Everolimus-Eluting Stent Shows Acute MI Safety

PARIS – The notable safety of the everolimus-eluting coronary stent in a prospective, randomized trial with about 1,500 patients with acute ST elevation myocardial infarctions may change the stent choice that many interventional cardiologists make when treating these patients.

Until now, interventionalists have often shied away from placing a drug-eluting coronary stent on an emergency basis in acute myocardial infarction (MI) patients undergoing primary percutaneous coronary intervention because it is often hard to assess the future ability of these patients to remain on dual-antiplatelet therapy for a year to cut their risk of stent thrombosis.

The new results, obtained in an all-comer trial in which 70% of presenting acute ST elevation MI (STEMI) patients qualified to enter the trial, showed that dual-antiplatelet therapy compliance ran 95% during the 1-year follow-up and that patients who received an everolimus-eluting stent had a substantially reduced stent thrombosis rate, compared with patients who received a bare metal stent, Dr. Manel Sabaté reported at the annual meeting of the European Society of Cardiology.

"The findings support the safety and efficacy profile of the Xience V [everolimus-eluting coronary] stent in a widely representative cohort of patients presenting with STEMI," said Dr. Sabaté, chief of cardiology at the Hospital Clinic in Barcelona.

"The results of this trial are reassuring. With first-generation drug-eluting stents [sirolimus- and paclitaxel-eluting stents], there was concern about stent thrombosis in STEMI. These data say that the everolimus-eluting stent is even safer than a bare metal stent. For the first time, you can feel reassured that you can implant a drug-eluting stent in patients with STEMI using the same criteria as in patients without acute coronary syndrome," Dr. Sabaté said.

In the EXAMINATION (Clinical Evaluation of Xience-V Stent in Acute Myocardial Infarction) trial during the first year of follow-up, definite or probable stent thrombosis occurred in 0.90% of patients who received an everolimus-eluting stent, and in 2.35% of those who received a bare-metal, cobalt-chromium stent, a statistically significant difference for this prespecified, secondary end point of the study. The study’s primary end point, the 1-year composite rate of all-cause death, MI, or any revascularization, occurred in 14.4% of the patients who received a bare-metal stent and in 12% of those who received an everolimus-eluting stent, a difference that did not achieve statistical significance.

Many cardiologists who heard the results viewed them as practice changing, although at least one expert cautioned that, strictly speaking, the secondary findings should be considered hypothesis generating only because the study failed to prove its primary end point.

"The trial was not powered for stent thrombosis" as a primary end point, commented Dr. William Wijns, a cardiologist at the Cardiovascular Research Center in Aalst, Belgium. Current treatment recommendations from the European Society of Cardiology say that an interventionalist could use a drug-eluting stent to treat a STEMI to reduce the patient’s risk for restenosis, "provided you feel comfortable with the patient’s [future] use of dual-antiplatelet therapy," he said in an interview.

Often with STEMI patients, that comfort level does not exist because "you can’t interrogate the patient and you don’t know the patient’s history, so you have to be cautious about drug-eluting stents." In addition, there was concern about stent thrombosis. "That’s where this result will change the perception," he said. "I cannot say the results change the evidence, because the trial did not reach its primary end point. A rigorous analysis would say this trial is only hypothesis generating, but some negative trials do influence practice. And it also comes as yet another piece of evidence regarding the new generation drug-eluting stents, and this brand of stent in particular. This is another positive signal" for the safety of the everolimus-eluting stent. "The signal is a reduced risk with the second-generation drug-eluting stent. It’s a fantastic opportunity," Dr. Wijns said.

Other experts were less guarded in foreseeing important treatment implications from the results.

"The data are very convincing," commented Dr. P. Gabriel Steg, a professor of cardiology at the University of Paris and director of the coronary care unit at the Bichat-Claude Bernard Hospital, also in Paris. "The results "will probably change the view of the interventional community and may possibly change the guidelines with respect to using a drug-eluting stent in this setting. To have a result with confidence, we’ll need a large trial, but this smaller trial points in a reassuring direction. What I like about the trial is its generalizability, because they enrolled 70% of their [STEMI] patients. The results are only from 1 year, and we need to remember that some of the concerns about drug-eluting stents in STEMI patients relate to late events. But the results are very reassuring in this setting for up to 1 year."

"When you compare the new generation of drug-eluting stents with the first generation, there is a significant improvement in safety. The limitation of drug-eluting stents was stent thrombosis, and we see with the new generation that this disappears," commented Dr. Jean Fajadet, codirector of the interventional cardiology unit at the Pasteur Clinic in Toulouse, France, and president of the European Association of Percutaneous Cardiac Interventions.

"What is important [in this trial] was the all-comer population. With the second-generation drug-eluting stents we see reduced restenosis and need for repeat revascularization and, at the same time, better safety. That is really important. This is one more step to lead interventionalists to be more aggressive in using drug-eluting stents in STEMI patients. But whatever drug-eluting stent is used, what’s also important is the patient’s tolerance of dual-antiplatelet therapy," said Dr. Fajadet in an interview.

He recommended more liberalized use of everolimus-eluting stents in STEMI patients who are well suited to remaining on dual-antiplatelet therapy for a year, while taking a more cautious approach in patients who are poor candidates for prolonged dual-antiplatelet therapy. A good candidate would be a STEMI patient who is relatively young – in his or her 50s or 60s – has no know comorbidities, and gives negative answers to a series of questions in the emergency room: Do you have a history of gastrointestinal bleeding, a history of cancer, a history of stroke, or an allergy to aspirin, and do you have any planned major surgery?

A patient who answers yes to one or more of these questions, or someone who is more than 75 years old or has comorbidities is less likely to reliably stay on dual-antiplatelet therapy for a year and probably should not receive an everolimus-eluting stent for an acute STEMI, Dr. Fajadet said.

The EXAMINATION trial ran at 12 centers in Spain, Italy, and the Netherlands, initially enrolled 1,498 patients, and had 1-year follow-up on 98%. The patients averaged 62 years old, and about 83% were men. More than 80% of the patients entered the study within 12 hours of the start of their STEMI, although enrollment was allowed up to 48 hours after the onset. Compliance with the daily aspirin and clopidogrel regimen during the first year following stenting ran 95% in the patients who received an everolimus-eluting stent and 90% among the patients who received a bare-metal stent. During the 1-year follow-up, the rates of cardiac death and MI were similar in the two subgroups, but for the secondary end point of need for a repeat target lesion or target vessel revascularization procedure, the patients who received the everolimus-eluting stent had, as expected, a significantly reduced rate, compared with patients who received a bare-metal stent. The target lesion revascularization rate was an absolute 2.9% lower and the target vessel rate was an absolute 3.1% lower with drug-eluting stents, compared with bare-metal stents, Dr. Sabaté reported.

EXAMINATION was supported by the Spanish Heart Foundation, which received an unrestricted grant from Abbott, the company that markets the everolimus-eluting coronary stent (Xience V). Dr. Sabaté said that he did not have any disclosures. Dr. Wijns said that any consulting fees or honoraria he receives go directly to the Cardiovascular Research Center, which has performed contracted research for numerous firms, including AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Abbott Vascular, Biotronik, Boston Scientific, Cordis, Johnson & Johnson, Edwards, Medtronic, and St. Jude. The Cardiovascular Research Center also cofounded Cardio BioSciences. Dr. Steg said that he has received speaking or consulting honoraria from numerous drug and device companies including AstraZeneca, Bayer, Medtronic, Merck, Pfizer, Roche, and Sanofi-Aventis; that he is a stockholder in Aterovax; and that he has received a research grant from Servier. Dr. Fajadet said that he had no disclosures.

PARIS – The notable safety of the everolimus-eluting coronary stent in a prospective, randomized trial with about 1,500 patients with acute ST elevation myocardial infarctions may change the stent choice that many interventional cardiologists make when treating these patients.

Until now, interventionalists have often shied away from placing a drug-eluting coronary stent on an emergency basis in acute myocardial infarction (MI) patients undergoing primary percutaneous coronary intervention because it is often hard to assess the future ability of these patients to remain on dual-antiplatelet therapy for a year to cut their risk of stent thrombosis.

The new results, obtained in an all-comer trial in which 70% of presenting acute ST elevation MI (STEMI) patients qualified to enter the trial, showed that dual-antiplatelet therapy compliance ran 95% during the 1-year follow-up and that patients who received an everolimus-eluting stent had a substantially reduced stent thrombosis rate, compared with patients who received a bare metal stent, Dr. Manel Sabaté reported at the annual meeting of the European Society of Cardiology.

"The findings support the safety and efficacy profile of the Xience V [everolimus-eluting coronary] stent in a widely representative cohort of patients presenting with STEMI," said Dr. Sabaté, chief of cardiology at the Hospital Clinic in Barcelona.

"The results of this trial are reassuring. With first-generation drug-eluting stents [sirolimus- and paclitaxel-eluting stents], there was concern about stent thrombosis in STEMI. These data say that the everolimus-eluting stent is even safer than a bare metal stent. For the first time, you can feel reassured that you can implant a drug-eluting stent in patients with STEMI using the same criteria as in patients without acute coronary syndrome," Dr. Sabaté said.

In the EXAMINATION (Clinical Evaluation of Xience-V Stent in Acute Myocardial Infarction) trial during the first year of follow-up, definite or probable stent thrombosis occurred in 0.90% of patients who received an everolimus-eluting stent, and in 2.35% of those who received a bare-metal, cobalt-chromium stent, a statistically significant difference for this prespecified, secondary end point of the study. The study’s primary end point, the 1-year composite rate of all-cause death, MI, or any revascularization, occurred in 14.4% of the patients who received a bare-metal stent and in 12% of those who received an everolimus-eluting stent, a difference that did not achieve statistical significance.

Many cardiologists who heard the results viewed them as practice changing, although at least one expert cautioned that, strictly speaking, the secondary findings should be considered hypothesis generating only because the study failed to prove its primary end point.

"The trial was not powered for stent thrombosis" as a primary end point, commented Dr. William Wijns, a cardiologist at the Cardiovascular Research Center in Aalst, Belgium. Current treatment recommendations from the European Society of Cardiology say that an interventionalist could use a drug-eluting stent to treat a STEMI to reduce the patient’s risk for restenosis, "provided you feel comfortable with the patient’s [future] use of dual-antiplatelet therapy," he said in an interview.

Often with STEMI patients, that comfort level does not exist because "you can’t interrogate the patient and you don’t know the patient’s history, so you have to be cautious about drug-eluting stents." In addition, there was concern about stent thrombosis. "That’s where this result will change the perception," he said. "I cannot say the results change the evidence, because the trial did not reach its primary end point. A rigorous analysis would say this trial is only hypothesis generating, but some negative trials do influence practice. And it also comes as yet another piece of evidence regarding the new generation drug-eluting stents, and this brand of stent in particular. This is another positive signal" for the safety of the everolimus-eluting stent. "The signal is a reduced risk with the second-generation drug-eluting stent. It’s a fantastic opportunity," Dr. Wijns said.

Other experts were less guarded in foreseeing important treatment implications from the results.

"The data are very convincing," commented Dr. P. Gabriel Steg, a professor of cardiology at the University of Paris and director of the coronary care unit at the Bichat-Claude Bernard Hospital, also in Paris. "The results "will probably change the view of the interventional community and may possibly change the guidelines with respect to using a drug-eluting stent in this setting. To have a result with confidence, we’ll need a large trial, but this smaller trial points in a reassuring direction. What I like about the trial is its generalizability, because they enrolled 70% of their [STEMI] patients. The results are only from 1 year, and we need to remember that some of the concerns about drug-eluting stents in STEMI patients relate to late events. But the results are very reassuring in this setting for up to 1 year."

"When you compare the new generation of drug-eluting stents with the first generation, there is a significant improvement in safety. The limitation of drug-eluting stents was stent thrombosis, and we see with the new generation that this disappears," commented Dr. Jean Fajadet, codirector of the interventional cardiology unit at the Pasteur Clinic in Toulouse, France, and president of the European Association of Percutaneous Cardiac Interventions.

"What is important [in this trial] was the all-comer population. With the second-generation drug-eluting stents we see reduced restenosis and need for repeat revascularization and, at the same time, better safety. That is really important. This is one more step to lead interventionalists to be more aggressive in using drug-eluting stents in STEMI patients. But whatever drug-eluting stent is used, what’s also important is the patient’s tolerance of dual-antiplatelet therapy," said Dr. Fajadet in an interview.

He recommended more liberalized use of everolimus-eluting stents in STEMI patients who are well suited to remaining on dual-antiplatelet therapy for a year, while taking a more cautious approach in patients who are poor candidates for prolonged dual-antiplatelet therapy. A good candidate would be a STEMI patient who is relatively young – in his or her 50s or 60s – has no know comorbidities, and gives negative answers to a series of questions in the emergency room: Do you have a history of gastrointestinal bleeding, a history of cancer, a history of stroke, or an allergy to aspirin, and do you have any planned major surgery?

A patient who answers yes to one or more of these questions, or someone who is more than 75 years old or has comorbidities is less likely to reliably stay on dual-antiplatelet therapy for a year and probably should not receive an everolimus-eluting stent for an acute STEMI, Dr. Fajadet said.

The EXAMINATION trial ran at 12 centers in Spain, Italy, and the Netherlands, initially enrolled 1,498 patients, and had 1-year follow-up on 98%. The patients averaged 62 years old, and about 83% were men. More than 80% of the patients entered the study within 12 hours of the start of their STEMI, although enrollment was allowed up to 48 hours after the onset. Compliance with the daily aspirin and clopidogrel regimen during the first year following stenting ran 95% in the patients who received an everolimus-eluting stent and 90% among the patients who received a bare-metal stent. During the 1-year follow-up, the rates of cardiac death and MI were similar in the two subgroups, but for the secondary end point of need for a repeat target lesion or target vessel revascularization procedure, the patients who received the everolimus-eluting stent had, as expected, a significantly reduced rate, compared with patients who received a bare-metal stent. The target lesion revascularization rate was an absolute 2.9% lower and the target vessel rate was an absolute 3.1% lower with drug-eluting stents, compared with bare-metal stents, Dr. Sabaté reported.

EXAMINATION was supported by the Spanish Heart Foundation, which received an unrestricted grant from Abbott, the company that markets the everolimus-eluting coronary stent (Xience V). Dr. Sabaté said that he did not have any disclosures. Dr. Wijns said that any consulting fees or honoraria he receives go directly to the Cardiovascular Research Center, which has performed contracted research for numerous firms, including AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Abbott Vascular, Biotronik, Boston Scientific, Cordis, Johnson & Johnson, Edwards, Medtronic, and St. Jude. The Cardiovascular Research Center also cofounded Cardio BioSciences. Dr. Steg said that he has received speaking or consulting honoraria from numerous drug and device companies including AstraZeneca, Bayer, Medtronic, Merck, Pfizer, Roche, and Sanofi-Aventis; that he is a stockholder in Aterovax; and that he has received a research grant from Servier. Dr. Fajadet said that he had no disclosures.

PARIS – The notable safety of the everolimus-eluting coronary stent in a prospective, randomized trial with about 1,500 patients with acute ST elevation myocardial infarctions may change the stent choice that many interventional cardiologists make when treating these patients.

Until now, interventionalists have often shied away from placing a drug-eluting coronary stent on an emergency basis in acute myocardial infarction (MI) patients undergoing primary percutaneous coronary intervention because it is often hard to assess the future ability of these patients to remain on dual-antiplatelet therapy for a year to cut their risk of stent thrombosis.

The new results, obtained in an all-comer trial in which 70% of presenting acute ST elevation MI (STEMI) patients qualified to enter the trial, showed that dual-antiplatelet therapy compliance ran 95% during the 1-year follow-up and that patients who received an everolimus-eluting stent had a substantially reduced stent thrombosis rate, compared with patients who received a bare metal stent, Dr. Manel Sabaté reported at the annual meeting of the European Society of Cardiology.

"The findings support the safety and efficacy profile of the Xience V [everolimus-eluting coronary] stent in a widely representative cohort of patients presenting with STEMI," said Dr. Sabaté, chief of cardiology at the Hospital Clinic in Barcelona.

"The results of this trial are reassuring. With first-generation drug-eluting stents [sirolimus- and paclitaxel-eluting stents], there was concern about stent thrombosis in STEMI. These data say that the everolimus-eluting stent is even safer than a bare metal stent. For the first time, you can feel reassured that you can implant a drug-eluting stent in patients with STEMI using the same criteria as in patients without acute coronary syndrome," Dr. Sabaté said.

In the EXAMINATION (Clinical Evaluation of Xience-V Stent in Acute Myocardial Infarction) trial during the first year of follow-up, definite or probable stent thrombosis occurred in 0.90% of patients who received an everolimus-eluting stent, and in 2.35% of those who received a bare-metal, cobalt-chromium stent, a statistically significant difference for this prespecified, secondary end point of the study. The study’s primary end point, the 1-year composite rate of all-cause death, MI, or any revascularization, occurred in 14.4% of the patients who received a bare-metal stent and in 12% of those who received an everolimus-eluting stent, a difference that did not achieve statistical significance.

Many cardiologists who heard the results viewed them as practice changing, although at least one expert cautioned that, strictly speaking, the secondary findings should be considered hypothesis generating only because the study failed to prove its primary end point.

"The trial was not powered for stent thrombosis" as a primary end point, commented Dr. William Wijns, a cardiologist at the Cardiovascular Research Center in Aalst, Belgium. Current treatment recommendations from the European Society of Cardiology say that an interventionalist could use a drug-eluting stent to treat a STEMI to reduce the patient’s risk for restenosis, "provided you feel comfortable with the patient’s [future] use of dual-antiplatelet therapy," he said in an interview.

Often with STEMI patients, that comfort level does not exist because "you can’t interrogate the patient and you don’t know the patient’s history, so you have to be cautious about drug-eluting stents." In addition, there was concern about stent thrombosis. "That’s where this result will change the perception," he said. "I cannot say the results change the evidence, because the trial did not reach its primary end point. A rigorous analysis would say this trial is only hypothesis generating, but some negative trials do influence practice. And it also comes as yet another piece of evidence regarding the new generation drug-eluting stents, and this brand of stent in particular. This is another positive signal" for the safety of the everolimus-eluting stent. "The signal is a reduced risk with the second-generation drug-eluting stent. It’s a fantastic opportunity," Dr. Wijns said.

Other experts were less guarded in foreseeing important treatment implications from the results.

"The data are very convincing," commented Dr. P. Gabriel Steg, a professor of cardiology at the University of Paris and director of the coronary care unit at the Bichat-Claude Bernard Hospital, also in Paris. "The results "will probably change the view of the interventional community and may possibly change the guidelines with respect to using a drug-eluting stent in this setting. To have a result with confidence, we’ll need a large trial, but this smaller trial points in a reassuring direction. What I like about the trial is its generalizability, because they enrolled 70% of their [STEMI] patients. The results are only from 1 year, and we need to remember that some of the concerns about drug-eluting stents in STEMI patients relate to late events. But the results are very reassuring in this setting for up to 1 year."

"When you compare the new generation of drug-eluting stents with the first generation, there is a significant improvement in safety. The limitation of drug-eluting stents was stent thrombosis, and we see with the new generation that this disappears," commented Dr. Jean Fajadet, codirector of the interventional cardiology unit at the Pasteur Clinic in Toulouse, France, and president of the European Association of Percutaneous Cardiac Interventions.

"What is important [in this trial] was the all-comer population. With the second-generation drug-eluting stents we see reduced restenosis and need for repeat revascularization and, at the same time, better safety. That is really important. This is one more step to lead interventionalists to be more aggressive in using drug-eluting stents in STEMI patients. But whatever drug-eluting stent is used, what’s also important is the patient’s tolerance of dual-antiplatelet therapy," said Dr. Fajadet in an interview.

He recommended more liberalized use of everolimus-eluting stents in STEMI patients who are well suited to remaining on dual-antiplatelet therapy for a year, while taking a more cautious approach in patients who are poor candidates for prolonged dual-antiplatelet therapy. A good candidate would be a STEMI patient who is relatively young – in his or her 50s or 60s – has no know comorbidities, and gives negative answers to a series of questions in the emergency room: Do you have a history of gastrointestinal bleeding, a history of cancer, a history of stroke, or an allergy to aspirin, and do you have any planned major surgery?

A patient who answers yes to one or more of these questions, or someone who is more than 75 years old or has comorbidities is less likely to reliably stay on dual-antiplatelet therapy for a year and probably should not receive an everolimus-eluting stent for an acute STEMI, Dr. Fajadet said.

The EXAMINATION trial ran at 12 centers in Spain, Italy, and the Netherlands, initially enrolled 1,498 patients, and had 1-year follow-up on 98%. The patients averaged 62 years old, and about 83% were men. More than 80% of the patients entered the study within 12 hours of the start of their STEMI, although enrollment was allowed up to 48 hours after the onset. Compliance with the daily aspirin and clopidogrel regimen during the first year following stenting ran 95% in the patients who received an everolimus-eluting stent and 90% among the patients who received a bare-metal stent. During the 1-year follow-up, the rates of cardiac death and MI were similar in the two subgroups, but for the secondary end point of need for a repeat target lesion or target vessel revascularization procedure, the patients who received the everolimus-eluting stent had, as expected, a significantly reduced rate, compared with patients who received a bare-metal stent. The target lesion revascularization rate was an absolute 2.9% lower and the target vessel rate was an absolute 3.1% lower with drug-eluting stents, compared with bare-metal stents, Dr. Sabaté reported.

EXAMINATION was supported by the Spanish Heart Foundation, which received an unrestricted grant from Abbott, the company that markets the everolimus-eluting coronary stent (Xience V). Dr. Sabaté said that he did not have any disclosures. Dr. Wijns said that any consulting fees or honoraria he receives go directly to the Cardiovascular Research Center, which has performed contracted research for numerous firms, including AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Abbott Vascular, Biotronik, Boston Scientific, Cordis, Johnson & Johnson, Edwards, Medtronic, and St. Jude. The Cardiovascular Research Center also cofounded Cardio BioSciences. Dr. Steg said that he has received speaking or consulting honoraria from numerous drug and device companies including AstraZeneca, Bayer, Medtronic, Merck, Pfizer, Roche, and Sanofi-Aventis; that he is a stockholder in Aterovax; and that he has received a research grant from Servier. Dr. Fajadet said that he had no disclosures.