JACC: CARDIOVASCULAR INTERVENTIONS ª 2014 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER INC.
VOL. 7, NO. 7, 2014 ISSN 1936-8798/$36.00 http://dx.doi.org/10.1016/j.jcin.2014.04.003
EDITORIAL COMMENT
Should Every Drug-Eluting Stent Be Deployed Directly?* Marco A. Magalhaes, MD, Sa’ar Minha, MD, Augusto D. Pichard, MD Washington, DC Stents are the most remarkable advance to occur in coronary artery disease management in the last 28 years. Stent reengineering transformed early hand-crimped, bulky systems into safer, balloon-crimped devices, substantially reducing strut thickness while maintaining radial strength. This made direct stenting feasible and led interventional cardiologists to pose the question, “Should every lesion undergo direct stenting?” to which the answer was a resounding “Yes!”.if eligible (1). See page 751
Direct stenting (DS) is both safe and effective. A metaanalysis of 24 randomized trials in the bare-metal stent (BMS) era, including a total of 6,803 enrolled patients, compared DS to stenting with pre-dilation and revealed a reduction in myocardial infarction of 23% in favor of DS (2). Both techniques enlarge the coronary lumen by similar mechanisms, as judged by intravascular ultrasound (IVUS), and both elicit an equivalent physiological response. However, there are distinct advantages to DS, including reduced vessel wall trauma, reduced microvascular injury, and improved myocardial perfusion grades in acute coronary syndromes. Additionally, DS reduces radiation time and procedural costs. On the other hand, primary failure can occur in up to 17% of patients assigned to DS (3) as a result of poor device performances, lack of operator expertise, and inappropriate lesion selection. Accurate determination of plaque and calcium distribution via IVUS decreases the likelihood of unsuccessful DS attempts, which otherwise may result in stent dislodgment and structural device damage, and may also uncover potentially undilatable
*Editorials published in JACC: Cardiovascular Interventions reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Interventions or the American College of Cardiology. From the Department of Internal Medicine, Division of Cardiology, MedStar Washington Hospital Center, Washington, DC. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
lesions that require plaque modification. One of the authors in this editorial utilizes IVUS guidance in all procedures as the first step. This strategy allows for DS in most patients except when IVUS suggests the presence of undilatable lesions. Drug-eluting stents (DES) have a more complex structure, with polymer and drug coatings that need to reach the target lesion intact to yield an effective drug elution. Thus, DS with DES is potentially susceptible to either unequal expansion or polymer damage with consequent inhomogeneous pharmacokinetics that would reduce its maximal benefit. However, the safety and effectiveness of DS with DES have been inferred primarily from observational (4,5) and post-hoc (6–9) studies, as well as 1 underpowered randomized trial (10). To date, no evidence for unequal expansion has been uncovered, and there are conflicting results on restenosis rates, with some studies showing a reduction, which would favor DS (5,7,10), whereas others document outcomes equivalent to stenting without predilation (6,9). Nevertheless, DS with DES has been increasingly adopted as standard practice (11), although it is technically “off-label,” and the available data are mostly restricted to first-generation DES. Contemporary, second-generation DES are constructed from a thin, highly flexible metal alloy making them more attractive for direct delivery. Also, mechanical damage to second-generation DES architecture, such as longitudinal deformation, has been occasionally reported (12,13). It is plausible that the lack of pre-dilation in DS may contribute to the need for post-dilation (12). Therefore, the question posed at the start of this paper acquires a different perspective in the modern DES era, “Should every DES be deployed directly?” In this issue of JACC: Cardiovascular Interventions, Remkes et al. (14) report on the STRESSED (direct Stenting To Reduce REStenosis in Stent Era with Drug elution) trial, the first prospective, randomized study addressing the safety and efficacy of direct second-generation DES. The population included patients undergoing elective percutaneous coronary interventions for simple de novo lesions with zotarolimus-eluting DES (Endeavor, Medtronic, Santa Rosa, California) or everolimus-eluting DES (Promus, Boston Scientific, Natick, Massachusetts) randomized to 3 strategies: 1) direct stenting; 2) stenting preceded by predilation; and 3) provisional stenting. The hypothesis assumed that DS with DES was superior to pre-dilation or provisional stenting. The primary endpoint was the minimal lumen diameter at 9 months. Secondary outcomes included major adverse cardiac events at 9 months and at 2 years follow-up. Exploratory analyses were post-procedural troponin release and binary restenosis. The authors demonstrated no evidence of a difference among DS, pre-dilation, or provisional stenting in regard to minimal lumen diameter at 9 months (2.12 0.58 mm
760
Magalhaes et al. Should Every Drug-Eluting Stent Be Deployed Directly?
vs. 2.17 0.67 mm vs. 1.99 0.69 mm, respectively; p ¼ 0.556). Although the restenosis rate was higher in provisional DES (3.4% vs. 6.7% vs. 11.5%; p ¼ 0.025), it did not translate into differences in major adverse cardiac events either at 9 months or at 2 years. Patients assigned to DS had a lower frequency of troponin release than those with conventional pre-dilation (11.2% vs. 24.8%; p ¼ 0.008) or provisional stenting (11.2% vs. 21.9%; p ¼ 0.031). One may ask what the relevance is when including a provisional stent arm in the DES era? In fact, this constitutes one of the unique aspects of the STRESSED study. In the BMS era, a “stent-like” result in certain lesions following balloon angioplasty had outcomes similar to BMS. The superiority of systematic second-generation DES compared with provisional stenting in reducing restenosis is remarkable. This difference was obtained even with a high crossover rate in which 77% of patients assigned to the provisional arm received a DES. In other words, the remaining 23% of patients skewed the late-loss distribution compared with DS or pre-dilation (0.36 0.49 mm vs. 0.24 0.47 mm vs. 0.29 0.55 mm, respectively; p ¼ 0.05). Thus, systematic second-generation DES implantation performs even better than a more restrictive “stent-like” result following provisional angioplasty. Some caveats of the trial require further discussion. First, the primary failure rate of DS at 18% is strikingly high, considering the device profile and the selection of noncomplex lesions. This highlights the angiographic limitations in accurately defining DS eligibility. Second, neither damage to the stent structure during DS failure attempts nor rates of stent thrombosis have been reported. Third, the sample chosen consists of patients with unusually simple lesions, even compared with pivotal trials, and generalization of these results to more complex scenarios may not be advisable. In summary, although DS with second-generation DES did not yield better restenosis results than conventional angioplasty, there were no harmful effects, and lower rates of troponin elevation. Thus, DS remains an excellent technique for most patients; however, in the absence of IVUS, operators should maintain a high level of awareness for potentially undilatable lesions. In addition, a strategy of systematic DES use reduces restenosis compared with provisional stenting and should be the preferable approach. We commend the investigators for providing evidence on one of the most desirable stent features, successful direct delivery, which is our real-life “bedside” test, showing that the Endeavor and Promus platforms can safely undergo direct
JACC: CARDIOVASCULAR INTERVENTIONS, VOL. 7, NO. 7, 2014 JULY 2014:759–60
deployment. Whether this represents a DES class effect cannot be determined, and should be the subject of additional studies. Reprint requests and correspondence: Dr. Augusto D. Pichard, MedStar Washington Hospital Center, 110 Irving Street, NW, Suite 4B-1, Washington, DC 20010. E-mail: [email protected].
REFERENCES
1. Satler LF, Pichard AD, Kent KM. Should every eligible lesion undergo direct stenting? Catheter Cardiovasc Interv 2001;54:164. 2. Piscione F, Piccolo R, Cassese S, et al. Is direct stenting superior to stenting with predilation in patients treated with percutaneous coronary intervention? Results from a meta-analysis of 24 randomised controlled trials. Heart 2010;96:588–94. 3. Barbato E, Marco J, Wijns W. Direct stenting. Eur Heart J 2003;24: 394–403. 4. Schultheiss HP, Grube E, Kuck KH, et al. Safety of direct stenting with the Endeavor stent: results of the Endeavor II continued access registry. EuroIntervention 2007;3:76–81. 5. Moses JW, Weisz G, Mishkel G, et al. The SIRIUS-DIRECT trial: a multi-center study of direct stenting using the sirolimus-eluting stent in patients with de novo native coronary artery lesions. Catheter Cardiovasc Interv 2007;70:505–12. 6. Schluter M, Schofer J, Gershlick AH, Schampaert E, Wijns W, Breithardt G. Direct stenting of native de novo coronary artery lesions with the sirolimus-eluting stent: a post hoc subanalysis of the pooled E- and C-SIRIUS trials. J Am Coll Cardiol 2005;45:10–3. 7. Ormiston JA, Mahmud E, Turco MA, et al. Direct stenting with the TAXUS Liberte drug-eluting stent: results from the Taxus Atlas Direct Stent Study. J Am Coll Cardiol Intv 2008;1:150–60. 8. Silber S, Hamburger J, Grube E, et al. Direct stenting with TAXUS stents seems to be as safe and effective as with predilatation. A post hoc analysis of TAXUS II. Herz 2004;29:171–80. 9. Abbott JD, Earl T, Vlachos HE, et al. Direct stenting compared to balloon predilation in drug-eluting stents: one-year outcomes from the DEScover Registry. Catheter Cardiovasc Interv 2012;79:84–9. 10. Katritsis DG, Korovesis S, Karvouni E, et al. Direct versus predilatation drug-eluting stenting: a randomized clinical trial. J Invasive Cardiol 2006;18:475–9. 11. Zahn R, Nienaber CA, Hamm CW, et al. The sirolimus-eluting coronary stent in clinical practice: impact of direct stenting versus stenting with balloon pre-dilatation. EuroIntervention 2007;2:459–66. 12. Mamas MA, Williams PD. Longitudinal stent deformation: insights on mechanisms, treatments and outcomes from the Food and Drug Administration Manufacturer and User Facility Device Experience database. EuroIntervention 2012;8:196–204. 13. Pitney M, Pitney K, Jepson N, et al. Major stent deformation/ pseudofracture of 7 Crown Endeavor/Micro Driver stent platform: incidence and causative factors. EuroIntervention 2011;7:256–62. 14. Remkes WS, Somi S, Roolvink V, et al. Direct drug-eluting stenting to reduce stent restenosis: a randomized comparison of direct stent implantation to conventional stenting with pre-dilation or provisional stenting in elective PCI patients. J Am Coll Cardiol Intv 2014;7: 751–8.
Key Words: direct stenting
-
outcomes
-
restenosis.
VOL. 7, NO. 7, 2014 ISSN 1936-8798/$36.00 http://dx.doi.org/10.1016/j.jcin.2014.04.003
EDITORIAL COMMENT
Should Every Drug-Eluting Stent Be Deployed Directly?* Marco A. Magalhaes, MD, Sa’ar Minha, MD, Augusto D. Pichard, MD Washington, DC Stents are the most remarkable advance to occur in coronary artery disease management in the last 28 years. Stent reengineering transformed early hand-crimped, bulky systems into safer, balloon-crimped devices, substantially reducing strut thickness while maintaining radial strength. This made direct stenting feasible and led interventional cardiologists to pose the question, “Should every lesion undergo direct stenting?” to which the answer was a resounding “Yes!”.if eligible (1). See page 751
Direct stenting (DS) is both safe and effective. A metaanalysis of 24 randomized trials in the bare-metal stent (BMS) era, including a total of 6,803 enrolled patients, compared DS to stenting with pre-dilation and revealed a reduction in myocardial infarction of 23% in favor of DS (2). Both techniques enlarge the coronary lumen by similar mechanisms, as judged by intravascular ultrasound (IVUS), and both elicit an equivalent physiological response. However, there are distinct advantages to DS, including reduced vessel wall trauma, reduced microvascular injury, and improved myocardial perfusion grades in acute coronary syndromes. Additionally, DS reduces radiation time and procedural costs. On the other hand, primary failure can occur in up to 17% of patients assigned to DS (3) as a result of poor device performances, lack of operator expertise, and inappropriate lesion selection. Accurate determination of plaque and calcium distribution via IVUS decreases the likelihood of unsuccessful DS attempts, which otherwise may result in stent dislodgment and structural device damage, and may also uncover potentially undilatable
*Editorials published in JACC: Cardiovascular Interventions reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Interventions or the American College of Cardiology. From the Department of Internal Medicine, Division of Cardiology, MedStar Washington Hospital Center, Washington, DC. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
lesions that require plaque modification. One of the authors in this editorial utilizes IVUS guidance in all procedures as the first step. This strategy allows for DS in most patients except when IVUS suggests the presence of undilatable lesions. Drug-eluting stents (DES) have a more complex structure, with polymer and drug coatings that need to reach the target lesion intact to yield an effective drug elution. Thus, DS with DES is potentially susceptible to either unequal expansion or polymer damage with consequent inhomogeneous pharmacokinetics that would reduce its maximal benefit. However, the safety and effectiveness of DS with DES have been inferred primarily from observational (4,5) and post-hoc (6–9) studies, as well as 1 underpowered randomized trial (10). To date, no evidence for unequal expansion has been uncovered, and there are conflicting results on restenosis rates, with some studies showing a reduction, which would favor DS (5,7,10), whereas others document outcomes equivalent to stenting without predilation (6,9). Nevertheless, DS with DES has been increasingly adopted as standard practice (11), although it is technically “off-label,” and the available data are mostly restricted to first-generation DES. Contemporary, second-generation DES are constructed from a thin, highly flexible metal alloy making them more attractive for direct delivery. Also, mechanical damage to second-generation DES architecture, such as longitudinal deformation, has been occasionally reported (12,13). It is plausible that the lack of pre-dilation in DS may contribute to the need for post-dilation (12). Therefore, the question posed at the start of this paper acquires a different perspective in the modern DES era, “Should every DES be deployed directly?” In this issue of JACC: Cardiovascular Interventions, Remkes et al. (14) report on the STRESSED (direct Stenting To Reduce REStenosis in Stent Era with Drug elution) trial, the first prospective, randomized study addressing the safety and efficacy of direct second-generation DES. The population included patients undergoing elective percutaneous coronary interventions for simple de novo lesions with zotarolimus-eluting DES (Endeavor, Medtronic, Santa Rosa, California) or everolimus-eluting DES (Promus, Boston Scientific, Natick, Massachusetts) randomized to 3 strategies: 1) direct stenting; 2) stenting preceded by predilation; and 3) provisional stenting. The hypothesis assumed that DS with DES was superior to pre-dilation or provisional stenting. The primary endpoint was the minimal lumen diameter at 9 months. Secondary outcomes included major adverse cardiac events at 9 months and at 2 years follow-up. Exploratory analyses were post-procedural troponin release and binary restenosis. The authors demonstrated no evidence of a difference among DS, pre-dilation, or provisional stenting in regard to minimal lumen diameter at 9 months (2.12 0.58 mm
760
Magalhaes et al. Should Every Drug-Eluting Stent Be Deployed Directly?
vs. 2.17 0.67 mm vs. 1.99 0.69 mm, respectively; p ¼ 0.556). Although the restenosis rate was higher in provisional DES (3.4% vs. 6.7% vs. 11.5%; p ¼ 0.025), it did not translate into differences in major adverse cardiac events either at 9 months or at 2 years. Patients assigned to DS had a lower frequency of troponin release than those with conventional pre-dilation (11.2% vs. 24.8%; p ¼ 0.008) or provisional stenting (11.2% vs. 21.9%; p ¼ 0.031). One may ask what the relevance is when including a provisional stent arm in the DES era? In fact, this constitutes one of the unique aspects of the STRESSED study. In the BMS era, a “stent-like” result in certain lesions following balloon angioplasty had outcomes similar to BMS. The superiority of systematic second-generation DES compared with provisional stenting in reducing restenosis is remarkable. This difference was obtained even with a high crossover rate in which 77% of patients assigned to the provisional arm received a DES. In other words, the remaining 23% of patients skewed the late-loss distribution compared with DS or pre-dilation (0.36 0.49 mm vs. 0.24 0.47 mm vs. 0.29 0.55 mm, respectively; p ¼ 0.05). Thus, systematic second-generation DES implantation performs even better than a more restrictive “stent-like” result following provisional angioplasty. Some caveats of the trial require further discussion. First, the primary failure rate of DS at 18% is strikingly high, considering the device profile and the selection of noncomplex lesions. This highlights the angiographic limitations in accurately defining DS eligibility. Second, neither damage to the stent structure during DS failure attempts nor rates of stent thrombosis have been reported. Third, the sample chosen consists of patients with unusually simple lesions, even compared with pivotal trials, and generalization of these results to more complex scenarios may not be advisable. In summary, although DS with second-generation DES did not yield better restenosis results than conventional angioplasty, there were no harmful effects, and lower rates of troponin elevation. Thus, DS remains an excellent technique for most patients; however, in the absence of IVUS, operators should maintain a high level of awareness for potentially undilatable lesions. In addition, a strategy of systematic DES use reduces restenosis compared with provisional stenting and should be the preferable approach. We commend the investigators for providing evidence on one of the most desirable stent features, successful direct delivery, which is our real-life “bedside” test, showing that the Endeavor and Promus platforms can safely undergo direct
JACC: CARDIOVASCULAR INTERVENTIONS, VOL. 7, NO. 7, 2014 JULY 2014:759–60
deployment. Whether this represents a DES class effect cannot be determined, and should be the subject of additional studies. Reprint requests and correspondence: Dr. Augusto D. Pichard, MedStar Washington Hospital Center, 110 Irving Street, NW, Suite 4B-1, Washington, DC 20010. E-mail: [email protected].
REFERENCES
1. Satler LF, Pichard AD, Kent KM. Should every eligible lesion undergo direct stenting? Catheter Cardiovasc Interv 2001;54:164. 2. Piscione F, Piccolo R, Cassese S, et al. Is direct stenting superior to stenting with predilation in patients treated with percutaneous coronary intervention? Results from a meta-analysis of 24 randomised controlled trials. Heart 2010;96:588–94. 3. Barbato E, Marco J, Wijns W. Direct stenting. Eur Heart J 2003;24: 394–403. 4. Schultheiss HP, Grube E, Kuck KH, et al. Safety of direct stenting with the Endeavor stent: results of the Endeavor II continued access registry. EuroIntervention 2007;3:76–81. 5. Moses JW, Weisz G, Mishkel G, et al. The SIRIUS-DIRECT trial: a multi-center study of direct stenting using the sirolimus-eluting stent in patients with de novo native coronary artery lesions. Catheter Cardiovasc Interv 2007;70:505–12. 6. Schluter M, Schofer J, Gershlick AH, Schampaert E, Wijns W, Breithardt G. Direct stenting of native de novo coronary artery lesions with the sirolimus-eluting stent: a post hoc subanalysis of the pooled E- and C-SIRIUS trials. J Am Coll Cardiol 2005;45:10–3. 7. Ormiston JA, Mahmud E, Turco MA, et al. Direct stenting with the TAXUS Liberte drug-eluting stent: results from the Taxus Atlas Direct Stent Study. J Am Coll Cardiol Intv 2008;1:150–60. 8. Silber S, Hamburger J, Grube E, et al. Direct stenting with TAXUS stents seems to be as safe and effective as with predilatation. A post hoc analysis of TAXUS II. Herz 2004;29:171–80. 9. Abbott JD, Earl T, Vlachos HE, et al. Direct stenting compared to balloon predilation in drug-eluting stents: one-year outcomes from the DEScover Registry. Catheter Cardiovasc Interv 2012;79:84–9. 10. Katritsis DG, Korovesis S, Karvouni E, et al. Direct versus predilatation drug-eluting stenting: a randomized clinical trial. J Invasive Cardiol 2006;18:475–9. 11. Zahn R, Nienaber CA, Hamm CW, et al. The sirolimus-eluting coronary stent in clinical practice: impact of direct stenting versus stenting with balloon pre-dilatation. EuroIntervention 2007;2:459–66. 12. Mamas MA, Williams PD. Longitudinal stent deformation: insights on mechanisms, treatments and outcomes from the Food and Drug Administration Manufacturer and User Facility Device Experience database. EuroIntervention 2012;8:196–204. 13. Pitney M, Pitney K, Jepson N, et al. Major stent deformation/ pseudofracture of 7 Crown Endeavor/Micro Driver stent platform: incidence and causative factors. EuroIntervention 2011;7:256–62. 14. Remkes WS, Somi S, Roolvink V, et al. Direct drug-eluting stenting to reduce stent restenosis: a randomized comparison of direct stent implantation to conventional stenting with pre-dilation or provisional stenting in elective PCI patients. J Am Coll Cardiol Intv 2014;7: 751–8.
Key Words: direct stenting
-
outcomes
-
restenosis.
