Biodegradable polymer drug-eluting stents versus second-generation drug-eluting stents in patients with and without diabetes mellitus: a single-center study.

BACKGROUND: To improve outcomes in patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention remain an unmet clinical need. The study aimed to evaluate the efficacy and safety of G2-DESs and BP-DESs in patients with and without DM in a single center in China. METHODS: A total of 7666 consecutive patients who exclusively had G2-DES or BP-DES implantation throughout 2013 in our center were studied. The primary efficacy endpoint was any target lesion revascularization (TLR), whereas the primary safety endpoint was a composite of death or myocardial infarction (MI) at 2-year follow-up. RESULTS: G2-DESs had a similar occurrence of death, non-fatal MI, TLR, stroke, and stent thrombosis compared with BP-DESs in patients with DM (all P > 0.05). The incidence of TVR and TLR was lower for G2-DESs than for BP-DESs in patients without DM (3.2% vs. 5.1%, P = 0.002; 2.2% vs. 4.5%, P < 0.001, respectively). Kaplan-Meier analysis also showed better TVR- and TLR-free survival rates for G2-DESs than for BP-DESs in patients without DM. Multivariate analysis showed that a BP-DES was an independent risk factor for TLR (hazard ratio 1.963, 95% confidence interval 1.390-2.772, P < 0.001) in patients without DM, which was not predictive of other components of major adverse cardiac events (P > 0.05). CONCLUSIONS: G2-DESs have better efficacy, represented by a reduced risk of TLR, and similar safety compared with BP-DESs in patients without DM. G2-DESs have similar efficacy and safety compared with BP-DESs in patients with DM at 2-year follow-up.

Immediate and long-term outcomes of drug-eluting stent implantation for unprotected left main coronary artery disease: comparison with bare-metal stent implantation.

BACKGROUND: The efficacy and safety of drug-eluting stent (DES) implantation for unprotected left main coronary artery (LMCA) disease remain to be established in different clinical settings. METHODS: Elective DES implantation for unprotected LMCA stenosis was performed in 220 patients at the Fu Wai Hospital, China, from April 2003 to February 2006. Data derived from the latter group were compared with those derived from 224 patients treated with bare-metal stents (BMSs) before March 2003 in a Chinese registry of unprotected LMCA stenting. RESULTS: Compared with the historical BMS control group, the DES group had more multivessel disease and underwent more bifurcation stenting. The inhospital major adverse cardiac events were significantly higher in the DES than in the BMS recipients (4.1% vs 0.9%, P = .030) because of more complex lesions and procedures in the DES group. During the 15-month mean follow-up period, cumulative cardiac death (0.5% vs 4.9%, P = .004), target-vessel revascularization (5.9% vs 11.6%, P = .034), and major adverse cardiac event (9.5% vs 16.5%, P = .029) rates were significantly lower in the DES than in the BMS group. There was no significant difference in clinical efficacy between sirolimus- and paclitaxel-eluting stents. Angiographic follow-up was performed in 46.4% of DES and 45.7% of BMS recipients, respectively; and the binary restenosis rate was significantly lower in the DES versus the BMS control group (16.7% vs 31.4%, P = .014). CONCLUSIONS: Based on this comparison with a historical control, DES implantation for unprotected LMCA appears safe in selected patients and might be more effective in preventing major adverse cardiac events compared with BMS implantation over a mean follow-up period of 15 months.

Sirolimus-eluting cobalt-chromium stents: two-year clinical results from first-in-man study on the Firebird 2 stent.

BACKGROUND: Drug-eluting stents (DES) have been shown to significantly reduce clinical events and angiographic restenosis in the treatment of coronary artery disease (CAD). This study was conducted to assess the long-term efficacy and safety of the polymer-based sirolimus-eluting cobalt-chromium Firebird 2 stents in the treatment of patients with CAD. METHODS: This first-in-man study using the Firebird 2 stent is a prospective, historically-controlled multicenter clinical study, which enrolled 67 patients with CAD who were treated with the sirolimus-eluting cobalt-chromium stent (Firebird 2, Microport Shanghai, Firebird 2 group), compared to another 49 patients treated with a bare cobalt alloy stent (Driver, Medtronic, control group). Continued 2-year clinical follow-up was performed after getting the initial 6-month angiographic and 1-year clinical follow-up. The incidence of major adverse cardiac events (MACE) including cardiac death, reinfarction and target lesion revascularization (TLR) and stent thrombosis were compared between the two groups. RESULTS: All patients in the Firebird 2 group (100.0%) and 48 patients in the control group (98.0%) completed the 2-year clinical follow-up. At the 1-year follow-up the use of the Firebird 2 stent was highly effective, resulting in a significant 94% decrease of TLR (26.5% in the control group and 1.5% in the Firebird 2 group, P<0.0001). A significant difference in TLR was maintained at 2-year follow-up, Firebird 2 group 1.5% and the control group 31.3% (P<0.0001). Between 1- and 2-year post-stenting, no more TLR occurred in the Firebird 2 group compared with two cases in the control group (P>0.05). There was a 1.5% incidence of MACE at 1- and 2-year follow-up in the Firebird 2 group, compared with 26.5% and 33.3% in the control group, respectively (all P<0.0001). The cumulative 1- and 2-year MACE free survival rates were 98.5% in the Firebird 2 group vs 73.5% and 66.7% in the control group (log rank P<0.0001). No case of stent thrombosis occurred during 2-year follow-up in the Firebird 2 group, compared with one case that suffered a definite stent thrombosis in the control group at 19-month post-stenting: this patient presented with unstable angina pectoris and was treated by balloon angioplasty. CONCLUSIONS: Compared with the bare cobalt alloy stent, the Firebird 2 sirolimus-eluting cobalt-chromium stent is safe and effective in treating patients with CAD. The use of this stent was associated with a sustained clinical benefit and significantly lower rate of TLR and MACE up to 2 years post-stenting.

A comparison of clinical and angiographic outcomes after Excel bioabsorbable polymer versus Firebird durable polymer rapamycin-eluting stent for the treatment of coronary artery disease in a "real world" setting: six-month follow-up results.

BACKGROUND: Several clinical trials have shown that rapamycin-eluting stents significantly reduce the risk of restenosis after percutaneous coronary intervention (PCI). The Firebird stent and the Excel stent (coated with bioabsorbable polymer) are two different types of rapamycin-eluting stents made in China, both have been recently approved for clinical use in China by State Food and Drug Administration. However, it is unclear whether there are differences in safety and efficacy between the two types of stents in daily practice. METHODS: In the month of June 2006, a total of 190 consecutive patients were treated exclusively with Firebird stents (n = 93, Firebird group) or Excel stents (n = 97, Excel group) in our center and were included in this study. The frequency of major adverse cardiac events (MACE, a composite of death, myocardial infarction or target lesion revascularization), binary restenosis, and late lumen loss and stent thrombosis during a six-month follow-up period were compared between the two groups. RESULTS: Patient and lesion characteristics were comparable between the groups. Major adverse cardiac event rates were low in hospital and at 6 months (2.1% in the Excel group and 0% in the Firebird group, P > 0.05). The 6-month angiographic in-stent restenosis rate was 0% in both groups, with an associated late loss of (0.15 +/- 0.21) mm versus (0.14 +/- 0.20) mm (P = 0.858) and the in-segment restenosis rate was also 0% for the Excel group and the Firebird group. There was no definite stent thrombosis identified in either group during the six-month follow-up period and only one patient in the Excel group had probable stent thrombosis in hospital. CONCLUSIONS: Results from this mid-term, single-center study showed that both of the Firebird and the Excel rapamycin eluting stent had similar effects on reducing the incidence of MACE and the risk of restenosis (both in-stent and in-segment binary restenosis) after PCI in daily practice.

Comparison of long-term in-stent vascular response between abluminal groove-filled biodegradable polymer sirolimus-eluting stent and durable polymer everolimus-eluting stent: 3-year OCT follow-up from the TARGET I trial.

The study sought to compare long-term optical coherence tomography (OCT)-based in-stent vascular response between the abluminal groove-filled biodegradable polymer sirolimus-eluting stent (SES) and the durable polymer everolimus-eluting stent (EES) in the TARGET I trial. The TARGET I trial was a prospective, multicenter, randomized clinical trial which enrolled 458 patients with single de novo lesions treated by abluminal groove-filled biodegradable polymer SES and EES. A subset of 43 patients underwent angiography and OCT examinations at 3 years. All OCT images were analyzed at 0.4 mm intervals. A similar increase in angiographic late lumen loss was observed in SES and EES (from 0.05 ± 0.05 vs. 0.05 ± 0.05 mm [p = 0.84] at 9 months to 0.25 ± 0.37 vs. 0.26 ± 0.19 mm [p = 0.99] at 3 years, respectively), without significant differences at 3 years in mean neointimal thickness of stent struts (SES: 0.13 ± 0.02 mm vs. EES: 0.13 ± 0.02 mm, p = 0.80); mean percentage of covered struts (SES: 99.2 % vs. EES: 99.3 %, p = 0.53), or malapposed strut rates (SES: 0.08 % vs. EES: 0.06 %, p = 0.15). The OCT-based in-stent vascular response evaluation found similar vascular healing for the two studied devices, indicating that the luminal loss in EES from 9 months to 3 years cannot be imputed on its coated biocompatible polymer.

Optical coherence tomography assessment of a PLGA-polymer with electro-grafting base layer versus a PLA-polymer sirolimus-eluting stent at three-month follow-up: the BuMA-OCT randomised trial.

AIMS: To compare stent strut coverage using optical coherence tomography (OCT) at three-month follow-up between a PLGA-polymer with electro-grafting base layer sirolimus-eluting stent (SES) (BuMA) and a PLA-polymer SES (EXCEL). METHODS AND RESULTS: This prospective, single-centre, non-inferiority randomised BuMA-OCT trial enrolled patients with de novo coronary artery lesions, treated with either the BuMA or the EXCEL stent. The study primary endpoint was OCT-evaluated stent strut coverage at three months. Secondary endpoints were neointimal thickness of stent struts, and incomplete stent apposition evaluated with OCT. A total of 80 patients were randomly assigned to receive the BuMA (n=40) or the EXCEL (n=40) stent. In OCT follow-up (achieved in 86.3% of cases: BuMA, n=33; EXCEL, n=36), the percentage of stent strut coverage was significantly higher in the BuMA vs. the EXCEL group (strut level: 94.2% vs. 90.0%, p<0.01; p(non-inferiority)<0.0001; p(superiority) <0.0001), while the proportion of malapposed struts (strut level: 1.28% vs. 1.80%, p=0.51) and the mean neointimal thickness (strut level: 0.07±0.03 mm vs. 0.06±0.02 mm, p=0.31) were similar. Rates of myocardial infarction (periprocedural non-Q-wave, 7.5% vs. 7.5%, p=1.00) and target lesion failure (7.5% vs. 7.5%, p=1.00) were similar between groups, with no cardiac death or stent thrombosis. CONCLUSIONS: In the BuMA-OCT randomised trial, the novel BuMA PLGA-polymer with electro-grafting base layer SES was superior to the EXCEL PLA-polymer SES in the primary endpoint of stent strut coverage at three-month follow-up.

A randomised comparison of a novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent with a durable polymer everolimus-eluting stent: clinical and angiographic follow-up of the TARGET I trial.

AIMS: The study sought to evaluate the safety and efficacy of FIREHAWK, a novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent (SES) for treating patients with single de novo coronary lesions compared with the durable polymer everolimus-eluting stent (EES) XIENCE V. METHODS AND RESULTS: A total of 458 patients with single de novo native coronary lesions ≤24 mm in length and a coronary artery ≥2.25 to ≤4.0 mm in diameter were enrolled in the TARGET I study, a prospective, randomised, non-inferiority trial. The primary endpoint was in-stent late lumen loss (LLL) at nine-month follow-up. The secondary endpoint, target lesion failure (TLF), was defined as the composite of cardiac death, target vessel myocardial infarction (TVMI), or ischaemia-driven target lesion revascularisation (iTLR). Patients were centrally randomised to treatment with either biodegradable polymer SES (n=227) or durable polymer EES (n=231). The nine-month in-stent LLL of the biodegradable polymer SES was comparable to the EES group (0.13 ± 0.24 mm vs. 0.13 ± 0.18 mm, p=0.94; difference and 95% confidence interval 0.00 [-0.04, 0.04] mm; p for non-inferiority <0.0001). Cardiac death (0.4% vs. 0.0%), TVMI (1.3% vs. 1.7%), iTLR (0.4% vs. 0.4%) and TLF (2.2% vs. 2.2%) were similar between the biodegradable polymer SES and durable polymer EES groups at 12-month follow-up (all p>0.05). No definite/probable stent thrombosis was observed in both of these groups. CONCLUSIONS: In the multicentre TARGET I trial, the novel abluminal groove-filled biodegradable polymer SES FIREHAWK was non-inferior to the durable polymer EES XIENCE V with respect to the primary endpoint of in-stent LLL at nine months for treating patients with single de novo coronary lesions. The incidences of clinical endpoints were low in both of the stents at 12-month follow-up. (ClinicalTrials.gov identifier: NCT01196819).

First report of a novel abluminal groove filled biodegradable polymer rapamycin-eluting stent in de novo coronary artery disease: results of the first in man FIREHAWK trial.

BACKGROUND: Durable polymers used for first-generation drug-eluting stents (DES) potentially contribute to persistent inflammation and late DES thrombosis. We report the first in human experience with the rapamycin-eluting biodegradable polymer coated cobalt-chromium FIREHAWK stent with abluminal groove. METHODS: A total of 21 patients with stable or unstable angina, or prior myocardial infarction, with single de novo native coronary stenoses < 30 mm in length in vessel sizes ranging from 2.25 to 4.0 mm were enrolled. The primary endpoint was major adverse cardiac events (MACE) at 30 days defined as the composite of cardiac death, myocardial infarction (Q and non-Q), or ischemia-driven target lesion revascularization. Secondary endpoints include device, lesion, and clinical success rates, 4-month in-stent late lumen loss by quantitative coronary angiography (QCA), proportion of uncovered or malapposed stent struts by optical coherence tomograpphy (OCT) at 4 months, and MACE at 4, 12, 24 and 36-month follow-up. RESULTS: Device success was 95.7%, lesion and clinical success was 100.0%. There were no MACE events at 30 days. One patient died of non-cardiac hemorrhagic stroke 5 days after index procedure. At 4 months, in-stent late loss was (0.13 ± 0.18) mm, and complete strut coverage was 96.2% by OCT with 0.1% strut malapposition. At 4-month follow-up there was no additional MACE events, and a single target vessel (non-target lesion) revascularization. CONCLUSIONS: The FIREHAWK abluminal groove biodegradable polymer rapamycin-eluting stent demonstrated feasibility, safety and efficacy in this first in human experience. OCT findings indicated excellent stent strut coverage 4 months after implantation. Larger studies are required to confirm whether the early FIREHAWK stent results translate into longer term restenosis and thrombosis benefits.

A prospective multicenter parallel-controlled trial of TIVOLI biodegradable-polymer-based sirolimus-eluting stent compared to ENDEAVOR zotarolimus-eluting stent for the treatment of coronary artery disease: 8-month angiographic and 2-year clinical follow-up results.

BACKGROUND: Available drug-eluting stents (DES) have achieved great success in reducing restenosis rates. Recently, investigators have demonstrated that the durable polymer carrier plays a significant role in DES-related hypersensitive reaction and delays vessel healing. TIVOLI stent is a novel sirolimus-eluting coronary stent with biodegradable coating containing sirolimus and polylactic-co-glycolic acid (PLGA) polymer. The present study sought to evaluate the effectiveness and safety of the TIVOLI biodegradable-polymer-based sirolimus-eluting stent in treating patients with coronary artery disease. METHODS: A prospective, multicenter clinical trial comparing TIVOLI biodegradable coated sirolimus-eluting stent with ENDEAVOR zotarolimus-eluting stent was conducted in 324 patients (TIVOLI group: 168 patients; ENDEAVOR group: 156 patients) at 12 centers in China to demonstrate the non-inferiority of in-stent late loss with TIVOLI stent compared to ENDEAVOR stent in subjects with a maximum of two de novo native coronary artery lesions (lesion length ≤ 40 mm, reference vessel diameter 2.25-4.00 mm). The primary end point was angiographic in-stent late loss at 8-month. The secondary end points were clinical outcomes at 2 years, including major adverse cardiac events (cardiac death, myocardial infarction, or target-lesion revascularization) and stent thrombosis. RESULTS: Angiographic late lumen loss at 8 months in the TIVOLI group was superior to the ENDEAVOR group (in-stent (0.25 ± 0.33) mm vs. (0.57 ± 0.55) mm, diff (95%CI) -0.23 (-0.32, -0.14), P < 0.0001; in-segment (0.25 ± 0.33) mm vs. (0.42 ± 0.55) mm, diff (95%CI) -0.13 (-0.23, -0.02), P = 0.0083). The rate of in-stent binary restenosis at 8 months was reduced from 8.6% in the ENDEAVOR group to 2.9% in the TIVOLI group (P = 0.0229). Compared to ENDEAVOR stent, TIVOLI stent resulted in a significant reduction in target-lesion revascularization (4.2% vs. 9.6%, P = 0.0495) at 2 years. The two-year major adverse cardiac events (MACE) rate was lower for the TIVOLI group, but not significantly different (6.6% vs. 10.9%, P = 0.1630). CONCLUSIONS: TIVOLI was superior to ENDEAVOR stent with respect to late lumen loss at 8 months, and it yielded both lower rates of angiographic binary restenosis at 8 months and target lesion revascularization (TLR) at 2 years. The MACE rate at 2 years was comparable in both groups.

Serum calciotropic hormone levels, and dental fluorisis in children exposed to different concentrations of fluoride and iodine in drinking water.

BACKGROUND: High fluoride exposure can result in dental fluorosis. Fluoride and iodine are coexistent in the drinking water of areas in China and may affect the prevalence of dental fluorosis and osteogenesis. The aim of this study was to investigate the relationship between serum calciotropic hormone level, and dental fluorisis in children exposed to different concentrations of fluoride and iodine in drinking water. METHODS: A pilot study was conducted in three villages located in the Kaifeng and Tongxu counties of Henan Province, China in 2006. Children aged 8 to 12 years, born and raised in the three villages were recruited. The fluoride levels in the samples of urine from these children were detected by fluoride ion selective electrode. Calcitonin and osteocalcin levels in the serum, and serum calcium were measured by radioimmunassay and flame atomic absorption spectrometry, respectively. RESULTS: Fluoride levels in urine were significantly lower in children from control area (CA) as compared with those from the high fluoride & iodine areas (HFIA) and the high fluoride area (HFA) (P < 0.05 respectively), and no statistically significant difference was found between the children from HFIA and HFA. Additionally, calcitonin levels in the serum were significantly lower in children from CA and HFA as compared with that from HFIA (P < 0.05 respectively), and osteocalcin levels in the serum was lower in children from CA than those from HFIA (P < 0.05). No statistically significant difference in serum osteocalcin concentrations was found between children from HFA and HFIA. CONCLUSION: This study provides an evidence that iodine exposure may modify the serum calciotropic hormone levels related to fluorine exposure.