EHI

Wer Bypass-Operationen am schlagenden Herzen (Off-Pump) vornimmt und damit die Vorstellung des schonenderen Verfahrens verbindet, muss offenbar dazu lernen. Es rsultiert aus dem Off-Pump-Verfahren ein schlechteres Ein-Jahres-Operationsergebnis als mit der konventionellen Methode unter Verwendung der Herz-Lungen-Maschine. Zwar sind beide Verfahren nach den Resultaten einer Studie von Professor A. Laurie Shroyer aus Northpot im US-Staat New York nach 30 Tagen bei den Resultaten gleichwertig. Die Ein-Jahres-Ergebnisse zeigen aber signifikante Nachteile bei der Zahl der realisierten Bypässe und deren noch bestehender Durchgängigkeit, wie im New England Journal of Medicine (2009, 361, 1827) berichtet worden ist. Das Off-Pump-Verfahren war außerdem nicht mit einem Rückgang neurokognitiver Komplikationen nach der Operation verbunden. Die Veterans Affairs Randomized On/Off Bypass Studiy ROO-BY-Studie wurden an 18 US-Kliniken mit 2.203 Patienten realisiert, die entweder On- oder Off-Pump- einen Bypass erhielten. Off-Pump wurde bei 17,8 % der Operationen ein vorgesehener Bypass nicht verlegt, On-Pump passierte das nur bei 11,1 % (p-Wert kleiner 0,001). Die Durchgängigkeit der Bypässe in der Kontrollangiograpfie war nach einem Jahr Off-Pump signifikant niedriger als mit der Herz-Lungen-Maschine (82,6 vs. 87,8 %). Der primäre Endpunkt der Studie, eine Kombination aus Tod, erneuter Revaskularisierung oder Herzinfarkt trat im ersten Jahr nach der Operation Off-pump häufiger auf: 9,9 vs. 7,4 % nach der On-Pump-Operation (p=0,04).
Kommentator Professor Eric David Peterson von der Duke University Medical Center in Durham/North Carolina stellt im gleichen NEJM-Heft (2009, 361 ,1897) en Zusammenhang von Kunst und Wissenschaft in der Chirurgie heraus und meint nicht, dass die Off-Pump-Operation keine Chance mehr hat. Er hält es für möglich, dass die Off-Pump-Operation bei älteren Frauen oder besonders bei begnadeten Vorreiter-Chirurgen („skilled surgeon adcocates“) besser sein könnte, was aber noch belegt werden muss.

BREAKING NEWS

Three-vessel and left main coronary artery:

Cardiac surgery remains the standard therapy

Background Percutaneous coronary intervention (PCI) involvingdrug-eluting stents is increasingly used to treat complex coronaryartery disease, although coronary-artery bypass grafting (CABG)has been the treatment of choice historically. Our trial compared PCI and CABG for treating patients with previously untreated three-vessel or left main coronary artery disease (or both).

Methods We randomly assigned 1800 patients with three-vesselor left main coronary artery disease to undergo CABG or PCI(in a 1:1 ratio). For all these patients, the local cardiacsurgeon and interventional cardiologist determined that equivalent anatomical revascularization could be achieved with either treatment.A noninferiority comparison of the two groups was performedfor the primary end point — a major adverse cardiac or cerebrovascular event (i.e., death from any cause, stroke, myocardialinfarction, or repeat revascularization) during the 12-monthperiod after randomization. Patients for whom only one of thetwo treatment options would be beneficial, because of anatomicalfeatures or clinical conditions, were entered into a parallel,nested CABG or PCI registry.

Results Most of the preoperative characteristics were similarin the two groups. Rates of major adverse cardiac or cerebrovascular events at 12 months were significantly higher in the PCI group (17.8%, vs. 12.4% for CABG; P=0.002), in large part becauseof an increased rate of repeat revascularization (13.5% vs.5.9%, P<0.001); as a result, the criterion for noninferioritywas not met. At 12 months, the rates of death and myocardialinfarction were similar between the two groups; stroke was significantly more likely to occur with CABG (2.2%, vs. 0.6% with PCI; P=0.003).

Conclusions CABG remains the standard of care for patients withthree-vessel or left main coronary artery disease, since theuse of CABG, as compared with PCI, resulted in lower rates ofthe combined end point of major adverse cardiac or cerebrovascularevents at 1 year. (ClinicalTrials.gov number, NCT00114972 [ClinicalTrials.gov] .)

N ENGL J MED Volume 360:961-972 March 5, 2009 Number 10

Percutaneous Coronary Intervention versus Coronary-Artery Bypass Grafting for Severe Coronary Artery Disease

Patrick W. Serruys, M.D., Ph.D., Marie-Claude Morice, M.D., A. Pieter Kappetein, M.D., Ph.D., Antonio Colombo, M.D., David R. Holmes, M.D., Michael J. Mack, M.D., Elisabeth Ståhle, M.D., Ted E. Feldman, M.D., Marcel van den Brand, M.D., Eric J. Bass, B.A., Nic Van Dyck, R.N., Katrin Leadley, M.D., Keith D. Dawkins, M.D., Friedrich W. Mohr, M.D., Ph.D., for the SYNTAX Investigators

E U R O P E A N H E A R T I N S T I T U T E

As a contribution to the controversial discussion for the use of drug-eluting stents the European Heart Institute of the European Academy of Sciences and Arts is emphasizing important factors: a) Drug Eluting Stents (DES) should be used only in accordance with their on-label indications for use. b) To avoid off-label use of DES and to assure that patients are apprized of all their revascularization options, patients should have informed consent between the patient, interventionalist and a cardiac surgeon. c) Without informed consent, off-label use of DES may be a legally actionable offense against the interventionalist. d) At onset of new symptoms, patients must be informed that surgery is a viable and recommended option.

Key words: drug eluting stents, coronary artery disease, coronary artery revascularization

It became publically evident as early as August 2006 at a meeting of cardiologists in Barcelona that Drug Eluting Stents (DES) pose a hazard to patient safety because of the long-term risk for thrombosis, myocardial infarction and death. The BASKET-Late Study [1] presented at the American College of Cardiology meeting in March 2006 -section on Late Thrombolic Events - suggested that complications such as stent thrombosis, myocardial infarction and death were more frequently encountered in DES as compared to bare metal stents (BMS). Public turmoil started after articles appeared in the New York Times [2] and in the New England Journal of Medicine [3] in 2007. Furthermore, papers by Spaulding, Stone and Lagerquist [4,5,6] drew similar conclusions that DES therapy carries a higher risk in the long term in comparison to BMS. Wallentin [5] et al. found an increased risk of death or myocardial infarction of up to 1%. These early studies stimulated further investigations and resulted in a number of ongoing randomized clinical trials comparing DES to BMS, also comparing stenting and coronary bypass surgery. The results of these studies vary, but there are new studies supporting the original BASKET-Late Study evidence that DES therapy is not superior to BMS. Other studies indicate that DES have not reached their predicted level of success in closed chest revascularization. The procedural mortality in stent grafting remains high. In addition, there are studies such as the ARTS Study [7] which clearly demonstrate a superior outcome when surgery is applied in regards to major adverse cardiac events (MACE): Especially for patients undergoing repeat revascularization procedures.

One major criticism of randomized DES studies conducted up to date is the fact that clinical results and MACE are presented at early endpoints. However, there exist many patients who have received multiple stents during various procedures. These cases seem to be not reported on, at least absent from a host of relatively short-term studies. Eminent cardiologist E. Topol chides his colleagues about their data collection methods, the presentation of their analysis and the paucity of data from outside studies. Daily cardiosurgical experience shows that most patients are referred for revascularization surgery only after receiving multiple stents in multiple vessels. It is common for cardiac surgeons to encounter patients who present with stents reinserted into recently restenosed stents or patients with their LADs appearing as rigid tubes with closed septal side branches.

A mayor problem with stenting is that stents are deployed directly within the diseased areas of the vessels. Histologically, bare metal stents become lined with endothelium, but in DES, the drug release causes necrosis of the endothelium, which causes thrombus formation and necessitates aggressive anticoagulation [8]. Of course, anticoagulation carries its own set of potential complications, too. Coronary artery surgery principally avoids an interaction with the diseased areas of coronary arteries by literally bypassing the diseased tissue part. Because of the favorable long term results and a reduced need for reintervention, the “Gold Standard” in coronary artery revascularization remains the use of arterial grafts, especially the internal thoracic artery [9].

Furthermore are we concerned that patients do not typically receive full disclosure of their revascularization options. Generally, patients are exposed only to the revascularization opinions presented by their cardiologist, who oftenly also is their interventionist:

There are clear indications for DES intervention and they are spelled out in the products’ on-label indications. An on-label indication for DES is its use for the treatment of a single stenosis in large vessels. On-label use of DES leads to a cumulative incidence of in-stent stenosis at 4 years which is comparable to BMS [10]. Unfortunately, it is evident that 60% to 75% of DES are used off-label in patients with complex coronary lesions, small vessels and at bifurcations and also in patients presenting with comorbidities such as unstable angina pectoris and diabetes.

For the reasons cited above, the European Heart Institute of the European Academy of Sciences and Arts is emphasizing:

1. Drug Eluting Stents (DES) should be used only in accordance with their on-label indications for use.

2. Off-label use of DES should be avoided and patients are to be assured and apprized of all their revascularization options. Patients should have informed consent from both interventionist and cardiac surgeon.

3. Without patients’ informed consent, off-label use of DES may be considered a legal offence of the interventionist.

4. At onset of new symptoms, patients must be informed that surgery is a viable and recommended option.

1. Pfisterer M, Brunner-La Rocca HP, Buser PT, Rickenbacher P, Hunziker P, Mueller C, Jeger R, Bader F, Osswald S, Kaiser C. Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: an observational study of drug-eluting versus bare-metal stents. J Am Coll Cardiol 2006 Dec 19;48(12):2584-91

2. Feder BJ. In the stent era, heart bypasses get a new look. New York Times, Feb.25th, 2007

3. Maisel WH. Unanswered questions—drug eluting stents and the risk of late thombosis. N Engl J Med 2007 Mar 8; 356(10), 981-984.

4. Spaulding C, Daemen J, Boersma E, DE Cutlip, PW Serruys. A pooled analysis of data comparing sirolimus-eluting stents with bare-metal stents. N Engl J Med. 2007 Mar 8;356(10):989-97

5. Stone GW, Moses JW, Ellis SG, Schofer J, KD Dawkins, Morice MC, Colombo A, Schampaert E, Grube E, Kirtane AJ, Cutlip DE, Fahy M, Pocock SJ, Mehran R, Leon MB. Safety and efficacy of sirolimus and paclitaxel-eluting coronary stents. N Engl J Med. 2007 Mar 8;356(10):998-1008.

6. Lagerquist B. Long-term outcomes with drug-eluting stents versus bare-metal stents in Sweden. NEJM 356, 1009-1020 (2007)

7. Unger F, Serruys PW, Yacoub MH, Ilsley C, Paulsen PK, Nielsen TT, Eysmann L, Kiemeneij F. Revascularization in multivessel disease: comparison between coronary bypass surgery and stenting. J Thorac Cardiovasc Surg. 2003 Apr;125(4):809-20.

8. Farb A., Boam AB. Stent thrombosis redux—the FDA perspective. N Engl J Med. 2007 Mar 8;356(10):984-7

9. Taggert DP. PCI versus ACB in the era of drug eluting stents. 25th Cardiosurgical Symposium, Arlberg, 2007

	EHI ONLINE - News
Home	Schlechtere Ergebnisse mit der Off-Pump-Operation Wer Bypass-Operationen am schlagenden Herzen (Off-Pump) vornimmt und damit die Vorstellung des schonenderen Verfahrens verbindet, muss offenbar dazu lernen. Es rsultiert aus dem Off-Pump-Verfahren ein schlechteres Ein-Jahres-Operationsergebnis als mit der konventionellen Methode unter Verwendung der Herz-Lungen-Maschine. Zwar sind beide Verfahren nach den Resultaten einer Studie von Professor A. Laurie Shroyer aus Northpot im US-Staat New York nach 30 Tagen bei den Resultaten gleichwertig. Die Ein-Jahres-Ergebnisse zeigen aber signifikante Nachteile bei der Zahl der realisierten Bypässe und deren noch bestehender Durchgängigkeit, wie im New England Journal of Medicine (2009, 361, 1827) berichtet worden ist. Das Off-Pump-Verfahren war außerdem nicht mit einem Rückgang neurokognitiver Komplikationen nach der Operation verbunden. Die Veterans Affairs Randomized On/Off Bypass Studiy ROO-BY-Studie wurden an 18 US-Kliniken mit 2.203 Patienten realisiert, die entweder On- oder Off-Pump- einen Bypass erhielten. Off-Pump wurde bei 17,8 % der Operationen ein vorgesehener Bypass nicht verlegt, On-Pump passierte das nur bei 11,1 % (p-Wert kleiner 0,001). Die Durchgängigkeit der Bypässe in der Kontrollangiograpfie war nach einem Jahr Off-Pump signifikant niedriger als mit der Herz-Lungen-Maschine (82,6 vs. 87,8 %). Der primäre Endpunkt der Studie, eine Kombination aus Tod, erneuter Revaskularisierung oder Herzinfarkt trat im ersten Jahr nach der Operation Off-pump häufiger auf: 9,9 vs. 7,4 % nach der On-Pump-Operation (p=0,04). Kommentator Professor Eric David Peterson von der Duke University Medical Center in Durham/North Carolina stellt im gleichen NEJM-Heft (2009, 361 ,1897) en Zusammenhang von Kunst und Wissenschaft in der Chirurgie heraus und meint nicht, dass die Off-Pump-Operation keine Chance mehr hat. Er hält es für möglich, dass die Off-Pump-Operation bei älteren Frauen oder besonders bei begnadeten Vorreiter-Chirurgen („skilled surgeon adcocates“) besser sein könnte, was aber noch belegt werden muss. Cardio News 11 – 12/2009, 12. Jhg. BREAKING NEWS The New England Journal of Medicine Three-vessel and left main coronary artery: Cardiac surgery remains the standard therapy Background Percutaneous coronary intervention (PCI) involvingdrug-eluting stents is increasingly used to treat complex coronaryartery disease, although coronary-artery bypass grafting (CABG)has been the treatment of choice historically. Our trial compared PCI and CABG for treating patients with previously untreated three-vessel or left main coronary artery disease (or both). Methods We randomly assigned 1800 patients with three-vesselor left main coronary artery disease to undergo CABG or PCI(in a 1:1 ratio). For all these patients, the local cardiacsurgeon and interventional cardiologist determined that equivalent anatomical revascularization could be achieved with either treatment.A noninferiority comparison of the two groups was performedfor the primary end point — a major adverse cardiac or cerebrovascular event (i.e., death from any cause, stroke, myocardialinfarction, or repeat revascularization) during the 12-monthperiod after randomization. Patients for whom only one of thetwo treatment options would be beneficial, because of anatomicalfeatures or clinical conditions, were entered into a parallel,nested CABG or PCI registry. Results Most of the preoperative characteristics were similarin the two groups. Rates of major adverse cardiac or cerebrovascular events at 12 months were significantly higher in the PCI group (17.8%, vs. 12.4% for CABG; P=0.002), in large part becauseof an increased rate of repeat revascularization (13.5% vs.5.9%, P<0.001); as a result, the criterion for noninferioritywas not met. At 12 months, the rates of death and myocardialinfarction were similar between the two groups; stroke was significantly more likely to occur with CABG (2.2%, vs. 0.6% with PCI; P=0.003). Conclusions CABG remains the standard of care for patients withthree-vessel or left main coronary artery disease, since theuse of CABG, as compared with PCI, resulted in lower rates ofthe combined end point of major adverse cardiac or cerebrovascularevents at 1 year. (ClinicalTrials.gov number, NCT00114972 [ClinicalTrials.gov] .) N ENGL J MED Volume 360:961-972 March 5, 2009 Number 10 Percutaneous Coronary Intervention versus Coronary-Artery Bypass Grafting for Severe Coronary Artery Disease Patrick W. Serruys, M.D., Ph.D., Marie-Claude Morice, M.D., A. Pieter Kappetein, M.D., Ph.D., Antonio Colombo, M.D., David R. Holmes, M.D., Michael J. Mack, M.D., Elisabeth Ståhle, M.D., Ted E. Feldman, M.D., Marcel van den Brand, M.D., Eric J. Bass, B.A., Nic Van Dyck, R.N., Katrin Leadley, M.D., Keith D. Dawkins, M.D., Friedrich W. Mohr, M.D., Ph.D., for the SYNTAX Investigators E U R O P E A N H E A R T I N S T I T U T E Drug Eluting Stents — A Nightmare? Felix Unger Short abstract: As a contribution to the controversial discussion for the use of drug-eluting stents the European Heart Institute of the European Academy of Sciences and Arts is emphasizing important factors: a) Drug Eluting Stents (DES) should be used only in accordance with their on-label indications for use. b) To avoid off-label use of DES and to assure that patients are apprized of all their revascularization options, patients should have informed consent between the patient, interventionalist and a cardiac surgeon. c) Without informed consent, off-label use of DES may be a legally actionable offense against the interventionalist. d) At onset of new symptoms, patients must be informed that surgery is a viable and recommended option. Key words: drug eluting stents, coronary artery disease, coronary artery revascularization Drug Eluting Stents — A Nightmare? It became publically evident as early as August 2006 at a meeting of cardiologists in Barcelona that Drug Eluting Stents (DES) pose a hazard to patient safety because of the long-term risk for thrombosis, myocardial infarction and death. The BASKET-Late Study [1] presented at the American College of Cardiology meeting in March 2006 -section on Late Thrombolic Events - suggested that complications such as stent thrombosis, myocardial infarction and death were more frequently encountered in DES as compared to bare metal stents (BMS). Public turmoil started after articles appeared in the New York Times [2] and in the New England Journal of Medicine [3] in 2007. Furthermore, papers by Spaulding, Stone and Lagerquist [4,5,6] drew similar conclusions that DES therapy carries a higher risk in the long term in comparison to BMS. Wallentin [5] et al. found an increased risk of death or myocardial infarction of up to 1%. These early studies stimulated further investigations and resulted in a number of ongoing randomized clinical trials comparing DES to BMS, also comparing stenting and coronary bypass surgery. The results of these studies vary, but there are new studies supporting the original BASKET-Late Study evidence that DES therapy is not superior to BMS. Other studies indicate that DES have not reached their predicted level of success in closed chest revascularization. The procedural mortality in stent grafting remains high. In addition, there are studies such as the ARTS Study [7] which clearly demonstrate a superior outcome when surgery is applied in regards to major adverse cardiac events (MACE): Especially for patients undergoing repeat revascularization procedures. One major criticism of randomized DES studies conducted up to date is the fact that clinical results and MACE are presented at early endpoints. However, there exist many patients who have received multiple stents during various procedures. These cases seem to be not reported on, at least absent from a host of relatively short-term studies. Eminent cardiologist E. Topol chides his colleagues about their data collection methods, the presentation of their analysis and the paucity of data from outside studies. Daily cardiosurgical experience shows that most patients are referred for revascularization surgery only after receiving multiple stents in multiple vessels. It is common for cardiac surgeons to encounter patients who present with stents reinserted into recently restenosed stents or patients with their LADs appearing as rigid tubes with closed septal side branches. A mayor problem with stenting is that stents are deployed directly within the diseased areas of the vessels. Histologically, bare metal stents become lined with endothelium, but in DES, the drug release causes necrosis of the endothelium, which causes thrombus formation and necessitates aggressive anticoagulation [8]. Of course, anticoagulation carries its own set of potential complications, too. Coronary artery surgery principally avoids an interaction with the diseased areas of coronary arteries by literally bypassing the diseased tissue part. Because of the favorable long term results and a reduced need for reintervention, the “Gold Standard” in coronary artery revascularization remains the use of arterial grafts, especially the internal thoracic artery [9]. Furthermore are we concerned that patients do not typically receive full disclosure of their revascularization options. Generally, patients are exposed only to the revascularization opinions presented by their cardiologist, who oftenly also is their interventionist: Mark Twain told us that a man with a hammer sees only things to hammer. There are clear indications for DES intervention and they are spelled out in the products’ on-label indications. An on-label indication for DES is its use for the treatment of a single stenosis in large vessels. On-label use of DES leads to a cumulative incidence of in-stent stenosis at 4 years which is comparable to BMS [10]. Unfortunately, it is evident that 60% to 75% of DES are used off-label in patients with complex coronary lesions, small vessels and at bifurcations and also in patients presenting with comorbidities such as unstable angina pectoris and diabetes. For the reasons cited above, the European Heart Institute of the European Academy of Sciences and Arts is emphasizing: 1. Drug Eluting Stents (DES) should be used only in accordance with their on-label indications for use. 2. Off-label use of DES should be avoided and patients are to be assured and apprized of all their revascularization options. Patients should have informed consent from both interventionist and cardiac surgeon. 3. Without patients’ informed consent, off-label use of DES may be considered a legal offence of the interventionist. 4. At onset of new symptoms, patients must be informed that surgery is a viable and recommended option. References: 1. Pfisterer M, Brunner-La Rocca HP, Buser PT, Rickenbacher P, Hunziker P, Mueller C, Jeger R, Bader F, Osswald S, Kaiser C. Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: an observational study of drug-eluting versus bare-metal stents. J Am Coll Cardiol 2006 Dec 19;48(12):2584-91 2. Feder BJ. In the stent era, heart bypasses get a new look. New York Times, Feb.25th, 2007 3. Maisel WH. Unanswered questions—drug eluting stents and the risk of late thombosis. N Engl J Med 2007 Mar 8; 356(10), 981-984. 4. Spaulding C, Daemen J, Boersma E, DE Cutlip, PW Serruys. A pooled analysis of data comparing sirolimus-eluting stents with bare-metal stents. N Engl J Med. 2007 Mar 8;356(10):989-97 5. Stone GW, Moses JW, Ellis SG, Schofer J, KD Dawkins, Morice MC, Colombo A, Schampaert E, Grube E, Kirtane AJ, Cutlip DE, Fahy M, Pocock SJ, Mehran R, Leon MB. Safety and efficacy of sirolimus and paclitaxel-eluting coronary stents. N Engl J Med. 2007 Mar 8;356(10):998-1008. 6. Lagerquist B. Long-term outcomes with drug-eluting stents versus bare-metal stents in Sweden. NEJM 356, 1009-1020 (2007) 7. Unger F, Serruys PW, Yacoub MH, Ilsley C, Paulsen PK, Nielsen TT, Eysmann L, Kiemeneij F. Revascularization in multivessel disease: comparison between coronary bypass surgery and stenting. J Thorac Cardiovasc Surg. 2003 Apr;125(4):809-20. 8. Farb A., Boam AB. Stent thrombosis redux—the FDA perspective. N Engl J Med. 2007 Mar 8;356(10):984-7 9. Taggert DP. PCI versus ACB in the era of drug eluting stents. 25th Cardiosurgical Symposium, Arlberg, 2007 10. Shuchman M. Debating the risks of drug-eluting stents. N Engl J Med. 2007 Jan 25;356(4):325-8. Impressum meetings · activities · news · contact · links	Director: Prof. DDr. h.c. mult. Felix Unger
Activities
News
Meetings
Contact
Links

BREAKING NEWS

Three-vessel and left main coronary artery:

Cardiac surgery remains the standard therapy

N ENGL J MED Volume 360:961-972 March 5, 2009 Number 10

E U R O P E A N H E A R T I N S T I T U T E