Impact of Diabetes Mellitus on Antithrombotic Management Patterns and Long-Term Clinical Outcomes in Patients With Acute Coronary Syndrome: Insights From the EPICOR Asia Study.

Background Long-term use of antiplatelet agents after acute coronary syndrome in diabetic patients is not well known. Here, we describe antiplatelet use and outcomes in such patients enrolled in the EPICOR Asia (Long-Term Follow-up of Antithrombotic Management Patterns in Acute Coronary Syndrome Patients in Asia) registry. Methods and Results EPICOR Asia is a prospective, observational study of 12 922 patients with acute coronary syndrome surviving to discharge, from 8 countries/regions in Asia. The present analysis included 3162 patients with diabetes mellitus (DM) and 9602 patients without DM. The impact of DM on use of antiplatelet agents and events (composite of death, myocardial infarction, and stroke, with or without any revascularization; individual components, and bleeding) was evaluated. Significant baseline differences were seen between patients with DM and patients without DM for age, sex, body mass index, cardiovascular history, angiographic findings, and use of percutaneous coronary intervention. At discharge, ≈90% of patients in each group received dual antiplatelet therapy. At 2-year follow-up, more patients with DM tended to still receive dual antiplatelet therapy (60% versus 56%). DM was associated with increased risk from ischemic but not major bleeding events. Independent predictors of the composite end point of death, myocardial infarction, and stroke in patients with DM were age ≥65 years and use of diuretics at discharge. Conclusions Antiplatelet agent use is broadly comparable in patients with DM and patients without DM, although patients with DM are more likely to be on dual antiplatelet therapy at 2 years. Patients with DM are at increased risk of ischemic events, suggesting an unmet need for improved antithrombotic treatment. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT01361386.

Analysis of failure factors in retrograde wire-guided intervention for chronic total occlusion.

OBJECTIVE: This study aims to investigate failure factors in retrograde wire-guided cannulation (retrograde approach) for the treatment of coronary chronic total occlusion (CTO). METHODS: Data of 285 patients treated for CTO using retrograde approach in the General Hospital of Shenyang Military Region from August 2004 to May 2016 were collected. RESULTS: The average age of the 285 patients was 63.89 ± 11.3 years old. Multivariate analysis revealed that the operation risk factors include the number of diseased vessels, collateral circulation, as well as whether anterograde intervention for CTO target vessels was previously performed (OR = 0.875, 95% CI = 0.779-0.940, P= 0.026) and whether other vessels were intervened (OR = 22.372, 95% CI = 2.059-243.031, P= 0.011). CONCLUSION: Based on the present study, the success rate of retrograde approach for CTO was negatively correlated with the number of diseased vessels and collateral circulation. It was furthermore of importance whether anterograde intervention for CTO target vessels was previously performed and whether other vessels beside CTO vessels were intervened, which were also risk factors.

Optimal use of fielder XT guidewire enhances the success rate of chronic total occlusion percutaneous coronary intervention.

BACKGROUND: Chronic total occlusion (CTO) is found in 18-31% of patients who undergo coronary angiography. Successful recanalization of CTOs is associated with reduced recurrent angina pectoris rates and increased long-term survival. Although the success rate of CTO percutaneous coronary intervention (CTO-PCI) has improved, CTO-PCI remains technically challenging. The Fielder XT guidewire was designed for CTO lesions. To validate whether the use of the guidewire increases the success rate, we compared the results of CTO-PCI with or without the guidewire. We hypothesized that the use of Fielder XT guidewire can increase the success rate of CTO-PCI. AIM: To investigate whether the use of Fielder XT guidewire increases the final procedural success of CTO-PCI via the anterograde approach. METHODS: Between January 2013 and December 2015, a retrospective study was conducted on 1230 consecutive patients with CTO who received PCI via the anterograde approach at the General Hospital of Northern Theater Command. The patients were divided into an XT Group (n = 686) and a no-XT Group (n = 544) depending on whether Fielder XT guidewire was used. Both groups were compared for clinical parameters, lesion-related characteristics, procedural outcomes and in-hospital complications. The data were statistically analyzed using Pearson's χ 2 test for categorical variables, and Students' t test was used to compare the quantitative data. Significant independent factors and a risk ratio with 95% confidence interval (CI) were assessed by multivariate logistic regression analysis. RESULTS: In total, 1230 patients were recruited; 75.4% of the patients were male, and 55.8% of the patients were in the XT group. The overall success rate was 83.9%, with 87.8% in the XT group. Based on multivariate logistic regression analysis, factors positively associated with procedural success were the use of Fielder XT guidewire (P = 0.005, 95%CI: 1.172-2.380) and systolic blood pressure (P = 0.011, 95%CI: 1.003-1.022), while factors negatively associated with procedural success were blunt stump (P = 0.013, 95%CI: 1.341-11.862), male sex (P = 0.016, 95%CI: 0.363-0.902), New York Heart Association (NYHA) class (P = 0.035, 95%CI: 0.553-0.979), contrast amount (P = 0.018, 95%CI: 0.983-0.998) and occlusion time (P = 0.009, 95%CI: 0.994-0.999). No significant differences were found between the XT group and the no-XT group with respect to clinical parameters, lesion-related characteristics, coronary artery rupture [3 (0.4%) vs 8 (1.5%), P = 0.056], in-hospital death [2 (0.3%) vs 6 (1.1%), P = 0.079] or in-hospital target lesion revascularization [3 (0.4%) vs 7 (1.3%), P < 0.099]. However, there were significant differences between the groups with respect to success rate [602 (87.8%) vs 430 (79.0%), P < 0.001], procedure time [(74 ± 23) vs (83 ± 21), P < 0.001], stent length [(32.0 ± 15.8) vs (37.3 ± 17.6), P < 0.001], contrast amount [(148 ± 46) vs (166 ± 43), P < 0.001], post-PCI myocardial infarction [43 (6.3%) vs 59 (10.8%), P = 0.004], major adverse cardiovascular event [44 (6.4%) vs 57 (10.7%), P = 0.007], side branch loss [31 (4.5%) vs 44 (8.1%), P = 0.009], contrast-induced nephropathy [29 (4.2%) vs 40 (7.4%), P = 0.018] and no reflow [8 (1.2%) vs 14 (2.9%), P = 0.034]. CONCLUSION: The use of Fielder XT guidewire shortens the Procedure and increases the success rate of CTO-PCI, and is also associated with reduced complication rates.

Simultaneous determination of phenolic acids and diterpenoids and their comparative pharmacokinetic study in normal and acute blood stasis rats by UFLC-MS/MS after oral administration of Guan-Xin-Shu-Tong capsules.

Guan-Xin-Shu-Tong capsules are one of the well-known and first-line Chinese traditional herbal formula for treating coronary heart disease. A validated and sensitive method via ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) was established to simultaneously determinate five phenolic acids and four diterpenoids in rats in order to investigate their pharmacokinetic profiles firstly. Analytes were extracted by ethyl acetate and determined via multiple reaction monitoring mode in both positive and negative ion modes. The values for limit of quantification were in range of 0.025-1.250ng/ml. Inter- and intra-day precisions were no more than 10.9% with accuracy of -11.0%-10.6%, meanwhile the stable and suitable extraction recoveries were also obtained. And finally such excellent method was used to compare the pharmacokinetics of nine compounds in normal and acute blood stasis rats after oral administration of Guan-Xin-Shu-Tong capsules.

Comprehensive Identification of Guan-Xin-Shu-Tong Capsule via a Mass Defect and Fragment Filtering Approach by High Resolution Mass Spectrometry: In Vitro and In Vivo Study.

The Guan-Xin-Shu-Tong capsule (GXSTC) is a well-known traditional Chinese medicine that is used for the treatment of coronary heart disease. Despite its common use in China, basic pharmacological research on its active components is limited. A comprehensive analytical method using quadrupole-time-of-flight mass spectrometry (Q-TOF/MS), specifically with the Triple TOF 5600 platform, was developed to characterize the compounds in the GXSTC powder itself (in vitro) as well as the active components in healthy and heart disease model rats after its oral administration (in vivo). The 5600 platform was operated in both positive and negative ion modes, before the raw data were processed using the extracted ion chromatography (EIC), mass defect filtering (MDF) and fragment filtering (FF) techniques. With the aid of reference compounds for retention time and fragment ion comparisons, 18 compounds were unambiguously identified in vitro. An additional 56 other compounds were tentatively characterized using the accurate quasi-molecular ion mass and Tandem mass spectrometry (MS/MS) fragmentation pattern strategies. Among them, 30 compounds were characterized based on the MDF and FF approaches. Normal rats in addition to hyperlipidemic (HL) and acute blood stasis (ABS) model rats were given a single oral dose of GXSTC solution for subsequent blood analysis at 1 and 2 h after administration. A total of 24 prototypecomponents and 20 metabolites derived from GXSTC were differentially detected across the three animal groups, including the absence of four phase II phenolic acid metabolites in the ABS group and the presence of three diterpenoid-related metabolites exclusive to the HL group. The use of reference compounds as well as the mass defect and fragment-filtering strategies were critical to identify GXSTC compounds in vitro and in vivo. This can be used for further quality control and pharmacological studies aimed at characterizing the active and potential beneficial compounds of this ancient medicine.

Efficacy and safety of individually tailored antiplatelet therapy in patients with acute coronary syndrome after coronary stenting: a single center, randomized, feasibility study.

BACKGROUND: Low responsiveness to clopidogrel (LRC) is associated with increased risk of ischemic events. This study was aimed to explore the feasibility of tailored antiplatelet therapy according to the responsiveness to clopidogrel. METHODS: A total of 305 clopidogrel naïve patients with acute coronary syndromes (ACS) undergoing coronary stenting were randomly assigned to receive standard (n = 151) or tailored (n = 154) antiplatelet therapy. The ADP-induced platelet aggregation tests by light transmission aggregometry were performed to identify LRC patients assigned to the tailored group. The standard antiplatelet regimen was dual antiplatelet therapy with aspirin and clopidogrel. The tailored antiplatelet therapy was standard regimen for non-LRC patients and an additional 6-month cilostazol treatment for LRC patients. The primary efficacy outcome was the composite of cardiovascular death, myocardial infarction or stroke at one year. RESULTS: LCR was present in 26.6% (41/154) of patients in the tailored group. The percentage platelet aggregation for LCR patients was significantly decreased at three days after adjunctive cilostazol treatment (77.5% ± 12.1% vs. 64.5% ± 12.1%, P < 0.001). At one year follow-up, a non-significant 37% relative risk reduction of primary events were observed in the tailored group as compared to the standard group (5.8% vs. 9.3%, P = 0.257). There were no differences in the rates of stent thrombosis and hemorrhagic events between the two groups. CONCLUSIONS: Tailored antiplatelet therapy for ACS patients after coronary stenting according to responsiveness to clopidogrel is feasible. However, its efficacy and safety need further confirmation by clinical trials with larger sample sizes.

First-in-man study evaluating the safety and efficacy of a second generation biodegradable polymer sirolimus-eluting stent in the treatment of patients with de novo coronary lesions: clinical, Angiographic, and OCT outcomes of CREDIT-1.

OBJECTIVE: To evaluate the preliminary safety and efficacy of the EXCEL II stent system. BACKGROUND: Although the first biodegradable polymer drug-eluting stent (BP-DES), EXCEL, was launched nearly a decade ago, in-stent restenosis and stent thrombosis remain pertinent clinical problems in practice. A new cobalt-chromium BP-DES EXCEL II has been developed with the aim of improving stent safety and efficacy. METHODS: Forty-five patients with single de novo native coronary lesions were enrolled and randomized to two groups in a 2:1 ratio, the 4-month follow-up group (n = 30) and the 12-month follow-up group (n = 15). All patients underwent percutaneous coronary intervention (PCI) with the EXCEL II stent system. Quantitative coronary angiography (QCA) and optical coherence tomography (OCT) were used to assess coronary vasculature at the designated 4- or 12-month follow-up. The primary outcome was major adverse cardiac events (MACE) at 30 days post-PCI. RESULTS: No MACE, thrombotic events, or target lesion failure was found in the 45 patients during the 12-month follow-up. There was no significant difference (P > 0.05) between the two groups in terms of in-stent and in-segment late lumen loss (LLL). No in-stent and in-segment restenosis was found in either group. At follow-up, the ratio of >10% uncovered struts per lesion was 26.67% in the 4-month group and 0% in the 12-month group (P < 0.05). Neointimal coverage in the 12-month group was significantly better than in the 4-month group (98.58% vs. 93.51%, P < 0.01). CONCLUSIONS: This first-in-man study demonstrates promising feasibility, safety, and efficacy of EXCEL II stents. These stents were found to have rapid endothelialization and low LLL rates at 4 and 12 months after implantation.

Clinical presentations, antiplatelet strategies and prognosis of patients with stent thrombosis: an observational study of 140 patients.

BACKGROUND: Until now there has been scarce evidence regarding an optimal antiplatelet strategy and clinical outcomes for patients who had suffered from stent thrombosis (ST). METHODS AND RESULTS: 140 patients who suffered from stent thrombosis were prospectively registered. Patients received dual (aspirin and 150 mg clopidogrel, N = 66) or triple (additional cilostazol, N = 74) antiplatelet therapy at the physician's discretion. Thereafter platelet reactivity and one year clinical outcomes were analyzed. The primary outcome included the composite of cardiac death, non-fatal myocardial infarction (MI) or stroke at one year,which developed in 41 (29.3%) patients, consisting of 31 (22.1%) cardiac death, 9 (6.4%) non-fatal MI and 1 (1.4%) stroke. Recurrent definite and probable ST according to ARC definition was observed in 8 (5.7%) and 14 (10.0%) patients, respectively. Triple therapy was associated with significantly lower platelet reactivities (50.2 ± 17.8, % vs. 59.6 ± 17.2, %, P = 0.002) compared to high dose dual antiplatelet therapy. However, the incidence of primary events (24.3% vs. 34.8%, P = 0.172) did not differ between triple and dual antiplatelet therapies. High on-treatment platelet reactivity (HR: 8.35, 95% CI: 2.234∼30.867, P = 0.002) and diabetes (HR: 3.732, 95% CI: 1.353∼10.298, P = 0.011) were independent predictors of primary events. CONCLUSIONS: Patients who suffered from stent thrombosis have a poor prognosis even after revascularization with intensive antiplatelet therapy. Triple antiplatelet therapy was more effective in reducing on-treatment platelet reactivity, compared to high dose dual antiplatelet therapy.

Incidence and predictors of definite stent thrombosis after coronary stent implantation.

BACKGROUND: Coronary stents are widely used in percutaneous coronary intervention (PCI) procedures. We aimed to explore the incidence, predictors and characteristics of stent thrombosis (ST) after coronary stent implantation in routine clinical practice. METHODS: From data of 18 063 consecutive patients who underwent successful stent implantation in Shenyang Northern Hospital from 2004 to 2010, we identified patients with definite ST (n = 140) and control patients (n = 280) matched on age, diagnosis, sex, current antiplatelet medication and stent type. The incidence, predictors and characteristics of ST after coronary stent implantation were investigated. RESULTS: The incidence of angiographically confirmed ST was 0.78% (140/18 063). The time distribution of ST was acute in 43 (30.7%), subacute in 50 (35.7%), and late in 47 (33.6%) patients. Binary Logistic regression analysis identied the angiotensin-converting enzyme inhibitor (ACEI) (odds ratio (OR) = 0.472, 95%CI: 0.276 - 0.807, P = 0.006) and heparin (OR = 0.477, 95%CI: 0.278 - 0.819, P = 0.007) were associated with an reduced risk of cumulative ST. Stent length (OR = 1.042, 95%CI: 1.026 - 1.058, P < 0.001), serum creatinine total (OR = 1.020, 95%CI: 1.004 - 1.035, P = 0.04), cholesterol (OR = 1.267, 95%CI: 1.021 - 1.573, P = 0.032), glucose (OR = 1.086, 95%CI: 1.002 - 1.176, P = 0.044), and platelet aggregation (OR = 1.113, 95%CI: 1.075 - 1.154, P < 0.001) were associated with an increased risk of cumulative ST. CONCLUSION: ST is associated with longer stent length and higher level of total cholesterol, glucose and platelet aggregation.

[Effects of intensive antiplatelet therapy for patients with high on-treatment platelet reactivity after coronary stent implantation].

OBJECTIVE: To explore the effects of intensive antiplatelet therapy for patients with high on-treatment platelet reactivity (HPR) after coronary stent implantation. METHODS: Between March 2009 and February 2011, a total of 3316 consecutive acute coronary syndrome patients undergoing drug-eluting stent implanting from 3 hospitals were enrolled. Among them, 840 patients (25.3%) were identified as HPR (defined as 20 µmol/L adenosine diphosphate induced platelet aggregation of ≥ 55% at 24 hours after administration of 300 mg clopidogrel loading dose and 300 mg aspirin). The HPR patients were randomly assigned to receive standard (aspirin 300 mg/d and clopidogrel 75 mg/d, n = 280) or intensified (n = 560) antiplatelet therapy by the ratio of 1:2. Patients in the intensive group were initially treated with a double maintenance dose of clopidogrel (150 mg/d) and aspirin (300 mg/d). After 3 days, patients with unsolved HPR received additional cilostazol treatment (50 - 100 mg, bid). The reversion rate of HPR and clinical events were observed. RESULTS: In the intensive group, HPR reversed in 304 out of 560 patients (54.3%) at 3 days post therapy and the remaining 256 patients with HPR were treated with additional cilostazol regimen for another 3 days and the total reversion rate of HPR was 81.1% (454/560). The reversion rate of HPR at 30 days in the intensified group was significantly higher than that of the standard group (69.9% vs. 55.7%, P = 0.000). At 30 days after percutaneous coronary intervention, 1 patient suffered from subacute stent thrombosis (0.2%) in intensified group and no stent thrombosis was observed in standard group (P = 1.000). There were no death, major or minor bleeding in both two groups. Minimal bleeding was also similar in the two groups (intensive: 4.28% vs. standard: 2.14%, P = 0.166). CONCLUSIONS: The intensified antiplatelet therapy regimens could significantly increase the reversion rate of HPR in acute coronary syndrome patients undergoing coronary stenting without increasing the risk of bleeding. The clinic impact of this strategy needs to be elucidated by long term follow-up outcome studies.

Comparison of drug-eluting stents with bare metal stents implantation for the treatment of acute ST-elevation myocardial infarction: 2-year clinical outcomes from single-center registry.

BACKGROUND: Some larger scale, randomized studies have demonstrated the superiority of drug-eluting stents (DES) over bare metal stents (BMS) for the treatment of acute myocardial infarction (AMI). This study aimed to investigate the impact of DES, in comparison with BMS, on the 2-year clinical outcomes in patients with ST-elevation myocardial infarction (STEMI). METHODS: From January 2002 to December 2008, a total of 1301 consecutive STEMI patients treated with coronary stenting in Shenyang Northern Hospital were prospectively registered. Patients received BMS (n = 868) or DES (n = 435) implantation in the infarction related artery according to physician's discretion. A propensity score analysis was performed and two well matched subgroups were selected (BMS, n = 288; DES, n = 288) to evaluate the 2-year clinical outcomes. The primary outcome was the occurrence of major adverse cardiac events (MACE), which was defined as a composite of all-cause death, myocardial infarction (MI), or target vessel revascularization (TVR). RESULTS: Survival salvage analysis showed that 2-year cumulative hazards were not significantly different between the two groups with respect to TVR (2.8% vs. 3.1%, log-rank P = 0.780), stent thrombosis (1.7% vs. 4.2%, log-rank P = 0.079) and MACE (8% vs. 10.8%, log-rank P = 0.236). Multivariate analysis showed that DES was an independent protective factor of MI (HR: 0.211, 95%CI: 0.049 to 0.908) and stent thrombosis (HR: 0.327, 95%CI: 0.107 to 0.994). CONCLUSION: DES was associated with similar 2-year clinical outcomes to those of BMS for the treatment of STEMI in daily practice.