Αναρτήσεις
Use of a biolimus-eluting stent with a biodegradable polymer (BioMatrix,
Biosensors Europe) in patients with ST-elevation MI (STEMI) results in
an almost 50% lower rate of major adverse cardiovascular events (MACE)
compared with using a bare-metal stent, according to the COMFORTABLE AMI study, which has just been published in the August 22, 2012 issue of the Journal of the American Medical Association [1].The findings, which look at outcomes to one year and also hint at
superior safety of this newer-generation drug-eluting stent (DES) over
bare-metal stents in this setting, were first presented at the EuroPCR 2012 meeting earlier this year, by Dr Lorenz Räber (Berne University Hospital, Switzerland), who is lead author on the current paper.
Senior author Dr Stephan Windecker (Berne University Hospital, Switzerland) told heartwire the COMFORTABLE AMI results, together with other studies looking at newer-generation DES for this patient population, seem to be tipping the scales away from the tradition to opt for bare-metal stents in STEMI.
In an accompanying editorial [2], Drs Salvatore Cassese and Adnan Kastrati (Deutsches Herzzentrum, Munich, Germany) broadly agree. "The COMFORTABLE AMI trial should make cardiologists feel more comfortable with the use of new-generation DES in patients with STEMI. The efficacy of DES vs [bare-metal stents] in STEMI is already established, and therefore further studies comparing these interventions might not be needed."
Worries about late safety issues with DES "are mostly related to first-generation DES," they note, adding that "larger randomized trials with longer follow-up and head-to-head comparisons of the [newer] available DES technologies are, however, required to completely eliminate these concerns."
Not Known How Newer-Generation Stents Compare With Each Other
Windecker explains that the newer DES, such as the Xience everolimus-eluting stent and the Resolute zotarolimus-eluting stent, release antiproliferative drugs from more biocompatible polymers than the older ones or they have biodegradable polymers--such as the BioMatrix employed in COMFORTABLE AMI--which degrade after the drug has been released to leave a stent surface more closely resembling a bare-metal stent.
In his institution they currently use just four newer-generation DES, the Xience, the Resolute, the BioMatrix, and another investigational stent with a biodegradable polymer, but this time sirolimus-eluting, called Orsiro (Biotronic).
He notes that the EXAMINATION trial comparing the Xience stent with bare-metal stents in STEMI patients also showed very favorable results for the newer stent, so "another question is whether there is a difference between newer-generation DES with durable and biodegradable polymers," he says. Currently, he notes, "we alternate [the newer DES] on a daily basis for all patient populations or we study them in a protocol. At this point in time, we couldn't say one is better or worse than the other."
But they also add that bare-metal stents should not be forgotten. "Although there is almost no rationale for performing DES vs bare-metal stent studies anymore, it might be conceivable to expect studies that test the hypothesis of noninferiority of new, improved bare-metal stents to available DES," they note.
COMFORTABLE AMI: A Suggestion of Superior Safety for Newer DES
Windecker says the published results of COMFORTABLE AMI are "very much what we presented at EuroPCR." In the study, 1161 patients presenting with STEMI at 11 sites in Europe and Israel between September 2009 and January 2011 were randomized 1:1 to receive the BioMatrix biolimus-eluting stent (n=572) or a bare-metal stent (n=582). The primary end point was the rate of MACE, a composite of cardiac death, target vessel–related reinfarction, and ischemia-driven target lesion revascularization (TLR) at one year.
MACE at one year occurred in 24 patients (4.3%) receiving the BioMatrix stent and 49 (8.7%) receiving a bare-metal stent (hazard ratio 0.49; p=0.004). This was mainly driven by the lower risk of target vessel reinfarction (0.5% vs 2.7%, HR 0.20; p=0.01) and ischemia-driven TLR (1.6% vs 5.7%, HR 0.28: p<0.001) in those receiving the BioMatrix compared with the bare-metal stent. Rates of cardiac death were not significantly different.
Windecker cautioned, however, that care must be taken in interpretation of the 80% relative risk reduction in target vessel reinfarction, a novel finding, because target vessel reinfarction "was not the primary end point."
In their editorial, Cassese and Kastrati caution that COMFORTABLE AMI "has neither the required sample size nor the sufficient length of follow-up to provide the definitive answer about the long-term safety of the new biodegradable DES in this setting."
Windecker concurs, although he points to previous four-year findings with this BioMatrix stent in the LEADERS trial, also performed at University of Bern, but this time comparing the newer stent with the older, now-defunct Cypher (sirolimus-eluting) DES in all-comers. The BioMatrix was noninferior and potentially better than Cypher in terms of MACE, with an 80% reduced risk of stent thrombosis.
The COMFORTABLE AMI findings, "in terms of safety, [are] comforting and reassuring, but we need a definitive trial to explore whether in fact DES may be superior in terms of safety," he comments.
GLOBAL-LEADERS Trial Will Compare Ticagrelor With Conventional DAPT
One of the issues that currently helps determine whether doctors use newer DES or bare-metal stents in STEMI patients is expected compliance with antiplatelet therapy. Newer DES are thought to have the edge in acute-STEMI cases if the patient adheres to dual antiplatelet therapy for up to a year. But if there is any question about compliance, clinicians may opt for a bare-metal stent instead.
Windecker and colleagues are now exploring whether single antiplatelet therapy with a more potent agent (ticagrelor [Brilinta, AstraZeneca]) for two years, with just a month's aspirin treatment, will be better than conventional dual antiplatelet therapy with aspirin and clopidogrel for one year in 16 000 patients receiving the BioMatrix stent in a trial called GLOBAL LEADERS.
"We would like to see the balance between ischemia and bleeding in this more simplified regimen. Really, what it's asking is whether we can live without aspirin with a more modern antiplatelet," he says.
Windecker reports receiving research contracts to his institution from Abbott, Boston Scientific, Biosensors, Biotronik, Coris, Medtronic, and St Jude Medical. Räber has no conflicts of interest. Disclosures for the coauthors are listed in the paper. Kastrati holds a patent related to polymer-free sirolimus and probucol coating and reports receiving honoraria from Abbott, Biosensors, Cordis, and Medtronic. Cassese reports no conflicts of interest.sourse medscape
Senior author Dr Stephan Windecker (Berne University Hospital, Switzerland) told heartwire the COMFORTABLE AMI results, together with other studies looking at newer-generation DES for this patient population, seem to be tipping the scales away from the tradition to opt for bare-metal stents in STEMI.
It's an important paradigm shift,
because . . . now we suddenly see that maybe the newer-generation DES is
even better in terms of safety.
And this is not least because worries about adverse effects seem to
be abating, he observes. "It's an important paradigm shift, because so
far we haven been concerned about the safety [with DES in STEMI], but
now we suddenly see that maybe the newer-generation DES are even better
in terms of safety [than bare-metal stents]," he commented.In an accompanying editorial [2], Drs Salvatore Cassese and Adnan Kastrati (Deutsches Herzzentrum, Munich, Germany) broadly agree. "The COMFORTABLE AMI trial should make cardiologists feel more comfortable with the use of new-generation DES in patients with STEMI. The efficacy of DES vs [bare-metal stents] in STEMI is already established, and therefore further studies comparing these interventions might not be needed."
Worries about late safety issues with DES "are mostly related to first-generation DES," they note, adding that "larger randomized trials with longer follow-up and head-to-head comparisons of the [newer] available DES technologies are, however, required to completely eliminate these concerns."
Not Known How Newer-Generation Stents Compare With Each Other
Windecker explains that the newer DES, such as the Xience everolimus-eluting stent and the Resolute zotarolimus-eluting stent, release antiproliferative drugs from more biocompatible polymers than the older ones or they have biodegradable polymers--such as the BioMatrix employed in COMFORTABLE AMI--which degrade after the drug has been released to leave a stent surface more closely resembling a bare-metal stent.
In his institution they currently use just four newer-generation DES, the Xience, the Resolute, the BioMatrix, and another investigational stent with a biodegradable polymer, but this time sirolimus-eluting, called Orsiro (Biotronic).
He notes that the EXAMINATION trial comparing the Xience stent with bare-metal stents in STEMI patients also showed very favorable results for the newer stent, so "another question is whether there is a difference between newer-generation DES with durable and biodegradable polymers," he says. Currently, he notes, "we alternate [the newer DES] on a daily basis for all patient populations or we study them in a protocol. At this point in time, we couldn't say one is better or worse than the other."
We alternate [the newer DES] on a daily
basis for all patient populations or we study them in a protocol. At
this point in time we couldn't say one is better or worse than the
other.
Cassese and Kastrati say any studies comparing newer DES should take
advantage of intravascular imaging techniques "to provide mechanistic
insight into the clinical findings."But they also add that bare-metal stents should not be forgotten. "Although there is almost no rationale for performing DES vs bare-metal stent studies anymore, it might be conceivable to expect studies that test the hypothesis of noninferiority of new, improved bare-metal stents to available DES," they note.
COMFORTABLE AMI: A Suggestion of Superior Safety for Newer DES
Windecker says the published results of COMFORTABLE AMI are "very much what we presented at EuroPCR." In the study, 1161 patients presenting with STEMI at 11 sites in Europe and Israel between September 2009 and January 2011 were randomized 1:1 to receive the BioMatrix biolimus-eluting stent (n=572) or a bare-metal stent (n=582). The primary end point was the rate of MACE, a composite of cardiac death, target vessel–related reinfarction, and ischemia-driven target lesion revascularization (TLR) at one year.
MACE at one year occurred in 24 patients (4.3%) receiving the BioMatrix stent and 49 (8.7%) receiving a bare-metal stent (hazard ratio 0.49; p=0.004). This was mainly driven by the lower risk of target vessel reinfarction (0.5% vs 2.7%, HR 0.20; p=0.01) and ischemia-driven TLR (1.6% vs 5.7%, HR 0.28: p<0.001) in those receiving the BioMatrix compared with the bare-metal stent. Rates of cardiac death were not significantly different.
Windecker cautioned, however, that care must be taken in interpretation of the 80% relative risk reduction in target vessel reinfarction, a novel finding, because target vessel reinfarction "was not the primary end point."
We need a definitive trial to explore whether in fact [newer] DES may be superior in terms of safety.
Definite stent thrombosis occurred in five patients treated with
BioMatrix (0.9%) and 12 (2.1%) of those receiving a bare-metal stent (HR
0.42, p=0.10).In their editorial, Cassese and Kastrati caution that COMFORTABLE AMI "has neither the required sample size nor the sufficient length of follow-up to provide the definitive answer about the long-term safety of the new biodegradable DES in this setting."
Windecker concurs, although he points to previous four-year findings with this BioMatrix stent in the LEADERS trial, also performed at University of Bern, but this time comparing the newer stent with the older, now-defunct Cypher (sirolimus-eluting) DES in all-comers. The BioMatrix was noninferior and potentially better than Cypher in terms of MACE, with an 80% reduced risk of stent thrombosis.
The COMFORTABLE AMI findings, "in terms of safety, [are] comforting and reassuring, but we need a definitive trial to explore whether in fact DES may be superior in terms of safety," he comments.
GLOBAL-LEADERS Trial Will Compare Ticagrelor With Conventional DAPT
One of the issues that currently helps determine whether doctors use newer DES or bare-metal stents in STEMI patients is expected compliance with antiplatelet therapy. Newer DES are thought to have the edge in acute-STEMI cases if the patient adheres to dual antiplatelet therapy for up to a year. But if there is any question about compliance, clinicians may opt for a bare-metal stent instead.
Windecker and colleagues are now exploring whether single antiplatelet therapy with a more potent agent (ticagrelor [Brilinta, AstraZeneca]) for two years, with just a month's aspirin treatment, will be better than conventional dual antiplatelet therapy with aspirin and clopidogrel for one year in 16 000 patients receiving the BioMatrix stent in a trial called GLOBAL LEADERS.
"We would like to see the balance between ischemia and bleeding in this more simplified regimen. Really, what it's asking is whether we can live without aspirin with a more modern antiplatelet," he says.
Windecker reports receiving research contracts to his institution from Abbott, Boston Scientific, Biosensors, Biotronik, Coris, Medtronic, and St Jude Medical. Räber has no conflicts of interest. Disclosures for the coauthors are listed in the paper. Kastrati holds a patent related to polymer-free sirolimus and probucol coating and reports receiving honoraria from Abbott, Biosensors, Cordis, and Medtronic. Cassese reports no conflicts of interest.sourse medscape
0 σχόλια:
Δημοσίευση σχολίου