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.
2012pharmaceutical
Aashir Awan, Phd
Alan F. Kaul, PharmD., MS, MBA, FCCP
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amnondanzig1724
anamikasarkar
apreconasia
aviralvatsa
David Orchard-Webb, PhD
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Demet Sag, Ph.D., CRA, GCP
Dror Nir
evelinacohn
Gail S Thornton
Irina Robu
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Ed Kislauskis
larryhbern
lmulligan13gmailcom
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Rosalind Codrington, PhD
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Rick Mandahl
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Dr. Sudipta Saha
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ClinicalTrials.gov processed this data on August 07, 2014
Link to the current ClinicalTrials.gov record.
http://clinicaltrials.gov/show/NCT02049229
SA-008
NCT02049229
Comparison of Titanium-Nitride-Oxide Coated Bio-Active-Stent (Optimax™) to the Drug (Everolimus) -Eluting Stent (Synergy™) in Acute Coronary Syndrome
TIDES-ACS
Comparison of Titanium-Nitride-Oxide Coated Bio-Active-Stent (Optimax™) to the Drug (Everolimus) -Eluting Stent (Synergy™) in Acute Coronary Syndrome
The Hospital District of Satakunta
Finland: Valvira – National Supervisory Authority for Welfare and Health
The purpose of the prospective, randomized and a multicenter trial is to compare clinical outcome in patients presenting with ACS, treated with PCI using Optimax-BAS versus Synergy-EES.
Second objective is to explore whether the Optimax-BAS use is superior compared with Synergy-EES use with respect of hard end points (cardiac death, MI and major bleeding).
Coronary artery disease (CAD) is the most frequent cause of death, accounting for approximately 13% of all deaths. In western countries, the incidence of ST-segment elevation myocardial infarction (STEMI) is around 77/100 000/year, whereas in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), the incidence is 132/100 000/year. Thus, the incidence of STEMI is decreasing, while there is a concomitant increase in the incidence of NSTE-ACS. NSTE-ACS and STEMI are usually considered to be different entities, but recent reports suggested that the prognosis of either subgroup of MI is similar despite different management strategies. In STEMI, primary percutaneous coronary intervention (PCI) is the recommended reperfusion therapy over fibrinolysis if performed by an experienced team within 2 hours of first medical contact. Treatment of patients with NSTE-ACS is based on their risk of acute thrombotic complications. A clear benefit from early angiography (<48 h) and PCI has been reported in the high-risk patients. However, deferral of interventions does not improve outcome. In addition, routine stenting is recommended on the basis of the predictability of the results and its safety. Consensus has emerged that early PCI use reslults in favourable outcomes, especially in high-risk patients.
The ESC guidelines for NSTE-ACS were updated in 20113 and for STEMI in 2012. Currently, PCI is the preferred reperfusion strategy in patients with both acute STEMI and NSTE-ACS.
Drug-eluting stents (DES) have been shown to reduce in-stent restenosis after PCI compared to bare metal stents (BMS). Over the previous decade, the appearance of first-generation drug-eluting stents (Taxus, Cypher™) in scene has revolutionized the practice of coronary intervention, resulting in a reduction of restenosis rates by one-half to two-thirds at 5 years follow-up, amounting to roughly 10-15% need for target vessel revascularization following DES at long-term. However, early randomized first-generation-DES trials excluded patients with acute myocardial infarction (MI), even though invasive approach is currently the preferred method for treatment of acute MI. Later randomized trials and meta-analyses of the clinical trials on the use of DES for treatment of acute STEMI demonstrated that the use of DES is safe and improves clinical outcomes mainly by decreasing the risk of re-intervention compared with BMS. However, accumulating evidence from meta-analyses and registries has questioned the long-term safety of first-generation DES, raising concerns about a higher risk of late – and very late – stent thrombosis (ST), a potentially life-threatening complication.
A further step forward was taken with the design of second-generation DES. In SPIRIT I-III trials, everolimus-eluting stent (EES) showed promising mid-term clinical outcome in selected patient groups resulting in FDA approval. Newer, second generation DES are now available in every day practice in interventional cardiology. In this context, Xience-V™-EES significantly reduced late lumen loss, as assessed by angiography, as compared with the paclitaxel-eluting stents (Taxus), with non-inferior rates of a composite outcome of safety and efficacy. Subsequent randomized trials demonstrated that, as compared with first-generation DES, Xience-V-EES was able to reduce both the restenosis and ST rates in overall elective patient population.
Reblogged this on Pharmaceutical Intelligence and commented:
revisions on 8-8-2014