Titanium-nitric-oxide-coated bioactive stents in acute coronary syndrome
Reporter: Larry Bernstein, MD, FCAP
REBLOG
Titanium-nitric-oxide-coated bioactive stents in acute coronary syndrome: towards a more clear landscape!
With full interest, we read the Editorial “Nitric-oxide Coated Bioactive Titanium Stents: Safer and More Effective Than Second-generation Drug-eluting Stents?” by Sabaté et al 1. I’d like to commend the authors for publishing this interesting analysis of recently published studies – including the BASE ACS randomized controlled trial– comparing titanium-nitric-oxide-coated bioactive stents (NO-BAS) with drug-eluting stents. Yet, since I’m one of the authors of the BASE ACS trial, I’d like to clarify some points. First, the BASE ACS trial was adequately powered to detect a difference of the primary composite endpoint at 12 months (827 patients), with a formal statistical power calculation 2. Second, as the authors reported, the NO-BAS were non-inferior to cobalt-chromium-based everolimus-eluting stents (EES) for the primary composite endpoint of major adverse cardiac events (MACE) that included cardiac death, non-fatal myocardial infarction (MI), and ischemia-driven target lesion revascularization, in patients presenting with the full spectrum of acute coronary syndrome at 12-month follow-up 2. The 12-month rates of the individual secondary endpoints of non-fatal MI and definite stent thrombosis (ST) were lower in patients who received NO-BAS versus those who received EES (2.2% versus 5.9%, and 0.7% versus 2.2%, p= 0.007 and 0.07, respectively) 3. And whereas the definition of MI adopted by the BASE ACS trial (based on CK MB or troponin ≥2 times the upper reference limit) was different from that employed in the EXAMINATION trial (extended definition of the World Health Organization), it cannot be held responsible for the difference in MI rates between NO-BAS and EES in the same BASE ACS trial, since the definition was equally applied to the two trial arms 2,3. Third, the early (within 30 days) divergence of safety endpoints between the 2 stent arms is hard to explain merely in view of peri-procedural bivalirudin monotherapy. In fact, out of 9 cases (2.2%) of definite ST in the EES arm, 3 were acute (within 24 hr); out of these 3, only 2 received peri-procedural bivalirudin as a sole anticoagulant 2. Moreover, peri-procedural bivalirudin use was comparable between the 2 stent arms: 14.1% versus 15.1% in NO-BAS versus EES arms, respectively. Furthermore, angiographic success was achieved in 99.8% in both stent arms; hence, technical issues (distal dissection, stent underexpansion) were probably similar in the 2 stent arms 2. More importantly, the rates of non-fatal MI and definite ST continued to diverge after one year: at 2-year follow-up, they were 2.9% versus 7.1%, and 1.0% versus 2.7%, p= 0.005 and 0.05, for NO-BAS versus EES, respectively 4. Since technical issues generally operate early (within 1 month) after stent implantation; therefore, they cannot fully account for the ‘very late’ events. References
1. Sabaté M, Brugaletta S. Nitric-oxide Coated Bioactive Titanium Stents: Safer and More Effective Than Second-generation Drug-eluting Stents? Rev Esp Cardiol. 2014;67:511-3. 2. Karjalainen PP, Niemela M, Airaksinen KEJ, et al. A prospective randomized comparison of titanium-nitride-oxide-coated bioactive stents with everolimus-eluting stents in acute coronary syndrome: the BASE-ACS trial. EuroIntervention. 2012;8:1769–74. 3. Sabate M, Cequier A, In˜iguez A, et al. Everolimus-eluting stent versus bare-metal stent in ST-segment elevation myocardial infarction (EXAMINATION): 1 year results of a randomised controlled trial. Lancet. 2012;380:1482–90. 4. Romppanen H, Nammas W, Kervinen K, et al. Stent-oriented versus patient-oriented outcome in patients undergoing early percutaneous coronary intervention for acute coronary syndrome: 2-year report from the BASE-ACS trial. Ann Med. 2013;45:488-93.
additional:
KeywordsBioactive stents. Everolimus-eluting stents. Paclitaxel-eluting stents. ST-segment elevation myocardial infarction. Outcome.
Pooled Analysis of Two Randomized Trials Comparing Titanium-nitride-oxide-coated Stent Versus Drug-eluting Stent in STEMI
Petri O. Tuomainenab, Jussi Siac, Wail Nammasb, Matti Niemeläd, Juhani K.E. Airaksinene, Fausto Biancarif, Pasi P. Karjalainenb,
a Department of Internal Medicine and Heart Center, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland b Department of Cardiology, Satakunta Central Hospital, Pori, Finland c Department of Cardiology, Kokkola Central Hospital, Kokkola, Finland d Department of Internal Medicine, Division of Cardiology, University of Oulu, Oulu, Finland e Department of Medicine, Turku University Hospital, Turku, Finland f Division ofCardiothoracic and Vascular Surgery, Department of Surgery, Oulu, Finland
Refers to
Keywords
Bioactive stents. Everolimus-eluting stents. Paclitaxel-eluting stents. ST-segment elevation myocardial infarction. Outcome.
Abstract
Introduction and objectivesWe performed a pooled analysis based on patient-level data from the TITAX-AMI and BASE-ACS trials to evaluate the outcome of titanium-nitride-oxide-coated bioactive stents vs drug-eluting stents in patients with ST-segment elevation myocardial infarction at 2-year follow-up. MethodsThe TITAX-AMI trial compared bioactive stents with paclitaxel-eluting stents in 425 patients with acute myocardial infarction. The BASE-ACS trial compared bioactive stents with everolimus-eluting stents in 827 patients with acute coronary syndrome. The primary endpoint for the pooled analysis was major adverse cardiac events: a composite of cardiac death, recurrent myocardial infarction, or ischemia-driven target lesion revascularization at 2-year follow-up. ResultsThe pooled analysis included 501 patients; 245 received bioactive stents, and 256 received drug-eluting stents. The pooled bioactive stent group was associated with a risk ratio of 0.85 for major adverse cardiac events (95% confidence interval, 0.53-1.35; P = .49) compared to the pooled drug-eluting stent group. Similarly, the pooled bioactive stent group was associated with a risk ratio of 0.71 for cardiac death (95% confidence interval, 0.26-1.95; P = .51), 0.44 for recurrent myocardial infarction (95% confidence interval, 0.20-0.97; P = .04), and 1.39 for ischemia-driven target lesion revascularization (95% confidence interval, 0.74-2.59; P = .30), compared to the pooled drug-eluting stent group. These results were confirmed by propensity-score adjusted analysis of the combined datasets. ConclusionsIn patients with ST-segment elevation myocardial infarction, bioactive stents were associated with lower rates of recurrent myocardial infarction compared to drug-eluting stents at 2-year follow-up; yet, the rates of cardiac death and ischemia-driven target lesion revascularization were similar.
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This is very insightful. There is no doubt that there is the bias you refer to. 42 years ago, when I was postdocing in biochemistry/enzymology before completing my residency in pathology, I knew that there were very influential mambers of the faculty, who also had large programs, and attracted exceptional students. My mentor, it was said (although he was a great writer), could draft a project on toilet paper and call the NIH. It can’t be true, but it was a time in our history preceding a great explosion. It is bizarre for me to read now about eNOS and iNOS, and about CaMKII-á, â, ã, ä – isoenzymes. They were overlooked during the search for the genome, so intermediary metabolism took a back seat. But the work on protein conformation, and on the mechanism of action of enzymes and ligand and coenzyme was just out there, and became more important with the research on signaling pathways. The work on the mechanism of pyridine nucleotide isoenzymes preceded the work by Burton Sobel on the MB isoenzyme in heart. The Vietnam War cut into the funding, and it has actually declined linearly since.
A few years later, I was an Associate Professor at a new Medical School and I submitted a proposal that was reviewed by the Chairman of Pharmacology, who was a former Director of NSF. He thought it was good enough. I was a pathologist and it went to a Biochemistry Review Committee. It was approved, but not funded. The verdict was that I would not be able to carry out the studies needed, and they would have approached it differently. A thousand young investigators are out there now with similar letters. I was told that the Department Chairmen have to build up their faculty. It’s harder now than then. So I filed for and received 3 patents based on my work at the suggestion of my brother-in-law. When I took it to Boehringer-Mannheim, they were actually clueless.
This is very insightful. There is no doubt that there is the bias you refer to. 42 years ago, when I was postdocing in biochemistry/enzymology before completing my residency in pathology, I knew that there were very influential mambers of the faculty, who also had large programs, and attracted exceptional students. My mentor, it was said (although he was a great writer), could draft a project on toilet paper and call the NIH. It can’t be true, but it was a time in our history preceding a great explosion. It is bizarre for me to read now about eNOS and iNOS, and about CaMKII-á, â, ã, ä – isoenzymes. They were overlooked during the search for the genome, so intermediary metabolism took a back seat. But the work on protein conformation, and on the mechanism of action of enzymes and ligand and coenzyme was just out there, and became more important with the research on signaling pathways. The work on the mechanism of pyridine nucleotide isoenzymes preceded the work by Burton Sobel on the MB isoenzyme in heart. The Vietnam War cut into the funding, and it has actually declined linearly since.
A few years later, I was an Associate Professor at a new Medical School and I submitted a proposal that was reviewed by the Chairman of Pharmacology, who was a former Director of NSF. He thought it was good enough. I was a pathologist and it went to a Biochemistry Review Committee. It was approved, but not funded. The verdict was that I would not be able to carry out the studies needed, and they would have approached it differently. A thousand young investigators are out there now with similar letters. I was told that the Department Chairmen have to build up their faculty. It’s harder now than then. So I filed for and received 3 patents based on my work at the suggestion of my brother-in-law. When I took it to Boehringer-Mannheim, they were actually clueless.