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Drug-eluting versus bare-metal coronary stents: where are we now? Drug-eluting stents have dramatically reduced the risk of restenosis, but concerns of an increased risk of stent thrombosis have provided uncertainty about their use. Recent studies have continued to show improved procedural and clinical outcomes with drug-eluting stents both in the setting of acute coronary syndromes and stable coronary artery disease. Newer generation drug-eluting stents (especially everolimus-eluting stents) have been shown to be not only efficacious but also safe with reduced risk of stent thrombosis when compared with bare-metal stents, potentially changing the benchmark for stent safety from bare-metal stents to everolimus-eluting stents. While much progress is being made in the development of bioabsorbable polymer stents, nonpolymer stents and bioabsorbable stent technology, it remains to be seen whether these stents will have superior safety and efficacy outcomes compared with the already much improved rates of revascularization and stent thrombosis seen with newer generation stents (everolimus-eluting stents and resolute zotarolimus-eluting stents).
Nicholas S Amoroso1 & Sripal Bangalore*1 Cardiovascular Clinical Research Center, The Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, NY 10016, USA *Author for correspondence: Tel.: +1 212 263 3540 Fax: +1 212 263 3988 [email protected] 1
KEYWORDS: bare-metal stent n coronary heart disease n drug-eluting stent
Since the first implantation of a balloon-mounted stent in humans by Puel and Sigwart in 1986, coronary stents are increasingly used [1], yet hotly debated [101]. While intracoronary stents were found to dramatically decrease the incidence of acute vessel closure and constrictive remodeling compared with balloon angioplasty in early trials, such as the BENESTENT trial, a serious risk of in-stent restenosis persisted [2]. In the early 1990s, approximately 15–20% of bare-metal stent (BMS) recipients required repeat revascularization within 6–12 months [2], with an even larger proportion in patients with diabetes and those with complex coronary disease. A steady stream of subsequent trials continued to establish the efficacy of intracoronary stents [3–5]. Experience with BMS gave way to US FDA approval of drug-eluting stents (DES; sirolimus or paclitaxel coated) for clinical use in 2003 in an attempt to overcome the problems with in-stent restenosis. During that first year, approximately 25–30% of all percutaneous coronary interventions (PCIs) were DES [102]. From 2002 to 2009, a large series of trials, including the RAVEL and SIRIUS trials, demonstrated less restenosis with sirolimus-eluting stents compared with BMS, with similar or improved safety [6,7]. Paclitaxel-eluting DES were shown to be beneficial in the TAXUS trials, proving their efficacy in the treatment of more complex lesions with subsequent TAXUS trial rendition [8,9]. By 2006, it was estimated that 919,100 DES were placed in the USA alone; 2.3-times more than the number of BMS placed that year. In the UK, PCI with stents has grown by approximately 150% per year through much of the past decade. However, the initial enthusiasm and rapid incorporation was tempered by a series of publications of increased risk of stent thrombosis, myocardial infarction (MI) and death with DES when compared with BMS [10]. An FDA Advisory Panel on the safety and efficacy of DES then released a statement recognizing a small but significant risk of late stent thrombosis with DES but endorsed them as safe and effective when used in the lesion subsets for which the original use was approved (i.e.,
10.2217/CER.12.64 © 2012 Future Medicine Ltd
1(6), 501–508 (2012)
part of
ISSN 2042-6305
501
REVIEW
Amoroso & Bangalore
for ‘on-label’ use) [11]. More recently, a number of large studies have shown that the short- and longterm risks are not greater for DES compared with BMS (1.5–1.8% thrombosis with DES compared with 1.4–1.7% with BMS) [12] and in fact, the outcomes might be better with newer generation DES when compared with BMS (short-term thrombosis with BMS was 0.18%, everolimuseluting stent [EES] was 0.08% and there was a 49% risk reduction in long-term thrombosis with EES compared with BMS) [13,14]. Despite the DES stent thrombosis scare, more than 528,000 PCIs with stents were performed in the USA in 2009 and DES are found in approximately 70% of all PCI across the world, including China, the UK and the USA [15]. This article reviews the status of the current DES when compared with BMS (Table 1). Acute MI
There is controversy over the efficacy and safety of DES versus BMS in patients with ST-elevation MI (STEMI) with earlier registry studies and clinical trials showing no difference in death or MI and even restenosis with DES [16,17], and with numerically excess stent thrombosis when compared with BMS [17]. Moreover, in patients presenting for an emergent PCI, it may be difficult to ascertain patient compliance with antiplatelet therapy, which is an important factor related to stent thrombosis. Consequently, the 2009 STEMI guidelines give a Class IIa recommendation for the use of a DES as an alternative to a BMS for primary PCI in STEMI [18]. However, more recent studies have restored the faith in DES in STEMI, showing a significant reduction in the risk of restenosis without any increase in postintervention major adverse cardiovascular events [19,20]. In a large-scale individual patient data meta-analysis of 11 trials with 6298 patients
with STEMI, DES implantation was associated with significant reduction in the risk of target vessel revascularization (TVR; hazard ratio: 0.57, 95% CI: 0.50–0.66) without any significant difference in mortality, reinfarction and stent thrombosis [21]. However, DES implantation was associated with an increased risk of very late stent thrombosis and reinfarction [21]. The DES evaluated were early generation DES only (sirolimus- and paclitaxel-eluting stents). In the clinical EXAMINATION trial, patients with STEMI randomized to a newer generation DES (EES) had lower 1‑year target-lesion revascularization (2.2 vs 5.1%; p = 0.003), TVR (3.9 vs 7.0%; p = 0.007) and no difference in death or MI when compared with BMS [22]. In addition, DES was associated with a significant reduction in definite stent thrombosis (0.5 vs 1.9%; p = 0.01) and definite/probable stent thrombosis (0.9 vs 2.6%; p = 0.01) when compared with BMS [22]. In short, patients with STEMI who receive newer generation DES have lower target-lesion revascularization rates compared with BMS without sacrifice of safety (Table 1). Accordingly, the 2011 American College of Cardiology/American Heart Association/Society of Cardiac Angiography and Intervention PCI guidelines state that once a decision for PCI has been made, there is a Class I recommendation for DES rather than BMS in patients with unstable angina, STEMI and non-STEMI at high risk for restenosis [23]. Stable coronary artery disease
Upwards of 85% of PCIs are performed electively for stable coronary artery disease [24]. The role of PCI versus optimal medical therapy in patients with stable coronary artery disease has been hotly debated. Recent trials and analyses indicate that
Table 1. Comparison of drug-eluting and bare-metal stent characteristics. Parameter
DES vs bare-metal stent
Death
Similar
Myocardial infarction
Similar, favors newer generation DES
Stent thrombosis
Similar, favors newer generation DES
Target vessel revascularization
Superior
Cost–effectiveness
Unclear
Use in diabetics
Superior
Use in STEMI
Similar/superior
Duration of DAPT
Inferior
DAPT: Dual antiplatelet therapy; DES: Drug-eluting stent; STEMI: ST-elevation myocardial infarction.
502
J. Compar. Effect. Res. (2012) 1(6)
future science group
Drug-eluting & bare-metal coronary stents
PCIs, when compared with optimal medical therapy alone, do not prevent death or MI [25,26]. However, PCI has been shown to reduce the risk of angina better than medical therapy alone [27]. The prior trials of PCI versus optimal medical therapy have been criticized as they recruited patients after coronary anatomy was defined (via cardiac catheterization), subjecting the studies to potential selection bias and not enrolling subjects with sufficient ischemia. In addition, the trials were carried out in an era when DES was not routinely used. The applicability of these results to modern day practice with routine use of DES and especially with newer generation DES is therefore questionable [27]. Nevertheless, PCI is an integral part of the treatment strategy for patients who are symptomatic despite medical treatment. The European Society of Cardiology guidelines gives a Class I recommendation supporting PCI for symptomatic relief in patients with either single or multivessel disease, but explicitly highlight the lack of evidence for survival [28]. Furthermore, PCI is indicated to improve prognosis for patients suffering from stable angina in those with reversible ischemia on functional testing (Class IIa) [28]. The 2011 American College of Cardiology/American Heart Association/Society of Cardiac Angiography and Intervention PCI guidelines similarly conclude that the evidence does not support an improvement in survival in patients with stable ischemic heart disease and provide a Class I (level of evidence: A) recommendation for PCI for unacceptable angina on aggressive medical therapy [23]. Guidelines recommend DES for reducing the risk of restenosis in patients who can tolerate prolonged dual antiplatelet therapy [23]. ■■ In-stent restenosis
BMS in-stent restenosis (ISR) rates are approximately 20–40% [29]. ISR is not a benign entity, with more than one-third to onehalf of patients presenting with acute coronary syndromes necessitating further intervention with balloon angioplasty, drug-eluting balloons, DES placement or coronary artery bypass grafts [30–33]. Early studies with DES showed up to a 60% relative reduction in angiographic restenosis compared with BMS. Since the early introduction and approval of the sirolimuseluting stent (SES) followed by the paclitaxeleluting stent, there has been considerable debate on the long-term efficacy and safety of these
future science group
REVIEW
stents. Newer DES have been developed that have claimed to be safer and more efficacious. However, for safety outcomes, the BMS is still considered the benchmark. There are currently five FDA-approved DES – SES, paclitaxeleluting stent, zotarolimus-eluting stent (ZES), EES and ZES-Resolute (ZES-R). The SES is out of the market as the manufacturer decided not to continue manufacturing these stents. In the largest and most comprehensive analysis on efficacy and safety of stents, we compared DES versus BMS with data from 76 randomized clinical trials with 117,762 patient-years of follow-up. When compared with BMS, each DES reduced short-term risk (1 year) of TVR (52–74%), but the magnitude varied by DES type in the following order: EES~SES~ZESR>paclitaxel-eluting stent~ZES>BMS. Among the stents, SES followed by ZES-R and EES had the lowest rate of TVR. The median TVR rate with BMS was 15.76%. DES (SES; TVR rate of 4.11%) resulted in a >11% absolute decrease in the rate of TVR. The data thus suggests that treatment of just eight patients with DES was required to prevent one TVR. Similar results were seen for long-term risk (>1 year) of TVR where DES was beneficial compared with BMS (39–61%), but the magnitude varied by DES type (Figure 1), with EES having the lowest TVR rate [13]. This effect remained true even when excluding trials with routine protocoldirected angiographic follow-up, which is important in excluding ‘oculostenotic reflex’ revascularizations [13]. ■■ Diabetes
The presence of diabetes has been associated with worse outcomes following PCI in both the BMS and DES era. While DES has reduced the risk of restenosis, there is controversy as to the relative efficacy of various DES in subjects with diabetes. From 42 trials with 22,844 patientyears of follow-up, we have shown that when compared with BMS, all of the currently used DES were associated with a significant reduction in TVR (37–69%). However, the efficacy varied with the type of stent, with EES being the most efficacious compared with all others, although there were limited usable data for the ZES-R stent in patients with diabetes [14]. ■■ Stent thrombosis
While DES works to reduce the risk of restenosis by reducing neointimal proliferation,
www.futuremedicine.com
503
REVIEW
Amoroso & Bangalore
Relative risk reduction TVR (% vs BMS)
70
61%
61%
60
56%
50 39%
40
39%
30 20 10 0 SES
PES
EES
ZES
ZES-R
Figure 1. Risk reduction of target-vessel revascularization with various drug-eluting stents when compared with bare-metal stents. BMS: Bare-metal stent; EES: Everolimus-eluting stent; PES: Paclitaxel-eluting stent; SES: Sirolimus-eluting stent; TVR: Target-vessel revascularization; ZES: Zotarolimus-eluting stent; ZES-R: Zotarolimus-eluting stent-Resolute. Adapted from [13].
an unintended consequence of this is delayed endothelial healing with subsequent risk of late (1 month to 1 year) or very late (>1 year) stent thrombosis. Stent thrombosis is a catastrophic event with a 30‑day rate of MI of 60% and a rate of death of 15–20% [34]. The increased risk of very late stent thrombosis seen with DES was mainly restricted to older DES. In the newer generation DES with thinner struts and more biocompatible polymers, the rate of stent thrombosis has been drastically reduced. In fact, in our analysis we did not observe any increase in the risk of any long-term safety outcomes (death, MI and stent thrombosis), with any DES. In addition, EES were associated with reduction in the risk of stent thrombosis (relative risk: 0.51, 95% CI: 0.35–0.73) even when compared with BMS [13]. There is thus reason to believe that the newer generation stents are not only efficacious but also safe and should be considered as benchmarks for efficacy and safety for future trials. ■■ Dual antiplatelet therapy
Recommendations for extended dua l antiplatelet therapy for patients receiving DES are aimed at reducing the risk of stent thrombosis [23]. Duration of dual antiplatelet therapy is one of the main differences discussed when considering placement of DES versus
504
J. Compar. Effect. Res. (2012) 1(6)
BMS. For patients undergoing PCI with BMS for nonacute coronary syndrome indications, guidelines currently recommend P2Y 12 inhibitor therapy for at least 1 month compared with 12 months or longer for DES [23]. Early cessation of dual antiplatelet therapy has been linked to higher risk of early and late stent thrombosis [35]. Trials are underway to test the efficacy of an extended dual antiplatelet therapy (12 vs 33 months) on the incidence of stent thrombosis and other major adverse vascular events [36]. However, with the advent of newer generation DES with thinner struts and more biocompatible polymers, attention has been turned to evaluate whether a shorter duration of dual antiplatelet therapy (
Drug-eluting versus bare-metal coronary stents: where are we now? Drug-eluting stents have dramatically reduced the risk of restenosis, but concerns of an increased risk of stent thrombosis have provided uncertainty about their use. Recent studies have continued to show improved procedural and clinical outcomes with drug-eluting stents both in the setting of acute coronary syndromes and stable coronary artery disease. Newer generation drug-eluting stents (especially everolimus-eluting stents) have been shown to be not only efficacious but also safe with reduced risk of stent thrombosis when compared with bare-metal stents, potentially changing the benchmark for stent safety from bare-metal stents to everolimus-eluting stents. While much progress is being made in the development of bioabsorbable polymer stents, nonpolymer stents and bioabsorbable stent technology, it remains to be seen whether these stents will have superior safety and efficacy outcomes compared with the already much improved rates of revascularization and stent thrombosis seen with newer generation stents (everolimus-eluting stents and resolute zotarolimus-eluting stents).
Nicholas S Amoroso1 & Sripal Bangalore*1 Cardiovascular Clinical Research Center, The Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, NY 10016, USA *Author for correspondence: Tel.: +1 212 263 3540 Fax: +1 212 263 3988 [email protected] 1
KEYWORDS: bare-metal stent n coronary heart disease n drug-eluting stent
Since the first implantation of a balloon-mounted stent in humans by Puel and Sigwart in 1986, coronary stents are increasingly used [1], yet hotly debated [101]. While intracoronary stents were found to dramatically decrease the incidence of acute vessel closure and constrictive remodeling compared with balloon angioplasty in early trials, such as the BENESTENT trial, a serious risk of in-stent restenosis persisted [2]. In the early 1990s, approximately 15–20% of bare-metal stent (BMS) recipients required repeat revascularization within 6–12 months [2], with an even larger proportion in patients with diabetes and those with complex coronary disease. A steady stream of subsequent trials continued to establish the efficacy of intracoronary stents [3–5]. Experience with BMS gave way to US FDA approval of drug-eluting stents (DES; sirolimus or paclitaxel coated) for clinical use in 2003 in an attempt to overcome the problems with in-stent restenosis. During that first year, approximately 25–30% of all percutaneous coronary interventions (PCIs) were DES [102]. From 2002 to 2009, a large series of trials, including the RAVEL and SIRIUS trials, demonstrated less restenosis with sirolimus-eluting stents compared with BMS, with similar or improved safety [6,7]. Paclitaxel-eluting DES were shown to be beneficial in the TAXUS trials, proving their efficacy in the treatment of more complex lesions with subsequent TAXUS trial rendition [8,9]. By 2006, it was estimated that 919,100 DES were placed in the USA alone; 2.3-times more than the number of BMS placed that year. In the UK, PCI with stents has grown by approximately 150% per year through much of the past decade. However, the initial enthusiasm and rapid incorporation was tempered by a series of publications of increased risk of stent thrombosis, myocardial infarction (MI) and death with DES when compared with BMS [10]. An FDA Advisory Panel on the safety and efficacy of DES then released a statement recognizing a small but significant risk of late stent thrombosis with DES but endorsed them as safe and effective when used in the lesion subsets for which the original use was approved (i.e.,
10.2217/CER.12.64 © 2012 Future Medicine Ltd
1(6), 501–508 (2012)
part of
ISSN 2042-6305
501
REVIEW
Amoroso & Bangalore
for ‘on-label’ use) [11]. More recently, a number of large studies have shown that the short- and longterm risks are not greater for DES compared with BMS (1.5–1.8% thrombosis with DES compared with 1.4–1.7% with BMS) [12] and in fact, the outcomes might be better with newer generation DES when compared with BMS (short-term thrombosis with BMS was 0.18%, everolimuseluting stent [EES] was 0.08% and there was a 49% risk reduction in long-term thrombosis with EES compared with BMS) [13,14]. Despite the DES stent thrombosis scare, more than 528,000 PCIs with stents were performed in the USA in 2009 and DES are found in approximately 70% of all PCI across the world, including China, the UK and the USA [15]. This article reviews the status of the current DES when compared with BMS (Table 1). Acute MI
There is controversy over the efficacy and safety of DES versus BMS in patients with ST-elevation MI (STEMI) with earlier registry studies and clinical trials showing no difference in death or MI and even restenosis with DES [16,17], and with numerically excess stent thrombosis when compared with BMS [17]. Moreover, in patients presenting for an emergent PCI, it may be difficult to ascertain patient compliance with antiplatelet therapy, which is an important factor related to stent thrombosis. Consequently, the 2009 STEMI guidelines give a Class IIa recommendation for the use of a DES as an alternative to a BMS for primary PCI in STEMI [18]. However, more recent studies have restored the faith in DES in STEMI, showing a significant reduction in the risk of restenosis without any increase in postintervention major adverse cardiovascular events [19,20]. In a large-scale individual patient data meta-analysis of 11 trials with 6298 patients
with STEMI, DES implantation was associated with significant reduction in the risk of target vessel revascularization (TVR; hazard ratio: 0.57, 95% CI: 0.50–0.66) without any significant difference in mortality, reinfarction and stent thrombosis [21]. However, DES implantation was associated with an increased risk of very late stent thrombosis and reinfarction [21]. The DES evaluated were early generation DES only (sirolimus- and paclitaxel-eluting stents). In the clinical EXAMINATION trial, patients with STEMI randomized to a newer generation DES (EES) had lower 1‑year target-lesion revascularization (2.2 vs 5.1%; p = 0.003), TVR (3.9 vs 7.0%; p = 0.007) and no difference in death or MI when compared with BMS [22]. In addition, DES was associated with a significant reduction in definite stent thrombosis (0.5 vs 1.9%; p = 0.01) and definite/probable stent thrombosis (0.9 vs 2.6%; p = 0.01) when compared with BMS [22]. In short, patients with STEMI who receive newer generation DES have lower target-lesion revascularization rates compared with BMS without sacrifice of safety (Table 1). Accordingly, the 2011 American College of Cardiology/American Heart Association/Society of Cardiac Angiography and Intervention PCI guidelines state that once a decision for PCI has been made, there is a Class I recommendation for DES rather than BMS in patients with unstable angina, STEMI and non-STEMI at high risk for restenosis [23]. Stable coronary artery disease
Upwards of 85% of PCIs are performed electively for stable coronary artery disease [24]. The role of PCI versus optimal medical therapy in patients with stable coronary artery disease has been hotly debated. Recent trials and analyses indicate that
Table 1. Comparison of drug-eluting and bare-metal stent characteristics. Parameter
DES vs bare-metal stent
Death
Similar
Myocardial infarction
Similar, favors newer generation DES
Stent thrombosis
Similar, favors newer generation DES
Target vessel revascularization
Superior
Cost–effectiveness
Unclear
Use in diabetics
Superior
Use in STEMI
Similar/superior
Duration of DAPT
Inferior
DAPT: Dual antiplatelet therapy; DES: Drug-eluting stent; STEMI: ST-elevation myocardial infarction.
502
J. Compar. Effect. Res. (2012) 1(6)
future science group
Drug-eluting & bare-metal coronary stents
PCIs, when compared with optimal medical therapy alone, do not prevent death or MI [25,26]. However, PCI has been shown to reduce the risk of angina better than medical therapy alone [27]. The prior trials of PCI versus optimal medical therapy have been criticized as they recruited patients after coronary anatomy was defined (via cardiac catheterization), subjecting the studies to potential selection bias and not enrolling subjects with sufficient ischemia. In addition, the trials were carried out in an era when DES was not routinely used. The applicability of these results to modern day practice with routine use of DES and especially with newer generation DES is therefore questionable [27]. Nevertheless, PCI is an integral part of the treatment strategy for patients who are symptomatic despite medical treatment. The European Society of Cardiology guidelines gives a Class I recommendation supporting PCI for symptomatic relief in patients with either single or multivessel disease, but explicitly highlight the lack of evidence for survival [28]. Furthermore, PCI is indicated to improve prognosis for patients suffering from stable angina in those with reversible ischemia on functional testing (Class IIa) [28]. The 2011 American College of Cardiology/American Heart Association/Society of Cardiac Angiography and Intervention PCI guidelines similarly conclude that the evidence does not support an improvement in survival in patients with stable ischemic heart disease and provide a Class I (level of evidence: A) recommendation for PCI for unacceptable angina on aggressive medical therapy [23]. Guidelines recommend DES for reducing the risk of restenosis in patients who can tolerate prolonged dual antiplatelet therapy [23]. ■■ In-stent restenosis
BMS in-stent restenosis (ISR) rates are approximately 20–40% [29]. ISR is not a benign entity, with more than one-third to onehalf of patients presenting with acute coronary syndromes necessitating further intervention with balloon angioplasty, drug-eluting balloons, DES placement or coronary artery bypass grafts [30–33]. Early studies with DES showed up to a 60% relative reduction in angiographic restenosis compared with BMS. Since the early introduction and approval of the sirolimuseluting stent (SES) followed by the paclitaxeleluting stent, there has been considerable debate on the long-term efficacy and safety of these
future science group
REVIEW
stents. Newer DES have been developed that have claimed to be safer and more efficacious. However, for safety outcomes, the BMS is still considered the benchmark. There are currently five FDA-approved DES – SES, paclitaxeleluting stent, zotarolimus-eluting stent (ZES), EES and ZES-Resolute (ZES-R). The SES is out of the market as the manufacturer decided not to continue manufacturing these stents. In the largest and most comprehensive analysis on efficacy and safety of stents, we compared DES versus BMS with data from 76 randomized clinical trials with 117,762 patient-years of follow-up. When compared with BMS, each DES reduced short-term risk (1 year) of TVR (52–74%), but the magnitude varied by DES type in the following order: EES~SES~ZESR>paclitaxel-eluting stent~ZES>BMS. Among the stents, SES followed by ZES-R and EES had the lowest rate of TVR. The median TVR rate with BMS was 15.76%. DES (SES; TVR rate of 4.11%) resulted in a >11% absolute decrease in the rate of TVR. The data thus suggests that treatment of just eight patients with DES was required to prevent one TVR. Similar results were seen for long-term risk (>1 year) of TVR where DES was beneficial compared with BMS (39–61%), but the magnitude varied by DES type (Figure 1), with EES having the lowest TVR rate [13]. This effect remained true even when excluding trials with routine protocoldirected angiographic follow-up, which is important in excluding ‘oculostenotic reflex’ revascularizations [13]. ■■ Diabetes
The presence of diabetes has been associated with worse outcomes following PCI in both the BMS and DES era. While DES has reduced the risk of restenosis, there is controversy as to the relative efficacy of various DES in subjects with diabetes. From 42 trials with 22,844 patientyears of follow-up, we have shown that when compared with BMS, all of the currently used DES were associated with a significant reduction in TVR (37–69%). However, the efficacy varied with the type of stent, with EES being the most efficacious compared with all others, although there were limited usable data for the ZES-R stent in patients with diabetes [14]. ■■ Stent thrombosis
While DES works to reduce the risk of restenosis by reducing neointimal proliferation,
www.futuremedicine.com
503
REVIEW
Amoroso & Bangalore
Relative risk reduction TVR (% vs BMS)
70
61%
61%
60
56%
50 39%
40
39%
30 20 10 0 SES
PES
EES
ZES
ZES-R
Figure 1. Risk reduction of target-vessel revascularization with various drug-eluting stents when compared with bare-metal stents. BMS: Bare-metal stent; EES: Everolimus-eluting stent; PES: Paclitaxel-eluting stent; SES: Sirolimus-eluting stent; TVR: Target-vessel revascularization; ZES: Zotarolimus-eluting stent; ZES-R: Zotarolimus-eluting stent-Resolute. Adapted from [13].
an unintended consequence of this is delayed endothelial healing with subsequent risk of late (1 month to 1 year) or very late (>1 year) stent thrombosis. Stent thrombosis is a catastrophic event with a 30‑day rate of MI of 60% and a rate of death of 15–20% [34]. The increased risk of very late stent thrombosis seen with DES was mainly restricted to older DES. In the newer generation DES with thinner struts and more biocompatible polymers, the rate of stent thrombosis has been drastically reduced. In fact, in our analysis we did not observe any increase in the risk of any long-term safety outcomes (death, MI and stent thrombosis), with any DES. In addition, EES were associated with reduction in the risk of stent thrombosis (relative risk: 0.51, 95% CI: 0.35–0.73) even when compared with BMS [13]. There is thus reason to believe that the newer generation stents are not only efficacious but also safe and should be considered as benchmarks for efficacy and safety for future trials. ■■ Dual antiplatelet therapy
Recommendations for extended dua l antiplatelet therapy for patients receiving DES are aimed at reducing the risk of stent thrombosis [23]. Duration of dual antiplatelet therapy is one of the main differences discussed when considering placement of DES versus
504
J. Compar. Effect. Res. (2012) 1(6)
BMS. For patients undergoing PCI with BMS for nonacute coronary syndrome indications, guidelines currently recommend P2Y 12 inhibitor therapy for at least 1 month compared with 12 months or longer for DES [23]. Early cessation of dual antiplatelet therapy has been linked to higher risk of early and late stent thrombosis [35]. Trials are underway to test the efficacy of an extended dual antiplatelet therapy (12 vs 33 months) on the incidence of stent thrombosis and other major adverse vascular events [36]. However, with the advent of newer generation DES with thinner struts and more biocompatible polymers, attention has been turned to evaluate whether a shorter duration of dual antiplatelet therapy (
