Drug-eluting stent meta-analyses & Long-term follow-up of high-risk subsets: Reconciling the evidence DES e BMS: riflessioni e pensieri 23 febbraio 2007, San Donato Milanese

Do you remember 2005? The rosy future… Buzzword = ?

Do you remember 2005? The rosy future… Buzzword = Late loss

Do you remember 2005? The rosy future…

Late 2006 surprise: the death/MI/thrombosis iceberg Buzzword = ?

Late 2006 surprise: the death/MI/thrombosis iceberg Buzzword = Thrombosis

Late 2006 surprise: the death/MI/thrombosis iceberg

Should we trust meta-analyses? –What is a meta-analysis? –How can I appraise the internal and external validity of a meta-analysis? –What are the meta-analysis results? What is the long-term outlook with DES in patients at high risk of restenosis? Major concerns

Should we trust meta-analyses? –What is a meta-analysis? –How can I appraise the internal and external validity of a meta-analysis? –What are the meta-analysis results? What is the long-term outlook with DES in patients at high risk of restenosis? Major concerns

What is a meta-analysis? What is a systematic review? –A systematic appraisal of the methodological quality, clinical relevance and consistency of published evidence on a specific clinical topic in order to provide clear suggestions for a specific healthcare problem What is a meta-analysis? –A quantitative synthesis that, preserving the identity of individual studies, tries to provide an estimate of the overall effect of an intervention, exposure, or diagnostic strategy

Should we trust meta-analyses? It depends on their internal validity!

Should we trust meta-analyses? –What is a meta-analysis? –How can I appraise the internal and external validity of a meta-analysis? –What are the meta-analysis results? What is the long-term outlook with DES in patients at high risk of restenosis? Major concerns

Oxman-Guyatt index of internal validity 1. Where the search methods used to find evidence stated? 2. Was the search for evidence reasonably comprehensive? 3. Were the criteria for deciding which studies to include in the overview reported 4. Was bias in the selection of studies avoided 5. Were the criteria used for assessing the validity of the included studies reported? 6. Was the validity of all studies referred to in the text assessed using appropriate criteria 7. Were the methods used to combine the findings of the relevant studies reported? 8. Were the findings of the relevant studies combined appropriately relative to the primary question the overview addresses? 9. Were the conclusions made by the author(s) supported by the data and/or analysis reported in the overview? Oxman, J Clin Epidemiol 1991

Should we trust meta-analyses? –What is a meta-analysis? –How can I appraise the internal and external validity of a meta-analysis? –What are the meta-analysis results? What is the long-term outlook with DES in patients at high risk of restenosis? Major concerns

Synopsis Meta-analyses showing a DES hazard Bavry et al, Am J Med 2006 Camenzind et al, WCC 2006 Kastrati et al, NEJM 2007 Nordmann et al, Eur Heart J 2006 Spaulding et al, NEJM 2007* Stone et al, NEJM 2007* Meta-analyses suggesting DES safety Boston Scientific, FDA 2006* Cordis, FDA 2006 * Holmes et al, Eur Heart J 2006 * Mauri et al, NEJM 2007* *likely stemming from the same analysis set STOP!GO!

Synopsis Meta-analyses showing a DES hazard Bavry et al, Am J Med 2006 Camenzind et al, WCC 2006 Kastrati et al, NEJM 2007 Nordmann et al, Eur Heart J 2006 Spaulding et al, NEJM 2007* Stone et al, NEJM 2007* Meta-analyses suggesting DES safety Boston Scientific, FDA 2006* Cordis, FDA 2006 * Holmes et al, Eur Heart J 2006 * Mauri et al, NEJM 2007* *likely stemming from the same analysis set STOP!GO!

Nordmann, Eur Heart J 2006

Synopsis Meta-analyses showing a DES hazard Bavry et al, Am J Med 2006 Camenzind et al, WCC 2006 Kastrati et al, NEJM 2007 Nordmann et al, Eur Heart J 2006 Spaulding et al, NEJM 2007* Stone et al, NEJM 2007* Meta-analyses suggesting DES safety Boston Scientific, FDA 2006* Cordis, FDA 2006 * Holmes et al, Eur Heart J 2006 * Mauri et al, NEJM 2007* *likely stemming from the same analysis set STOP!GO!

Synopsis Meta-analyses showing a DES hazard Bavry et al, Am J Med 2006 Camenzind et al, WCC 2006 Kastrati et al, NEJM 2007 Nordmann et al, Eur Heart J 2006 Spaulding et al, NEJM 2007* Stone et al, NEJM 2007* Meta-analyses suggesting DES safety Boston Scientific, FDA 2006* Cordis, FDA 2006 * Holmes et al, Eur Heart J 2006 * Mauri et al, NEJM 2007* *likely stemming from the same analysis set STOP!GO!

Bavry, Am J Med 2006

Synopsis Meta-analyses showing a DES hazard Bavry et al, Am J Med 2006 Camenzind et al, WCC 2006 Kastrati et al, NEJM 2007 Nordmann et al, Eur Heart J 2006 Spaulding et al, NEJM 2007* Stone et al, NEJM 2007* Meta-analyses suggesting DES safety Boston Scientific, FDA 2006* Cordis, FDA 2006 * Holmes et al, Eur Heart J 2006 * Mauri et al, NEJM 2007* *likely stemming from the same analysis set STOP!GO!

Synopsis Meta-analyses showing a DES hazard Bavry et al, Am J Med 2006 Camenzind et al, WCC 2006 Kastrati et al, NEJM 2007 Nordmann et al, Eur Heart J 2006 Spaulding et al, NEJM 2007* Stone et al, NEJM 2007* Meta-analyses suggesting DES safety Boston Scientific, FDA 2006* Cordis, FDA 2006 * Holmes et al, Eur Heart J 2006 * Mauri et al, NEJM 2007* *likely stemming from the same analysis set STOP!GO!

Synopsis Meta-analyses showing a DES hazard Bavry et al, Am J Med 2006 Camenzind et al, WCC 2006 Kastrati et al, NEJM 2007 Nordmann et al, Eur Heart J 2006 Spaulding et al, NEJM 2007* Stone et al, NEJM 2007* Meta-analyses suggesting DES safety Boston Scientific, FDA 2006* Cordis, FDA 2006 * Holmes et al, Eur Heart J 2006 * Mauri et al, NEJM 2007* *likely stemming from the same analysis set STOP!GO!

Update 1 NEJM 2007

Update 1 Spaulding, NEJM 2007c

Synopsis Meta-analyses showing a DES hazard Bavry et al, Am J Med 2006 Camenzind et al, WCC 2006 Kastrati et al, NEJM 2007 Nordmann et al, Eur Heart J 2006 Spaulding et al, NEJM 2007* Stone et al, NEJM 2007* Meta-analyses suggesting DES safety Boston Scientific, FDA 2006* Cordis, FDA 2006 * Holmes et al, Eur Heart J 2006 * Mauri et al, NEJM 2007* *likely stemming from the same analysis set STOP!GO!

Update 2

Kasdtrati, NEJM 2007 P=0.02

Synopsis Meta-analyses showing a DES hazard Bavry et al, Am J Med 2006 Camenzind et al, WCC 2006 Kastrati et al, NEJM 2007 Nordmann et al, Eur Heart J 2006 Spaulding et al, NEJM 2007* Stone et al, NEJM 2007* Meta-analyses suggesting DES safety Boston Scientific, FDA 2006* Cordis, FDA 2006 * Holmes et al, Eur Heart J 2006 * Mauri et al, NEJM 2007* *likely stemming from the same analysis set STOP!GO!

Update 3 NEJM 2007

Update 3 Mauri, NEJM 2007

Synopsis Meta-analyses showing a DES hazard Bavry et al, Am J Med 2006 Camenzind et al, WCC 2006 Kastrati et al, NEJM 2007 Nordmann et al, Eur Heart J 2006 Spaulding et al, NEJM 2007* Stone et al, NEJM 2007* Meta-analyses suggesting DES safety Boston Scientific, FDA 2006* Cordis, FDA 2006 * Holmes et al, Eur Heart J 2006 * Mauri et al, NEJM 2007* *likely stemming from the same analysis set STOP!GO!

Update 4 Stone, NEJM 2007

Update 4 Stone, NEJM 2007

Should we trust meta-analyses? –What is a meta-analysis? –How can I appraise the internal and external validity of a meta-analysis? –What are the meta-analysis results? What is the long-term outlook with DES in patients at high risk of restenosis? Major concerns

left main

Meta-analysis on 16 studies-1278 pts with unprotected left main DES implantation Biondi-Zoccai, Eur Heart J - submitted 19,0 9,1 54,0 8,8 25,5 23,7 26,2 10,6 4,6 10,9 14,3 5,8 7,1 32, , Wood et al (2006, 100 pts) Sheiban et al (2006, 85 pts) Price et al (2006, 50 pts) Park et al (2005, 102 pts) Palmerini et al (2006, 94 pts) Migliorini et al (2006, 156 pts) Lozano et al (2005, 42 pts) Lee et al (2006, 50 pts) KOMATE (2005, 54 pts) Han et al (2006, 138 pts) Dudek et al (2006, 28 pts) de Lezo et al (2004, 52 pts) Christiansen et al (2006, 42 pts) Chieffo et al (2005, 85 pts) Carriè et al (2006, 120 pts) Agostoni et al (2005, 58 pts) Study Rate of mid-term MACE (%) 16,5 (11,7-21,3) Overall estimate (95%CI)

Prevalence of non-bifurcational ULM Log 10 transformed MACE rate at mid-term follow-up ,2 -,4 -,6 -,8 -1,0 -1,2 -1,4 Beta= P=0.001 Meta-analysis on 16 studies-1278 pts with unprotected left main DES implantation Biondi-Zoccai, Eur Heart J - submitted

Meta-analysis on 5 studies-1230 pts with DES implantation for ISR: death/MI Dibra, J Am Coll Cardiol 2007

Meta-analysis on 5 studies-1230 pts with DES implantation for ISR: TLR Dibra, J Am Coll Cardiol 2007

sheiban Sheiban, Eur Heart J - submitted Long-term follow-up of 271 pts treated with SES for ISR Event rate (%)

Conclusions Hogson, Catheter Cardiovasc Interv 2007

In light of the observed small increased incidence of very late thrombosis seen after DES implantation we advise the following: 1. Prior to any stent implantation, patients should meet criteria for PCI according to published guidelines. 2. The decision to implant a DES vs. an alternative revascularization strategy (including BMS or surgical revascularization) must be made on an individual patient basis after consideration of the relative risks and benefits of each therapy. 3. Careful evaluation of the patient with respect to compliance and the risks of long-term dual antiplatelet therapy must be performed prior to implanting a DES. Conclusions

4. Careful attention must be paid to implantation technique. The use of intravascular ultrasound, screening for calcification, and careful lesion preparation are encouraged. 5. Dual antiplatelet therapy should be prescribed for >3 months (SES) or 6 months (PES) for those meeting FDA indications. In patients not at high risk for bleeding, we strongly recommend the continuation of dual antiplatelet therapy for 12 months. Until the issue of very late stent thrombosis is further studied, we recommend that patients at higher risk for thrombosis be considered for dual antiplatelet therapy for >12 months after careful review of the risks and benefits. Conclusions

6. The discontinuation of dual antiplatelet therapy (either transiently or permanently) requires careful consideration of the relative risks of continuation (primarily bleeding and cost) and the potential risks of late stent thrombosis. This decision must be individualized. There are no tested “bridging" strategies. 7. The medical decision making process, risks and benefits of all appropriate therapies, and the need for dual antiplatelet therapy should be discussed with the patient and documented in the medical record. 8. Patients should be reassured that the implantation of a DES, after careful consideration with their physician, remains a very effective method for the treatment for symptoms associated with the disabling problem of coronary artery disease. Conclusions

For further slides on these topics please feel free to visit the metcardio.org website: