardiography revealed decreased motion in the apico-anteroseptal and inferoposterior wall of the left ventricle. A routine blood test showed pancytopenia (platelet 11 9 103/lL, hemoglobin 6.4 g/dL, white blood cell 3730/lL) and increases in cardiac enzymes and serum creatinine (CPK 1714 IU/L, CPK-MB 186 IU/mL, troponin T 2.5 ng/mL, creatinine 2.33 mg/dL). The patient was diagnosed with AMI with heart failure and acute kidney injury; however, we first selected conservative treatment without coronary angiography (CAG)/PCI because of severe thrombocytopenia. The clinical condition gradually improved after intravenous administration of nicorandil and unfractionated heparin, as well as transfusions of Platelet Concentrates (PC) and Red Cell Concentrates (RCC) without antiplatelet agents, and the patient was discharged on the 18th hospital day. The peak value of CPK was 3385 IU/L. During the admission period, coronary computed tomography revealed severe stenosis in the just proximal LAD and in the distal right coronary artery (RCA), in addition to total occlusion in the LCx. Approximately 1 month after discharge, the patient was re-admitted for recurrent AMI complicated with heart failure. An ECG showed a similar but marked ST-segment change (Fig. 1), compared with that in the prior admission. A routine blood test showed pancytopenia (platelet 9 9 103/lL, hemoglobin 6.7 g/dL, and white blood cell 3580/lL) and increases in cardiac enzymes and
Fig. 1 Electrocardiogram at admission and before discharge for recurrent AMI. Significant resolution of ST-segment change was observed before discharge
At Admission V1
serum creatinine (CPK 318 IU/L, creatinine 2.72 mg/dL). On the second hospital day, despite conservative treatment, including PC and RCC transfusions, refractory heart failure status concomitant with renal failure persisted, and CPK and serum creatinine increased to 2306 IU/L and 3.11 mg/ dL, respectively, while thrombocytopenia and anemia became less severe due to the PC/RCC transfusions (platelet 71 9 103/lL, hemoglobin 10.7 g/dL) (Fig. 2). To relieve this critical condition, immediate transradial CAG/ PCI was performed. A 6-Fr sheath (Glidesheath Slender, TERUMO) was introduced into the left radial artery. After administration of unfractionated heparin (2000 U) through the sheath, emergency CAG was performed. Right CAG indicated a subtotal occlusion in the distal RCA (Fig. 3a). Left CAG revealed severe stenosis in the LAD take-off and in-stent stenosis in the intermediate branch in addition to total occlusion in the mid LCx (Fig. 3b–d). The distal segment of the RCA was poorly delineated via collaterals from the septal perforator and distal intermediate branch. Based on the clinical history and CAG findings, the LAD ostial lesion was concluded to be the current AMI culprit site. Therefore, we performed transradial PCI without intraaortic balloon pumping (IABP) support against the in-stent stenosis in the intermediate branch, using scoring-balloon dilation, and the stenosis in the LAD take-off, using a single crossover BMS implantation from the left main coronary artery (LMCA) to the proximal LAD, under onsite coronary artery bypass grafting surgery backup. After loading of aspirin 200 mg and additional intravenous administration of unfractionated heparin (5000 U), using a 6-Fr guiding catheter (Autobahn, BUL 3.5 CY, Nipro), a floppy guidewire was advanced into the distal
Left main crossover stenting in a patient with severe thrombocytopenia due to aplastic anemia
Fig. 2 Clinical course during second admission due to recurrent ACS. CSH chronic subdural hematoma, RCC red cell concentrates, PC platelet concentrates
Fig. 3 Emergency CAG and PCI for intermediate in-stent lesion and LAD take-off lesion. a Right CAG depicted subtotal occlusion in the distal RCA (left anterior view). b–d Left CAG revealed severe stenosis in the LAD take-off (white arrowheads) and in-stent stenosis in the intermediate branch (black arrows) in addition to total occlusion in the mid LCx (white arrows) (b right anterior caudal
LAD without difficulty. After another guidewire crossing across the intermediate branch, intravascular ultrasound imaging (IVUS) depicted much plaque with a heterogeneous echo intensity concomitant with deep calcification and a cavity, which was probably due to plaque rupture at the culprit site in the just proximal LAD (Fig. 4a, b), and in-stent intimal thickening with superficial calcification in the intermediate branch (Fig. 4c). First, the intermediate in-stent lesion was dilated with a 2.0 mm balloon catheter and another 2.25 mm scoring-balloon catheter. Second, a BMS (Integrity, 3.5/12 mm, Medtronic) was directly implanted from the LMCA to the proximal LAD under IVUS guidance, jailing the LCx and intermediate branch. After wire-recrossing of the intermediate branch, we added kissing balloon inflation with an optimal angiographic result (Fig. 3e, f). The distal segment of the RCA could be
view; c left anterior caudal view; and d anterior–posterior cranial view). e, f Final left CAG after PCI (e anterior–posterior cranial view; f anterior–posterior caudal view). Distal RCA was delineated by contralateral collaterals through septal perforator from the LAD and from the distal intermediate branch
M. Nishikawa et al. Fig. 4 Intravascular ultrasound imaging (IVUS) during PCI for intermediate in-stent lesion and LAD take-off lesion. a Eccentric plaque with heterogeneous echo intensity concomitant with deep calcification at the just proximal LAD. b (Just proximal to the a) large cavity in the plaque at the just proximal LAD (white arrowheads) and a protection wire in the intermediate branch (white arrow). c In-stent intimal thickening with superficial calcification in the intermediate branch. d Optimal stent expansion and apposition at the left main–intermediate branch bifurcation
clearly depicted via collaterals from the left coronary artery (Fig. 3f). Final IVUS showed complete stent apposition with optimal placement (Fig. 4d). After the procedure, the patient received intravenous infusion of unfractionated heparin for 2 weeks and oral aspirin 100 mg/day thereafter (Fig. 2). The heparin infusion was titrated using the activated partial thromboplastin time to a therapeutic range of 1.5–2.0 times normal. PC transfusion was performed approximately once a week to maintain the peripheral platelet count at [10 9 103/lL, and on the PC transfusion day during admission heparin infusion and additional aspirin, 100 mg/day (total 200 mg/day) were administered expectantly to prevent fatal stent thrombosis (Fig. 2). The peak value of CPK was 2306 IU/L and scintigraphy with 99 m-technetium pyrophosphate showed distribution in the anteroseptal wall (Fig. 5a). After PCI, heart failure improved markedly and serum creatinine gradually decreased to 1.36 mg/dL before discharge. On the ninth hospital day, the patient complained of epistaxis, which spontaneously healed with PC transfusion (Fig. 2). He was discharged under single antiplatelet therapy with aspirin on the 18th hospital day.
A few days after discharge, however, he became conscious of right-sided hemiparesis. He was, therefore, readmitted to our hospital 8 days after discharge, and diagnosed with left-sided chronic subdural hematoma (Figs. 2, 5b). The platelet count at re-admission was 10 9 103/lL. After PC transfusion, he immediately underwent one burr hole evacuation on the first hospital day, percutaneous hematoma evacuation on the 6th hospital day, and one burr hole irrigation on the 14th hospital day, resulting in complete neurological recovery and discharge on the 24th hospital day. At re-admission for chronic subdural hematoma, he had no choice but to stop taking aspirin. However, even without antiplatelet/anticoagulant therapy, repeat percutaneous hematoma evacuation was performed for worsening of chronic subdural hematoma 10 days after the last discharge. Regardless of persistent mild dyspnea on effort due to anemia and heart failure, as well as refractory severe aplastic anemia, he has since been free of cardiovascular events and bleeding complications under PC/RCC transfusion approximately once a week without antiplatelet or anticoagulant therapy for 7 months.
Left main crossover stenting in a patient with severe thrombocytopenia due to aplastic anemia Fig. 5 a Short-axis views of dual single-photon emission computed tomography (SPECT) with 99-m-technetium pyrophosphate (99m-Tc PYP, red color) and 201-thallium (201-Tl, green color) after the PCI. Accumulation of 99m-Tc PYP in the anteroseptal wall and defect of 201-Tl in the posterior wall were delineated. b Head CT revealed left-sided chronic subdural hematoma concomitant with midline shift
Discussion Dual antiplatelet therapy (DAPT) with aspirin and thienopyridines, such as clopidogrel or prasugrel, is an established therapy for patients with coronary artery disease (CAD) undergoing stent implantation, including those with acute coronary syndrome (ACS). In contrast, regardless of the ACS status, no guidelines and only a few case reports are available on the safety and tolerance of DAPT in stent-implanted CAD patients complicated with thrombocytopenia [5–7]. There are no established definitions of mild, moderate, or severe thrombocytopenia, but a series of reports suggest that thrombocytopenia may be graded as mild (100–150 9 103/lL), moderate (50–100 9 103/lL), and severe (\50 9 103/lL) [3–5]. In daily clinical practice, DAPT is usually prescribed in stent-implanted CAD patients with mild thrombocytopenia in the long term and even in those with moderate thrombocytopenia over a short-term period [5–7]. In contrast, cardiologists tend to hesitate to administer DAPT in patients with severe thrombocytopenia, and even avoid single antiplatelet therapy in those with extremely severe thrombocytopenia (\20 9 103/lL) because of the increased risk of hemorrhagic complications. In single antiplatelet therapy, aspirin is related to significantly improved 7-day survival in ACS patients with cancer and moderate thrombocytopenia . In severe thrombocytopenia, reduced platelet aggregation causes culprit lesions to tend not to be total or persistent occlusions in initial CAG, and the frequency of stent thrombosis may be low. Therefore, single antiplatelet therapy rather than DAPT might be more appropriate for stent-implanted CAD patients complicated with severe thrombocytopenia from the perspective of risks of bleeding complications and stent thrombosis.
Moderate-to-severe thrombocytopenia has been associated with in-hospital net adverse clinical events (NACE) comprising major bleeding and major adverse cardiovascular events in patients undergoing PCI, and even mild thrombocytopenia is related to in-hospital NACE in patients with ST-elevation AMI [9, 10]. In the present case of AMI with extremely severe thrombocytopenia, PC transfusion was carried out before CAG/PCI, and aspirin and continuous heparin infusion for 2 weeks were administered after PCI. The peripheral blood platelet count was kept at [10 9 103/lL by PC transfusion approximately once a week after PCI, but occurrence of subdural hematoma after discharge required surgical treatment and cessation of antiplatelet therapy with aspirin in a patient who had undergone LMCA-LAD crossover stenting in the presence of 2-vessel total occlusions 3 weeks earlier. This case suggests that even single antiplatelet therapy with aspirin might have a risk of a serious bleeding complication in patients with severe thrombocytopenia. On the other hand, PC transfusion, which is not exposed to antiplatelet agents, might theoretically be a risk for stent thrombosis, particularly early after stent implantation; however, there are few case reports on stent thrombosis that may be due to PC transfusion [2, 11]. According to the ESC guideline and the ACCF/AHA guideline, loading dose of aspirin (150–300 and 162–325 mg, respectively) is recommended as an initial therapy to quickly inhibit TXA2-dependent platelet aggregation for patients with ST-segment elevation AMI undergoing primary PCI [12, 13]. Therefore, on the day of PC transfusion during hospitalization, we added aspirin 100 mg/day (total 200 mg/day), as loading dose of aspirin, to continuous heparin infusion expectantly to prevent fatal stent thrombosis; however, there is no proof of clinical benefit of such a strategy.
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Bleeding complication due to thrombocytopenia is a common cause of morbidity and mortality in patients with aplastic anemia. Indeed, peripheral blood platelet counts of \50 9 103 and 20 9 103/lL are diagnostic criteria for moderate and severe aplastic anemia, respectively. In general, bleeding is not observed until platelet counts decrease below 10–20 9 103/lL, and PC transfusion reduces hemorrhagic complications. Most guidelines recommend prophylactic PC transfusion in patients with thrombocytopenia when the platelet count decreases below 10 9 103/lL . However, long-term follow-up studies have shown that approximately 10% of patients with aplastic anemia finally die of hemorrhage even under prophylactic/therapeutic PC transfusion , and intracranial hemorrhage is a life-threatening bleeding complication in these patients. In addition to supportive therapy, such as transfusion and iron chelation, immunosuppressive therapy is standard for patients with aplastic anemia. Unfortunately, the patient in the present case was resistant to immunosuppressive treatment, such as cyclosporine A, and was not a suitable candidate for allogeneic bone-marrow transplantation because of advanced age. If treated with supportive therapy alone, the average life expectancy in patients with severe aplastic anemia is 6–12 months. Collectively, the patient with AMI in our case had severe aplastic anemia with a poor prognosis as an underlying disease, and suffered from subdural hematoma, even under single antiplatelet therapy with aspirin and prophylactic PC transfusion. For patients with severe thrombocytopenia receiving antiplatelet/anticoagulant therapy, it might be suitable to increase the threshold platelet count for prophylactic PC transfusion to 20–30 9 103/ lL. We did not perform platelet function tests examining platelet reactivity or capability of platelet aggregation in the present case. Accumulating studies have already shown that high platelet reactivity is associated with stent thrombosis and myocardial infarction, and low platelet reactivity might be related to bleeding complication, among patients receiving DAPT ; however, those results might not be applicable in patients with severe thrombocytopenia, as in the present case. In addition to platelet reactivity, platelet count itself might play a major role in stent thrombosis and bleeding complication among those patients. Severe thrombocytopenia is generally a contraindication in coronary stenting. It has been proposed that the feasible elective PCI strategy might differ depending on the preprocedural level of thrombocytopenia, with possible use of a drug-eluting stent (DES)/BMS in patients with mild thrombocytopenia, BMS use in patients with moderate thrombocytopenia, and non-stenting PCI in patients with severe thrombocytopenia . More importantly, tolerability of antiplatelet agents should be confirmed in advance of elective
PCI for patients with thrombocytopenia. In contrast, in ACS cases with moderate or severe thrombocytopenia at admission, it is difficult to evaluate the stability of thrombocytopenia itself and the tolerability of antiplatelet agents. Therefore, a non-stenting interventional procedure, such as thrombectomy and/or balloon dilation alone followed by provisional stenting, might be preferable, rather than primary/direct stenting during primary PCI. For ACS cases with extremely severe thrombocytopenia at baseline, cardiologists may have no choice but to use conservative treatment, rather than PCI; however, for patients complicated with life-threatening hemodynamic instability, PCI with or without platelets transfusion may be an alternative therapy. In the present case with subtotal RCA occlusion and total LCx occlusion, LMCA-LAD crossover stenting was essential to stabilize the critical condition, while balloon dilation-induced acute closure at the LMCA-proximal LAD might have a critical risk of hemodynamic collapse. In addition, accomplishment of PCI without mechanical support devices, such as IABP, might be desirable because of a high risk of bleeding complication. Thus, it is reasonable to propose that ‘‘direct’’ LMCA-LAD crossover stenting without IABP support could be an acceptable PCI strategy in cases, such as the present case. Clinical trials and meta-analyses have shown consistently low rates of stent thrombosis after implantation of new-generation DES [17–19]. In particular, a cobalt-chromium everolimus-eluting stent (CoCr-EES) has been reported to reduce stent thrombosis compared with BMS [17, 18, 20]. However, these favorable results with a CoCrEES were obtained under use of DAPT. Since even a newgeneration DES theoretically has delayed intimal coverage of the stent strut compared with a BMS, the anti-thrombotic property of CoCr-EES might not be applicable without DAPT early after stent implantation, as in the present case. On the other hand, there is a possibility that significant restenosis in the LMCA-LAD crossover-implanted stent might lead to a serious clinical course, as in the present case. Therefore, during PCI, we speculated that without DAPT early after stent implantation, BMS might even be superior to a new-generation DES for prevention of stent thrombosis, and that in choosing the type of stent, safety should be prioritized over anti-restenosis properties. In AMI patients with thrombocytopenia, interventional treatment and antiplatelet/anticoagulant therapy should be individualized to maximize the life-saving benefit, as well as minimize bleeding and thrombosis risk.
Conclusion This case suggests that PCI using a BMS with preceding PC transfusion and single antiplatelet/anticoagulation therapy with aspirin/heparin infusion could be an
Left main crossover stenting in a patient with severe thrombocytopenia due to aplastic anemia
alternative revascularization therapy for non-option AMI patients complicated with severe thrombocytopenia due to aplastic anemia. However, in such cases, attention should be paid to a possible bleeding complication, even under prophylactic PC transfusion and single antiplatelet therapy. Acknowledgements This article does not contain any studies with human participants or animals performed by any of the authors. Compliance with ethical standards Conflict of interest The authors have no conflicts of interest regarding the content of the manuscript.
References 1. Toyama M, Watanabe S, Kobayashi T, Iida K, Koseki S, Yamaguchi I, et al. Two cases of acute myocardial infarction associated with aplastic anemia during treatment with anabolic steroids. Jpn Heart J. 1994;35:369–73. 2. Shin HS, Kang TS. A case of late stent thrombosis following platelet transfusion in a patient with aplastic anemia. Korean Circ J. 2012;42:54–7. 3. Overgaard CB, Ivanov J, Seidelin PH, Todorov M, Mackie K, Dzavı´k V. Thrombocytopenia at baseline is a predictor of inhospital mortality in patients undergoing percutaneous coronary intervention. Am Heart J. 2008;156:120–4. 4. Williamson DR, Albert M, Heels-Ansdell D, Arnold DM, Lauzier F, Zarychanski R, et al. PROTECT collaborators; Canadian Critical Care Trials Group; Australian and New Zealand Intensive Care Society Clinical Trials Group. Thrombocytopenia in critically ill patients receiving thromboprophylaxis: frequency, risk factors, and outcomes. Chest. 2013;144:1207–15. 5. Morici N, Cantoni S, Savonitto S. Antiplatelet therapy for patients with stable ischemic heart disease and baseline thrombocytopenia: ask the hematologist. Platelets. 2014;25:455–60. 6. Stouffer GA, Hirmerova J, Moll S, Rubery B, Napoli M, Ohman EM, et al. Percutaneous coronary intervention in a patient with immune thrombocytopenia purpura. Catheter Cardiovasc Interv. 2004;61:364–7. 7. Yusuf SW, Iliescu C, Bathina JD, Daher IN, Durand JB. Antiplatelet therapy and percutaneous coronary intervention in patients with acute coronary syndrome and thrombocytopenia. Tex Heart Inst J. 2010;37:336–40. 8. Sarkiss MG, Yusuf SW, Warneke CL, Botz G, Lakkis N, HirchGinsburg C, Champion JC, Swafford J, Shaw AD, Lenihan DJ, Durand JB. Impact of aspirin therapy in cancer patients with thrombocytopenia and acute coronary syndromes. Cancer. 2007;109:621–7. 9. Hakim DA, Dangas GD, Caixeta A, Nikolsky E, Lansky AJ, Moses JW, et al. Impact of baseline thrombocytopenia on the early and late outcomes after ST-elevation myocardial infarction treated with primary angioplasty: analysis from the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial. Am Heart J. 2011;161:391–6.
10. Ali ZA, Qureshi YH, Karimi Galougahi K, Poludasu S, Roye S, et al. Effects of baseline and early acquired thrombocytopaenia on long-term mortality in patients undergoing percutaneous coronary intervention with bivalirudin. Eurointervention. 2016;11:e1627–38. 11. Cornet AD, Klein LJ, Groeneveld AB. Coronary stent occlusion after platelet transfusion: a case series. J Invasive Cardiol. 2007;19:E297–9. 12. Steg PG, James SK, Atar D, Badano LP, Blo¨mstrom-Lundqvist C, Borger MA, et al. Task Force on the management of STsegment elevation acute myocardial infarction of the European Society of Cardiology (ESC). ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2012;33:2569–619. 13. O’Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA, American College of Cardiology Foundation, American Heart Association Task Force on Practice Guidelines, et al. ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;2013(127):e362–425. 14. Marsh JC, Ball SE, Cavenagh J, Darbyshire P, Dokal I, GordonSmith EC, et al. British Committee for Standards in Haematology. Guidelines for the diagnosis and management of aplastic anaemia. Br J Haematol. 2009;147:43–70. 15. Viollier R, Passweg J, Gregor M, Favre G, Ku¨hne T, Nissen C, et al. Quality-adjusted survival analysis shows differences in outcome after immunosuppression or bone marrow transplantation in aplastic anemia. Ann Hematol. 2005;84:47–55. 16. Tantry US, Bonello L, Aradi D, Price MJ, Jeong YH, Angiolillo DJ, et al. Working Group on On-Treatment Platelet Reactivity. Consensus and update on the definition of on-treatment platelet reactivity to adenosine diphosphate associated with ischemia and bleeding. J Am Coll Cardiol. 2013;62:2261–73. 17. Sabate M, Cequier A, In˜iguez A, Serra A, Hernandez-Antolin R, Mainar V, et al. Everolimus-eluting stent versus bare-metal stent in ST-segment elevation myocardial infarction (EXAMINATION): 1 year results of a randomised controlled trial. Lancet. 2012;380:1482–90. 18. Palmerini T, Biondi-Zoccai G, Della Riva D, Mariani A, Sabate´ M, Valgimigli M, et al. Clinical outcomes with drug-eluting and bare-metal stents in patients with ST-segment elevation myocardial infarction: evidence from a comprehensive network meta-analysis. J Am Coll Cardiol. 2013;62:496–504. 19. Sabate´ M, Ra¨ber L, Heg D, Brugaletta S, Kelbaek H, Cequier A, et al. Comparison of newer-generation drug-eluting with baremetal stents in patients with acute ST-segment elevation myocardial infarction: a pooled analysis of the EXAMINATION (clinical Evaluation of the Xience-V stent in Acute Myocardial INfArcTION) and COMFORTABLE-AMI (Comparison of Biolimus Eluted From an Erodible Stent Coating With Bare Metal Stents in Acute ST-Elevation Myocardial Infarction) trials. JACC Cardiovasc Inter. 2014;7:55–63. 20. Palmerini T, Biondi-Zoccai G, Della Riva D, Stettler C, Sangiorgi D, D’Ascenzo F, et al. Stent thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis. Lancet. 2012;379:1393–402.