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Percutaneous coronary angioplasty compared with exercise training in patients with stable coronary artery disease. A randomized trial
of platelet inhibition with short-term clopidogrel 300 mg. At 2.5 hours after clopidogrel, enhanced platelet inhibition was present in 40% of the patients. Perspective: This study suggests that the patients undergoing elective PCI may not obtain the expected platelet inhibitory effect with acetylsalicylic acid combined with shortterm 300 mg loading dose of clopidogrel. Further studies will help determine whether increasing the dose or earlier administration of clopidogrel from hours to days will improve the efficacy in all or some patients. The large individual variability in platelet activity suggests the need to tailor antiplatelet medication to meet the individual needs both in acute and chronic settings. Whether using functional tests to optimize platelet inhibition during PCI improves patient outcome needs to be studied. DM
with either oral agents or insulin. However, a higher incidence of in-hospital CABG, a higher 1-year revascularization rate, and a lower 1- year survival rate were observed in diabetic patients, especially those treated with insulin, compared with nondiabetic patients. If multivessel stenting is performed in treated patients with DM, meticulous postprocedural adjunctive medical management is warranted to optimize outcomes. These data underscore the notion that diabetic coronary disease is, on average, more diffuse and less successfully treated by techniques that treat regional epicardial stenoses. DM
Percutaneous Coronary Angioplasty Compared With Exercise Training in Patients With Stable Coronary Artery Disease. A Randomized Trial Hambrecht R, Walther C, Mobius-Winkler S, et al. Circulation 2004;109:1371– 8.
Short- and Long-Term Results After Multivessel Stenting in Diabetic Patients
Study Question: Is a program of regular exercise a costeffective alternative to percutaneous coronary intervention/ stent in men with coronary disease? Methods: 101 male patients aged ⱕ70 years with CCS I–III angina, ischemia by ECG or myocardial perfusion imaging and one coronary artery stenosis ⱖ75% were recruited after routine coronary angiography and randomized to 12 months of exercise training (20 minutes of bicycle ergometry per day) or to PCI with stenting (enrolled 1997–2001). Exclusion criteria included the following: an ACS within 2 months, previous CABG or PCI within 12 months, high grade proximal LAD lesions, smoking, insulin-dependent diabetes and conditions that precluded exercise. Medical therapy was adjusted to current guidelines and continued at the discretion of the private physician. Outcome variables at 1 year included angina class, angina-free exercise capacity, myocardial perfusion and quantitative angiography assessment of progression/regression of coronary atherosclerosis with significant change defined as at least ⫾10%. A combined clinical end point included cardiac death, stroke, CABG, PCI, acute MI and hospitalization for angina. Cost efficiency was calculated as the average expense ($US) needed to improve the Canadian Cardiovascular Society class by one class. The first 2 weeks of exercise training was in the hospital 6 times per day for 10 minutes on a bicycle ergometer at 70% of symptom limited maximum heart rate (MHR). Home training was anticipated to be 20 minutes a day at 70% of MHR and participation in one 60 minute group training session per week. Results: Mean age was 61 years, BMI was 27.5 kg/m2 and LVEF was 63%. There was no difference between groups for smoking (17%), hyperlipidemia (80%), hypertension (75%), mean LDL-C (124 mg/dL) or HDL-C (50 mg/dL) and concurrent therapy (ACEi ⬃80%, statins ⬃75%, betablockers ⬃87% and ASA 98%). More than 90% were CCS angina class I and II, and about 60% had one-vessel, 27% had two-vessel and 14% had three-vessel CAD. Two pa-
Mehran R, Dangas GD, Kobayashi Y, et al. J Am Coll Cardiol 2004;43:1348 –54. Study Question: Multivessel angioplasty studies have reported decreased survival in diabetic patients undergoing conventional balloon angioplasty compared with coronary artery bypass graft (CABG) surgery. However, several studies have demonstrated excellent procedural success and acceptable clinical outcomes after multivessel stenting. The present study evaluated clinical outcomes in diabetic patients after multivessel stenting. Methods: Multivessel stenting was performed in 689 patients with 1639 native coronary lesions. Patients were classified into three groups according to diabetes mellitus (DM) status: 1) no DM (501 patients/1200 lesions), 2) DM treated with oral agents (102 patients/235 lesions) and 3) DM treated with insulin (86 patients/204 lesions). Results: In-hospital CABG was higher in diabetics treated with insulin compared with the other two groups (3.5% vs. 0.4% vs. 1.0%, p⫽0.02). There were no significant differences in the incidence of in-hospital cardiac death and myocardial infarction. Diabetic patients treated with oral agents or insulin had higher 1-year target lesion revascularization rates than nondiabetic patients (25% vs. 35% vs. 16%, p⬍0.001). Lower 1-year survival was observed in diabetic patients treated with either oral agents or insulin, compared with nondiabetic patients (85% vs. 86% vs. 95%, p⬍0.001). On multivariable analysis, DM was an independent predictor of 1-year mortality, myocardial infarction and target lesion revascularization after multivessel stenting. Conclusions: The authors concluded that despite a high technical success rate of multivessel stenting, diabetic patients, especially those treated with insulin, have higher in-hospital CABG, higher subsequent revascularization rates and lower 1-year survival than nondiabetic patients. Perspective: This study demonstrated high technical success rates for multivessel stenting in diabetic patients treated
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tients from each group dropped out. Exercise training compliance was 70% and was not associated with any adverse events. Exercise was associated with a higher event-free survival (88% vs. 70% in the PCI group, OR 0.33, 95% CI 0.12– 0.90, p⫽0.023) and increased maximal oxygen uptake (⫹16%, from 22.7⫾0.7 to 26.2⫾0.8 mL O2/kg, p⬍0.001 vs. baseline, p⬍0.001 vs. PCI group after 12 months). 15% of the PCI group had target lesion restenosis. There was no change in target lesion stenosis with exercise. Total CAD progression was less in the exercise group (p⫽0.035). In the multivariate analysis, only training intervention was found to influence the rate of ischemic events (p⫽0.009). Clinical symptoms improved comparably in both groups by about one CCS class. To gain one Canadian Cardiovascular Society class, $6956 was spent in the PCI group vs. $3429 in the training group (p⬍0.001). Conclusions: Compared with PCI, a 12-month program of regular physical exercise in selected patients with stable coronary artery disease resulted in superior event-free survival and exercise capacity at lower costs, notably owing to reduced rehospitalization and repeat revascularization. Perspective: I am a strong proponent of exercise as part of cardiovascular risk reduction. But this small randomized study comparing PCI/stent with exercise needed a control group of the same excellent pharmacologic management and standard guidelines regarding nutrition and exercise. This type of study is subject to recruitment bias and the characteristics of willing participants. Nevertheless, it confirms the findings in randomized controlled studies in the PCI/stent era. In stable patients and the absence of large areas of ischemia and resistance to comprehensive medical treatment, elective PCI/stenting has not been proven to be cost-effective and does not reduce MI or death. MR
of 6.5⫾2.2 months. The cumulative MACE rate was 22.3%: three (2.7%) deaths (one for cardiac reasons), four (3.6%) MIs and target lesion revascularization (TLR) in 16 (14.3%) patients with 24 (6.7%) lesions. Target vessel revascularization was required in 18 (16.1%) patients due to TLR of lesions treated with SES or to disease progression (1.8% of patients). Cox regression analysis revealed total stent length per patient as the most powerful independent predictor of MACE. Overall stent thrombosis occurred in 3 (1.9%) patients. Conclusions: The authors concluded that multivessel SES implantation can be safely performed on patients with complex coronary artery disease. The need for revascularization increases because of the cumulative effect of TLR on patients with multiple lesions. Perspective: This small pilot study suggests that use of the SES allows reasonably safe treatment of patients with complex multivessel coronary artery disease. The persistence of new revascularization procedures during the follow-up suggests the need for a better understanding of the reasons for the failure to further optimize and improve the percutaneous approach in patients with multivessel coronary artery disease. DM
Randomized Study to Evaluate Sirolimus-Eluting Stents Implanted at Coronary Bifurcation Lesions Colombo A, Moses JW, Morice MC, et al. Circulation 2004;109: 1244 –9. Study Question: Sirolimus-eluting stents have been reported to markedly decrease restenosis in selected lesions; but efficacy in higher-risk lesions, including coronary bifurcations, have not been studied. This study was performed to evaluate this stent in coronary bifurcations using two different strategies. Methods: The study was an open-labeled, prospective randomized trial. Patients were randomly assigned to either stenting of both branches (group A) or stenting of the main branch with provisional stenting of the side branch (SB) (group B). Eighty-five patients (86 lesions) were enrolled. There was 1 case of unsuccessful delivery of any device at the bifurcation site. Given the high crossover, more lesions were treated with two stents (n⫽63) than with stent/balloon (n⫽22). Clinical follow-up at 6 months was completed in all patients and angiographic follow-up in 53 patients in group A (85.5%) and 21 in group B (95.4%). Results: One patient died suddenly 4.5 months after the procedure. There were 3 cases of stent thrombosis (3.5%). The total restenosis rate at 6 months was 25.7%, and it was not significantly different between the double-stenting (28.0%) and the provisional SB-stenting (18.7%) groups. Fourteen of the restenosis cases occurred at the ostium of the SB and were focal. Target lesion revascularization was performed in 7 cases; target vessel failure occurred in 15 cases (17.6%). Conclusions: The authors concluded that these results are an improvement compared with historical controls using bare
Treatment of Multivessel Coronary Artery Disease With Sirolimus-Eluting Stent Implantation: Immediate and Mid-Term Results Orlic D, Bonizzoni E, Stankovic G, et al. J Am Coll Cardiol 2004; 43:1154 – 60. Study Question: This study evaluated clinical outcome after multivessel stenting with sirolimus-eluting stents (SESs) in unselected lesions. Methods: The study was a prospective single-center cohort design. Major adverse cardiac events (MACEs) (death, myocardial infarction [MI] and repeat revascularization) were analyzed at 30 days and at 6 months after multivessel SES implantation. Results: In 155 consecutive patients, 573 SES were implanted in 3.3⫾1.3 lesions per patient. At 30 days, the cumulative MACE rate was 10.3%: 7.1% patients developed a non–Q-wave MI, 1.9% developed a Q-wave MI, 0.6% died for noncardiac reasons and 0.6% had a repeat revascularization. Clinical follow-up was obtained in all 112 eligible patients treated for 359 lesions at a mean time
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with either oral agents or insulin. However, a higher incidence of in-hospital CABG, a higher 1-year revascularization rate, and a lower 1- year survival rate were observed in diabetic patients, especially those treated with insulin, compared with nondiabetic patients. If multivessel stenting is performed in treated patients with DM, meticulous postprocedural adjunctive medical management is warranted to optimize outcomes. These data underscore the notion that diabetic coronary disease is, on average, more diffuse and less successfully treated by techniques that treat regional epicardial stenoses. DM
Percutaneous Coronary Angioplasty Compared With Exercise Training in Patients With Stable Coronary Artery Disease. A Randomized Trial Hambrecht R, Walther C, Mobius-Winkler S, et al. Circulation 2004;109:1371– 8.
Short- and Long-Term Results After Multivessel Stenting in Diabetic Patients
Study Question: Is a program of regular exercise a costeffective alternative to percutaneous coronary intervention/ stent in men with coronary disease? Methods: 101 male patients aged ⱕ70 years with CCS I–III angina, ischemia by ECG or myocardial perfusion imaging and one coronary artery stenosis ⱖ75% were recruited after routine coronary angiography and randomized to 12 months of exercise training (20 minutes of bicycle ergometry per day) or to PCI with stenting (enrolled 1997–2001). Exclusion criteria included the following: an ACS within 2 months, previous CABG or PCI within 12 months, high grade proximal LAD lesions, smoking, insulin-dependent diabetes and conditions that precluded exercise. Medical therapy was adjusted to current guidelines and continued at the discretion of the private physician. Outcome variables at 1 year included angina class, angina-free exercise capacity, myocardial perfusion and quantitative angiography assessment of progression/regression of coronary atherosclerosis with significant change defined as at least ⫾10%. A combined clinical end point included cardiac death, stroke, CABG, PCI, acute MI and hospitalization for angina. Cost efficiency was calculated as the average expense ($US) needed to improve the Canadian Cardiovascular Society class by one class. The first 2 weeks of exercise training was in the hospital 6 times per day for 10 minutes on a bicycle ergometer at 70% of symptom limited maximum heart rate (MHR). Home training was anticipated to be 20 minutes a day at 70% of MHR and participation in one 60 minute group training session per week. Results: Mean age was 61 years, BMI was 27.5 kg/m2 and LVEF was 63%. There was no difference between groups for smoking (17%), hyperlipidemia (80%), hypertension (75%), mean LDL-C (124 mg/dL) or HDL-C (50 mg/dL) and concurrent therapy (ACEi ⬃80%, statins ⬃75%, betablockers ⬃87% and ASA 98%). More than 90% were CCS angina class I and II, and about 60% had one-vessel, 27% had two-vessel and 14% had three-vessel CAD. Two pa-
Mehran R, Dangas GD, Kobayashi Y, et al. J Am Coll Cardiol 2004;43:1348 –54. Study Question: Multivessel angioplasty studies have reported decreased survival in diabetic patients undergoing conventional balloon angioplasty compared with coronary artery bypass graft (CABG) surgery. However, several studies have demonstrated excellent procedural success and acceptable clinical outcomes after multivessel stenting. The present study evaluated clinical outcomes in diabetic patients after multivessel stenting. Methods: Multivessel stenting was performed in 689 patients with 1639 native coronary lesions. Patients were classified into three groups according to diabetes mellitus (DM) status: 1) no DM (501 patients/1200 lesions), 2) DM treated with oral agents (102 patients/235 lesions) and 3) DM treated with insulin (86 patients/204 lesions). Results: In-hospital CABG was higher in diabetics treated with insulin compared with the other two groups (3.5% vs. 0.4% vs. 1.0%, p⫽0.02). There were no significant differences in the incidence of in-hospital cardiac death and myocardial infarction. Diabetic patients treated with oral agents or insulin had higher 1-year target lesion revascularization rates than nondiabetic patients (25% vs. 35% vs. 16%, p⬍0.001). Lower 1-year survival was observed in diabetic patients treated with either oral agents or insulin, compared with nondiabetic patients (85% vs. 86% vs. 95%, p⬍0.001). On multivariable analysis, DM was an independent predictor of 1-year mortality, myocardial infarction and target lesion revascularization after multivessel stenting. Conclusions: The authors concluded that despite a high technical success rate of multivessel stenting, diabetic patients, especially those treated with insulin, have higher in-hospital CABG, higher subsequent revascularization rates and lower 1-year survival than nondiabetic patients. Perspective: This study demonstrated high technical success rates for multivessel stenting in diabetic patients treated
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tients from each group dropped out. Exercise training compliance was 70% and was not associated with any adverse events. Exercise was associated with a higher event-free survival (88% vs. 70% in the PCI group, OR 0.33, 95% CI 0.12– 0.90, p⫽0.023) and increased maximal oxygen uptake (⫹16%, from 22.7⫾0.7 to 26.2⫾0.8 mL O2/kg, p⬍0.001 vs. baseline, p⬍0.001 vs. PCI group after 12 months). 15% of the PCI group had target lesion restenosis. There was no change in target lesion stenosis with exercise. Total CAD progression was less in the exercise group (p⫽0.035). In the multivariate analysis, only training intervention was found to influence the rate of ischemic events (p⫽0.009). Clinical symptoms improved comparably in both groups by about one CCS class. To gain one Canadian Cardiovascular Society class, $6956 was spent in the PCI group vs. $3429 in the training group (p⬍0.001). Conclusions: Compared with PCI, a 12-month program of regular physical exercise in selected patients with stable coronary artery disease resulted in superior event-free survival and exercise capacity at lower costs, notably owing to reduced rehospitalization and repeat revascularization. Perspective: I am a strong proponent of exercise as part of cardiovascular risk reduction. But this small randomized study comparing PCI/stent with exercise needed a control group of the same excellent pharmacologic management and standard guidelines regarding nutrition and exercise. This type of study is subject to recruitment bias and the characteristics of willing participants. Nevertheless, it confirms the findings in randomized controlled studies in the PCI/stent era. In stable patients and the absence of large areas of ischemia and resistance to comprehensive medical treatment, elective PCI/stenting has not been proven to be cost-effective and does not reduce MI or death. MR
of 6.5⫾2.2 months. The cumulative MACE rate was 22.3%: three (2.7%) deaths (one for cardiac reasons), four (3.6%) MIs and target lesion revascularization (TLR) in 16 (14.3%) patients with 24 (6.7%) lesions. Target vessel revascularization was required in 18 (16.1%) patients due to TLR of lesions treated with SES or to disease progression (1.8% of patients). Cox regression analysis revealed total stent length per patient as the most powerful independent predictor of MACE. Overall stent thrombosis occurred in 3 (1.9%) patients. Conclusions: The authors concluded that multivessel SES implantation can be safely performed on patients with complex coronary artery disease. The need for revascularization increases because of the cumulative effect of TLR on patients with multiple lesions. Perspective: This small pilot study suggests that use of the SES allows reasonably safe treatment of patients with complex multivessel coronary artery disease. The persistence of new revascularization procedures during the follow-up suggests the need for a better understanding of the reasons for the failure to further optimize and improve the percutaneous approach in patients with multivessel coronary artery disease. DM
Randomized Study to Evaluate Sirolimus-Eluting Stents Implanted at Coronary Bifurcation Lesions Colombo A, Moses JW, Morice MC, et al. Circulation 2004;109: 1244 –9. Study Question: Sirolimus-eluting stents have been reported to markedly decrease restenosis in selected lesions; but efficacy in higher-risk lesions, including coronary bifurcations, have not been studied. This study was performed to evaluate this stent in coronary bifurcations using two different strategies. Methods: The study was an open-labeled, prospective randomized trial. Patients were randomly assigned to either stenting of both branches (group A) or stenting of the main branch with provisional stenting of the side branch (SB) (group B). Eighty-five patients (86 lesions) were enrolled. There was 1 case of unsuccessful delivery of any device at the bifurcation site. Given the high crossover, more lesions were treated with two stents (n⫽63) than with stent/balloon (n⫽22). Clinical follow-up at 6 months was completed in all patients and angiographic follow-up in 53 patients in group A (85.5%) and 21 in group B (95.4%). Results: One patient died suddenly 4.5 months after the procedure. There were 3 cases of stent thrombosis (3.5%). The total restenosis rate at 6 months was 25.7%, and it was not significantly different between the double-stenting (28.0%) and the provisional SB-stenting (18.7%) groups. Fourteen of the restenosis cases occurred at the ostium of the SB and were focal. Target lesion revascularization was performed in 7 cases; target vessel failure occurred in 15 cases (17.6%). Conclusions: The authors concluded that these results are an improvement compared with historical controls using bare
Treatment of Multivessel Coronary Artery Disease With Sirolimus-Eluting Stent Implantation: Immediate and Mid-Term Results Orlic D, Bonizzoni E, Stankovic G, et al. J Am Coll Cardiol 2004; 43:1154 – 60. Study Question: This study evaluated clinical outcome after multivessel stenting with sirolimus-eluting stents (SESs) in unselected lesions. Methods: The study was a prospective single-center cohort design. Major adverse cardiac events (MACEs) (death, myocardial infarction [MI] and repeat revascularization) were analyzed at 30 days and at 6 months after multivessel SES implantation. Results: In 155 consecutive patients, 573 SES were implanted in 3.3⫾1.3 lesions per patient. At 30 days, the cumulative MACE rate was 10.3%: 7.1% patients developed a non–Q-wave MI, 1.9% developed a Q-wave MI, 0.6% died for noncardiac reasons and 0.6% had a repeat revascularization. Clinical follow-up was obtained in all 112 eligible patients treated for 359 lesions at a mean time
ACC CURRENT JOURNAL REVIEW Jun 2004
42