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Gender Differences in Outcomes After Primary Angioplasty Versus Primary Stenting With and Without Abciximab for Acute Myocardial Infarction: Results of the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) Trial
Interventional Cardiology
Gender Differences in Outcomes After Primary Angioplasty Versus Primary Stenting With and Without Abciximab for Acute Myocardial Infarction: Results of the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) Trial
Abstracts Randomized Trial of High Loading Dose of Clopidogrel for Reduction of Periprocedural Myocardial Infarction in Patients Undergoing Coronary Intervention: Results From the ARMYDA-2 (Antiplatelet therapy for Reduction of Myocardial Damage during Angioplasty) Study
Lansky AJ, Piedras C, Costa RA, et al. Circulation 2005;111:1611– 8. Study Question: Investigators analyzed the database from a large, interventional, prospective, multicenter randomized trial of different reperfusion modalities for acute myocardial infarction (AMI) to assess the contemporary outcomes of women compared with men and to evaluate the optimal interventional approach in women. Methods: In the CADILLAC trial, 2082 patients (27% women) with AMI within 12 h of symptom onset were randomized either to balloon angioplasty (PTCA; n⫽518), PTCA⫹abciximab (n⫽528), stenting (n⫽512) or stenting⫹abciximab (n⫽524). The outcomes of the female population were examined on the basis of randomized treatment allocation to determine the best reperfusion strategy for women specifically. Results: As compared with men, women had a lower body surface area (BSA); they also had a greater prevalence of diabetes, hypertension, and hyperlipidemia; experienced significant delays to treatment; and had better baseline and final TIMI grade 3 flows. Unadjusted 1-year event rates were higher for women, including death (7.6% vs. 3.0%; p⬍0.001), ischemic target-vessel revascularization (TVR; 16.7% vs. 12.1%; p⫽0.006) and major adverse cardiac events (MACE; 23.9% vs. 15.3%; p⬍0.001). Female gender was an independent predictor of MACE and bleeding complications, although comorbid risk factors and BSA but not gender predicted 1-year death. For women, primary stenting resulted in a reduction in 1-year MACE from 28.1% to 19.1% (p⫽0.01) and in ischemic TVR from 20.4% to 10.8% (p⫽0.002) compared with PTCA. The addition of abciximab to primary stenting significantly reduced the 30-day ischemic TVR without increasing bleeding or stroke rates. Conclusions: The investigators concluded that the higher mortality rate in women compared with men after interventional treatment for AMI may be explained by differences in body size and clinical risk factors, although female gender remains an important independent determinant of overall adverse outcomes. Perspective: In the CADILLAC trial, women had higher mortality rates compared with men after interventional treatment for AMI. This may be related to their generally smaller BSA and higher prevalence of comorbidities, which predicted death, MACE and bleeding complications at 1 year. Primary stenting reduced clinical and angiographic restenosis and significantly reduced MACE in women. Adjunctive abciximab use in primary stenting for women
Patti G, Colonna G, Pasceri V, Pepe LL, Montinaro A, Di Sciascio G. Circulation 2005;111:2099 –106. Study Question: The study evaluated the safety and efficacy of pretreatment with a 600-mg versus a 300-mg loading dose of clopidogrel in improving ischemic complications during coronary intervention. Methods: A total of 255 patients scheduled to undergo percutaneous coronary intervention (PCI) were randomized either to a 600-mg (n⫽126) or 300-mg (n⫽129) loading regimen of clopidogrel given 4 to 8 h before the procedure. Creatine kinase-MB, troponin I and myoglobin levels were measured at baseline and at 8 and 24 h after intervention. The primary end point was the 30-day occurrence of death, myocardial infarction (MI) or target vessel revascularization. Results: The primary end point occurred in 4% of patients in the high loading dose versus 12% of those in the conventional loading dose group (p⫽0.041) and was due entirely to periprocedural MI. Peak values of all markers were significantly lower in patients treated with the 600-mg regimen (pⱕ0.038). Safety end points were similar in the two arms. At multivariable analysis, the high loading regimen was associated with a 50% risk reduction of MI (OR 0.48; 95% CI 0.15– 0.97; p⫽0.044). An incremental benefit was observed in patients randomized to the 600-mg dose who were receiving statins, with an 80% risk reduction. Conclusions: The researchers concluded that pretreatment with a 600-mg loading dose of clopidogrel 4 to 8 h before the procedure is safe and, as compared with the conventional 300-mg dose, significantly reduced periprocedural MI in patients undergoing PCI. Perspective: The ARMYDA-2 trial shows that pretreatment with a 600-mg loading dose of clopidogrel given 6 h before the procedure is safe and, as compared with the 300-mg dose, reduces periprocedural MI and improves short-term prognosis in patients undergoing percutaneous revascularization. The low risk of this pharmacological regimen may support its routine use in patients before planned coronary angioplasty and may influence practice patterns with regard to antiplatelet therapy before percutaneous intervention. DM
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reduced 30-day ischemia-driven revascularization, without increasing major bleeding or stroke rates. Efforts to reduce the time delays to reperfusion experienced by women offer the potential to improve further their overall prognosis. DM
patients with ACS undergoing early invasive therapy and should be routinely considered. DM
Reduction of Treatment Delay in Patients With ST-Elevation Myocardial Infarction: Impact of Prehospital Diagnosis and Direct Referral to Primary Percutanous Coronary Intervention
Long-term Benefits of an Early Invasive Management in Acute Coronary Syndromes Depend on Intracoronary Stenting and Aggressive Antiplatelet Treatment: A Meta-regression
Terkelsen CJ, Lassen JF, Nrgaard BL, et al. Eur Heart J 2005;26:770 –7. Study Question: The purpose of this study was to assess and compare the treatment delay in three groups of patients suspected of STEMI, who were scheduled for admission to one of two local hospitals serving the study region and who were transferred to an interventional center for primary PCI. The groups were: (A) patients diagnosed at a local hospital, (B) patients diagnosed pre-hospitally and initially admitted to a local hospital and (C) patients diagnosed pre-hospitally and referred directly to the interventional center. Methods: Two local hospitals without primary PCI facilities were serving the study region. Pre-hospital diagnoses were established with the use of telemedicine, by ambulance physicians or by general practitioners. Primary PCI was accepted as the preferred reperfusion therapy in patients with STEMI. From October 2002 to January 2004, all patients transported by ambulance and transferred for primary PCI were registered. Results: Patients with STEMI were divided into three groups: (A) patients diagnosed at a local hospital (n⫽55), (B) patients diagnosed pre-hospitally and admitted to a local hospital (n⫽85), and (C) patients diagnosed prehospitally and referred directly to the interventional center (n⫽21). When comparing group A with groups B and C, no difference was found in age, gender, infarct location or distance from the scene of event to the interventional center, whereas the median time from ambulance call to first balloon inflation was 41 min shorter in group B compared with group A (p⬍0.001) and 81 min shorter in group C compared with group A (p⬍0.001). Conclusions: The investigators concluded that patients with STEMI diagnosed pre-hospitally had shorter treatment delay compared with those diagnosed in hospital. Perspective: The study shows that in patients with STEMI scheduled for admission to a local hospital and subsequently transferred to an interventional center for primary PCI, those diagnosed pre-hospitally had shorter treatment delay compared with those diagnosed in hospital, both in the setting of initial admission to a local hospital, and to an even larger extent in the setting of referral directly to the interventional center. Thus, a first step in reducing treatment delay may be the widespread implementation of prehospital diagnostic strategies wherever feasible. Future studies should evaluate whether a strategy of referral directly to an interventional center, bypassing local hospitals,
Biondi-Zoccai GGL, Abbate A, Agostoni P, et al. Am Heart J 2005;149:504 –11. Study Question: Investigators performed a meta-regression analysis to explore the impact of intracoronary stenting and aggressive antiplatelet treatment on the risk/benefit ratio of an early invasive approach in acute coronary syndromes (ACS). Methods: The investigators searched several databases up to March 2004 for randomized trials comparing an early invasive versus delayed invasive or conservative management in ACS. Random-effects odds ratios (ORs) were computed for death and/or myocardial infarction (MI) at the longest follow-up. Log ORs were tested for interaction with stenting and aggressive antiplatelet treatment (i.e., glycoprotein [GP] IIb/IIIa inhibitors or thienopyridines in addition to aspirin). Results: Ten trials (9990 patients, median follow-up 12 months) were pooled. Overall, an early invasive management was associated with significantly reduced rates of death or (p⫽0.01). Meta-regression analysis showed that the two most significant predictors of the benefits of an early invasive strategy in patients with ACS on event-free survival were the use, in subjects managed invasively, of aggressive antiplatelet treatment (p⫽0.005) and stenting (p⫽0.011). Moreover, both stenting and aggressive antiplatelet treatment were significantly associated with reduced mortality (respectively, p⫽0.014 and p⫽0.009) and correlated to each other (r⫽0.76; p⫽0.01). Conclusions: The research team concluded that the benefits of an early invasive approach in patients with ACS are significantly associated with concomitant aggressive antiplatelet treatment and stenting. Perspective: The present analysis of randomized studies comparing an early invasive versus a delayed invasive or conservative management shows that the benefits of an early invasive approach in patients with ACS are significantly associated with the concomitant use of aggressive antiplatelet treatment and stenting. The present findings also confirm that an invasive management is significantly superior to a conservative approach in ACS as long as state-of-the-art interventions and therapies are used. Aggressive antiplatelet treatment with GPIIb/IIIa inhibitors or thienopyridines in addition to aspirin significantly benefits
ACC CURRENT JOURNAL REVIEW August 2005
45
Gender Differences in Outcomes After Primary Angioplasty Versus Primary Stenting With and Without Abciximab for Acute Myocardial Infarction: Results of the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) Trial
Abstracts Randomized Trial of High Loading Dose of Clopidogrel for Reduction of Periprocedural Myocardial Infarction in Patients Undergoing Coronary Intervention: Results From the ARMYDA-2 (Antiplatelet therapy for Reduction of Myocardial Damage during Angioplasty) Study
Lansky AJ, Piedras C, Costa RA, et al. Circulation 2005;111:1611– 8. Study Question: Investigators analyzed the database from a large, interventional, prospective, multicenter randomized trial of different reperfusion modalities for acute myocardial infarction (AMI) to assess the contemporary outcomes of women compared with men and to evaluate the optimal interventional approach in women. Methods: In the CADILLAC trial, 2082 patients (27% women) with AMI within 12 h of symptom onset were randomized either to balloon angioplasty (PTCA; n⫽518), PTCA⫹abciximab (n⫽528), stenting (n⫽512) or stenting⫹abciximab (n⫽524). The outcomes of the female population were examined on the basis of randomized treatment allocation to determine the best reperfusion strategy for women specifically. Results: As compared with men, women had a lower body surface area (BSA); they also had a greater prevalence of diabetes, hypertension, and hyperlipidemia; experienced significant delays to treatment; and had better baseline and final TIMI grade 3 flows. Unadjusted 1-year event rates were higher for women, including death (7.6% vs. 3.0%; p⬍0.001), ischemic target-vessel revascularization (TVR; 16.7% vs. 12.1%; p⫽0.006) and major adverse cardiac events (MACE; 23.9% vs. 15.3%; p⬍0.001). Female gender was an independent predictor of MACE and bleeding complications, although comorbid risk factors and BSA but not gender predicted 1-year death. For women, primary stenting resulted in a reduction in 1-year MACE from 28.1% to 19.1% (p⫽0.01) and in ischemic TVR from 20.4% to 10.8% (p⫽0.002) compared with PTCA. The addition of abciximab to primary stenting significantly reduced the 30-day ischemic TVR without increasing bleeding or stroke rates. Conclusions: The investigators concluded that the higher mortality rate in women compared with men after interventional treatment for AMI may be explained by differences in body size and clinical risk factors, although female gender remains an important independent determinant of overall adverse outcomes. Perspective: In the CADILLAC trial, women had higher mortality rates compared with men after interventional treatment for AMI. This may be related to their generally smaller BSA and higher prevalence of comorbidities, which predicted death, MACE and bleeding complications at 1 year. Primary stenting reduced clinical and angiographic restenosis and significantly reduced MACE in women. Adjunctive abciximab use in primary stenting for women
Patti G, Colonna G, Pasceri V, Pepe LL, Montinaro A, Di Sciascio G. Circulation 2005;111:2099 –106. Study Question: The study evaluated the safety and efficacy of pretreatment with a 600-mg versus a 300-mg loading dose of clopidogrel in improving ischemic complications during coronary intervention. Methods: A total of 255 patients scheduled to undergo percutaneous coronary intervention (PCI) were randomized either to a 600-mg (n⫽126) or 300-mg (n⫽129) loading regimen of clopidogrel given 4 to 8 h before the procedure. Creatine kinase-MB, troponin I and myoglobin levels were measured at baseline and at 8 and 24 h after intervention. The primary end point was the 30-day occurrence of death, myocardial infarction (MI) or target vessel revascularization. Results: The primary end point occurred in 4% of patients in the high loading dose versus 12% of those in the conventional loading dose group (p⫽0.041) and was due entirely to periprocedural MI. Peak values of all markers were significantly lower in patients treated with the 600-mg regimen (pⱕ0.038). Safety end points were similar in the two arms. At multivariable analysis, the high loading regimen was associated with a 50% risk reduction of MI (OR 0.48; 95% CI 0.15– 0.97; p⫽0.044). An incremental benefit was observed in patients randomized to the 600-mg dose who were receiving statins, with an 80% risk reduction. Conclusions: The researchers concluded that pretreatment with a 600-mg loading dose of clopidogrel 4 to 8 h before the procedure is safe and, as compared with the conventional 300-mg dose, significantly reduced periprocedural MI in patients undergoing PCI. Perspective: The ARMYDA-2 trial shows that pretreatment with a 600-mg loading dose of clopidogrel given 6 h before the procedure is safe and, as compared with the 300-mg dose, reduces periprocedural MI and improves short-term prognosis in patients undergoing percutaneous revascularization. The low risk of this pharmacological regimen may support its routine use in patients before planned coronary angioplasty and may influence practice patterns with regard to antiplatelet therapy before percutaneous intervention. DM
ACC CURRENT JOURNAL REVIEW August 2005
44
reduced 30-day ischemia-driven revascularization, without increasing major bleeding or stroke rates. Efforts to reduce the time delays to reperfusion experienced by women offer the potential to improve further their overall prognosis. DM
patients with ACS undergoing early invasive therapy and should be routinely considered. DM
Reduction of Treatment Delay in Patients With ST-Elevation Myocardial Infarction: Impact of Prehospital Diagnosis and Direct Referral to Primary Percutanous Coronary Intervention
Long-term Benefits of an Early Invasive Management in Acute Coronary Syndromes Depend on Intracoronary Stenting and Aggressive Antiplatelet Treatment: A Meta-regression
Terkelsen CJ, Lassen JF, Nrgaard BL, et al. Eur Heart J 2005;26:770 –7. Study Question: The purpose of this study was to assess and compare the treatment delay in three groups of patients suspected of STEMI, who were scheduled for admission to one of two local hospitals serving the study region and who were transferred to an interventional center for primary PCI. The groups were: (A) patients diagnosed at a local hospital, (B) patients diagnosed pre-hospitally and initially admitted to a local hospital and (C) patients diagnosed pre-hospitally and referred directly to the interventional center. Methods: Two local hospitals without primary PCI facilities were serving the study region. Pre-hospital diagnoses were established with the use of telemedicine, by ambulance physicians or by general practitioners. Primary PCI was accepted as the preferred reperfusion therapy in patients with STEMI. From October 2002 to January 2004, all patients transported by ambulance and transferred for primary PCI were registered. Results: Patients with STEMI were divided into three groups: (A) patients diagnosed at a local hospital (n⫽55), (B) patients diagnosed pre-hospitally and admitted to a local hospital (n⫽85), and (C) patients diagnosed prehospitally and referred directly to the interventional center (n⫽21). When comparing group A with groups B and C, no difference was found in age, gender, infarct location or distance from the scene of event to the interventional center, whereas the median time from ambulance call to first balloon inflation was 41 min shorter in group B compared with group A (p⬍0.001) and 81 min shorter in group C compared with group A (p⬍0.001). Conclusions: The investigators concluded that patients with STEMI diagnosed pre-hospitally had shorter treatment delay compared with those diagnosed in hospital. Perspective: The study shows that in patients with STEMI scheduled for admission to a local hospital and subsequently transferred to an interventional center for primary PCI, those diagnosed pre-hospitally had shorter treatment delay compared with those diagnosed in hospital, both in the setting of initial admission to a local hospital, and to an even larger extent in the setting of referral directly to the interventional center. Thus, a first step in reducing treatment delay may be the widespread implementation of prehospital diagnostic strategies wherever feasible. Future studies should evaluate whether a strategy of referral directly to an interventional center, bypassing local hospitals,
Biondi-Zoccai GGL, Abbate A, Agostoni P, et al. Am Heart J 2005;149:504 –11. Study Question: Investigators performed a meta-regression analysis to explore the impact of intracoronary stenting and aggressive antiplatelet treatment on the risk/benefit ratio of an early invasive approach in acute coronary syndromes (ACS). Methods: The investigators searched several databases up to March 2004 for randomized trials comparing an early invasive versus delayed invasive or conservative management in ACS. Random-effects odds ratios (ORs) were computed for death and/or myocardial infarction (MI) at the longest follow-up. Log ORs were tested for interaction with stenting and aggressive antiplatelet treatment (i.e., glycoprotein [GP] IIb/IIIa inhibitors or thienopyridines in addition to aspirin). Results: Ten trials (9990 patients, median follow-up 12 months) were pooled. Overall, an early invasive management was associated with significantly reduced rates of death or (p⫽0.01). Meta-regression analysis showed that the two most significant predictors of the benefits of an early invasive strategy in patients with ACS on event-free survival were the use, in subjects managed invasively, of aggressive antiplatelet treatment (p⫽0.005) and stenting (p⫽0.011). Moreover, both stenting and aggressive antiplatelet treatment were significantly associated with reduced mortality (respectively, p⫽0.014 and p⫽0.009) and correlated to each other (r⫽0.76; p⫽0.01). Conclusions: The research team concluded that the benefits of an early invasive approach in patients with ACS are significantly associated with concomitant aggressive antiplatelet treatment and stenting. Perspective: The present analysis of randomized studies comparing an early invasive versus a delayed invasive or conservative management shows that the benefits of an early invasive approach in patients with ACS are significantly associated with the concomitant use of aggressive antiplatelet treatment and stenting. The present findings also confirm that an invasive management is significantly superior to a conservative approach in ACS as long as state-of-the-art interventions and therapies are used. Aggressive antiplatelet treatment with GPIIb/IIIa inhibitors or thienopyridines in addition to aspirin significantly benefits
ACC CURRENT JOURNAL REVIEW August 2005
45