Impact of concomitant use of proton pump inhibitors on anti-platelet therapy of clopidogrel in patients undergoing percutaneous coronary intervention

Background In clopidogrel-treated patients undergoing percutaneous coronary intervention （PCI）, the effect of concomitant use of PPIs on prognosis remains unclear. Methods From July 2010 to June 2012, 600 patients after implantation of drug-eluting stent （DES） were assigned to 3 groups according to the medical therapy： group 1 （n = 200） received dural antiplatelet therapy （DAPT） alone （aspirine 100 mg daily plus clopidogrel 75 mg daily）, group 2（n = 199） received DAFT plus pantoprazole 20 mg daily while group 3（n = 201） received DAFT plus omeprazole 20 mg daily for 1 year. The primary outcome was major adverse cardiovascular events （MACEs） which compose of death, nonfatal myocardial infarction （MI）, nonfatal stroke, target vessel revascularization （TVR） or stent thrombosis （ST） at 1 year. Platelet reactivity was evaluated for all patients before PCI and 1 year after PCI. Results There was no significant difference in the platelet reactivity among the 3 groups at 1-year follow-up（27.3% versus 29.9% versus 29.3%, respectively, P = 0.339）. Neither was there significant difference in the incidence of 1-year MACEs （13% versus 14.6% versus 12.4%, respectively, P = 0.809）. Conclusions Concomitant use of pantoprazole or omeprazole did not influence platelet reactivity or clinical events in patients receiving DAPT after implantation of DES.     

Cost‐effectiveness analysis of 30‐month vs 12‐month dual antiplatelet therapy with clopidogrel and aspirin after drug‐eluting stents in patients with acute coronary syndrome

Continuation of dual antiplatelet therapy (DAPT) beyond 1 year reduces late stent thrombosis and ischemic events after drug‐eluting stents (DES) but increases risk of bleeding. We hypothesized that extending DAPT from 12 months to 30 months in patients with acute coronary syndrome (ACS) after DES is cost‐effective. A lifelong decision‐analytic model was designed to simulate 2 antiplatelet strategies in event‐free ACS patients who had completed 12‐month DAPT after DES: aspirin monotherapy (75–162 mg daily) and continuation of DAPT (clopidogrel 75 mg daily plus aspirin 75–162 mg daily) for 18 months. Clinical event rates, direct medical costs, and quality‐adjusted life‐years (QALYs) gained were the primary outcomes from the US healthcare provider perspective. Base‐case results showed DAPT continuation gained higher QALYs (8.1769 vs 8.1582 QALYs) at lower cost (USD42 982 vs USD44 063). One‐way sensitivity analysis found that base‐case QALYs were sensitive to odds ratio (OR) of cardiovascular death with DAPT continuation and base‐case cost was sensitive to OR of nonfatal stroke with DAPT continuation. DAPT continuation remained cost‐effective when the ORs of nonfatal stroke and cardiovascular death were below 1.241 and 1.188, respectively. In probabilistic sensitivity analysis, DAPT continuation was the preferred strategy in 74.75% of 10 000 Monte Carlo simulations at willingness‐to‐pay threshold of 50 000 USD/QALYs. Continuation of DAPT appears to be cost‐effective in ACS patients who were event‐free for 12‐month DAPT after DES. The cost‐effectiveness of DAPT for 30 months was highly subject to the OR of nonfatal stroke and OR of death with DAPT continuation.     

Meta-Analysis of the Efficacy and Safety of P2Y12 Inhibitor Monotherapy After Short Course of Dual-Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Intervention

BackgroundGuidelines recommend dual antiplatelet therapy (DAPT) following drug-eluting stent (DES) placement for ≥12 months in acute coronary syndrome or 6 months in stable coronary artery disease. However, with the advent of newer-generation stents, the optimal duration of DAPT to balance bleeding and thrombotic risks has been debated.ObjectivesWe aimed to perform a meta-analysis of randomized controlled trials (RCT) comparing P2Y₁₂ monotherapy in short-duration group (SDG) vs. standard treatment group (STG) course of DAPT in patients undergoing PCI.MethodsElectronic databases were searched for RCTs of patients undergoing percutaneous coronary intervention (PCI) with DES placement who received short (≤ 3 months) vs. standard DAPT course (≥12 months) and were followed for ≥12-months. Rates of major adverse cardiovascular events (a composite of cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke) were the primary outcome. Study-specific odds ratios (OR) and corresponding 95% confidence intervals were calculated using random-effects model.ResultsA total of 20,706 patients (10,344 in the SDG and 10,362 in the STG) were analysed from four studies. There was no significant difference observed for MACE (OR = 0.95, 95% CI: 0.81–1.08, P = .92, I² = 0%) myocardial infarction or stent thrombosis. However, lower rates of major bleeding were noted in the SDG (1.20 vs. 1.80%; OR: 0.61; 95% CI: 0.37–0.99; P = .04; I² = 71%) albeit with increased heterogeneity.ConclusionA short duration of DAPT followed by P2Y₁₂ inhibitor monotherapy was comparable to 12 months of DAPT with respect to MACE and thrombotic events, with lower rates of major bleeding events in select group of patients undergoing PCI. More data is needed to assess efficacy in patients with complex lesions and high risk ACS population including those with STEMI presentation.     

涂层可降解雷帕霉素洗脱支架术后6个月双联抗血小板治疗的长期疗效与安全性: CREATE研究4年随访结果分析

目的探讨涂层可降解雷帕霉素药物洗脱支架（DES）术后应用6个月双联抗血小板治疗（DAPT）的长期疗效和安全性。方法多中心、前瞻性CREATE研究中术后6个月随访时未发生主要不良心脏事件（MACE）的存活患者共2034例,全部接受Excel涂层可降解雷帕霉素DES治疗,其中1626例（79．9％）于术后6个月内停用氯吡格雷（DAPT≤6个月）,408例（20．1％）于6个月后继续服用氯吡格雷（DAPT〉6个月）。对比两组患者在6个月至4年随访期间的MACE和支架内血栓发生率。结果DAPT〉6个月者与≤6个月者相比,心性死亡（2．0％VS2．2％,P：0．753）、心肌梗死（0．2％VSO．4％,P=1．0）和靶病变血运重建（1．7％vs2．4％,P=0．407）发生率差异均无统计学意义。两组总的MACE发生率差异亦无统计学意义（3．7％VS3．4％,P=0．819）。两组总的血栓事件发生率分别为1．5％和0．7％,差异无统计学意义（P=0．128）。两组明确的及很可能的血栓累计发生率差异亦无统计学意义（0．7％VS0．5％,P=0．469）。多因素分析结果表明,陈旧性心肌梗死是支架内血栓的独立危险因素（OR=15-313,95％CI：4．02-58．25,P〈0．001）。DAPT疗程≤6个月与MACE（OR=0．987,95％CI=0．5451．787,P=0．965）及支架血栓事件发生率（OR=0．847,95％CI=0．2083．439,P=0．816）无显著相关性。结论4年临床随访结果表明,冠心病患者置入涂层可降解DES术后使用6个月DAPT安全、有效,但还需随机、对照研究进一步证实。     

Clinical Outcome of First‐ vs Second‐Generation DES According to DAPT Duration: Results of ARCTIC‐Generation

There is an apparent benefit with extension of dual antiplatelet therapy (DAPT) beyond 1 year after implantation of drug‐eluting stents (DES). Assessment by a Double Randomization of a Conventional Antiplatelet Strategy vs a Monitoring‐Guided Strategy for Drug‐Eluting Stent Implantation, and of Treatment Interruption vs Continuation One Year After Stenting (ARCTIC)‐Generation assessed whether there is a difference of outcome between first‐ vs second‐generation DES and if there is an interaction with DAPT duration in the ARCTIC‐Interruption study. ARCTIC‐Interruption randomly allocated 1259 patients 1 year after stent implantation to a strategy of interruption of DAPT (n = 624), in which aspirin antiplatelet treatment only was maintained, or DAPT continuation (n = 635) for 6 to 18 additional months. The primary endpoint was the composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization. A total of 520 and 722 patients received a first‐ and a second‐generation DES, respectively. After a median follow‐up of 17 months (interquartile range, 15–18 months) after randomization, the primary endpoint occurred in 32 (6.2%) and 19 (2.6%) patients with first‐ and second‐generation DES, respectively (hazard ratio: 2.31, 95% confidence interval: 1.31‐4.07, P = 0.004). This was observed irrespective of the strategy of interruption or continuation of DAPT and timing of study recruitment. Major bleeding events occurred in 4 (0.8%) and 3 patients (0.4%) with first‐ and second‐generation DES, respectively (hazard ratio: 1.79, 95% confidence interval: 0.40‐8.02, P = 0.44). Results did not change after multiple adjustments for potential confounding variables. ARCTIC‐Generation showed worse clinical outcome with first‐ vs second‐generation DES, a difference that appeared to persist even with prolonged DAPT.     

Long-term follow-up of drug-eluting stents when inserted for on- and off-label indications

This study reports long-term follow-up of the on- and off-label implantation of drug-eluting stents (DESs) in a retrospective study of 1,044 patients. Off-label implantation of DESs was performed for left main coronary artery lesions, bifurcation lesions, bare metal stent restenosis, ostial disease, chronic total occlusions, saphenous vein graft lesions, internal mammary artery graft lesions, left ventricular ejection fraction <30%, and acute myocardial infarction. End points examined were procedural complications, in-hospital myocardial infarction, and acute stent thrombosis; end points examined at follow-up were subacute stent thrombosis, late stent thrombosis, target vessel revascularization, myocardial infarction, death, and major adverse clinical events (MACEs; a composite of death, myocardial infarction, and target vessel revascularization). The study included 364 patients who received a DES on an on-label basis and 680 patients who received a DES on an off-label basis. Patient characteristics were not significantly different between the 2 groups, and there was no difference in procedural complications or acute stent thrombosis (on-label, 0%; off-label, 0.3%; p=0.55). There were no significant differences in subacute stent thrombosis (0% vs 0.6%, p=0.3), late stent thrombosis (1.4% vs 1.2%, p=0.78), death at follow-up (4.9% vs 4.1%, p=0.53), or myocardial infarction (1.9% vs 2.4%, p=0.83). Off-label DES implantation was associated with higher rates of target vessel revascularization (13.2% vs 24.1%, p=0.0001) and MACEs (17.6% vs 28.2%, p=0.0001). Multivariate analysis showed associations between target vessel revascularization and MACEs (respective p values) with bare metal stent restenosis (p=0.001 and p=0.001), diabetes mellitus (p=0.002 and p=0.001), and previous coronary artery bypass grafting (p=0.04 and p=0.01), but not off-label DES implantation (p=1.36 and p=1.16). In conclusion, DES use in the off-label situations studied was safe and was not associated with increased stent thrombosis, myocardial infarction, or death. Multivariate analysis showed that off-label DES implantation was not a risk factor for target vessel revascularization or MACEs.     

Safety and Efficacy of Ultra Short-duration Dual Antiplatelet Therapy After Percutaneous Coronary Interventions: A Meta-analysis of Randomized Controlled Trials

Dual antiplatelet therapy (DAPT) is required after percutaneous coronary intervention (PCI) to reduce stent thrombosis, but DAPT increases bleeding risks. The optimal duration of DAPT that provides the maximum protective ischemic effect along with the minimum bleeding risk is unclear. This is the first meta-analysis comparing outcomes for 1-month versus longer DAPT strategies following PCI.We searched PubMed, Cochrane, and ClinicalTrials.gov databases (from inception to October 2021) for randomized controlled trials that compared 1-month duration vs > 1-month duration of DAPT following PCI. We used a random-effects model to calculate risk ratio (RR) with 95% confidence interval (CI). The co-primary outcomes for study selection were all-cause mortality, major bleeding, and stent thrombosis. Secondary outcomes included myocardial infarction (MI), cardiovascular mortality, ischemic stroke and target vessel revascularization. A total of five randomized controlled trials were included [n = 29,355; 1-month DAPT(n = 14,662) vs > 1-month DAPT (n = 14,693)]. There was no statistically significant difference between the two groups in terms of all-cause mortality (RR 0.89; 95% CI 0.78-1.03; P = 0.12) and stent thrombosis (RR 1.07; 95% CI 0.80-1.43; P = 0.65). Similarly, there were no significant differences in MI, cardiovascular mortality, ischemic stroke, and target vessel revascularization. The rate of major bleeding was significantly lower in the group treated with DAPT for 1-month (RR 0.74; 95% CI 0.56-0.99, P = 0.04).There is no difference in all-cause mortality, cardiovascular mortality, MI, stent thrombosis, ischemic stroke, and target vessel revascularization with 1-month of DAPT following PCI with contemporary drug eluting stents compared to longer DAPT duration.     

Stent Thrombosis in Drug-Eluting or Bare-Metal Stents in Patients Receiving Dual Antiplatelet Therapy

ObjectivesThis study sought to compare rates of stent thrombosis and major adverse cardiac and cerebrovascular events (MACCE) (composite of death, myocardial infarction, or stroke) after coronary stenting with drug-eluting stents (DES) versus bare-metal stents (BMS) in patients who participated in the DAPT (Dual Antiplatelet Therapy) study, an international multicenter randomized trial comparing 30 versus 12 months of dual antiplatelet therapy in subjects undergoing coronary stenting with either DES or BMS.BackgroundDespite antirestenotic efficacy of coronary DES compared with BMS, the relative risk of stent thrombosis and adverse cardiovascular events is unclear. Many clinicians perceive BMS to be associated with fewer adverse ischemic events and to require shorter-duration dual antiplatelet therapy than DES.MethodsProspective propensity-matched analysis of subjects enrolled into a randomized trial of dual antiplatelet therapy duration was performed. DES- and BMS-treated subjects were propensity-score matched in a many-to-one fashion. The study design was observational for all subjects 0 to 12 months following stenting. A subset of eligible subjects without major ischemic or bleeding events were randomized at 12 months to continued thienopyridine versus placebo; all subjects were followed through 33 months.ResultsAmong 10,026 propensity-matched subjects, DES-treated subjects (n = 8,308) had a lower rate of stent thrombosis through 33 months compared with BMS-treated subjects (n = 1,718, 1.7% vs. 2.6%; weighted risk difference −1.1%, p = 0.01) and a noninferior rate of MACCE (11.4% vs. 13.2%, respectively, weighted risk difference −1.8%, p = 0.053, noninferiority p < 0.001).ConclusionsDES-treated subjects have long-term rates of stent thrombosis that are lower than BMS-treated subjects. (The Dual Antiplatelet Therapy Study [DAPT study]; NCT00977938)     

Optimal duration of dual antiplatelet therapy following treatment with the endeavor zotarolimus‐eluting stent in real‐world Japanese patients with coronary artery disease (OPERA): Study design and rationale

Background: In patients with coronary artery disease (CAD), there is an increasing therapeutic need among interventional cardiologists to conduct dual antiplatelet therapy (DAPT) whose duration is shorter than current guideline‐recommended 6–12 months after the implantation of drug‐eluting stents. However, no clinical grounds sufficient to rationalize the need are available. Objectives: To define the optimal duration of DAPT and to examine the safety and efficacy of the Endeavor zotarolimus‐eluting stent (E‐ZES) in real‐world Japanese patients with CAD. Study design: The present prospective, nonrandomized, multicenter, controlled study is uniquely designed to examine the analysis set to be formulated after integrating two different databases consisting of the following two study arms: the 3‐month DAPT arm, in which 1,210 patients were consecutively enrolled at 106 medical institutions; and the 12‐month DAPT arm, in which 1,210 patients will be consecutively extracted from the Endeavor Japan post‐marketing surveillance at 60 medical institutions. The primary endpoint is “net adverse cardiac and cerebrovascular events—death, myocardial infarction, cerebrovascular accident, and major bleeding)” at 12 months after implantation. The secondary endpoints are as follows: major adverse cardiac events at 1, 3, 6, 9, and 12 months after implantation; target vessel revascularization and target lesion revascularization at 9 and 12 months after implantation; and stent thrombosis, DAPT compliance, and bleeding events at 12 months after implantation. Noninferiority in the E‐ZES's profiles between the study arms will be investigated. Conclusions: The present study will provide insight into the optimal duration of DAPT after the E‐ZES implantation in individual, real‐world patients with CAD. © 2013 Wiley Periodicals, Inc.     

1-Month Dual-Antiplatelet Therapy Followed by Aspirin Monotherapy After Polymer-Free Drug-Coated Stent Implantation: One-Month DAPT Trial

ObjectivesThe aim of this study was to determine whether 1 month of dual-antiplatelet therapy (DAPT) followed by aspirin monotherapy after polymer-free drug-coated stent (PF-DCS) implantation is noninferior to 6 to 12 months of DAPT after biodegradable-polymer drug-eluting stent (BP-DES) implantation.BackgroundIt is necessary to determine the optimal minimal duration of DAPT followed by aspirin monotherapy after percutaneous coronary intervention (PCI).MethodsIn this trial, 3,020 patients with coronary artery disease considered for PCI for noncomplex lesions were randomized to 1-month DAPT after PF-DCS (n = 1,507) or 6- to 12-month DAPT after BP-DES (n = 1,513). The primary endpoint was the 1-year composite of cardiac death, nonfatal myocardial infarction, target vessel revascularization, stroke, or major bleeding (noninferiority hypothesis margin of 3%).ResultsThe primary endpoint occurred in 88 patients (5.9%) in the 1-month DAPT after PF-DCS group and 98 patients (6.5%) in the 6- to 12-month DAPT after BP-DES group (absolute difference −0.7%; upper limit of 1-sided 97.5% confidence interval: 1.33%; P < 0.001 for noninferiority). The occurrence of major bleeding was not different (1.7% vs 2.5%; P = 0.136). There was no difference in the occurrence of stent thrombosis (0.7% vs 0.8%; P = 0.842).ConclusionsAmong patients who underwent PCI for noncomplex lesions, 1-month DAPT followed by aspirin monotherapy after PF-DCS implantation was noninferior to 6- to 12-month DAPT after BP-DES implantation for the 1-year composite of cardiovascular events or major bleeding. The present findings need to be interpreted in the setting of different types of stents according to antiplatelet strategy. (A Randomized Controlled Comparison Between One Versus More Than Six Months of Dual Antiplatelet Therapy After Biolimus A9-Eluting Stent Implantation; NCT02513810)     

Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents

Background Dual antiplatelet therapy is recommended after coronary stenting to prevent thrombotic complications, yet the benefits and risks of treatment beyond 1 year are uncertain.Methods Patients were enrolled after they had undergone a coronary stent procedure in which a drug-eluting stent was placed. After 12 months of treatment with a thienopyridine drug(clopidogrel or prasugrel) and aspirin, patients were randomly assigned to continue receiving thienopyridine treatment or to receive placebo for another18 months; all patients continued receiving aspirin. The coprimary efficacy end points were stent thrombosis and major adverse cardiovascular and cerebrovascular events(a composite of death, myocardial infarction, or stroke) during the period from 12 to 30 months. The primary safety end point was moderate or severe bleeding.Results A total of 9961 patients were randomly assigned to continue thienopyridine treatment or to receive placebo.Continued treatment with thienopyridine, as compared with placebo, reduced the rates of stent thrombosis(0.4% vs. 1.4%; hazard ratio, 0.29 [95% confidence interval {CI}, 0.17 to 0.48]; P 0.001) and major adverse cardiovascular and cerebrovascular events(4.3% vs. 5.9%; hazard ratio, 0.71 [95% CI, 0.59 to 0.85];P 0.001). The rate of myocardial infarction was lower with thienopyridine treatment than with placebo(2.1% vs. 4.1%; hazard ratio, 0.47; P 0.001). The rate of death from any cause was 2.0% in the group that continued thienopyridine therapy and 1.5% in the placebo group(hazard ratio, 1.36 [95% CI, 1.00 to 1.85];P = 0.05). The rate of moderate or severe bleeding was increased with continued thienopyridine treatment(2.5% vs. 1.6%, P = 0.001). An elevated risk of stent thrombosis and myocardial infarction was observed in both groups during the 3 months after discontinuation of thienopyridine treatment.Conclusions Dual antiplatelet therapy beyond 1 year after placement of a drug-eluting stent, as compared with aspirin therapy alone, significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events but was associated with an increased risk of bleeding.(Funded by a consortium of eight device and drug manufacturers and others; DAPT Clinical Trials.gov number, NCT00977938.)(From: N Engl J Med 2014; 371:2155-2166 December 4, 2014DOI: 10.1056 / NEJMoa1409312)     

Comparison of three-year clinical outcomes with nonextended versus extended dual antiplatelet therapy between first- and second-generation drug-eluting stent implantation in patients with acute myocardial infarction: data from the infarct prognosis study registry

Background: The difference of the clinical outcomes between nonextended (≤12 months) and extended (>12 months) dual antiplatelet therapy (DAPT) remains unclear in patients with acute myocardial infarction (AMI) implanted by different generations of drug‐eluting stent (DES). Methods: We identified 790 consecutive patients with AMI who were free from major adverse cardiac events for 12 months after first‐generation (n = 537) or second‐generation DES (n = 253) implantation; each DES generation group was further divided into nonextended and extended DAPT. Results: During follow‐up (median: 40 months), nonextended DAPT in the first‐generation DES group showed a higher rate of cardiac death or MI than was observed in the extended DAPT group (14% vs 2%, P < 0.001). However, in the second‐generation DES group, there was no difference in the occurrence of cardiac death and MI between the extended and nonextended groups (4% vs 3%, P = 0.809). Nonextended DAPT was the most significant predictor of cardiac death and MI for first‐generation DES implantation [hazard ratio (HR) = 5.47, 95% confidence interval (CI) = 1.53–19.59, P = 0.009] but not for second‐generation DES implantation [HR = 3.21, 95% CI = 0.21–50.65, P = 0.401]. Conclusion: This study suggested that the clinical outcomes between nonextended and extended DAPT might be different depending on the generation of implanted DESs in patients with AMI. (J Interven Cardiol 2012;25:245–252)     

Optimal Duration of Dual Antiplatelet Therapy Following Percutaneous Coronary Intervention: An Umbrella Review

BackgroundThe optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention with stenting requires consideration of patient characteristics, and decision makers require a comprehensive overview of the evidence.MethodsWe performed an umbrella review of systematic reviews (SRs) of randomized controlled trials of extended DAPT (> 12 months) compared with DAPT for 6 to 12 months after percutaneous coronary intervention with stenting. Outcomes of interest were death, myocardial infarction (MI), stroke, stent thrombosis, major adverse cardiac and cerebrovascular events, bleeding, and urgent revascularization. We aimed to assess the evidence of benefits and harms among clinically important subgroups (eg, elderly patients, those with diabetes, prior MI, acute coronary syndrome). We assessed the quality of the included reviews by use of A Measurement Tool to Assess Systematic Reviews (AMSTAR).ResultsSixteen SRs involving 8 randomized controlled trials were included. Most scored 7 or more points on the AMSTAR checklist. There was no significant difference in outcomes with extended DAPT compared with 6 months of DAPT in most SRs, with the exception of an increased risk of major bleeding. Compared with 12 months, extended DAPT may reduce the risk of MI and stent thrombosis; however, the findings were not consistent across all reviews. There have been conflicting reports of an increased risk of death with extended DAPT. Few SRs assessed outcomes among patient subgroups.ConclusionsExtended DAPT may reduce the risk of MI and stent thrombosis but increase the risk of major bleeding and death. Whether the effects of extended DAPT are consistent across patient subgroups is unclear, and future SRs should address this knowledge gap.     

Impact of "off-label" utilization of drug-eluting stents on clinical outcomes in patients undergoing percutaneous coronary intervention

The utilization of drug-eluting stents (DES) in "real world" practice has deviated from Food and Drug Administration-approved indications. Safety concerns have arisen from recent reports that suggested increased mortality and nonfatal myocardial infarction (MI) with DES usage. Little is known about the clinical outcomes of patients undergoing intracoronary DES implantation for unapproved indications as a group compared with outcomes after bare metal stent (BMS) placement. The clinical outcomes of 546 patients undergoing DES implantation for >or=1 non-Food and Drug Administration-approved ("off label") indication since the approval of the device were assessed. The group was then matched by propensity score with 546 patients receiving BMSs prior to DES approval for the same indications. The primary endpoint was major adverse cardiac events (cardiac death, nonfatal Q-wave myocardial infarction [MI], and target vessel revascularization) at 12 months. Baseline clinical and angiographic characteristics were well matched between BMS and DES groups. The use of debulking devices was higher in the BMS group. Patients in the BMS group were more likely to be treated with larger diameter and shorter stents. There was no significant difference in the rate of in-hospital and 30-day adverse cardiac events. At 12 months, the primary endpoint of major adverse cardiac events was significantly reduced in the DES group (23.6% vs 16.7%, p=0.004), driven by reductions in the need for repeat revascularization (target lesion revascularization: 16.4% vs 7.8%, p<0.001; target vessel revascularization: 20.2% vs 13.1%, p=0.003). There was no significant difference in freedom from cardiac death or nonfatal Q-wave MI between groups (p=0.27). In conclusion, the utilization of DES for non-Food and Drug Administration-approved indications proved to be efficacious and safe when compared with a BMS cohort matched by propensity score. The advantage for DES was driven by reductions in repeat revascularization. "Off-label" DES use was not associated with increased rates of cardiac death and nonfatal MI at 12 months.     

替格瑞洛在补救PCI患者中的疗效及安全性

目的 观察替格瑞洛在溶栓失败后补救性经皮冠状动脉介入治疗（PCI）患者中的疗效及安全性。方法 入选2013~2014年因急性ST段抬高型心肌梗死（STEMI）的溶栓失败后12 h内于我院行补救PCI的患者246例。随机将符合条件的患者分为替格瑞洛组（n=121）和氯吡格雷组（n=125）,替格瑞洛组术前给予替格瑞洛180 mg,术后90 mg bid联合阿司匹林100 mg qd;氯吡格雷组术前给予氯吡格雷300 mg,术后75 mg qd联合阿司匹林100 mg qd。采用TIMI血流分级（TFG）、校正的TIMI记帧（CTFC）和TIMI心肌灌注分级（TMPG）评价比较两组术后心肌灌注水平。随访12月比较两组患者的主要不良心脑血管事件（MACCE）的发生率和出血事件及其它不良事件的发生率。结果 两组心肌灌注水平差异无统计学意义。替格瑞洛组与氯吡格雷组相比MACCE复合终点累计发生率降低,差异具有统计学意义（6.6% vs. 15.2% HR=0.395,95%CI:0.166-0.940,P<0.05）。两组总体主要出血、主要致命/危及生命的出血事件发生率差异无统计学意义。结论 替格瑞洛在溶栓失败后补救PCI患者中同样安全有效。     

Comparison of benefit and safety between different loading dose of clopidogrel on elderly patients undergoing primary percutaneous cronary intervention for ST-segment elevation myocardial infarction

Background Despite the proven benefit of 600-mg loading dose of clopidogrel in patients with acute ST-segment elevation myocardial infarction (STEMI) who undergo primary percutaneous cronary intervention (PCI), there is still concern about its benefit and safety on elderly population. Methods Data of 172 consecutive elderly patients (≥75 years) with STEMI who underwent primary PCI at Guangdong Provincial Cardiovascular Institute from January 2008 to December 2011 were retrospectively collected. Patients were divided into 600-mg loading clopidogrel group and 300-mg clopidogrel group accoring to the loading dose of clopidogrel before primary percunaeous coronary intervention(PCI). Enzymatic myocardial infarction size estimated by peak creatine kinase-myocardial band (CK-MB) and patency of the infarct-related artery (IRA) were compared. Thirty-day major adverse cardiac events (MACEs), which consist of death, nonfatal myocardial infarction (MI), nonfatal stroke, target vessel revascularization (TVR) or stent thrombosis (ST) were compared to assess the efficacy of different loading dose. Bleeding information was compared as well to assess the safety of different pretreatment stragety before primary PCI. Results 96 patients were adminstered with 600-mg loading clopidogrel before primary PCI while 76 were administered with 300-mg. Patency of the IRA was significantly higher in patients administered with 600-mg loading clopidogrel therapy as compared with those who received 300-mg loading clopidogrel (94.8% vs. 85.5%, P = 0.038). 600-mg loading dose of clopidogrel was associated with lower incidence of 30-day MACEs compared with 300-mg loading dose of clopidogrel (8.3% vs. 19.7%, P = 0.029) while did not increase the risk of TIMI major (3.1% vs. 3.9%, P = 0.770) and minor bleeding (10.4% vs. 6.6%, P = 0.376). Conclusion 600-mg loading clopidogrel improves final patency of the IRA and clinical outcome as compared with 300-mg loading clopidogrel without increasing bleeding hazard.     

Procedural results and outcomes after extensive stent coverage with drug-eluting stent implantation in single coronary lesions

Longer stent length has remained associated with the incidence of major adverse cardiac events (MACEs) in the drug-eluting stent (DES) era; therefore, we aimed to determine clinical outcomes after extensive stent coverage with DES implantations in single coronary lesions. We evaluated the data from 99 consecutive patients treated with extensive DES coverage, defined as > or = 50 mm (mean 63.3 +/- 13.2, range 50 to 115), and a concurrent series of 466 patients with < or = 24-mm DES length (mean 18.4 +/- 3.8, range 8 to 24). The periprocedural, 1-, and 6-month outcomes were compared between the 2 groups. The baseline characteristics were mostly comparable between the 2 groups, and procedural and in-hospital outcomes were similar. Although the incidence of death and myocardial infarction at follow-up were comparable, the combined end points of target lesion revascularization plus MACEs at 6 months occurred more often with extensive stent coverage. Multivariate analysis revealed stent length to be the only independent predictor of target lesion revascularization plus MACEs. Patients treated with extensive DES coverage had similar procedural success, major in-hospital complications, and death and myocardial infarction at follow-up, but had more combined adverse events because of an overall higher target lesion revascularization rate.     

24- and 6-month dual antiplatelet therapy after coronary stenting did not differ for clinical outcomes

QUESTION What is the relative efficacy of dual antiplatelet therapy (DAPT) given for 24 months compared with 6 months after coronary stent implantation? METHODS DESIGN Randomized controlled trial (RCT) (Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study [PRODIGY]). ClinicalTrials.gov NCT00611286. ALLOCATION Unclear allocation concealment.* BLINDING Blinded* (event adjudication committee). FOLLOW-UP PERIOD 2 years. SETTING 3 referral centers in Italy. PATIENTS 1970 patients ≥?18 years of age (mean age 68 y, 77% men) who had chronic, stable coronary artery disease or an acute coronary syndrome; ≥?1 lesion with ≥?50% diameter stenosis in a vessel ≥?2.25 mm in diameter that was suitable for coronary stent implantation; and elective, urgent, or emergent coronary angioplasty with 1 of 4 randomly assigned types of stent (bare metal or everolimus-, paclitaxel-, or zotarolimus-eluting) 30 days before DAPT randomization. Exclusion criteria included planned surgery within 24 months unless DAPT could be continued, major surgery within 15 days, history of bleeding diathesis, active bleeding or stroke in the past 6 months, expected need for oral anticoagulation therapy, pregnancy, or life expectancy <?24 months. INTERVENTION DAPT using oral clopidogrel, loading dose of 300 or 600 mg and then 75 mg/d, plus aspirin, loading dose of 160 to 325 mg orally or IV 500 mg and then 80 to 160 mg/d orally for 24 months (n =?987); or for 6 months followed by aspirin alone (n =?983). OUTCOMES Primary composite endpoint (all-cause mortality, nonfatal myocardial infarction, or cerebrovascular accident). Other outcomes included components of the composite endpoint, stent thrombosis, and bleeding. 1700 patients were needed to detect a 40% relative reduction in the primary endpoint at 2 years from 8% in the 6-month group (80% power, 2-sided α =?0.05). PATIENT FOLLOW-UP 99.6% (intention-to-treat analysis). MAIN RESULTS The main results are in the Table. CONCLUSION 24-month dual antiplatelet therapy after stent implantation increased bleeding and did not improve a composite of mortality, myocardial infarction, and cerebrovascular accident more than 6-month therapy.24 mo vs 6 mo of dual antiplatelet therapy after coronary stent implantation?Outcomes24-mo treatment6-mo treatmentAt 2 yRRI (95% CI)NNH (CI)Primary composite?10.1%10.0%2% (-27 to 25)Not significantBleeding§7.4%3.5%53% (30 to 68)26 (20 to 45)RRR (CI)NNT (CI)Definite or probable stent thrombosis1.3%1.5%15% (-45 to 139)Not significant?Abbreviations defined in Glossary. RRI, RRR, NNH, and CI calculated from hazard ratios and event rates in article.?All-cause mortality (6.6% vs 6.6%, P =?0.98), myocardial infarction (4.0% vs 4.2%, P =?0.80), and cerebrovascular accident (2.1% vs 1.4%, P =?0.17).§Bleeding Academic Research Consortium classification type 5, 3, or 2.     

Prognostic implications of early and long-term bleeding events in patients on one-year dual antiplatelet therapy following drug-eluting stent implantation

Background : Bleeding has emerged as a predictor of early and late mortality after percutaneous coronary interventions. However, the prevalence and predictors of long‐term bleeding events in patients on prolonged dual antiplatelet therapy (DAPT) after drug‐eluting stent (DES) implantation has been poorly explored. Methods : A total of 1,437 patients undergoing DES implantation discharged on DAPT with aspirin and clopidogrel for 1 year were studied. Patients were followed for up to 4 years (34.3 ± 14.4 months) and the prevalence and predictors of in‐hospital and long‐term thrombolysis in myocardial infarction (TIMI) major and minor bleeding events evaluated. The impact of bleeding events on major adverse cardiac events (MACE), overall death, and stent thrombosis (ST) was also assessed. Results : The incidences of 30 days major and minor bleeding were 1.3 and 3.3%, respectively. The incidences of 1‐year major and minor bleeding were 3.0 and 5.6%, respectively. The incidences of major and minor bleeding up to 4‐year follow‐up were 3.6 and 6.9%, respectively. At multivariable analysis, 1‐year major bleeding was positively predicted by use of oral anticoagulants at hospital discharge [odds ratio (OR) = 13.4, 95% confidence interval (CI) 3.0–59.2, P = 0.001], anemia at admission (OR = 6.7, 95% CI = 2.7–16.5, P < 0.001) and use of glycoprotein IIb/IIIa inhibitors (OR = 2.7, 95% CI = 1.1–6.5, P = 0.03) and negatively predicted by male gender (OR = 0.39, 95% CI = 0.16–0.97, P = 0.042). Overall, major bleeding at 1 year and at long‐term follow‐up was associated with an increased risk of MACE, cardiac death and ST. Patients who had any bleeding event were more likely to prematurely discontinue antiplatelet therapy (50% vs. 9.6%, P < 0.001). Conclusions : In DES‐treated patients on prolonged DAPT, major bleeding occurring at 1 year and up to 4 years following DES implantation in patients on prolonged DAPT is associated with poor long‐term prognosis. © 2012 Wiley Periodicals, Inc.     

Drug-eluting stent thrombosis during perioperative period

Recently, the number of patients in whom a drug-eluting stent (DES) has recently been implanted and who need to undergo surgery or the most invasive procedure is increasing. However, there are limited data about the risk of perioperative thrombosis of DES. We evaluated the incidence and the risk factors of DES thrombosis during the perioperative period. Between January 2002 and December 2006, 141 patients who underwent surgery requiring discontinuation of a dual antiplatelet agent within 12 months of DES implantation were enrolled in one of the 3 study hospitals. We reviewed the clinical and procedural characteristics of the patients who developed stent thrombosis during the perioperative period. Stent thrombosis occurred in 7 cases (5.0%). The clinical outcomes of the patients with stent thrombosis were death in 5 cases and nonfatal MI in 2 cases. The patients with stent thrombosis were found to be older (64.2 +/- 9.7 versus 71.7 +/- 6.0 years, P = 0.045), to use a Taxus stent more frequently (36.6 versus 85.7%, P = 0.014), and to have a more prolonged period of discontinuation of clopidogrel (12.7 +/- 10.0 versus 51.3 +/- 33.2 days, P = 0.022) than the patients without stent thrombosis. Multivariate analysis revealed that 7 days or longer discontinuation of clopidogrel (OR 12.8, 95% CI 1.3-121.6, P = 0.021) and the use of a Taxus stent (OR 10.2, 95% CI 1.1-95.7, P = 0.043) were significant independent predictors of stent thrombosis during the perioperative period. A prolonged period of discontinuation of clopidogrel was associated with higher risk of stent thrombosis during the perioperative period. An earnest effort to continue antiplatelet therapy throughout the perioperative period can minimize the risk of stent thrombosis.