TIOMAX: A Spanish Multicenter Registry of the real-world use of the TItanium OptiMAX® biostent: TIOMAX: Registro Español Multicéntrico Del Biostent De Titanio OptiMAX® En La Vida Real.

OBJECTIVES: To compare the safety and efficacy of the new cobalt-chromium bioactive stent Titan Optimax® (Hexacath, France) with its predecessor, Titan-2® . BACKGROUND: The TIOMAX registry includes 784 patients who underwent percutaneous coronary intervention with these stents in 21 Spanish hospitals. METHODS: Analysis of all patients in the registry without exclusion criteria, candidates for revascularization (March-2013/July-2014). Initially 273 patients received Titan-2® , and the next 511 received the Optimax® after its launch. RESULTS: Mean age was 65.8 ± 13.0 (78.1% men); 49.2% were STEACS patients (n = 322), 29.8% NSTEACS, and 27.3% had stable angina or silent ischemia. Most STEACS patients (76.4% of n = 322) were treated <24 hr after developing symptoms. All-cause death (D), cardiac death (CD), acute myocardial infarction (AMI), and stent thrombosis (ST) at 1 month were 1.1, 0.8, 0.1, and 0.5%, respectively, with no significant differences between groups. At 1 year, the death rate was 5.5% for Titan-2 vs. 4.1% for Optimax® , CD was 1.8% for both groups, ST 1.1 vs. 0.6%, new AMI 3.3 vs. 2.5% and target lesion revascularization (TLR) 3.7 vs. 2.9%. The primary endpoint of the composite event (CE) of D/AMI/TLR/ST occurred in 10.3% vs. 7.6% (p = 0.211). Patients with STEACS (N = 322: Titan-2/Optimax: 103/209) had better outcomes for secondary events, device-oriented failure CD/AMI/TLR (7.8% vs. 5.0%; p = 0.330), and non-fatal CE of AMI/ST/TLR (7.8% vs. 2.7%, p = 0.039). CONCLUSIONS: The Titan Optimax retains the efficacy and safety of Titan 2. It appears to perform better in the subgroup of STEACS patients, by reducing the non-fatal CE of AMI/ST/TLR.

Optical coherence tomography follow-up 18 months after titanium-nitride-oxide-coated versus everolimus-eluting stent implantation in patients with acute coronary syndrome.

Background Inadequate neointimal coverage of stent struts is associated with late stent thrombosis. Purpose To demonstrate the extent of neointimal coverage and strut malapposition in titanium-nitride-oxide-coated bioactive stents (BAS) versus everolimus-eluting stents (EES) by optical coherence tomography (OCT) performed at 18-month follow-up. Material and Methods In the BASE-ACS trial, 827 patients presenting with acute coronary syndrome were randomized to receive either BAS or EES. Forty patients (20 BAS, 20 EES) underwent OCT at 18-month follow-up for evaluation of stent strut coverage, malapposition, and neointimal hyperplasia (NIH). Primary endpoint was binary stent strut coverage (ratio of covered struts to all analyzed struts multiplied by 100). Co-primary endpoint was the percentage of malapposed struts. Results We analyzed 3465 struts in 330 cross-sections of BAS and 3327 struts in 316 cross-sections of EES. Binary stent strut coverage, based on strut-level analysis, was higher with BAS versus EES (99.5% versus 94.2%, respectively; P < 0.001), the strut-level percentage of malapposed struts was lower with BAS (0.6% versus 2.5%, respectively; P < 0.001). Yet, the mean NIH thickness was greater with BAS (237 ± 125 versus 108 ± 62 µm, respectively; P < 0.001). Conclusion In the current post-hoc analysis with OCT performed at 18 months, binary strut coverage, based on strut-level analysis, was higher with BAS versus EES; strut-level malapposed struts were fewer with BAS; yet, BAS induced thicker NIH.

Clinical outcome of titanium-nitride-oxide-coated cobalt-chromium stents in patients with de novo coronary lesions: 12-month results of the OPTIMAX first-in-man study.

OBJECTIVES: We explored the 12-month clinical outcome of the titanium-nitride-oxide-coated OPTIMAX stent based on cobalt-chromium platform. BACKGROUND: The OPTIMAX stent demonstrated a satisfactory 6-month clinical outcome in de novo coronary lesions. METHODS: We enrolled 224 consecutive symptomatic patients with significant (50%) stenosis in de novo coronary lesions, who were treated with OPTIMAX stent implantation. The primary endpoint was major adverse cardiac events at 12-month follow-up, defined as a composite of cardiac death, non-fatal myocardial infarction (MI), or ischemia-driven target lesion revascularization (TLR). Stent thrombosis was adjudicated according to the definition of the Academic Research Consortium. RESULTS: The mean age of the cohort was 67 ± 8 years (75% males). Patients presented with acute coronary syndrome in 62.1%. Radial access was used in 92%; complex (type B and C) lesions were treated in 79.9%. Both procedural and clinical success occurred in 100% of the cases. The mean follow-up period was 366 ± 22 days. At 12-month follow-up, the primary endpoint occurred in 14 (6.3%) patients. Cardiac death occurred in three (1.3%) patients, non-fatal MI in seven (3.1%) patients, and ischemia-driven TLR in seven (3.1%) patients. No definite stent thrombosis occurred. CONCLUSIONS: In the current prospective observational study, implantation of the OPTIMAX stent demonstrated an adequate 12-month clinical outcome, with a low rate of major adverse cardiac events, and no stent thrombosis.

4-Year outcome of bioactive stents versus everolimus-eluting stents in acute coronary syndrome.

OBJECTIVES: The BASE-ACS trial demonstrated non-inferiority of titanium-nitride-oxide-coated bioactive stents (BAS), versus everolimus-eluting stents (EES), for major adverse cardiac events (MACE) at 1- and 2-year follow-up, in patients with acute coronary syndrome (ACS). We presented the 4-year outcome of the BASE-ACS trial. DESIGN: We randomized 827 patients with ACS to receive either BAS (417) or EES (410). MACE was a composite of cardiac death, non-fatal myocardial infarction (MI) or ischemia-driven target lesion revascularization (TLR) at 12-month follow-up. Analyses were performed by intention to treat. Follow-up was planned at 12 months, and yearly thereafter for 5 years. RESULTS: Four-year clinical follow-up was completed in 753 (91.1%) patients. At 4 years, BAS were non-inferior to EES for MACE (14.7% versus 17.8%, respectively; p = 0.24 for superiority; p = 0.001 for non-inferiority). Non-fatal MI was less frequent with BAS (5.0% versus 9.2%, respectively; p = 0.025). Cardiac death and ischemia-driven TLR were comparable (2.9% versus 3.5%, and 8.6% versus 9.2%; p = 0.62 and p = 0.80, respectively). Independent predictors of MACE were calcified lesions (HR 1.54, p = 0.021), the number of vessels treated (HR 1.53, p = 0.025), and reference vessel diameter (HR 0.54, p = 0.006). CONCLUSIONS: In patients presenting with ACS, BAS was associated with a clinical outcome non-inferior to EES at 4-year follow-up.

Five-Year Efficacy and Safety of TiNO-Coated Stents Versus Drug-Eluting Stents in Acute Coronary Syndrome: A Meta-Analysis.

(1) Background: Percutaneous coronary interventions (PCI) in patients with acute coronary syndrome (ACS) are performed with titanium-nitride-oxide-coated stents (TiNOSs) or drug-eluting stents (DESs). The initial completion of this prospective systematic literature review (SLR) of prospective randomized controlled trials (RCTs) showed that TiNOSs are non-inferior to DESs in major adverse cardiac event (MACE) rates and present a lower risk of recurrent myocardial infarction (MI) at 1-year follow-up. This iteration of the SLR protocol performs the critical assessment of 5-year follow-up outcomes with clinical validity and generalizability assessments. (2) Methods: The previously described SLR and meta-analysis protocol, per PRISMA, Cochrane methods, and GRADE, was applied to 5-year follow-up outcomes. (3) Results: Three RCTs were eligible, comprising 1620 patients with TiNOS vs. 1123 with DES. The pooled risk ratios (RRs) and 95% confidence intervals were MACE 0.82 [0.68, 0.99], MI 0.58 [0.44, 0.78], cardiac death (CD) 0.46 [0.28, 0.76], ischemia-driven target lesion revascularization (TLR) 1.03 [0.79, 1.33], probable or definite stent thrombosis (ST) 0.32 [0.21, 0.59], and all-cause mortality (TD) 0.84 [0.63, 1.12]. The evidence certainty was high in MACE, CD, MI, and ST, and moderate in TLR and TD. (4) Conclusions: TiNOSs in ACS at 5-year follow-up appear safer than DESs and equally efficacious. The pooled RRs stratified by clinical presentation and stent type will be required to test this meta-analysis's clinical validity and generalize its results to patient populations with varying proportions of clinical presentations and DES options.

Bioactive or Drug-Eluting Stents in 75 Years or Older Patients: The BIODES-75 Registry.

BACKGROUND: TiNO-coated BAS have demonstrated competitive outcomes compared to drug-eluting stents (DES). These devices allow short antiplatelet regimens and may be a good option for the growing elderly population undergoing percutaneous coronary intervention (PCI). METHODS: Multicenter observational trial in routine clinical practice. A propensity-score matched analysis compared a prospective cohort of patients ≥ 75 years undergoing PCI with BAS, with a contemporary and retrospective cohort treated with last-generation DES. The co-primary endpoints of the study were the Target-Lesion-Failure (Cardiac death, non-fatal myocardial infarction, or target lesion revascularization) and Major Adverse Cardiovascular Events (total death, non-fatal myocardial infarction, stroke, or new revascularization) at 1 year. RESULTS: Whole population included 1000 patients, and 326 patients in each group were matched for analysis. No differences in primary endpoints were found: TLF 10.4% vs. 11% (HR 0.96 (Confidence Interval 95%, 0.36-1.7; p = 0.87)) and MACE 16.3% vs. 17.2% (HR 0.98 (Confidence Interval 95%; 0.3-1.5, p = 0.93)). Patients treated with BAS received shorter antiplatelets regimens (dual antiplatelet therapy at 1 year, 25.7% vs. 70.6%, p = 0.0001), and they presented lower incidence of bleeding (3.7% vs. 11.7%, HR 0.3 (IC 95% 0.16-0.6, p = 0.001)). CONCLUSION: In this real-life registry of patients ≥ 75 years, BAS were similar to the latest-generation DES in terms of efficacy and reduced the duration of the antithrombotic therapy, lowering bleeding events.

Efficacy and Safety of TiNO-Coated Stents versus Drug-Eluting Stents in Acute Coronary Syndrome: Systematic Literature Review and Meta-Analysis.

(1) Background: Practice guidelines define drug-eluting stents (DES) as the standard of care in coronary percutaneous coronary intervention (PCI), including in acute coronary syndrome (ACS). This is based on comparisons with bare-metal stents (BMS). However, non-drug-eluting titanium-nitride-oxide-coated stents (TiNOS) have not been taken into account. The objective of this study is to determine whether TiNOS can be used as an alternative to DES in ACS. (2) Methods: A prospective systematic literature review (SLR), conducted according to the PRISMA guidelines, was performed, wherein multiple literature databases from 2018 and 2022 were searched. Prospective, randomised, controlled trials comparing outcomes after PCI with TiNOS vs. DES in any coronary artery disease (CAD) were searched. Clinical outcomes were meta-analytic pooled risk ratios (RR) of device-oriented Major Adverse Cardiac Events (MACE) and their components. The analysis stratified outcomes reported with ACS-only vs. ACS jointly with chronic coronary syndrome (CCS). (3) Results: Five RCTs were eligible, comprising 1855 patients with TiNOS vs. 1363 with DES at a 1-year follow-up. Three enrolled patients presented with ACS only and two with ACS or CCS. The latter accounted for most of the patients. The one-year pooled RRs in those three RCTs were as follows: MACE 0.93 [0.72, 1.20], recurrent myocardial infarction (MI) 0.48 [0.31, 0.73], cardiac death (CD) 0.66 [0.33, 1.31], clinically driven target lesion revascularization (TLR) 1.55 [1.10, 2.19], and stent thrombosis (ST) 0.35 [0.20, 0.64]. Those results were robust to a sensitivity analysis. The evidence certainty was high in MACE and moderate or low in the other endpoints. (4) Conclusions: TiNOS are a non-inferior and safe alternative to DES in patients with ACS.

Titanium-Nitride-Oxide-Coated Versus Everolimus-Eluting Stents in Acute Coronary Syndrome: The Randomized TIDES-ACS Trial.

OBJECTIVES: This study sought to compare next-generation cobalt-chromium-based titanium-nitride-oxide (TiNO)-coated stents with a platinum-chromium-based biodegradable polymer everolimus-eluting stent (EES) in patients with acute coronary syndrome (ACS). BACKGROUND: Previous generation TiNO-coated stents showed acceptable performance in patients with ACS. METHODS: In a multicenter, randomized trial, we randomly assigned 1,491 ACS patients (2:1) to receive either a TiNO-coated stent (n = 989) or EES (n = 502). The primary endpoint was the rate of a composite of cardiac death, myocardial infarction (MI), or ischemia-driven target lesion revascularization at 12-month follow-up. The co-primary endpoint was a composite of cardiac death, MI, or major bleeding at 18 months. RESULTS: A primary endpoint event occurred in 6.3% of patients in the TiNO-coated stent group versus in 7.0% in the EES group (hazard ratio: 0.93; 95% confidence interval: 0.71 to 1.22; p = 0.66 for superiority; p < 0.001 for noninferiority). A co-primary endpoint event occurred in 3.7% of the patients in the TiNO group and in 7.8% in the EES group (hazard ratio: 0.64; 95% confidence interval: 0.51 to 0.80; p = 0.001). TiNO-coated stents were associated with lower rates of cardiac death (0.6% vs. 2.6%; p = 0.002) and MI (2.2% vs. 5.0%; p = 0.007) at 18 months of follow-up. Rates of target lesion revascularization were not significantly different at 18 months (5.8% vs. 4.4%; p = 0.27). CONCLUSIONS: In patients with ACS, cobalt-chromium-based TiNO-coated stents were noninferior to platinum-chromium-based biodegradable polymer EES for major cardiac events at 12 months, and were superior for the co-primary endpoint of cardiac death, MI, and bleeding at 18 months. (Comparison of Titanium-Nitride-Oxide-Coated Bio-Active-Stent (Optimax™) to the Drug (Everolimus) -Eluting Stent (Synergy™) in Acute Coronary Syndrome [TIDES-ACS]; NCT02049229).

Titanium-nitride-oxide-coated coronary stents: insights from the available evidence.

Coating of stent surface with a biocompatible material is suggested to improve stent safety profile. A proprietary process was developed to coat titanium-nitride-oxide on the stent surface, based on plasma technology that uses the nano-synthesis of gas and metal. Preclinical in vitro and in vivo investigation confirmed blood compatibility of titanium (nitride-) oxide films. Titanium-nitride-oxide-coated stents demonstrated a better angiographic outcome, compared with bare-metal stents at mid-term follow-up; however, they failed to achieve non-inferiority for angiographic outcome versus second-generation drug-eluting stents. Observational studies showed adequate clinical outcome at mid-term follow-up. Non-randomized studies showed an outcome of titanium-nitride-oxide-coated stents comparable to - or better than - first-generation drug-eluting stents at long-term follow-up. Two randomized controlled trials demonstrated comparable efficacy outcome, and a better safety outcome of titanium-nitride-oxide-coated stents versus drug-eluting stents at long-term follow-up. Evaluation by optical coherence tomography at mid-term follow-up revealed better neointimal strut coverage associated with titanium-nitride-oxide-coated stents versus drug-eluting stents; yet, neointimal hyperplasia thickness was greater. Key messages Stents coated with titanium-nitride-oxide demonstrated biocompatibility in preclinical studies: they inhibit platelet and fibrin deposition, and reduce neointimal growth. In observational and non-randomized studies, titanium-nitride-oxide-coated stents were associated with adequate safety and efficacy outcome. In randomized trials of patients with acute coronary syndrome, titanium-nitride-oxide-coated stents were associated with a better safety outcome, compared with drug-eluting stents; efficacy outcome was comparable.

Long-term clinical outcome of elderly patients with acute coronary syndrome treated with early percutaneous coronary intervention: Insights from the BASE ACS randomized controlled trial: Bioactive versus everolimus-eluting stents in elderly patients.

BACKGROUND: The BASE ACS trial demonstrated an outcome of titanium-nitride-oxide-coated bioactive stents (BAS) that was non-inferior to everolimus-eluting stents (EES) in patients presenting with acute coronary syndrome (ACS). We performed a post hoc analysis of elderly versus non-elderly patients from the BASE ACS trial. METHODS: We randomized 827 patients (1:1) presenting with ACS to receive either BAS or EES. The primary endpoint was major adverse cardiac events (MACE): a composite of cardiac death, non-fatal myocardial infarction (MI), or ischemia-driven target lesion revascularization (TLR). Follow-up was planned at 12months and yearly thereafter for up to 7years. Elderly age was defined as ≥65years. RESULTS: Of the 827 patients enrolled in the BASE ACS trial, 360 (43.5%) were elderly. Mean follow-up duration was 4.2±1.9years. MACE was more frequent in elderly versus younger patients (19.7% versus 12.0%, respectively, p=0.002), probably driven by more frequent cardiac death and non-fatal MI events (5.3% versus 1.5%, and 9.7% versus 4.5%, p=0.002 and p=0.003, respectively). The rates of ischemia-driven TLR were comparable (p>0.05). In propensity score-matched analysis (215 pairs), only cardiac death was more frequent in elderly patients (6% versus 1.4%, respectively, p=0.01). Diabetes independently predicted both MACE and cardiac death in elderly patients. CONCLUSIONS: Elderly patients treated with stent implantation for ACS had worse long-term clinical outcome, compared with younger ones, mainly due to a higher death rate.

Impact of Preexisting Vascular Disease on the Outcome of Patients With Acute Coronary Syndrome: Insights From the Comparison of Bioactive Stent to the Everolimus-Eluting Stent in Acute Coronary Syndrome Trial.

The Comparison of Bioactive-Stent to the Everolimus-Eluting Stent in Acute Coronary Syndrome (BASE-ACS) trial demonstrated an outcome of titanium-nitride-oxide-coated bioactive stents (BAS) non-inferior to everolimus-eluting stents (EES) in patients presenting with acute coronary syndrome (ACS). We performed a post hoc analysis of the BASE-ACS trial in patients with, versus those without, preexisting vascular disease. We randomized 827 patients (1:1) presenting with ACS to receive either BAS or EES. The primary end point was major adverse cardiac events (MACE): a composite of cardiac death, non-fatal myocardial infarction (MI), or ischemia-driven target lesion revascularization (TLR). A total of 169 (20.4%) patients had preexisting vascular disease. Median follow-up was 5.0 years. The incidence of MACE was higher in patients with, versus those without, preexisting vascular disease (22.5% vs 13.5%, respectively, P = .004). This was driven by more frequent cardiac death and non-fatal MI (5.9% vs 2.4% and 11.8% vs 5.5%, P = .02 and P = .003, respectively). The rates of ischemia-driven TLR were comparable ( P > .05). All events were comparable between the 2 matched-pair subgroups ( P > .05 for all). In patients treated with early percutaneous coronary intervention for ACS, the long-term outcome was worse in patients with, versus those without, preexisting vascular disease.

Modulation of osteoblast behavior on TiNxOy coatings by altering the N/O stoichiometry while maintaining a high thrombogenic potential.

INTRODUCTION: Titanium nitride oxide (TiNxOy) coatings are known to stimulate osteoblast proliferation and osseointegration when compared to microrough titanium implants. The objectives of the present study were to determine whether the beneficial effects of TiNxOy coatings observed with implant osseointegration are dependent on N/O stoichiometry, with the final goal of optimizing these benefits. MMS: TiNxOy coatings with various N/O compositions were deposited on microrough titanium plates (Ti-SLA, 11 × 11 mm). Human primary osteoblast (hOBs) proliferation and gene expression were analyzed for a time course of three weeks, with or without additional stimulation by 1.25 (OH)2 vitamin D3 100 nM. Platelet adhesion/activation and thrombin generation were also assessed. RESULTS: hOBs proliferation gradually increased with the amount of oxygen contained in the coatings. The effect was observed from day 7 to reach a maximum at day 10, with a 1.8 fold increase for the best coating as compared to Ti-SLA. SEM views indicated that cells adhered, spread and elongated faster on oxygen-rich TiNxOy films, while the differentiation process as well as the thombogenic potential was not affected. CONCLUSIONS: The effect of TiNxOy coatings on osteoblast is dependent on their chemical composition; it increases with the amount of oxygen. TiNxOy coatings may act as a catalyst for cell-adhesion and proliferation early after seeding. In contrast, thrombogenicity of Ti-SLA surface is not affected by TiNxOy application.

Long-term clinical outcome of titanium-nitride-oxide-coated stents versus everolimus-eluting stents in acute coronary syndrome: Final report of the BASE ACS trial.

BACKGROUND: The BASE ACS randomized trial demonstrated non-inferiority of titanium-nitride-oxide-coated bioactive stents (BAS), compared with everolimus-eluting stents (EES), for the primary endpoint of major adverse cardiac events (MACE) in patients presenting with acute coronary syndrome (ACS) at 12-month follow-up. We report the final long-term clinical outcome of the trial. METHODS: We randomly assigned 827 patients with ACS to receive either BAS (417) or EES (410). The primary endpoint was MACE: a composite of cardiac death, non-fatal myocardial infarction (MI) or ischemia-driven target lesion revascularization (TLR) at 12-month follow-up. Analysis was performed by intention to treat. Follow-up was planned at 12months, and yearly thereafter through 7years. RESULTS: Mean follow-up duration was 4.2±1.9years (median 5.0years). At 5-year follow-up, BAS was non-inferior to EES for the primary endpoint of MACE (14.4% versus 17.8%, respectively; hazard ratio for BAS versus EES, 0.82; 95% confidence interval, 0.58-1.16; p=0.26 for superiority; p<0.001 for non-inferiority). The rate of non-fatal MI was lower in the BAS group (5.9% versus 9.7%, respectively, p=0.028). The rates of cardiac death and ischemia-driven TLR were comparable (2.8% versus 3.8%, and 8.3% versus 9.9%; p=0.76 and p=0.58, respectively). CONCLUSIONS: In the current final report of the randomized BASE ACS trial in patients with ACS, BAS implantation was associated with a rate of cumulative MACE at long-term follow-up that was statistically non-inferior to EES.

Long-term outcome of early percutaneous coronary intervention in diabetic patients with acute coronary syndrome: insights from the BASE ACS trial.

BACKGROUND: The BASE ACS trial demonstrated an outcome of titanium-nitride-oxide-coated bioactive stents (BAS) that was non-inferior to everolimus-eluting stents (EES) in patients with acute coronary syndrome (ACS). We performed a post-hoc analysis of diabetic versus non-diabetic patients from the trial. METHODS: We randomised 827 patients (1:1) with ACS to receive either BAS or EES. The primary endpoint was major adverse cardiac events (MACE): a composite of cardiac death, non-fatal myocardial infarction (MI) or ischaemia-driven target lesion revascularisation (TLR). Follow-up was planned yearly through 7 years. RESULTS: Of 827 patients, 140 (16.9%) were diabetic; of these, 36 (25.7%) were insulin-treated. Mean follow-up duration was 4.2 ± 1.9 years. MACE was more frequent in diabetics versus non-diabetics (23.6% versus 13.7%, respectively, p = 0.003), mainly driven by more frequent cardiac death (7.9% versus 2.2%, respectively, p = 0.002). The rates of non-fatal MI, ischaemia-driven TLR were comparable (p > 0.05 for all). In diabetic patients, MACE was comparable between the two stent arms (18.5% versus 28.0%, for BAS versus EES, respectively, p = 0.18). CONCLUSIONS: Diabetic patients treated with early percutaneous coronary intervention for ACS had worse long-term outcome, compared with non-diabetics, mainly driven by more frequent cardiac death. The long-term outcome of BAS was comparable to EES in diabetics. Key Messages Diabetic patients presenting with acute coronary syndrome who were treated with early percutaneous coronary intervention had worse long-term clinical outcome, compared with non-diabetics, mainly driven by a high incidence of cardiac death. Age independently predicted both major adverse cardiac events and cardiac death in diabetic patients. The long-term clinical outcome of titanium-nitride-oxide-coated bioactive stents was comparable to that of everolimus-eluting stents in the diabetic, as well as in the non-diabetic subgroup.