Prolonged dual antiplatelet therapy after drug-eluting stent implantation improves long-term prognosis for acute coronary syndrome:five-year results from a large cohort study

BACKGROUND:To investigate the most appropriate dual antiplatelet therapy(DAPT)duration for patients with acute coronary syndrome(ACS)after drug-eluting stent(DES)implantation in the largest cardiovascular center of China.METHODS:We enrolled 5,187 consecutive patients with ACS who received DES from January to December 2013.Patients were divided into four groups based on DAPT duration:standard DAPT group(11-13 months,n=1,568)and prolonged DAPT groups(13-18 months[n=308],18-24 months[n=2,125],and>24 months[n=1,186]).Baseline characteristics and 5-year clinical outcomes were recorded.RESULTS:Baseline characteristics were similar across the four groups.Among the four groups,those with prolonged DAPT(18-24 months)had the lowest incidence of major adverse cardiovascular and cerebrovascular events(MACCEs)(14.1%vs.11.7%vs.9.6%vs.24.2%,P<0.001),all-cause death(4.8%vs.3.9%vs.2.1%vs.2.6%,P<0.001),cardiac death(3.1%vs.2.6%vs.1.4%vs.1.9%,P=0.004),and myocardial infarction(MI)(3.8%vs.4.2%vs.2.5%vs.5.8%,P<0.001).The incidence of bleeding was not different among the four groups(9.9%vs.9.4%vs.11.0%vs.9.4%,P=0.449).Cox multivariable analysis showed that prolonged DAPT(18-24 months)was an independent protective factor for MACCEs(hazard ratio[HR]0.802,95%confidence interval[CI]0.729-0.882,P<0.001),all-cause death(HR 0.660,95%CI 0.547-0.795,P<0.001),cardiac death(HR 0.663,95%CI 0.526-0.835,P<0.001),MI(HR 0.796,95%CI 0.662-0.957,P=0.015),and target vessel revascularization(HR 0.867,95%CI 0.755-0.996,P=0.044).Subgroup analysis for high bleeding risk showed that prolonged DAPT remained an independent protective factor for all-cause death and MACCEs.CONCLUSION:For patients with ACS after DES,appropriately prolonging the DAPT duration may be associated with a reduced risk of adverse ischemic events without increasing the bleeding risk.

Association of α_(2A)-Adrenergic Receptor Genetic Variants with Platelet Reactivity in Chinese Patients on Dual Antiplatelet Therapy Undergoing Percutaneous Coronary Intervention

Objective The alpha 2A-adrenergic receptor gene （ADRA2A） polymorphism in individuals antiplatelet response to sympathetic stimulation. The aim of this study was to investigate ADRA2A variants on platelet reactivity in Chinese patients on dual antiplatelet therapy undergoing percutaneous coronary intervention （PCI）. modifies the the effect of （DAPT） after Methods From March 2011 to March 2013, 1,024 patients were enrolled in this prospective, single-center, observational study in China. Four single nucleotide polymorphisms （SNPs） of ADRA2A gene （rs11195419, rs3750625, rs13306146, and rs553668） and CYP2C19^＊2 were detected by ligase detection reaction （LDR）, and adenosine diphosphate （ADP） inhibition was detected by thromboelastography （TEG）. Results The minor allele frequencies of ADRA2A SNPs were common. Platelet ADP inhibition was significantly different among patients carrying rs11195419 （adjusted P = 0.022） and rs3750625 （adjusted P = 0.016）. The homozygous allele carriers had the lowest ADP inhibition. However, ADP inhibition was not significantly different in rs553668 and rs13306146. At the multivariate analysis, rs11195419 （P = 0.033）, rs3750625 （P = 0.020） and CYP2C19＂2 （P = 0.002） were independent predictors of ADP inhibition. Subgroups analysis based on sex showed rs11195419 （P = 0.003） and rs3750625 （P = 0.002） were significantly associated with ADP inhibition in males, but not in females. Conclusion ADRA2A genetic variations were associated with ADP-induced platelet aggregation during DAPT in Chinese patients undergoing PCI, and the effect was particularly more pronounced in males.

Shortened dual antiplatelet therapy in contemporary percutaneous coronary intervention era

Percutaneous coronary intervention with stenting is followed by a duration of dual antiplatelet therapy(DAPT)to reduce stent thrombosis and avoid target lesion failure.The period of DAPT recommended in international guidelines following drug-eluting stent implantation is 12 mo for most patients with acute coronary syndrome,and 6 mo for patients with chronic coronary syndrome or high bleeding risk.The new generation of drug-eluting stents have metallic platforms with thinner struts,associated with significantly less stent thrombosis.Shortened DAPT has been investigated with these stents,with evidence from randomised clinical trials for some individual stents showing non-inferior safety and efficacy outcomes.This has to be balanced by the effect of DAPT on secondary prevention of systemic cardiovascular disease especially in high-risk populations.This review will outline the current evidence for individual stents with regards to DAPT duration for both acute coronary syndrome and chronic coronary syndrome and discuss further directions for research and personalised medicine in this contemporary percutaneous coronary intervention era.

Efficacy of Dual Antiplatelet Therapy Combined with Naoxintong Capsules(脑心通胶囊) Following Coronary Microembolization Induced by Homologous Microthrombi in Rats

Objective： To evaluate the efficacy of dual antiplatelet therapy combined with Naoxintong Capsule （脑心通胶囊, NXTC） in a rat model of coronary microembolization （CME）. Methods： A total of 95 rats were randomly divided into 6 groups： control, sham-operation, CME model, NXTC, dual antiplatelet （clopidogrel and aspirin） intervention （DA）, and NXTC combined with DA （NDA） groups. The complete data in 69 rats were obtained. The number of CME, myocardial apoptosis rate, bleeding time, clotting time, and adensosine diphosphate （ADP）-induced platelet aggregation were assessed. Results： Compared with the CME group, the number of CME and myocardial apoptosis rates were significantly decreased in the NXTC, DA, and NDA groups （P〈0.01）. Compared with other intervention groups, the number of CME and myocardial apoptosis rates were the least in the NDA group （P〈0.01）, and the incidence of surgical bleeding was the highest in the DA group （P〈0.01）. Compared with the CME group, ADP-induced maximum platelet aggregation rate was significantly inhibited in the NXTC, DA, and NDA groups （P〈0.01）, both bleeding time and clotting time were significantly increased in the NXTC, DA, and NDA groups （P〈0.01）, while the above parameters were the highest in the DA group （P〈0.05）. Conclusion： The combination therapy of NXTC and DA enhanced the anti-CME effect of either therapy alone and reduced the risk of the DA therapy-associated bleeding, demonstrating an improved benefit/ risk ratio in the rat model of CME.

Shorter- versus Longer-duration Dual Antiplatelet Therapy in Patients with Diabetes Mellitus Undergoing Drug-eluting Stents Implantation： A Meta-analysis of Randomized Controlled Trials

Background： Patients with diabetes mellitus （DM） have a higher risk of thromboembolic events： however, the optimal duration of dual antiplatelet therapy （DAPT） remains unclear. The goal of this study was to assess the efficacy and safety of various DAPT durations in patients with DM undergoing drug-eluting stent implantation. Methods： We conducted a literature search for randomized controlled trials （RCTs）. We searched databases including EMBASE, PubMed, Cochrane Library, and Scopus up to June 2016. Investigators extracted data independently, including outcomes, characteristics, and study quality. A random-effect model was used to pool odds ratios （ORs） with 95% confidence intervals （C/s） of the clinical outcomes. Results： Six RCTs totaling 6040 patients with DM were included in the study. Shorter-duration DAPT resulted in an increased rate of stent thrombosis （ST） （OR, 1.83, 95% CI： 1.03-3.26, P = 0.04）, but did not increase the risk of myocardial inihrction （OR. 1.33, 95% CI： 0.71 2.47, P=0.37）, stroke （OR, 0.96, 95% CI： 0.52-1.77, P 0.90）, target vessel revascularization （OR, 1.19, 95% CI： 0.46-3.07, P = 0.71 ）, all-cause death （OR： 0.72, 95% CI： 0.48-1.09, P = 0.12）, or cardiac death （OR, 0.82, 95% CI： 0.49-1.36, P= 0.44） significantly. Shorter-duration DAPT was associated with a decreased risk of major bleeding （OR. 0.60, 95% CI： 0.38-0.94, P = 0.02）. Conclusion： In patients with DM, longer-duration DAPT had a lower risk of ST, but was associated with an increased bleeding risk.

Impact of prolonged dual antiplatelet therapy on patients after drug-eluting stents implantation

Background Impact of dual antiplatelet therapy beyond 12 months on patients implanted with DES remains unsolved.Methods From January 2010 to June 2011,1873 patients who have been taking DAPT and free from death,myocardial infarction,stroke,repeat coronary revascularization,stent thrombosis,and major or minor bleeding according to TIMI criteria for 12 months after implantation of DES were randomly assigned to continuous （prolonged DAPT group） or discontinuous （standard DAPT group） clopidogrel （75 mg/day）.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 180 days.Results There was no significant difference in the incidence of 180-day MACEs between prolonged DAPT group and standard DAPT group （8.98 % versus 10.13 %,respectively,P=0.400）.The frequency of major bleeding was 0.64 % in prolonged DAPT arm and 0.43% in standard DAPT arm （P=0.523）,that of minor bleeding was 3.32 % versus 2.87 % （P=0.585）,respectively.Conclusions Prolonged DAPT beyond 12 months neither improve prognosis nor increase risk of bleeding in patients implanted with DES.

Aspirin alone just as good as dual antiplatelet therapy beyond 12 months

Key points： At 2 years, aspirin alone provides similar protection against ischemic events as dual therapy in DES patients Findings maintained across multiple subgroups Less bleeding seen with aspirin alone at full 4-year follow-up By Jason Kahn Monday, March 11, 2013 SAN FRANCISCO, CA--Aspirin monotherapy results in similar rates of ischemic outcomes while decreas- ing bleeding compared with dual antiplatelet therapy beyond 12 months in stable patients who receive drug-e- luting stents （DES）. Results from the DES LATE trial were presented March 10, 2013, at the American Col- lege of Cardiology/i2 Scientific Session.

Efficacy and safety of different dual antiplatelet strategies in patients undergoing percutaneous coronary intervention:A systematic review and network meta-analysis

Background:Dual antiplatelet therapy(DAPT)is key for preventing ischaemic events post-percutaneous coronary intervention(PCI).Various DAPT modifications like the shortened duration or P2Y12 inhibitor(P2Y12i)de-escalation are implemented to reduce bleeding risk.However,these strategies lack direct comparative studies.This study aimed to assess the efficacy and safety of such DAPT strategies,including de-escalated and short DAPT,in patients undergoing PCI.Methods:We searched PubMed,Embase,Cochrane Central Register of Controlled Trials,and ClinicalTrials.gov databases for relevant randomized controlled trials(RCTs).We performed a network meta-analysis(NMA)to estimate risk ratios(RRs)and 95%confidence intervals(CIs).The primary efficacy endpoint was major adverse cardiac events(MACEs),and the primary safety endpoint was major bleeding.Secondary endpoints included individual components of MACEs and net adverse clinical events(NACEs).Results:A total of 17 RCTs comprising 53,156 patients(median age,62.0 years,24.8%female)were included.NMA suggested that de-escalation DAPT was associated with a significantly lower risk of MACEs(risk ratio[RR]=0.79,95%confidence interval[CI]=0.64-0.98),bleeding(RR=0.63,95%CI=0.49-0.82),and NACEs(RR=0.69,95%CI=0.60-0.79)compared with standard DAPT.Short DAPT followed by P2Y12i monotherapy exhibited a significantly decreased risk of major bleeding(RR=0.63,95%CI=0.46-0.86)compared with standard DAPT.Conclusions:De-escalation DAPT was the most effective strategy for preventing the risk of MACEs without increasing bleeding events,while short DAPT followed by P2Y12i monotherapy was the most effective strategy for reducing the risk of bleeding among patients undergoing PCI.

Efficacy and safety of triple-antiplatelet therapy after percutaneous coronary intervention： a meta-analysis

Background The combination of cilostazol, aspirin and clopidogrel （triple antiplatelet therapy, TAT） after a percutaneous coronary intervention has been used as an alternative therapy. We performed a meta-analysis to evaluate the efficacy and safety of TAT for patients after percutaneous coronary intervention （PCI）. Methods We systematically searched Pubmed, Embase and Web of Science databases to identify all randomized controlled trials （RCTs） that compared dual antiplatelet therapy （DAT） with and without cilostazol after PCI. All analyses were conducted using Review Manager 5.0. Results The final analysis consisted of 4474 patients from ten studies. The combined results suggested that there was a lower risk of cardiac death （relative risk （RR）=0.55, 95% confidence interval （Cl）： 0.31-0.98, P 〈0.05） and major adverse cardiac events （MACEs） （RR=0.63, 95% Cl： 0.54-0.74, P 〈0.05） in patients treated with TAT as compared to those with DAT follow-ups after six months to one year; no significant difference was observed in bleeding and non-fatal myocardial infarction （MI） （RR=1.14, 95% Cl： 0.80-1.64, P 〉0.055 RR=0.87, 95% Cl： 0.42-1.83, P 〉0.05）. However, the rate of adverse drug reaction was higher in patients receiving TAT than in patients receiving DAT （RR=2.21, 95% Cl： 1.84-2.66, P 〈0.05）. Moreover, there was a lower risk of stent thrombosis in patients treated with TAT as compared to those treated with DAT （RR=0.44, 95% Cl： 0.21-0.94, P 〈0.05）. The TAT group had a reduced risk of target lesion revascularization （TLR） （RR=0.60, 95% Cl： 0.43-0.82, P=-0.001） and target vessel revascularization （TVR） than the DAT group （RR=0.56, 95% Cl： 0.45-0.71, P 〈0.05）. The number of MACEs was lower for patients in the TAT group than in the DAT group with diabetes mellitus sub-analysis （RR=0.41, 95% Cl： 0.28-0.61, P 〈0.05）. But no significant difference was observed between the two groups regarding MACEs in patients with drug-eluting stent implantations （RR=0.82, 95% Cl： 0.65-1.03, P 〉0.05）. Conclusion TAT could significantly reduce the rates of MACEs and cardiac death in comparison to DAT, but more attention should be paid to adverse side effects of the drugs.

Restenosis of a drug eluting stent on the previous bioresorbable vascular scaffold successfully treated with a drug-coated balloon: A case report

BACKGROUND The in-stent restenosis(ISR)rates are reportedly inconsistent despite the increased use of second-generation drug eluting stent(DES).Although bioresorbable vascular scaffold(BVS)have substantial advantages with respect to vascular restoration,the rate of scaffold thrombosis is higher with BVS than with DES.Optimal treatment strategies have not been established for DES-ISR to date.CASE SUMMARY We report on a case of a 60-year-old man patient with acute coronary syndrome.He had a history of ST-segment elevation myocardial infarction associated with very late scaffold thrombosis and treated with a DES.Coronary angiography revealed significant stenosis,suggesting DES-ISR on the previous BVS.Optical coherence tomography(OCT)identified a plaque rupture and a disrupted scaffold strut in the neointimal proliferation of DES.To treat the DES-ISR on the previous BVS,we opted for a drug-coated balloon(DCB)after a balloon angioplasty using a semi-compliant and non-compliant balloon.The patient did not experience adverse cardiovascular events on using a DCB following the use of intensive dual antiplatelet therapy and statin for 24 mo.CONCLUSION This case highlights the importance of OCT as an imaging modality for characterizing the mechanism of target lesion failure.The use of a DCB following the administration of optimal pharmacologic therapy may be an optimal strategy for the treatment and prevention of recurrent BVS thrombosis and DES-ISR.

Drug-coated balloons are not inferior to drug-coated stents in the treatment of acute myocardial infarction and shorten the duration of dual antiplatelet treatment

Background:Drug-coated balloons(DCBs)are an up-and-coming tactic in treating in-stent restenosis and coronary artery small vessel disease,but their efficacy in treating acute myocardial infarction needs to be further explored.Methods:A meta-analysis of 7 studies was conducted to make a comparison with the results of DCB and drug-eluting stent implantation after a median follow-up of 15 months.Results:A total of 922 patients were included in this analysis in total,including 375 patients in the DCB group and 547 patients in the stent group.A total of 962 vascular diseases were manifested in the 2 groups.After 6 to 24 months of follow-up,there was no statistically significant difference with respect to major adverse cardiovascular events(odds ratio[OR]:0.82;95%confidence interval[CI]:0.52–1.29;Z=0.85;P=0.39),cardiac death(OR:0.92;95%CI:0.39–2.12;Z=0.21;P=0.84),target lesion revascularization(OR:1.09;95%CI:0.53–2.25;Z=0.24;P=0.81),late lumen loss(MD:−0.05;95%CI:−0.15 to 0.06;Z=0.85;P=0.40),or dual antiplatelet therapy(DAPT)(OR:1.04;95%CI:0.53–2.05;Z=0.11;P=0.91)between the 2 groups.In the DCB group,persistent residual stenosis or C-F dissection occurrence necessitated that a total of 30 patients receive extra bailout implantations.The rate of bailout stenting was 11.8%(95%CI:7.1–16).Moreover,the DCB group had a shorter DAPT duration compared with the stent group.Conclusion:Drug-coated balloons with shorter DAPT durations may be as effective and safe as stent therapy in treating acute myocardial infarction.

Antiplatelet and myocardial protective effect of Shexiang Tongxin Dropping Pill in patients undergoing percutaneous coronary intervention:A randomized controlled trial

Background:High on-clopidogrel platelet reactivity could be partially explained by loss-of-function alleles of CYP2 C19,the enzyme that converts clopidogrel into its active form.Shexiang Tongxin Dropping Pill(STDP)is a traditional Chinese medicine to treat angina pectoris.STDP has been shown to improve blood flow in patients with slow coronary flow and attenuate atherosclerosis in apolipoprotein E-deficient mice.However,whether STDP can affect platelet function remains unknown.Objective:The purpose of this study is to examine the potential effects of STDP on platelet function in patients undergoing percutaneous coronary intervention(PCI)for unstable angina.The interaction between the effects of STDP with polymorphisms of CYP2 C19 was also investigated.Design,participants and intervention:This was a single-center,randomized controlled trial in patients undergoing elective PCI for unstable angina.Eligible subjects were randomized to receive STDP(210 mg per day)plus dual antiplatelet therapy(DAPT)with clopidogrel and aspirin or DAPT alone.Main outcome measures:The primary outcome was platelet function,reflected by adenosine diphosphate(ADP)-induced platelet aggregation and platelet microparticles(PMPs).The secondary outcomes were major adverse cardiovascular events(MACEs)including recurrent ischemia or myocardial infarction,repeat PCI and cardiac death;blood biomarkers for myocardial injury including creatine kinase-MB isoenzyme(CK-MB)and high-sensitive troponin I(hs Tn I);and biomarkers for inflammation including intercellular cell adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1),monocyte chemoattractant protein-1(MCP-1)and galectin-3.Results:A total of 118 subjects(mean age:[66.8±8.9]years;male:59.8%)were included into analysis:58 in the control group and 60 in the STDP group.CYP2 C19 genotype distribution was comparable between the 2 groups.In comparison to the control group,the STDP group had significantly lower CKMB(P<0.05)but similar hs Tn I(P>0.05)at 24 h after PCI,lower ICAM-1,VCAM-1,MCP-1 and galectin-3 at 3 months(all P<0.05)but not at 7 days after PCI(P>0.05).At 3 months,the STDP group had lower PMP number([42.9±37.3]vs.[67.8±53.1]counts/μL in the control group,P=0.05).Subgroup analysis showed that STDP increased percentage inhibition of ADP-induced platelet aggregation only in slow metabolizers(66.0%±20.8%in STDP group vs.36.0%±28.1%in the control group,P<0.05),but not in intermediate or fast metabolizers.The rate of MACEs during the 3-month follow-up did not differ between the two groups.Conclusion:STDP produced antiplatelet,anti-inflammatory and cardioprotective effects.Subgroup analysis indicated that STDP inhibited residual platelet reactivity in slow metabolizers only.

Structural and temporal dynamics analysis on drug-eluting stents: History, research hotspots and emerging trends

Purpose:This review aims to explore the history,research hotspots,and emerging trends of drug-eluting stents(DES)in the last two decades from the perspective of structural and temporal dynamics.Methods:Publications on DES were retrieved from WoSCC.The bibliometric tools including CiteSpace and HistCite were used to identify the historical features,the evolution of active topics,and emerging trends on the DES field.Results:In the last 20 years,the field of DES is still in the hot phase and there is a wide range of extensive scientific collaborations.In addition,active topics emerge in different periods,as evidenced by a total of 41 disciplines,511 keywords,and 1377 papers with citation bursts.Keyword clustering anchored five emerging research subfields,namely#0 dual antiplatelet therapy,#3 drug-coated balloon,#4 bifurcation,5#rotational atherectomy,and 6#quantitative flow ratio.The keyword alluvial map shows that the most persistent research concepts in this field are thrombosis,restenosis,etc.,and the emerging keywords are paclitaxel eluting balloon,coated balloon,drug-eluting balloon,etc.There are 7 recent research subfields anchored by reference clustering,namely#2 dual antiplatelet therapy,#4 drug-coated balloon,#5 peripheral artery disease,#8 fractional flow reserve,#10 bioresorbable vascular scaffold,#13 intravascular ultrasound,#14 biodegradable polymer.Conclusion:The findings based on the bibliometric studies provide the current status and trends in DES research and may help researchers to identify hot topics and explore new research directions in this field.

Evaluation of CRUSADE and ACUITY-HORIZONS Scores for Predicting Long-term Out-of-Hospital Bleeding after Percutaneous Coronary Interventions

Background：There is scanty evidence concerning the ability of Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines （CRUSADE） and Acute Catheterization and Urgent Intervention Triage Strategy and Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction （ACUITY-HORIZONS） scores to predict out-of-hospital bleeding risk after percutaneous coronary interventions （PCIs） with drug-eluting stents （DES） in patients receiving dual antiplatelet therapy.We aimed to assess and compare the long-term prognostic value of these scores regarding out-of-hospital bleeding risk in such patients.Methods：We performed a prospective observational study of 10,724 patients undergoing PCI between January and December 2013 in Fuwai Hospital,China.All patients were followed up for 2 years and evaluated through the Fuwai Hospital Follow-up Center.Major bleeding was defined as Types 2,3,and 5 according to Bleeding Academic Research Consortium Definition criteria.Results：During a 2-year follow-up,245 of 9782 patients （2.5%） had major bleeding （MB）.CRUSADE （21.00 [12.00,29.75] vs.18.00 [11.00,26.00],P 〈 0.001） and ACUITY-HORIZONS （9.00 [3.00,14.00] vs.6.00 [3.00,12.00],P 〈 0.001） risk scores were both significantly higher in the MB than non-MB groups.Both scores showed a moderate predictive value for MB in the whole study cohort （area under the receiver-operating characteristics curve [AUROC],0.565;95% confidence interval [CI],0.529-0.601,P =0.001;AUROC,0.566;95% CI,0.529-0.603,P 〈 0.001,respectively） and in the acute coronary syndrome （ACS） subgroup （AUROC：0.579,95% CI：0.531-）.627,P =0.001;AUROC,0.591;95% CI,0.544-0.638,P 〈 0.001,respectively）.However,neither score was a significant predictor in the non-ACS subgroup （P 〉 0.05）.The value of CRUSADE and ACUITY-HORIZONS scores did not differ significantly （P 〉 0.05） in the whole cohort,ACS subgroup,or non-ACS subgroup.Conclusions：CRUSADE and ACUITY-HORIZONS scores showed statistically significant but relatively limited long-term prognostic value for out-of-hospital MB after PCI with DES in a cohort of Chinese patients.The value of CRUSADE and ACUITY-HORIZONS scores did not differ significantly （P 〉 0.05） in the whole cohort,ACS subgroup,or non-ACS subgroup.

Recurrent myocardial infarctions with normal coronary arteries in a patient with atrial flutter: A case report

Coronary embolism secondary to atrial fibrillation can lead to myocardial infarction independently of atherosclerotic coronary arteries. We encountered a patient repeatedly tortured by atrial fibrillation who presented with recurrent myocardial infarctions with normal coronary anatomy and ischemic stroke. We were frustrated by repeated failures because of some probably inappropriate decisions.