pci vs medical therapy for stable angina

1. PCI vs Medical Therapy for Stable Angina AJ Conrad Smith, MD University of Pittsburgh

3. The Choice

4. COURAGE Inclusion Exclusion Criteria Inclusion CCS Class I, II, III angina 70% stenosis proximal or mid coronary artery with objective evidence of ischemia (resting ECG, or stress test) 80% stenosis and classic angina w/o testing Exclusion Class IV angina Acute Coronary Syndromes Markedly positive stress test (stage 1) Refractory CHF/shock, or EF <30% Revascularization within 6 months Coronary anatomy not suitable for PCI

5. Spectrum of CAD

6. COURAGE Patient Enrollment

7. Anginal Class and Angiography

8. COURAGE Trial Cumulative Event Rates at a median of 4.6 years*

9. COURAGE TrialFreedom from Angina

10. COURAGE Medical Therapy At all time poinst there was a greater use of nitrates and ca channel blockers in the OMT arm. More medical therapy was necessary to render the patients angina free.At all time poinst there was a greater use of nitrates and ca channel blockers in the OMT arm. More medical therapy was necessary to render the patients angina free.

12. Meta Analysis of 11 studies

13. Summary of Trials Comparing PCI vs Medical Therapy for Stable Angina

14. Let�s get a little Mavericky, also

15. SWISSI II PCI vs Med Therapy for post MI* Silent ischemiaCardiac Death, MI, symptom driven revasc.

16. SWISSI IIPatients with recent MI and Silent Ischemia

17. Cardiac MortalityMedical Therapy vs Revascularization10,627 patients followed 1.9�0.6yrs

18. Courage Nuclear Substudy:n= 314 / 2287

19. Nuclear Substudy II

21. Reduction in Ischemic Myocardium by >5%Primary Endpoint

22. Rates of Death or MI by Ischemia Reduction

23. Event Free Survival Mod � Severe Ischemia >5% Reduction in Ischemic Myocardium vs No significant ischemia reduction

24. Residual Ischemia and Death or MI

25. Mortality Comparing PCI-Based With Medical Treatment Strategy: Meta-Analysis of 17 Trials

26. Cardiac Death PCI-Based vs Medical Treatment Strategy: Meta-Analysis of 13 Trials

27. Conclusions I In selected stable angina patients in the COURAGE trial PCI did not further improve on the low annual death (1.7%/year, 0.45% cardiac death/year) and MI (3.5%/year) rates seen with OMT PCI is safe, and not associated with an increase in adverse events at any time point PCI provides such patients significantly better angina relief than medical therapy at 1 and 3 years

28. COURAGE Conclusions II PCI reduces %myocardial ischemia better than OMT, and that significant reductions in myocardial ischemia lead to lower MI and death rates OMT is a critical component of both arms of this trial and achieving high levels of compliance is necessary for optimal outcomes Risk stratifying stable angina patients by MPS and treating those higher risk patients with initial PCI + OMT is a reasonable/preferable strategy. Greater use of Drug Eluting Stents would decrease the need for PCI revascularization and further improve QOL of PCI Recent meta analysis suggests that there may be a mortality benefit for PCI in this setting

29. The Choice

30. Clinical Events Following BMS or DES*+

31. Clinical Events Following BMS or DES*

32. What to Do? Determine extent and severity of symptoms and ischemia Clinical assessment Stress testing Those patients with the most frequent and severe symptoms will benefit most from PCI+OMT Greater symptomatic benefit Potential MI/Death benefit Those with mild ischemia OMT first then PCI if necessary Use of DES when possible for greatest symptomatic benefit Additional studies are necessary to confirm these findings INSPIRE,

34. Conclusions PCI and OMT improved symptoms and quality of life immediately and significantly better than OMT alone PCI led to decrease in number of medications needed to control symptoms compared with OMT PCI improved objective parameters of ischemia better than OMT PCI is safe, it led to no increase in MI stroke death rehospitalization or other measured morbidity.

35. So One should choose OMT over PCI and OMT If your patient would like to wait five years for symptom improvement. would like to take more medications. Has severe ischemia and is willing to risk a potential increase in MI and death. Would prefer not to have a procedure that is associated with no increase in morbidity or mortality compared with just taking more medicines. And would like a 32% chance they will continue to have angina take more medicines and have that same procedure in the next year anyway.

36. Use your BRAIN, have a HEART and think of COURAGE

37. Positive Stress and Cath

39. DES vs BMSFreedom From Cardiac Death Although drug-eluting stents effectively reduce the rate of target lesion revascularization compared with bare-metal stents, the rate of cardiac death is virtually identical for the two types of stent for the first 3 years after stenting.1,2Although drug-eluting stents effectively reduce the rate of target lesion revascularization compared with bare-metal stents, the rate of cardiac death is virtually identical for the two types of stent for the first 3 years after stenting.1,2

40. Long-term Outcomes With DES vs BMS in SwedenCumulative Risk of Death or MI at 6 months and after 6 months This study evaluated 6,033 patients treated with drug-eluting stents and 13,738 patients treated with bare-metal stents in 2003 and 2004, using data from the Swedish Coronary Angiography and Angioplasty Registry. The outcome analysis covering a period of up to 3 years was based on 1,424 deaths and 2,463 myocardial infarctions and was adjusted for differences in baseline characteristics. Results showed that the unadjusted event rate tended to be lower in the group with drug-eluting stents during the initial 6 months. Thereafter, there was a continuous separation of the curves, with a significantly higher rate of events in patients with drug-eluting stents (adjusted relative risk, 1.20; 95% confidence interval [CI], 1.05 to 1.37). Overall, the analysis of the composite of death and myocardial infarction indicated a lower event rate during the first 6 months but thereafter an increase of approximately 20%, which corresponded to an absolute increase of 0.5% to 1.0% per year. This study evaluated 6,033 patients treated with drug-eluting stents and 13,738 patients treated with bare-metal stents in 2003 and 2004, using data from the Swedish Coronary Angiography and Angioplasty Registry. The outcome analysis covering a period of up to 3 years was based on 1,424 deaths and 2,463 myocardial infarctions and was adjusted for differences in baseline characteristics. Results showed that the unadjusted event rate tended to be lower in the group with drug-eluting stents during the initial 6 months. Thereafter, there was a continuous separation of the curves, with a significantly higher rate of events in patients with drug-eluting stents (adjusted relative risk, 1.20; 95% confidence interval [CI], 1.05 to 1.37). Overall, the analysis of the composite of death and myocardial infarction indicated a lower event rate during the first 6 months but thereafter an increase of approximately 20%, which corresponded to an absolute increase of 0.5% to 1.0% per year.

41. Pooled Analysis of Data Comparing SES With BMSEstimated 4-year cumulative incidence of stent thrombosis, death, MI, and target lesion revasc. This study was a pooled analysis of data from 1,748 patients in four randomized trials comparing sriolimus-etuting stents with bare-metal stents (the Randomized Study with the Sirolimus-Coated Bx Velocity Balloon Expandable Stent in the Treatment of Patients with De Novo Native Coronary Artery Lesions [RAVEL], the Sirolimus-Eluting Balloon-Expandable Stent in the Treatment of Patients with De Novo Native Coronary-Artery Lesions [SIRIUS] trial, the European SIRIUS [E-SIRIUS] trial, and the Canadian SIRIUS [C-SIRIUS] trial) and 5 double-blind trials in which 3,513 patients were randomly assigned to receive either paclitaxel-eluting stents or bare-metal stents (TAXUS-I, TAXUS-II, TAXUS-IV, TAXUS-V, and TAXUS-VI). Major clinical end points of the trials were analyzed.1 There was a nonsignificant decrease in stent thrombosis for the sirolimus-stent group versus the bare-metal stent group (P=.20). However, after 1 year, there were five episodes of stent thrombosis in patients with SES versus none in patients with BMS (P=.30). Four-year rates of target lesion revascularization were significantly reduced in the SES versus BMS group (P<.001), but there were no significant differences in the rates of myocardial infarction or death.1 A separate pooled analysis of 1,748 patients in four randomized trials (the Randomized Study with the Sirolimus-Coated Bx Velocity Balloon Expandable Stent in the Treatment of Patients with De Novo Native Coronary Artery Lesions [RAVEL], the Sirolimus-Eluting Balloon-Expandable Stent in the Treatment of Patients with De Novo Native Coronary-Artery Lesions [SIRIUS] trial, the European SIRIUS [E-SIRIUS] trial, and the Canadian SIRIUS [C-SIRIUS] trial), evaluated the safety of sirolimus-eluting stents as compared with bare-metal stents.2 The primary safety end point was survival at 4 years. The survival rate at 4 years was 93.3% in the sirolimus-stent group, as compared with 94.6% in the bare-metal�stent group (hazard ratio for death, 1.24; 95% confidence interval [CI], 0.84 to 1.83; P=.28). Rates of myocardial infarction overall were similar between the sirolimus-stent and BMS group (6.4% vs. 6.2%, respectively; P=.86). According to the protocol definitions, there were 10 stent thromboses in the sirolimus- stent group and 5 in the bare-metal�stent group. However, this difference did not reach clinical significance. Overall, results from this pooled analysis found no significant differences between the two treatments in rates of death, myocardial infarction, or stent thrombosis.2 This study was a pooled analysis of data from 1,748 patients in four randomized trials comparing sriolimus-etuting stents with bare-metal stents (the Randomized Study with the Sirolimus-Coated Bx Velocity Balloon Expandable Stent in the Treatment of Patients with De Novo Native Coronary Artery Lesions [RAVEL], the Sirolimus-Eluting Balloon-Expandable Stent in the Treatment of Patients with De Novo Native Coronary-Artery Lesions [SIRIUS] trial, the European SIRIUS [E-SIRIUS] trial, and the Canadian SIRIUS [C-SIRIUS] trial) and 5 double-blind trials in which 3,513 patients were randomly assigned to receive either paclitaxel-eluting stents or bare-metal stents (TAXUS-I, TAXUS-II, TAXUS-IV, TAXUS-V, and TAXUS-VI). Major clinical end points of the trials were analyzed.1 There was a nonsignificant decrease in stent thrombosis for the sirolimus-stent group versus the bare-metal stent group (P=.20). However, after 1 year, there were five episodes of stent thrombosis in patients with SES versus none in patients with BMS (P=.30). Four-year rates of target lesion revascularization were significantly reduced in the SES versus BMS group (P<.001), but there were no significant differences in the rates of myocardial infarction or death.1 A separate pooled analysis of 1,748 patients in four randomized trials (the Randomized Study with the Sirolimus-Coated Bx Velocity Balloon Expandable Stent in the Treatment of Patients with De Novo Native Coronary Artery Lesions [RAVEL], the Sirolimus-Eluting Balloon-Expandable Stent in the Treatment of Patients with De Novo Native Coronary-Artery Lesions [SIRIUS] trial, the European SIRIUS [E-SIRIUS] trial, and the Canadian SIRIUS [C-SIRIUS] trial), evaluated the safety of sirolimus-eluting stents as compared with bare-metal stents.2 The primary safety end point was survival at 4 years. The survival rate at 4 years was 93.3% in the sirolimus-stent group, as compared with 94.6% in the bare-metal�stent group (hazard ratio for death, 1.24; 95% confidence interval [CI], 0.84 to 1.83; P=.28). Rates of myocardial infarction overall were similar between the sirolimus-stent and BMS group (6.4% vs. 6.2%, respectively; P=.86). According to the protocol definitions, there were 10 stent thromboses in the sirolimus- stent group and 5 in the bare-metal�stent group. However, this difference did not reach clinical significance. Overall, results from this pooled analysis found no significant differences between the two treatments in rates of death, myocardial infarction, or stent thrombosis.2

42. Pooled Analysis of Data Comparing PES With BMS (cont.)Estimated 4-year cumulative incidence of stent thrombosis, death, MI, and target lesion revasc. In this pooled analysis by Stone et al, four-year rates of stent thrombosis were 1.3% in the paclitaxel-stent group versus 0.9% in the bare-metal stent group (P=.03). The four-year rate of target-lesion revascularization was also significantly reduced in the paclitaxel-stent group (10.1%) versus the bare-metal stent group (20%), P<.001. There were no significant differences in four-year rates of myocardial infarction or death between the paclitaxel-stent or bare-metal stent groups (P=.66 and .68, respectively).In this pooled analysis by Stone et al, four-year rates of stent thrombosis were 1.3% in the paclitaxel-stent group versus 0.9% in the bare-metal stent group (P=.03). The four-year rate of target-lesion revascularization was also significantly reduced in the paclitaxel-stent group (10.1%) versus the bare-metal stent group (20%), P<.001. There were no significant differences in four-year rates of myocardial infarction or death between the paclitaxel-stent or bare-metal stent groups (P=.66 and .68, respectively).

43. Risk of Stent Thrombosis With DESin the Real World: Milan/Siegburg Experience Iakovou and colleagues noted that while drug-eluting stents reduce the thrombosis rate at 30 days, delayed endothelialization related to the drug may mean an extended risk of thrombosis. They prospectively observed 2229 patients successfully implanted with a sirolimus- or paclitaxel-eluting stent; patients were followed up for at least 6 months. Fourteen patients (0.6%) had subacute thrombosis (within the first 30 days), while 15 (0.7%) had late thrombosis (after 30 days). The overall incidence of thrombosis was higher than in published randomized controlled trials. The slide shows the risk of associated with certain variables; the strongest predictor of thrombosis was premature discontinuation of antiplatelet therapy (5 thromboses in 17 patients discontinued; P <0.001).Iakovou and colleagues noted that while drug-eluting stents reduce the thrombosis rate at 30 days, delayed endothelialization related to the drug may mean an extended risk of thrombosis. They prospectively observed 2229 patients successfully implanted with a sirolimus- or paclitaxel-eluting stent; patients were followed up for at least 6 months. Fourteen patients (0.6%) had subacute thrombosis (within the first 30 days), while 15 (0.7%) had late thrombosis (after 30 days). The overall incidence of thrombosis was higher than in published randomized controlled trials. The slide shows the risk of associated with certain variables; the strongest predictor of thrombosis was premature discontinuation of antiplatelet therapy (5 thromboses in 17 patients discontinued; P <0.001).

44. Angioscopy Follow-up 6 Months After SES or BMS Implantation

45. Clopidogrel and Long-termClinical Outcomes After DES The findings of the Eisenstein et al study extend those of the BASKET-LATE study. Eisenstein and colleagues conducted an observational study that assessed the association between clopidogrel use and long-term clinical outcomes in 4666 patients treated with PCI and stenting between January 1, 2000, and July 31, 2005, with follow-up at 6, 12, and 24 months. In all, 3165 patients received bare-metal stents and 1501 received drug-eluting stents (DES). At 6 and 12 months, surviving patients who had not had an MI or revascularization procedure were divided into groups based on the type of stent and whether or not they were taking clopidogrel at that time point. At 24-month follow-up, DES-treated patients who were event-free at 6 months and still taking clopidogrel at that time were significantly less likely to have died or suffered an MI compared with DES-treated patients not taking clopidogrel; however, no such differences were seen among bare-metal-stent�treated patients on or off clopidogrel. When the same analysis was conducted based on clopidogrel usage in event-free patients at 12 months (data depicted above), again clopidogrel usage predicted lower rates of death or MI in DES-treated patients at 24 months, but was not relevant to patients treated with bare-metal stents. The investigators concluded that extended use of clopidogrel in patients with DES may be associated with a reduced risk of death and death or MI but that the appropriate duration for clopidogrel administration can only be determined in the context of a large-scale randomized clinical trial.The findings of the Eisenstein et al study extend those of the BASKET-LATE study. Eisenstein and colleagues conducted an observational study that assessed the association between clopidogrel use and long-term clinical outcomes in 4666 patients treated with PCI and stenting between January 1, 2000, and July 31, 2005, with follow-up at 6, 12, and 24 months. In all, 3165 patients received bare-metal stents and 1501 received drug-eluting stents (DES). At 6 and 12 months, surviving patients who had not had an MI or revascularization procedure were divided into groups based on the type of stent and whether or not they were taking clopidogrel at that time point. At 24-month follow-up, DES-treated patients who were event-free at 6 months and still taking clopidogrel at that time were significantly less likely to have died or suffered an MI compared with DES-treated patients not taking clopidogrel; however, no such differences were seen among bare-metal-stent�treated patients on or off clopidogrel. When the same analysis was conducted based on clopidogrel usage in event-free patients at 12 months (data depicted above), again clopidogrel usage predicted lower rates of death or MI in DES-treated patients at 24 months, but was not relevant to patients treated with bare-metal stents. The investigators concluded that extended use of clopidogrel in patients with DES may be associated with a reduced risk of death and death or MI but that the appropriate duration for clopidogrel administration can only be determined in the context of a large-scale randomized clinical trial.

47. New Societal Recommendations 1 year or Dual Antiplatelet TherapyApproach to patients given data Individual risk benefit analysis risk of restenosis as calculated by vessel size, lesion length and the presence or absence of diabetes Knowledge of likelihood of compliance for one year Potential need for surgery Postponement of elective surgery Perform urgent surgery on plavix Stop for intracranial procedures and spinal procedure Unclear if any bridging technique antithrombins or IV antiplatelets will be of benefit

51. Before and After Stenting

52. COURAGE Conclusions In selected stable angina patients, PCI does not further improve on the low annual death (1.7%/year, 0.45% cardiac death/year) and MI (3.5%/year) rates seen with OMT PCI is safe, and not associated with an increase in adverse events at any time point PCI provides such patients significantly better angina relief than medical therapy at 1 and 3 years

53. COURAGE Conclusions II The Nuclear substudy shows PCI significantly reduces %myocardial ischemia, and that significant reductions in myocardial ischemia lead to lower MI and death rates OMT is a critical component of both arms of this trial and achieving high levels of compliance is necessary for optimal outcomes Risk stratifying stable angina patients by MPS and treating those higher risk patients with initial PCI + OMT is a reasonable/preferable strategy. Greater use of Drug Eluting Stents may decrease the need for PCI revascularization but their use should be limited to patients able to take Clopidogrel for one year