OVER THE PAST 2 DECADES, NUMEROUS RANDOMized trials have been performed to define the optimal rep... more OVER THE PAST 2 DECADES, NUMEROUS RANDOMized trials have been performed to define the optimal reperfusion therapy in patients with acute ST-segment elevation myocardial infarction (STEMI). An analysis of 23 randomized trials has assessed the relative merits of primary percutaneous coronary intervention (PCI) vs thrombolysis in approximately 8000 patients with STEMI and demonstrated a clear advantage for PCI. Fewer trials were required to establish the implantation of bare-metal stents (BMSs) compared with plain balloon-angioplasty as the first-choice PCI option in these patients. More recently, assessment of the role of drugeluting stents (DESs) during primary PCI has drawn considerable attention with approximately 10 000 patients with acute myocardial infarction (AMI) enrolled in randomized trials comparing DESs with BMSs in the last decade alone. Indeed, in no other setting has DES use elicited as much skepticism as in patients with STEMI. The use of first-generation DESs has substantially reduced the risk of restenosis compared with BMSs without any significant trade-off in safety. Initial randomized trials of patients with STEMI demonstrated that DESs were better than BMSs in outcomes at 1 year. However, although there is general agreement about the higher anti-restenotic efficacy of DESs in patients with STEMI, concerns exist regarding the longterm safety of these devices in this setting. Pathologic samples of patients with stent thrombosis confirmed that firstgeneration DESs led to delayed arterial healing, incomplete endothelialization, and persistent fibrin deposition. Moreover, patients receiving first-generation DESs for AMI, compared with patients receiving DESs for stable angina, had evidence of less neointimal thickness at the stented site as well as more uncovered stent struts and inflammation. The differential arterial response to DESs depending on plaque morphology of the culprit lesions might increase the intrinsic thrombotic risk of patients presenting with STEMI. Stent strut penetration of a necrotic core may inhibit neointimal growth, resulting in uncovered stent struts, especially with DESs. Stent undersizing due to poor epicardial flow, vasoconstriction, or thrombus dissolution or embolization may lead to incomplete stent apposition. In fact, the incidence of positive arterial remodelling and late-acquired incomplete stent apposition was significantly higher in patients with STEMI. Although concerns generated by preclinical and pathological investigations have not always been validated by clinical studies, long-term analyses at 3 to 5 years after the procedure suggest that compared with use of BMSs the use of first-generation DESs in STEMI is associated with an excess of very late thrombotic complications. A meta-analysis of 15 trials, including 7867 patients randomly assigned to firstgeneration DESs or BMSs in STEMI, unravelled the significant interaction existing between DESs and time of observation regarding thrombotic events. Although the overall risk of definite and definite or probable stent thrombosis was similar for DESs and BMSs, very late (after the first year) thrombotic events were more likely to occur in the DES group. Second-generation DESs may overcome some of the limitations of first-generation DESs. New alloys, improved biocompatibility of durable polymer coatings, biodegradable polymer coatings, and reduced toxicity of the antiproliferative drugs are increasing the safety of current DES technology while maintaining or even improving its efficacy. The second-generation permanent polymer stents eluting everolimus significantly reduced the risk of stent thrombosis compared with paclitaxeland sirolimus-eluting stents. Newergeneration DESs eluting limus drugs from a biodegradable polymer coating are emerging as an effective and safe treatment option over the long term. A pooled patient-level metaanalysis of 3 randomized trials (4062 patients) found not only increased efficacy but also a significant reduction in the risk of stent thrombosis over 4 years with biodegradable polymer DES vs permanent polymer sirolimus-eluting stent. Patients with AMI obtained the major benefit from these DESs. Two opposite, time-dependent effects have been described for polymers used in DES technology—an early protective effect against stent thrombosis and a late proinflammatory and prothrombotic effect. By their very nature, the biodegradable polymers used in newergeneration DESs might offer the early advantages of polymers while avoiding the very late hazards, which may turn out to be especially useful in patients with STEMI.
OVER THE PAST 2 DECADES, NUMEROUS RANDOMized trials have been performed to define the optimal rep... more OVER THE PAST 2 DECADES, NUMEROUS RANDOMized trials have been performed to define the optimal reperfusion therapy in patients with acute ST-segment elevation myocardial infarction (STEMI). An analysis of 23 randomized trials has assessed the relative merits of primary percutaneous coronary intervention (PCI) vs thrombolysis in approximately 8000 patients with STEMI and demonstrated a clear advantage for PCI. Fewer trials were required to establish the implantation of bare-metal stents (BMSs) compared with plain balloon-angioplasty as the first-choice PCI option in these patients. More recently, assessment of the role of drugeluting stents (DESs) during primary PCI has drawn considerable attention with approximately 10 000 patients with acute myocardial infarction (AMI) enrolled in randomized trials comparing DESs with BMSs in the last decade alone. Indeed, in no other setting has DES use elicited as much skepticism as in patients with STEMI. The use of first-generation DESs has substantially reduced the risk of restenosis compared with BMSs without any significant trade-off in safety. Initial randomized trials of patients with STEMI demonstrated that DESs were better than BMSs in outcomes at 1 year. However, although there is general agreement about the higher anti-restenotic efficacy of DESs in patients with STEMI, concerns exist regarding the longterm safety of these devices in this setting. Pathologic samples of patients with stent thrombosis confirmed that firstgeneration DESs led to delayed arterial healing, incomplete endothelialization, and persistent fibrin deposition. Moreover, patients receiving first-generation DESs for AMI, compared with patients receiving DESs for stable angina, had evidence of less neointimal thickness at the stented site as well as more uncovered stent struts and inflammation. The differential arterial response to DESs depending on plaque morphology of the culprit lesions might increase the intrinsic thrombotic risk of patients presenting with STEMI. Stent strut penetration of a necrotic core may inhibit neointimal growth, resulting in uncovered stent struts, especially with DESs. Stent undersizing due to poor epicardial flow, vasoconstriction, or thrombus dissolution or embolization may lead to incomplete stent apposition. In fact, the incidence of positive arterial remodelling and late-acquired incomplete stent apposition was significantly higher in patients with STEMI. Although concerns generated by preclinical and pathological investigations have not always been validated by clinical studies, long-term analyses at 3 to 5 years after the procedure suggest that compared with use of BMSs the use of first-generation DESs in STEMI is associated with an excess of very late thrombotic complications. A meta-analysis of 15 trials, including 7867 patients randomly assigned to firstgeneration DESs or BMSs in STEMI, unravelled the significant interaction existing between DESs and time of observation regarding thrombotic events. Although the overall risk of definite and definite or probable stent thrombosis was similar for DESs and BMSs, very late (after the first year) thrombotic events were more likely to occur in the DES group. Second-generation DESs may overcome some of the limitations of first-generation DESs. New alloys, improved biocompatibility of durable polymer coatings, biodegradable polymer coatings, and reduced toxicity of the antiproliferative drugs are increasing the safety of current DES technology while maintaining or even improving its efficacy. The second-generation permanent polymer stents eluting everolimus significantly reduced the risk of stent thrombosis compared with paclitaxeland sirolimus-eluting stents. Newergeneration DESs eluting limus drugs from a biodegradable polymer coating are emerging as an effective and safe treatment option over the long term. A pooled patient-level metaanalysis of 3 randomized trials (4062 patients) found not only increased efficacy but also a significant reduction in the risk of stent thrombosis over 4 years with biodegradable polymer DES vs permanent polymer sirolimus-eluting stent. Patients with AMI obtained the major benefit from these DESs. Two opposite, time-dependent effects have been described for polymers used in DES technology—an early protective effect against stent thrombosis and a late proinflammatory and prothrombotic effect. By their very nature, the biodegradable polymers used in newergeneration DESs might offer the early advantages of polymers while avoiding the very late hazards, which may turn out to be especially useful in patients with STEMI.
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Papers by Adnan Kastrati