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Safety of elective—including “high risk”—percutaneous coronary interventions without on-site cardiac surgery
Late Thrombosis in Drug-Eluting Coronary Stents After Discontinuation of Antiplatelet Therapy
5.
McFadden EP, Stabile E, Regar E, et al. Lancet 2004;364:1519 –21.
6.
Study Question: Although the safety profiles of coronary stents eluting sirolimus or paclitaxel do not seem to differ from those of bare-metal stents in the short-to-medium term, concern has arisen about the potential for late stent thromboses related to delayed endothelialization of the stent struts. Methods: The study is a case series. Results: The investigators report four cases of angiographically confirmed stent thrombosis that occurred late after elective implantation of polymer-based paxlitaxel-eluting (343 and 442 d) or sirolimus-eluting (335 and 375 d) stents, and which resulted in myocardial infarction. All cases arose soon after antiplatelet therapy was interrupted. Conclusions: The investigators concluded that if confirmed in systematic long-term follow-up studies, these findings have potentially serious clinical implications. Perspective: The study suggests that the potential risk of stent occlusion should be considered when discontinuation of antiplatelet therapy is contemplated in patients with drug-eluting stents. As the use of drug-eluting stents becomes widespread, careful long-term follow-up of patients with such stents is needed to assess the true rate of late thrombosis. The potential issue is increasingly encountered among patients with a previous drug-eluting coronary stent who are facing major noncardiac surgery and where dual antiplatelet therapy must be discontinued to avoid excessive bleeding risk. DM/KE
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Safety of Elective—Including “High Risk”—Percutaneous Coronary Interventions Without On-Site Cardiac Surgery Zavala-Alarcon E, Cecena F, Ashar F, et al. Am Heart J 2004; 148:676 – 83.
Antithrombotic Therapy During Percutaneous Coronary Intervention: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy
Study Question: Is it safe to perform elective percutaneous coronary intervention (PCI) in hospitals without on-site cardiac surgery? Methods: Data from 1000 elective PCIs performed in a single center without cardiac surgery on-site were reviewed. End points evaluated included angiographic characteristics and clinical outcomes before hospital discharge. Procedures were performed by two experienced interventional cardiologists who routinely performed PCI at facilities with on-site cardiac surgery. All patients were given the option to be transferred to a facility with on-site cardiac surgery before PCI. Results: Only 11 patients (1.1%) elected to be transferred to a facility with cardiac surgery on-site. In 96% of cases, PCI was performed immediately after the initial diagnostic cardiac catheterization (ad hoc procedure). On average, 1.7 vessels per patient were treated. Unsuccessful revascularization occurred in 38 cases (3.8%), of which 35 were chronic total occlusions. Elective referral for coronary artery bypass graft surgery (CABG) was required in seven
Popma JJ, Berger P, Ohman EM, Harrington RA, Grines C, Weitz JI. Chest 2004;126:576S–99S. The report describes guidelines developed for the seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Grade-1 key recommendations are listed below: 1.
2. 3.
4.
(ticlopidine or clopidogrel) over systemic anticoagulation therapy is recommended (Grade 1A). Clopidogrel is recommended over ticlopidine (Grade 1A). After PCI, in addition to aspirin, clopidogrel (75 mg/d) for at least 9 –12 months is recommended (Grade 1A). For all patients undergoing PCI, particularly those undergoing primary PCI, or those with refractory unstable angina or other high-risk features, use of a glycoprotein (GP)IIb/IIIa antagonist (abciximab or eptifibatide) is recommended (Grade 1A). In patients undergoing PCI for ST-segment elevation MI, abciximab over eptifibatide is recommended (Grade 1B). In patients after uncomplicated PCI, routine postprocedural infusion of heparin should not be used (Grade 1A). For patients undergoing PCI who are not treated with a GPIIb/IIIa antagonist, bivalirudin over heparin during PCI is recommended (Grade 1A). In PCI patients who are at low risk for complications, bivalirudin as an alternative to heparin as an adjunct to GPIIb/IIIa antagonists is recommended (Grade 1B). In PCI patients who are at high risk for bleeding, bivalirudin over heparin as an adjunct to GPIIb/IIIa antagonists is recommended (Grade 1B). DM
For patients undergoing PCI, the guidelines recommend pretreatment with aspirin, 75–325 mg (Grade 1A). For long-term treatment after PCI, aspirin 75–162 mg/d, is recommended (Grade 1A). For long-term treatment after PCI in patients who receive clopidogrel or warfarin, lower-dose aspirin, 75–100 mg/d, is recommended (Grade 1C⫹). For patients who undergo stent placement, the combination of aspirin and a thienopyridine derivative
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with EDG ISR treated in the balloon and stent arms had similar baseline characteristics. However, after intervention, the immediate angiographic result was better in the stent arm (MLD 2.79⫾0.4 vs. 2.35⫾0.3 mm; p⫽0.001). This difference persisted at late follow-up: MLD (1.93⫾0.7 vs. 1.39⫾0.7 mm; p⫽0.01), recurrent restenosis (20% vs. 50%; p⫽0.03). In addition, the 1-year event-free survival was significantly better (83% vs. 52%, log rank p⫽0.01; Cox HR 0.28; 95% CI 0.09 – 0.79) in the stent arm. Moreover, stent implantation was an independent predictor of freedom from target-vessel revascularization (HR 0.15; 95% CI 0.03– 0.67; p⫽0.003). Conclusions: The investigators concluded that in patients with EDG ISR, repeat stent implantation provides better clinical and angiographic outcome than conventional balloon angioplasty. Perspective: Patients with EDG ISR represent a relatively small but unique subgroup of patients, with major therapeutic implications, thus allowing an early triage. The current study suggests that in these patients, repeat stenting provides better long-term clinical and angiographic results than does conventional balloon angioplasty and, therefore, may be the preferred approach. DM
patients (0.7%) after failed PCI. Seven patients (0.7%) required placement of an intra-aortic balloon pump due to hemodynamic instability, while coronary perforations occurred in nine patients (0.9%). Periprocedural death occurred in two patients (0.2%). None required emergency CABG. Conclusions: Elective PCI can be performed safely in centers without cardiac surgery on-site. Perspective: Although emergency PCI for acute myocardial infarction in facilities without cardiac surgery on-site has recently been approved by state regulatory agencies in the United States following endorsement of the American College of Cardiology/American Heart Association guidelines for PCI, elective PCI in facilities without cardiac surgery on-site continues to be contraindicated. The result of this single-center study suggests that in the appropriate setting, and with experienced operators, elective PCI can be performed safely in facilities without cardiac surgery on-site. However, a recent analysis from the Medicare database using a much larger multicenter dataset has shown worse outcomes and an increased risk of death for patients undergoing elective PCI in facilities without cardiac surgery onsite, and particularly in low-volume institutions. Thus, it appears that elective PCI without cardiac surgery on-site is not yet ready for prime time, and that we will need more data before its use can be endorsed. MM
A Randomized Controlled Trial of Intravenous Nacetylcysteine for the Prevention of ContrastInduced Nephropathy After Cardiac Catheterization: Lack of Effect
Therapeutic Implications of In-stent Restenosis Located at the Stent Edge: Insights From the Restenosis Intra-stent Balloon Angioplasty Versus Elective Stenting (RIBS) Randomized Trial
Webb JG, Pate GE, Humphries KH, et al. Am Heart J 2004;148: 422–9. Study Question: What is the effectiveness of N-acetylcysteine in reducing the risk of contrast nephropathy following cardiac catheterization in patients with pre-existing baseline renal insufficiency? Methods: A total of 487 patients with baseline renal dysfunction defined as glomerular filtration rate (GFR) of less than 50 mL/min were randomized in a blinded fashion to receive either 500 mg of N-acetylcysteine intravenously (242 patients) or to receive placebo (245 patients). The study drug was administered over 15 min starting within 1 h of the procedure and before the first injection of contrast. The primary end point was a decline in creatinine clearance greater than 5 mL/min. Additional end points included: 1) change in glomerular filtration rate (GFR) ⬎5 mL/min; 2) an increase in serum creatinine of ⬎0.5 mg/dL; filtration rate (GFR) ⬎5 mL/min; 2) an increase in serum creatinine of ⬎0.5 mg/dL; cardiac catheterization using low-osmolarity contrast media, and all patients received 200 mL of IV saline before contrast administration and 1.5 mL/kg/h of saline following the procedure for 6 h or until discharge. Results: No significant differences existed in the incidence of the primary end point (23.3% in the N-acetylcysteine group and 20.7% in the placebo group, p⫽0.51). There
Alfonso F, Melgares R, Mainar V, et al. for the Restenosis Intrastent: Balloon Angioplasty versus Elective Stenting (RIBS) Investigators. Eur Heart J 2004;25:1829 –35. Study Question: In patients with in-stent restenosis (ISR), several anatomic subgroups have been identified. The ISR affecting the stent edge (EDG) is a poorly characterized subgroup with undefined therapeutic implications. The investigators sought to determine the implications of ISR affecting the EDG. Methods: A total of 450 patients included in the Restenosis Intra-stent: Balloon angioplasty vs elective Stenting (RIBS) randomized study were analyzed. The EDG ISR was predefined in the protocol and the pattern of ISR analyzed in a centralized core laboratory. Results: Fifty-two patients (12%) had EDG ISR (29 stent group, 23 balloon arm). Patients with EDG ISR had less severe (minimal lumen diameter [MLD] [0.78⫾0.3 vs. 0.66⫾0.3 mm; p⫽0.05]) and shorter lesions (lesion length 10.2⫾6 vs. 13.2⫾7 mm; p⫽0.003). Patients with EDG ISR more frequently required crossover (12% vs. 3%; p⫽0.006) but eventually both the immediate angiographic result and the long-term clinical and angiographic outcomes were similar to that found in patients without EDG ISR. Patients
ACC CURRENT JOURNAL REVIEW February 2005
47
5.
McFadden EP, Stabile E, Regar E, et al. Lancet 2004;364:1519 –21.
6.
Study Question: Although the safety profiles of coronary stents eluting sirolimus or paclitaxel do not seem to differ from those of bare-metal stents in the short-to-medium term, concern has arisen about the potential for late stent thromboses related to delayed endothelialization of the stent struts. Methods: The study is a case series. Results: The investigators report four cases of angiographically confirmed stent thrombosis that occurred late after elective implantation of polymer-based paxlitaxel-eluting (343 and 442 d) or sirolimus-eluting (335 and 375 d) stents, and which resulted in myocardial infarction. All cases arose soon after antiplatelet therapy was interrupted. Conclusions: The investigators concluded that if confirmed in systematic long-term follow-up studies, these findings have potentially serious clinical implications. Perspective: The study suggests that the potential risk of stent occlusion should be considered when discontinuation of antiplatelet therapy is contemplated in patients with drug-eluting stents. As the use of drug-eluting stents becomes widespread, careful long-term follow-up of patients with such stents is needed to assess the true rate of late thrombosis. The potential issue is increasingly encountered among patients with a previous drug-eluting coronary stent who are facing major noncardiac surgery and where dual antiplatelet therapy must be discontinued to avoid excessive bleeding risk. DM/KE
7.
8.
9.
10.
11.
12.
Safety of Elective—Including “High Risk”—Percutaneous Coronary Interventions Without On-Site Cardiac Surgery Zavala-Alarcon E, Cecena F, Ashar F, et al. Am Heart J 2004; 148:676 – 83.
Antithrombotic Therapy During Percutaneous Coronary Intervention: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy
Study Question: Is it safe to perform elective percutaneous coronary intervention (PCI) in hospitals without on-site cardiac surgery? Methods: Data from 1000 elective PCIs performed in a single center without cardiac surgery on-site were reviewed. End points evaluated included angiographic characteristics and clinical outcomes before hospital discharge. Procedures were performed by two experienced interventional cardiologists who routinely performed PCI at facilities with on-site cardiac surgery. All patients were given the option to be transferred to a facility with on-site cardiac surgery before PCI. Results: Only 11 patients (1.1%) elected to be transferred to a facility with cardiac surgery on-site. In 96% of cases, PCI was performed immediately after the initial diagnostic cardiac catheterization (ad hoc procedure). On average, 1.7 vessels per patient were treated. Unsuccessful revascularization occurred in 38 cases (3.8%), of which 35 were chronic total occlusions. Elective referral for coronary artery bypass graft surgery (CABG) was required in seven
Popma JJ, Berger P, Ohman EM, Harrington RA, Grines C, Weitz JI. Chest 2004;126:576S–99S. The report describes guidelines developed for the seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Grade-1 key recommendations are listed below: 1.
2. 3.
4.
(ticlopidine or clopidogrel) over systemic anticoagulation therapy is recommended (Grade 1A). Clopidogrel is recommended over ticlopidine (Grade 1A). After PCI, in addition to aspirin, clopidogrel (75 mg/d) for at least 9 –12 months is recommended (Grade 1A). For all patients undergoing PCI, particularly those undergoing primary PCI, or those with refractory unstable angina or other high-risk features, use of a glycoprotein (GP)IIb/IIIa antagonist (abciximab or eptifibatide) is recommended (Grade 1A). In patients undergoing PCI for ST-segment elevation MI, abciximab over eptifibatide is recommended (Grade 1B). In patients after uncomplicated PCI, routine postprocedural infusion of heparin should not be used (Grade 1A). For patients undergoing PCI who are not treated with a GPIIb/IIIa antagonist, bivalirudin over heparin during PCI is recommended (Grade 1A). In PCI patients who are at low risk for complications, bivalirudin as an alternative to heparin as an adjunct to GPIIb/IIIa antagonists is recommended (Grade 1B). In PCI patients who are at high risk for bleeding, bivalirudin over heparin as an adjunct to GPIIb/IIIa antagonists is recommended (Grade 1B). DM
For patients undergoing PCI, the guidelines recommend pretreatment with aspirin, 75–325 mg (Grade 1A). For long-term treatment after PCI, aspirin 75–162 mg/d, is recommended (Grade 1A). For long-term treatment after PCI in patients who receive clopidogrel or warfarin, lower-dose aspirin, 75–100 mg/d, is recommended (Grade 1C⫹). For patients who undergo stent placement, the combination of aspirin and a thienopyridine derivative
ACC CURRENT JOURNAL REVIEW February 2005
46
with EDG ISR treated in the balloon and stent arms had similar baseline characteristics. However, after intervention, the immediate angiographic result was better in the stent arm (MLD 2.79⫾0.4 vs. 2.35⫾0.3 mm; p⫽0.001). This difference persisted at late follow-up: MLD (1.93⫾0.7 vs. 1.39⫾0.7 mm; p⫽0.01), recurrent restenosis (20% vs. 50%; p⫽0.03). In addition, the 1-year event-free survival was significantly better (83% vs. 52%, log rank p⫽0.01; Cox HR 0.28; 95% CI 0.09 – 0.79) in the stent arm. Moreover, stent implantation was an independent predictor of freedom from target-vessel revascularization (HR 0.15; 95% CI 0.03– 0.67; p⫽0.003). Conclusions: The investigators concluded that in patients with EDG ISR, repeat stent implantation provides better clinical and angiographic outcome than conventional balloon angioplasty. Perspective: Patients with EDG ISR represent a relatively small but unique subgroup of patients, with major therapeutic implications, thus allowing an early triage. The current study suggests that in these patients, repeat stenting provides better long-term clinical and angiographic results than does conventional balloon angioplasty and, therefore, may be the preferred approach. DM
patients (0.7%) after failed PCI. Seven patients (0.7%) required placement of an intra-aortic balloon pump due to hemodynamic instability, while coronary perforations occurred in nine patients (0.9%). Periprocedural death occurred in two patients (0.2%). None required emergency CABG. Conclusions: Elective PCI can be performed safely in centers without cardiac surgery on-site. Perspective: Although emergency PCI for acute myocardial infarction in facilities without cardiac surgery on-site has recently been approved by state regulatory agencies in the United States following endorsement of the American College of Cardiology/American Heart Association guidelines for PCI, elective PCI in facilities without cardiac surgery on-site continues to be contraindicated. The result of this single-center study suggests that in the appropriate setting, and with experienced operators, elective PCI can be performed safely in facilities without cardiac surgery on-site. However, a recent analysis from the Medicare database using a much larger multicenter dataset has shown worse outcomes and an increased risk of death for patients undergoing elective PCI in facilities without cardiac surgery onsite, and particularly in low-volume institutions. Thus, it appears that elective PCI without cardiac surgery on-site is not yet ready for prime time, and that we will need more data before its use can be endorsed. MM
A Randomized Controlled Trial of Intravenous Nacetylcysteine for the Prevention of ContrastInduced Nephropathy After Cardiac Catheterization: Lack of Effect
Therapeutic Implications of In-stent Restenosis Located at the Stent Edge: Insights From the Restenosis Intra-stent Balloon Angioplasty Versus Elective Stenting (RIBS) Randomized Trial
Webb JG, Pate GE, Humphries KH, et al. Am Heart J 2004;148: 422–9. Study Question: What is the effectiveness of N-acetylcysteine in reducing the risk of contrast nephropathy following cardiac catheterization in patients with pre-existing baseline renal insufficiency? Methods: A total of 487 patients with baseline renal dysfunction defined as glomerular filtration rate (GFR) of less than 50 mL/min were randomized in a blinded fashion to receive either 500 mg of N-acetylcysteine intravenously (242 patients) or to receive placebo (245 patients). The study drug was administered over 15 min starting within 1 h of the procedure and before the first injection of contrast. The primary end point was a decline in creatinine clearance greater than 5 mL/min. Additional end points included: 1) change in glomerular filtration rate (GFR) ⬎5 mL/min; 2) an increase in serum creatinine of ⬎0.5 mg/dL; filtration rate (GFR) ⬎5 mL/min; 2) an increase in serum creatinine of ⬎0.5 mg/dL; cardiac catheterization using low-osmolarity contrast media, and all patients received 200 mL of IV saline before contrast administration and 1.5 mL/kg/h of saline following the procedure for 6 h or until discharge. Results: No significant differences existed in the incidence of the primary end point (23.3% in the N-acetylcysteine group and 20.7% in the placebo group, p⫽0.51). There
Alfonso F, Melgares R, Mainar V, et al. for the Restenosis Intrastent: Balloon Angioplasty versus Elective Stenting (RIBS) Investigators. Eur Heart J 2004;25:1829 –35. Study Question: In patients with in-stent restenosis (ISR), several anatomic subgroups have been identified. The ISR affecting the stent edge (EDG) is a poorly characterized subgroup with undefined therapeutic implications. The investigators sought to determine the implications of ISR affecting the EDG. Methods: A total of 450 patients included in the Restenosis Intra-stent: Balloon angioplasty vs elective Stenting (RIBS) randomized study were analyzed. The EDG ISR was predefined in the protocol and the pattern of ISR analyzed in a centralized core laboratory. Results: Fifty-two patients (12%) had EDG ISR (29 stent group, 23 balloon arm). Patients with EDG ISR had less severe (minimal lumen diameter [MLD] [0.78⫾0.3 vs. 0.66⫾0.3 mm; p⫽0.05]) and shorter lesions (lesion length 10.2⫾6 vs. 13.2⫾7 mm; p⫽0.003). Patients with EDG ISR more frequently required crossover (12% vs. 3%; p⫽0.006) but eventually both the immediate angiographic result and the long-term clinical and angiographic outcomes were similar to that found in patients without EDG ISR. Patients
ACC CURRENT JOURNAL REVIEW February 2005
47