Difference In Stent Thrombosis Research Articles

Preclinical Direct Endoluminal Assessment of Endothelialization After Flow Diversion With Microangioscopy

BACKGROUND Direct endoluminal imaging, such as with our previously described microangioscope, is an emerging adjunct in endovascular cerebral aneurysm management that enables clinicians to delineate between thrombi and visualize neoepithelialization after stent placement with high resolution. The present study sought to study flow diversion in vivo under direct endoluminal imaging, and to validate our findings with histopathology. METHODS In a rabbit model, we implanted each left common carotid artery with a shielded flow diverter (FD) (Medtronic Pipeline Vantage) and nonshielded FD (Medtronic Pipeline Flex) in the right common carotid artery. We studied 9 animals in 3 groups: (1) no periprocedural antiplatelet therapy, (2) aspirin 81 mg daily, and (3) aspirin 81 mg and clopidogrel 75 mg daily. FD thrombosis, stenosis, malapposition, and neoepithelialization were all evaluated by diagnostic cerebral angiography and microangioscopy after 30 days. Diagnostic cerebral angiography and angioscopic video were analyzed by independent evaluators and compared with histopathologic analysis. RESULTS In the aspirin and dual antiplatelet therapy groups, there were no significant observed differences in stent thrombosis, stenosis, malapposition, or neoepithelialization between the shielded and non‐shielded FD groups. There was significantly more thrombus formation in Group 1. Neointimal thickness as measured by the microangioscope was highly correlated with histology (r = 0.72; P = 0.016). Interrater agreement of microangioscope videos was highest for FD thrombosis and stenosis. CONCLUSION In‐stent thrombosis, stenosis, malapposition, and neopithelialization demonstrated no significant difference between shielded and non‐shielded FDs. Microangioscopy measurements for neointimal thickness were highly correlated with pathology and may be a helpful adjunct to diagnostic cerebral angiography in FD follow‐up.

158 Preclinical Direct Endoluminal Assessment of Endothelialization After Flow Diversion With Microangioscopy

INTRODUCTION: Endoluminal imaging (ELI) is an emerging adjunct in endovascular cerebral aneurysm management. Indirect ELI, as with optical coherence tomography, may be useful in detecting malapposition after flow diversion (FD). Direct ELI technologies, such as with our previous described microangioscope, have been shown to be able to delineate between different thrombi and visualize neoepithelialization after stent placement with high resolution. METHODS: In a rabbit model we implanted each left common carotid artery (CCA) with a shielded FD (Medtronic Pipeline Vantage) and non-shielded FD (Medtronic Pipeline Flex) in the right CCA. We studied 9 animals in 3 groups: 1) no periprocedural antiplatelet therapy, 2) aspirin 81 mg daily, 3) aspirin 81 mg and clopidogrel 75 mg daily. FD thrombosis, stenosis, malapposition, and neoepithelialization were all evaluated by diagnostic cerebral angiography (DSA) and microangioscopy after 30 days. DSA and angioscopic video were analyzed by independent evaluators and compared with histopathologic analysis. RESULTS: In the aspirin and DAPT groups, there were no significant observed differences in stent thrombosis, stenosis, malapposition, or neoepithelialization between the shielded and non-shielded FDs in each rabbit as measured by histologic analysis. There was significantly more thrombus formation in Group 1. Neointimal thickness as measured by the microangioscope was highly correlated with histology (r = 0.72, p = 0.016). Inter-rater agreement of microangioscope videos was highest for FD thrombosis and stenosis. CONCLUSIONS: There were no significant differences between in-stent thrombosis, stenosis, malapposition, or neopithelialization between shielded and non-shielded FDs. Microangioscopy measurements for neointimal thickness were highly correlated with pathology, and thus may be a helpful adjunct to DSA in FD follow-up.

A Bayesian meta-analysis of double kissing (DK) crush or provisional stenting for coronary artery bifurcation lesions

ObjectiveDespite the development of dedicated, two-stent strategies, including the double kissing (DK) crush technique, the ideal technique for coronary artery bifurcation stenting has not been identified. We aimed to compare and determine the absolute risk difference (ARD) of the DK crush technique alone versus provisional stenting approaches for coronary bifurcation lesions, using the Bayesian technique. MethodWe queried PubMed/MEDLINE to identify randomized controlled trials (RCTs) that compared DK crush technique with provisional stenting for bifurcation lesions, published till January 2023. We used Bayesian methods to calculate the ARD and 95% credible interval (CrI). ResultsWe included three RCTs, with 916 patients, in the final analysis. The ARD of cardiac death was centered at −0.01 (95% CrI: −0.04 to 0.02; Tau: 0.02, 85% probability of ARD of DK crush vs. provisional stenting <0). ARD for myocardial infarction was centered at −0.03 (95%CrI: −0.9 to 0.03; Tau: 0.05, 87% probability of ARD of DK crush vs. provisional stenting <0). ARD for stent thrombosis was centered at 0.00 (95% CrI: −0.04 to 0.03, Tau: 0.03, 51% probability of ARD for DK crush vs. provisional stenting <0). Finally, ARD for target lesion revascularization was centered at −0.05 (95% CrI: −0.08 to −0.03, Tau: 0.02, 99.97% probability of ARD for DK crush vs. provisional stenting <0). ConclusionsBayesian analysis demonstrated a lower probability of cardiac death, myocardial infarction and target lesion revascularization, with DK crush compared with provisional stenting techniques, and a minimal probability of difference in stent thrombosis.

Intracoronary Imaging Versus Coronary Angiography Guidance for Implantation of Second and Third Generation Drug Eluting Stents in a Systematic Review and Meta-Analysis of Randomized Controlled Trials

Intracoronary imaging (ICI) facilitates stent implant by characterizing the lesion calcification, providing accurate vessel dimensions, and optimizing the stent results. We sought to investigate the outcomes of routine ICI versus coronary angiography (CA) to guide percutaneous coronary intervention (PCI) with second- and third-generation drug-eluting stents. A systematic search of PubMed, Medline, and Cochrane databases was conducted from their inception to July 16, 2022 for randomized controlled trials comparing routine ICI with CA. The primary outcome was major adverse cardiovascular events. The secondary outcomes of interest were target lesion revascularization, target vessel revascularization, myocardial infarction, stent thrombosis, and cardiac and all-cause mortality. A random-effects model was used to calculate the pooled incidence and relative risk (RR) with 95% confidence intervals (CIs). A total of 9 randomized controlled trials with 5,879 patients (2,870 ICI-guided and 3,009 CA-guided PCI) met the inclusion criteria. The ICI and CA groups were similar in demographic characteristics and co-morbidity profiles. Compared with CA, patients in the routine ICI-guided PCI group had lower rates of major adverse cardiovascular events (RR 0.61, 95% CI 0.48 to 0.78, p <0.0001), target lesion revascularization (RR 0.60, 95% CI 0.43 to 0.83, p=0.002), target vessel revascularization (RR 0.72, 95% CI 0.51 to 1.00, p=0.05), and myocardial infarction (RR 0.48, 95% CI 0.25 to 0.95, p=0.03). There were no significant differences in stent thrombosis or cardiac/all-cause mortality between the 2 strategies. In conclusion, routine ICI-guided PCI strategy, compared with CA guidance alone, is associated with improved clinical outcomes, largely driven by lower repeat revascularization.

One-Year COMBO Stent Outcomes in Acute Coronary Syndrome: from the COMBO Collaboration.

The COMBO biodegradable polymer sirolimus-eluting stent includes endothelial progenitor cell capture (EPC) technology for rapid endothelialization, which may offer advantage in acute coronary syndromes (ACS). We sought to analyze the performance of the COMBO stent by ACS status and ACS subtype. The COMBO collaboration (n = 3614) is a patient-level pooled dataset from the MASCOT and REMEDEE registries. We evaluated outcomes by ACS status, and ACS subtype in patients with ST segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) versus unstable angina (UA). The primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization. Secondary outcomes included stent thrombosis (ST). We compared 1965 (54%) ACS and 1649 (46.0%) non-ACS patients. ACS presentations included 40% (n = 789) STEMI, 31% (n = 600) NSTEMI, and 29% (n = 576) UA patients. Risk of 1-year TLF was greater in ACS patients (4.5% vs. 3.3%, HR 1.51 95% CI 1.01-2.25, p = 0.045) without significant differences in definite/probable ST (1.1% vs 0.5%, HR 2.40, 95% CI 0.91-6.31, p = 0.08). One-year TLF was similar in STEMI, NSTEMI, and UA (4.8% vs 4.8% vs. 3.7%, p = 0.60), but definite/probable ST was higher in STEMI patients (1.9% vs 0.5% vs 0.7%, p = 0.03). Adjusted outcomes were not different in MI versus UA patients. Despite the novel EPC capture technology, COMBO stent PCI was associated with somewhat greater risk of 1-year TLF in ACS than in non-ACS patients, without significant differences in stent thrombosis. No differences were observed in 1-year TLF among ACS subtypes.

Short dual antiplatelet therapy followed by P2Y12 inhibitor monotherapy vs. prolonged dual antiplatelet therapy after percutaneous coronary intervention with second-generation drug-eluting stents: a systematic review and meta-analysis of randomized clinical trials.

After percutaneous coronary intervention (PCI) with second-generation drug-eluting stent (DES), whether short dual antiplatelet therapy (DAPT) followed by single antiplatelet therapy (SAPT) with a P2Y12 receptor inhibitor confers benefits compared with prolonged DAPT is unclear. Multiple electronic databases, including PubMed, Scopus, Web of Sciences, Ovid, and ScienceDirect, were searched to identify randomized clinical trials comparing ≤3 months of DAPT followed by P2Y12 inhibitor SAPT vs. 12 months of DAPT after PCI with second-generation DES implantation. The primary and co-primary outcomes of interest were major bleeding and stent thrombosis 1 year after randomization. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by fixed-effect and random-effects models. Multiple sensitivity analyses including random-effects models 95% CI adjustment were applied. A sensitivity analysis comparing trials using P2Y12 inhibitor SAPT with those using aspirin SAPT was performed. A total of five randomized clinical trials (32145 patients) were available. Major bleeding was significantly lower in the patients assigned to short DAPT followed by P2Y12 inhibitor SAPT compared with those assigned to 12-month DAPT (random-effects model: HR 0.63, 95% 0.45-0.86). No significant differences between groups were observed in terms of stent thrombosis (random-effects model: HR 1.19, 95% CI 0.86-1.65) and the secondary endpoints of all-cause death (random-effects model: HR 0.85, 95% CI 0.70-1.03), myocardial infarction (random-effects model: HR 1.05, 95% CI 0.89-1.23), and stroke (random-effects model: HR 1.08, 95% CI 0.68-1.74). Sensitivity analyses showed overall consistent results. By comparing trials testing ≤3 months of DAPT followed by P2Y12 inhibitor SAPT vs. 12 months of DAPT with trials testing ≤3 months of DAPT followed by aspirin SAPT vs. 12-month of DAPT, there was no treatment-by-subgroup interaction for each endpoint. By combining all these trials, regardless of the type of SAPT, short DAPT was associated with lower major bleeding (random-effects model: HR 0.63, 95% CI 0.48-0.83) and no differences in stent thrombosis, all-cause death, myocardial infarction, and stroke were observed between regimens. After second-generation DES implantation, 1-3 months of DAPT followed by P2Y12 inhibitor SAPT is associated with lower major bleeding and similar stent thrombosis, all-cause death, myocardial infarction, and stroke compared with prolonged DAPT. Whether P2Y12 inhibitor SAPT is preferable to aspirin SAPT needs further investigation.

1-Year COMBO stent outcomes stratified by the PARIS bleeding prediction score: From the MASCOT registry.

BackgroundThe COMBO stent is a biodegradable-polymer sirolimus-eluting stent with endothelial progenitor cell capture technology for faster endothelialization.ObjectiveWe analyzed COMBO stent outcomes in relation to bleeding risk using the PARIS bleeding score.MethodsMASCOT was an international registry of all-comers undergoing attempted COMBO stent implantation. We stratified patients as low bleeding-risk (LBR) for PARIS score ≤ 3 and intermediate-to-high (IHBR) for score > 3 based on baseline age, body mass index, anemia, current smoking, chronic kidney disease and need for triple therapy. Primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, myocardial infarction (MI) not clearly attributed to a non-target vessel or clinically-driven target lesion revascularization (TLR). Bleeding was adjudicated using the Bleeding Academic Research Consortium (BARC) definition. Dual antiplatelet therapy (DAPT) cessation was independently adjudicated.ResultsThe study included 56% (n = 1270) LBR and 44% (n = 1009) IHBR patients. Incidence of 1-year TLF was higher in IHBR patients (4.1% vs. 2.6%, p = 0.047) driven by cardiac death (1.7% vs. 0.7%, p = 0.029) with similar rates of MI (1.8% vs. 1.1%, p = 0.17), TLR (1.5% vs. 1.6%, p = 0.89) and definite/ probable stent thrombosis (1.2% vs. 0.6%, p = 0.16). Incidence of 1-year major BARC 3 or 5 bleeding was significantly higher in IHBR patients (2.3% vs. 0.9%, p = 0.0094), as was the incidence of DAPT cessation (29.3% vs. 22.8%, p < 0.01), driven by physician-guided discontinuation.ConclusionsPatients with intermediate-to-high PARIS bleeding risk in the MASCOT registry experienced greater incidence of 1-year TLF, major bleeding and DAPT cessation than LBR patients, without significant differences in stent thrombosis.

Antithrombotic regimens for percutaneous coronary intervention of the left main coronary artery: The EXCEL trial.

We compared the effect of bivalirudin or heparin and use or nonuse of glycoprotein IIb/IIIa inhibitors (GPI) on the outcome of left main coronary artery (LMCA) percutaneous coronary intervention (PCI) in the randomized EXCEL trial. The optimal antithrombotic regimen to support PCI of the LMCA remains controversial because of low representation of this subset in clinical trials. The PCI cohort (n = 928) in EXCEL was divided according to bivalirudin versus heparin antithrombin treatment and compared for the primary composite endpoint of death, myocardial infarction (MI), or stroke at 30 days and 5 years. Bivalirudin was used in 319 patients (34.4%). The composite endpoint at 30 days occurred in 7.2% versus 3.8% bivalirudin and heparin patients, respectively, p = .02; at 5 years, the composite endpoint occurred in 26.3% versus 19.9% bivalirudin and heparin patients, respectively, p = .02. Major bleeding was more frequent in bivalirudin patients (4.1% versus 1.3%, p = .008). There were no differences in stent thrombosis between the groups. Bivalirudin use was an independent predictor of the 30-day composite endpoint (OR 2.88, 95% CI 1.28-6.48, p = .01) but not of the 5-year composite endpoint (OR 1.30, 95% CI 0.84-2.02, p = .23). GPI use was infrequent (n = 67, 7.2%) and was not associated with adverse outcomes. Among patients undergoing LMCA PCI in the EXCEL trial, procedural use of bivalirudin was associated with greater rates of periprocedural MI and the 30-day composite endpoint without reducing bleeding complications. Five-year outcomes were similar. GPIs were used infrequently and were not associated with clinical outcomes.

NOAC-Based Sual Therapy Versus Warfarin-Based Triple Therapy After Percutaneous Coronary Intervention or Acute Coronary Syndrome in Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis

BackgroundSeveral randomized clinical trials (RCTs) have compared the use of dual therapy (DT), or one of the non-vitamin K antagonist oral anticoagulants (NOAC) with a P2Y12 agent, versus triple therapy (TT), consisting of a vitamin-K antagonist (VKA) along with dual antiplatelet therapy, in patients with concomitant atrial fibrillation after percutaneous coronary intervention (PCI) or acute coronary syndrome (ACS). We performed a meta-analysis and systematic review of RCTs to evaluate the safety and efficacy of NOAC-based DT in such patients. MethodsThe major efficacy outcome was major adverse cardiovascular and cerebrovascular events (MACCE), defined as a composite of mortality, myocardial infarction, stroke, stent thrombosis (ST), and urgent revascularization. The International Society on Thrombosis and Hemostasis (ISTH) major or clinically relevant non-major bleeding (CRNM) was the major primary safety outcome. ResultsA total of 4 RCTs were included in the meta-analysis with 7942 total patients for analysis (DT: 4377 & TT: 3565). Compared to TT, DT resulted in similar risk of MACCE (OR: 1.12; 95% CI: 0.94–1.34; P = 0.20) and other efficacy endpoints with a trend in increased risk of ST in the DT group (1.55; 0.99–2.44; P = 0.06). DT resulted in lower risk of ISTH major or CRNM bleeding (0.56; 0.41–0.76; P < 0.01), and all other bleeding outcomes except for a trend of reduced risk of TIMI minor bleeding. ConclusionIn conclusion, patients with atrial fibrillation who undergo PCI or develop ACS, NOAC-based dual therapy reduces bleeding outcomes without significantly increasing ischemic outcomes. Future trials should explore the possible differences in stent thrombosis.

Meta-Analysis Comparing Double Versus Triple Antithrombotic Therapy in Patients With Atrial Fibrillation and Coronary Artery Disease

Atrial fibrillation (AF) and concomitant coronary artery disease (CAD) create a therapeutic dilemma as the risk of bleeding with triple antithrombotic therapy (TATT) must be balanced against the risk of ischemic events with double antithrombotic therapy (DATT). The aim of this meta-analysis is to compare the efficacy and safety of DATT versus TATT in AF and CAD. MEDLINE, Cochrane, and ClinicalTrials.gov databases were searched for relevant articles published from inception to May 1, 2019. Studies comparing the safety and efficacy of DATT versus TATT in patients with AF and CAD were included. Among 9 studies, where 6,104 patients received DATT and 7,333 patients received TATT, there was no statistically significant difference in the outcomes of mortality, nonfatal myocardial infarction, stent thrombosis, and stroke. There was a lower rate of major bleeding in DATT (risk ratio [RR] 0.64 [95% confidence interval [CI] 0.54 to 0.75]; p <0.001). There was no significant difference in stent thrombosis (RR 1.52 [95% CI 0.97 to 2.38]; p = 0.07). However, subgroup analysis of trials with direct oral anticoagulant use demonstrated a borderline higher rate of stent thrombosis in DATT (RR 1.66 [95% CI 1.01 to 2.73]; p = 0.05). In conclusion, DATT showed no difference in the outcomes of mortality, stroke, nonfatal myocardial infarction, and stent thrombosis compared with TATT. DATT demonstrated a lower rate of major bleeding. DATT demonstrated a borderline higher rate of stent thrombosis in the subgroup analysis of trials with direct oral anticoagulant which needs to be evaluated in further studies.

Stent thrombosis associated with drug eluting stents on addition of cilostazol to the standard dual antiplatelet therapy following percutaneous coronary intervention: a systematic review and meta-analysis of published randomized controlled trials

BackgroundIn this analysis, we aimed to systematically compare stent thrombosis (ST) and its different subtypes following treatment with DAPT (aspirin + clopidogrel) versus TAPT (aspirin + clopidogrel + cilostazol).MethodsStudies were included if: they were randomized controlled trials (RCTs) comparing TAPT (cilostazol + aspirin + clopidogrel) with DAPT (aspirin + clopidogrel); they reported ST or its subtype including definite, probable, acute, sub-acute and late ST as their clinical outcomes. RevMan software (version 5.3) was used to carry out this analysis whereby odds ratios (OR) and 95% confidence intervals (CI) were generated.ResultsStatistical analysis of the data showed no significant difference in total ST with the addition of cilostazol to the standard DAPT with OR: 0.65, 95% CI: 0.38–1.10; P = 0.11, I2 = 6%. Moreover, when ST was further subdivided and analyzed, still, no significant difference was observed in acute, sub-acute, late, definite and probable ST with OR: 0.48, 95% CI: 0.13–1.74; P = 0.27, I2 = 0%, OR: 0.56, 95% CI: 0.22–1.40; P = 0.21, I2 = 0%, OR: 0.72, 95% CI: 0.23–2.28; P = 0.58, I2 = 0%, OR: 1.18, 95% CI: 0.38–3.69; P = 0.77, I2 = 3% and OR: 0.75, 95% CI: 0.17–3.55; P = 0.70, I2 = 0% respectively. No change was observed during a short term (≤ 6 months) and a longer (≥ 1 year) follow-up time period.ConclusionsThis current analysis showed no significant difference in stent thrombosis with the addition of cilostazol to the standard dual antiplatelet therapy during any follow-up time period after PCI.

Bivalirudin versus heparin in percutaneous coronary intervention-a systematic review and meta-analysis of randomized trials stratified by adjunctive glycoprotein IIb/IIIa strategy.

Bivalirudin has been shown to be associated with less major bleeding than heparin in patients undergoing percutaneous coronary intervention (PCI); but the confounding effect of concomitant glycoprotein IIb/IIIa inhibitors (GPI) limits meaningful comparison. We performed a systematic review and meta-analysis to compare bivalirudin to heparin, with and without adjunctive GPI in PCI. We searched PubMed, Cochrane, EMBASE, CINAHL and WOS from January 2000 to December 2017 for clinical trials comparing bivalirudin to heparin, with and without adjunctive GPI during PCI. Cochrane's Q statistics were used to determine heterogeneity. Random effects model was used. Twenty-six comparison groups (22 original studies and 4 subgroup analyses) with 53,364 patients were included. Mean follow-up was 192±303 days. There was no difference between the two groups in all-cause mortality [risk ratio (RR: 0.93; 95% CI: 0.82-1.05, P=0.260), target vessel revascularization (TVR) (RR: 1.17; 95% CI: 0.93-1.46, P=0.174) or stroke (RR: 0.91; 95% CI: 0.71-1.18, P=0.490). Major bleeding was lower in the bivalirudin group with concomitant GPI in one or both arms (RR: 0.64; 95% CI: 0.53-0.77, P<0.001) and without (RR: 0.71; 95% CI: 0.51-0.99, P=0.041) provisional or routine GPIs. Bivalirudin appeared to have a higher risk of stent thrombosis (RR: 1.32; 95% CI: 1.04-1.68, P=0.022) and a trend towards more myocardial infarction (RR: 1.12; 95% CI: 0.98-1.28, P=0.098) though without statistical significance. However, exclusion of studies with GPI showed no difference in stent thrombosis or myocardial infarction with bivalirudin. Bivalirudin is associated with less major bleeding compared to heparin, regardless of GPI use. The lower anticoagulant effect of bivalirudin is linked with higher stent thrombosis and a trend towards more MI, however a confounding effect of GPI use in the heparin arm cannot be excluded.

Long-Term Outcomes of Stenting the Proximal Left Anterior Descending Artery in the PROTECT Trial

ObjectivesThis study sought to compare the outcomes of patients undergoing drug-eluting stent implantation according to lesion location within or outside the proximal left anterior descending (LAD) artery. BackgroundProximal LAD artery involvement is considered uniquely in revascularization guidelines. The impact of LAD lesion location on long-term outcomes after revascularization is poorly understood in context of current percutaneous coronary intervention and medical therapy. MethodsAmong 8,709 patients enrolled in PROTECT (Patient Related Outcomes with Endeavor Versus Cypher Stenting Trial), a multicenter percutaneous coronary intervention trial, we compared the outcomes of 2,534 patients (29.1%) (3,871 lesions [31.5%]) with stents implanted in the proximal LAD to 6,172 patients (70.9%) (8,419 lesions [68.5%]) with stents implanted outside the proximal LAD. ResultsAt the 4-year follow-up, death rates were the same (5.8% vs. 5.8%; p > 0.999), but more myocardial infarctions occurred in the proximal LAD group (6.2% vs. 4.9%; p = 0.015). The rate of clinically driven target vessel failure (TVF) (14.8% vs. 13.5%; p = 0.109), major adverse cardiac event(s) (MACE) (15.0% vs. 13.7%; hazard ratio: 1.1; 95% confidence interval: 0.97 to 1.31; p = 0.139), and stent thrombosis (2.1% vs. 2.0%; p = 0.800) were similar. Drug-eluting stent type had no interaction with MACE or TVF. In multivariate analysis, the proximal LAD was a predictor of myocardial infarction (p = 0.038) but not of TVF (p = 0.149) or MACE (p = 0.069). ConclusionsIn this study of contemporary percutaneous coronary intervention, proximal LAD location was associated with higher rates of myocardial infarction during the long-term follow-up, but there were no differences in stent thrombosis, death, TVF, or overall MACE. This finding may suggest that, in the drug-eluting stent era, proximal LAD no longer confers a different prognosis than other lesion sites. (Randomized Study Comparing Endeavor With Cypher Stents [PROTECT]; NCT00476957)

Five-year outcomes of chronic total occlusion treatment with a biolimus A9-eluting biodegradable polymer stent versus a sirolimus-eluting permanent polymer stent in the LEADERS all-comers trial.

Few data are available on long-term follow-up of drug-eluting stents in the treatment of chronic total occlusion (CTO). The LEADERS CTO sub-study compared the long-term results in CTO and non-CTO lesions of a Biolimus A9™-eluting stent (BES) with a sirolimus-eluting stent (SES). Among 1,707 patients enrolled in the prospective, multi-center, all-comers LEADERS trial, 81 with CTOs were treated with either a BES (n = 45) or a SES (n = 36). The primary endpoint was the occurrence of major adverse cardiac events (MACE): cardiac death, myocardial infarction (MI) and clinically-indicated target vessel revascularization (TVR). At 5 years, the rate of MACE was numerically higher in the CTO group than in the non-CTO group (29.6% vs. 23.3%; p = 0.173), with a significant increase in the incidence of target lesion revascularization (TLR) (21.0 vs. 12.6; p = 0.033), but no difference in stent thrombosis (ST). Patients with CTO receiving a BES demonstrated a lower incidence of MACE (22.2% vs. 38.9%; p = 0.147) with a significant reduction in TLR compared to patients receiving a SES (11.1% vs. 33.3%, p = 0.0214) with an incidence similar to that observed in the non-CTO group treated with BES (11.6%). Definite ST at 5 years nearly halved in the BES group (4.4% vs. 8.3%, p = 0.478) with no ST in the BES group after the first year (0% vs. 8.3%, p for interaction = 0.009). The use of a BES showed a reduction in MACE, TVR, TLR, and ST over time in the CTO subset with similar outcome as for non-CTO lesions.

What is the Optimal Duration of Dual Antiplatelet Therapy After Stenting?

The optimal duration of dual antiplatelet therapy (DAPT) of aspirin and a P2Y12 receptor blocker after stenting is still being debated. The current recommendations for DAPT duration are significantly focused on reducing stent thrombosis; a less frequent event with later than earlier generation drug eluting stents (DES). A persistent occurrence of late and very late stent thrombosis with first generation DES supported extended use of DAPT beyond one year. However, recent studies have demonstrated that extended duration DAPT is associated with increased bleeding; an independent predictor for poor outcomes, including long-term mortality. Second-generation DES are associated with less late and very late stent thrombosis. Some recent studies have supported a shorter duration of DAPT for second generation DES. However, these studies were inadequately powered to assess significant differences in stent thrombosis. Furthermore, extended duration DAPT has been associated with a reduced risk of thrombotic events in non-culprit vessels in addition to stent thrombosis in patients with acute coronary syndromes (ACS). The higher risk of bleeding associated with extended DAPT therapy provides a strong rationale for personalized DAPT based on patient risk factors (e.g. ACS vs. non-ACS), type of stents, and cost-benefit analyses.

Five-year outcomes of ST-elevation myocardial infarction versus non-ST-elevation acute coronary syndrome treated with biodegradable polymer-coated sirolimus-eluting stents: Insights from the CREATE trial

BackgroundLong-term outcome of drug-eluting stents (DES) for ST-elevation myocardial infarction (STEMI) versus non-ST-elevation acute coronary syndrome (NSTE-ACS) remains unclear. This study sought to compare the long-term outcomes of biodegradable polymer-coated DES in patients with STEMI versus NSTE-ACS. MethodsWe explored a post hoc analysis of the 5-year outcome of the CREATE trial in the subgroup of patients with STEMI (n=318) versus NSTE-ACS (n=1223) who were implanted with biodegradable polymer-coated DES. The primary outcome was the rate of major adverse cardiac events (MACE) at 5 years. Clopidogrel and aspirin for 6 months followed by chronic aspirin therapy were recommended. ResultsSTEMI patients showed a trend of increase in MACE (8.7% vs. 6.8%, log rank p=0.289) compared to NSTE-ACS patients at 5 years, and a greater risk of cardiac death (5.4% vs. 2.1%, log rank p=0.003), mainly driven by the higher cardiac death rate within the first month after stent placement (log rank p=0.003) and the last year of follow-up (log rank p=0.001). No significant difference in stent thrombosis was found between them (3.1% vs. 2.5%, log rank p=0.653). Prolonged clopidogrel therapy (>6 months) showed no effect on risk of MACE or stent thrombosis between the two groups (both p for interaction >0.1). ConclusionsSTEMI patients have a higher risk of cardiac mortality compared with NSTE-ACS patients after biodegradable polymer-coated DES placement, primarily attribute to more cardiac deaths that happened within the first month after the event and the last year of follow-up.

Risk Factors and Clinical Impacts of Peri-Stent Contrast Staining After Second-Generation Drug-Eluting Stent Implantation.

Peri-stent contrast staining (PSS) after sirolimus-eluting stent implantation is associated with target lesion revascularization (TLR) and very late stent thrombosis. However, the risk factors and clinical sequelae of PSS after second-generation DES implantation remain unclear. This study comprised 2,090 patients with 2,883 lesions treated with second-generation DES from April 2009 to February 2013. Angiographic findings and clinical outcomes were compared between PSS and non-PSS groups. Follow-up angiography was available for 2,411 lesions. PSS was observed in 23 lesions: 4 in biolimus-eluting stents, 4 in zotarolimus-eluting stents (ZES), and 15 in everolimus-eluting stents (EES). Right coronary artery lesions, chronic total occlusion (CTO), and lesions with severe angulation (>90°) were more frequent in the PSS group compared with the non-PSS group. Lesions were longer and the cumulative TLR incidence at 3 years was higher in the PSS group than those in the non-PSS group (27.9 mm vs. 19.4 mm, P < 0.0001; 27.4% vs. 8.6%, P = 0.0002). There was no significant difference in stent thrombosis between the two groups. Multivariable analysis identified CTO [odds ratio (OR) 3.75, 95%CI 1.52-8.88, P = 0.005] as an independent predictor of PSS. PSS after second-generation DES implantation was associated with an increased risk of subsequent TLR. CTO was the independent predictor of PSS.

Comparing the effectiveness and safety between triple antiplatelet therapy and dual antiplatelet therapy in type 2 diabetes mellitus patients after coronary stents implantation: a systematic review and meta-analysis of randomized controlled trials.

BackgroundSince antiplatelet therapy in type 2 diabetes mellitus (T2DM) patients is very important after intracoronary stenting, and because the most commonly used therapies have been the dual antiplatelet therapy (DAPT) consisting of aspirin and clopidogrel and the triple antiplatelet therapy (TAPT) consisting of aspirin, clopidogrel and cilostazol, we aim to compare the effectiveness and safety between triple antiplatelet therapy and dual antiplatelet therapy in T2DM patients.MethodsSystematic literature search was done from the databases of PubMed, Cochrane, Embase, China National Knowledge Infrastructure (CNKI) and WanFang. Randomized controlled trials (RCTs) comparing the effectiveness and safety between triple therapy and dual therapy in T2DM patients after coronary stents placement were included. Endpoints included major adverse cardiac effects (MACEs), target lesion revascularization (TLR), target vessel revascularization (TVR), death, stent thrombosis, bleeding and adverse drug reactions during a 9–12 months period, as well as platelet activities.ResultsFour studies including 1005 patients reporting the adverse clinical outcomes and six studies including 519 patients reporting the platelet activities, with a total of 1524 patients have been analyzed in this meta-analysis. The pooling analysis shows that TAPT has significantly decreased the occurrence of MACEs (RR: 0.55; 95 % CI: 0.36–0.86, P = 0.009), TLR (RR 0.41; 95 % CI: 0.21–0.80, P = 0.008), TVR (RR 0.55; 95 % CI: 0.34–0.88, P = 0.01) and the overall incidence of Death/ Myocardial Infarction (MI)/TVR (RR 0.54; 95 % CI: 0.31–0.94, P = 0.03) during this 9 to 12 months follow up period after stents implantation. Stent thrombosis was almost similar in both groups. Bleeding seemed to favor DAPT but the result was not statistically significant. Platelet aggregation, platelet reactivity index (PRI) and platelet reactivity unit (PRU) were also reduced with Weight Mean Difference (WMD) of (−13.80; 95 % CI: −17.03 to −10.56, P < 0.00001), (−22.87; 95 % CI: −23.66 to −22.07, P < 0.00001) and (−44.17; 95 % CI: −58.56 to −29.77, P < 0.00001) respectively.ConclusionSince MACEs have been significantly decreased in the triple group, TAPT appears to be more effective than DAPT in T2DM patients after intracoronary stenting. No significant difference in stent thrombosis and bleeding risks between these 2 groups shows TAPT to be almost as safe as DAPT in these diabetic patients.

Safety of short-term dual antiplatelet therapy after drug-eluting stents: An updated meta-analysis with direct and adjusted indirect comparison of randomized control trials

BackgroundDuration of dual antiplatelet therapy (DAPT) following drug-eluting stents (DES) remains controversial and is a topic of ongoing research. MethodsDirect and adjusted indirect comparisons of all the recent randomized control trials (RCTs) were performed to evaluate the safety of short-term versus long-term DAPT following DES. Results8 RCTs were identified and 7 (16,318 subjects) were included. 4 groups of 3 vs 12months, 6 vs 12months, 6 vs 24months and 12 vs 24months of DAPT were used for direct comparison. There was no significant difference in stent thrombosis, myocardial infarction (MI), stroke and revascularization, cardiovascular and all-cause mortality between the different durations in all 4 groups. Pooling trials of 3–6months of DAPT against 12months, we found a significant reduction in the risk of total bleeding (RR 0.61, 95% CI 0.43–0.87). Adjusted indirect comparison between 3 vs 6months, 3 vs 24months and 6 vs 24month duration of DAPT showed no significant differences in risk of death or MI, or revascularization between 3 or 6months and 24months. However, 24months of DAPT was associated with significantly more bleeding than 3 or 6months. Conclusions3 to 6months of DAPT following second generation DES and above is safe with no increased risk of thrombotic complications and mortality, and lower bleeding risk. However a tailored approach may be more appropriate for high-risk patients.

6- Versus 24-Month Dual Antiplatelet Therapy After Implantation of Drug-Eluting Stents in Patients Nonresistant to Aspirin: The Randomized, Multicenter ITALIC Trial

BackgroundThe currently recommended duration of dual antiplatelet therapy (DAPT) in drug-eluting stent (DES) recipients is 12 months to reduce the risk of late stent thrombosis, particularly in those with acute coronary syndrome (ACS). ObjectivesThis study hypothesized that antiplatelet treatment with DAPT for 6 months may be noninferior to 24-month DAPT in aspirin-sensitive patients. MethodsA multicenter, randomized study assigned patients undergoing implantation of everolimus-eluting stents with confirmed nonresistance to aspirin to receive 6- or 24-month DAPT. The primary endpoint was a composite of death, myocardial infarction, urgent target vessel revascularization, stroke, and major bleeding at 12 months post-stenting. ResultsA total of 2,031 patients were enrolled in 70 European and Middle Eastern centers. The trial was prematurely terminated due to recruitment problems, leaving 941 patients randomized to 24-month DAPT and 953 to 6-month DAPT. The 2 treatment groups had similar baseline and procedural characteristics. There was no significant difference in the primary endpoint (24-month: 1.5% vs. 6-month: 1.6%; p = 0.85). Noninferiority was demonstrated for 6- versus 24-month DAPT, with an absolute risk difference of 0.11% (95% confidence interval: −1.04% to 1.26%; p for noninferiority = 0.0002). There were no significant differences in stent thrombosis or bleeding complications. In the 792 (44%) high-risk patients with ACS, primary and secondary endpoints did not significantly differ (hazard ratio: 1.7 [95% confidence interval: 0.519 to 6.057; p = 0.361]). ConclusionsRates of bleeding and thrombotic events were not significantly different according to 6- versus 24-month DAPT after PCI with new-generation DES in good aspirin responders. (Is There A LIfe for DES After Discontinuation of Clopidogrel [ITALICplus]; NCT01476020)