Ticagrelor monotherapy beyond 1 month versus standard dual antiplatelet therapy after drug-eluting coronary stenting: a pre-specified per-protocol analysis of the GLOBAL LEADERS trial

Abstract Background In the GLOBAL LEADERS trial, the intention-to-treat (ITT) effect of ticagrelor monotherapy after 1 month of dual antiplatelet therapy (DAPT) was not superior to that of 12-month DAPT followed by aspirin alone in the prevention of 2-year all-cause mortality or new Q-wave myocardial infarction (MI) after coronary stenting. Intention-to-treat analyses can be affected by incomplete protocol adherence. We present a pre-specified per-protocol analysis. Purpose To determine whether 1 month of ticagrelor plus aspirin followed by 23 months of ticagrelor monotherapy is superior to 12 months of DAPT followed by aspirin alone in the per-protocol population of the GLOBAL LEADERS (NCT01813435). Methods The GLOBAL LEADERS compared two antiplatelet strategies after drug-eluting stenting for stable coronary artery disease or acute coronary syndromes. Per-protocol population consisted of randomized patients fulfilling enrollment criteria and receiving protocol-mandated treatment. Adherence to the allocated antiplatelet therapy was evaluated at discharge, 30 days, and 3, 6, 12, 18, and 24 months, with non-adherence reasons categorized following a hierarchical approach. A protocol-deviation was defined in the case of high perceived bleeding/thrombotic risk, a medical decision without evident clinical reason, patients unwilling to take study drugs, prescription error, logistical issues, unclear reasons. Baseline characteristics, including (but not limited to) age, sex, diabetes, prior PCI, were used to construct time-varying inverse probabilities for not deviation from the protocol to reconstruct a study population with no protocol-deviations. Protocol deviators were artificially censored at the time at which they deviated. The primary endpoint was the composite of 2-year all-cause mortality or non-fatal new Q-wave MI. We used a weighted pooled logistic regression to estimate the per-protocol rate ratio (RR) of experimental vs. control treatment for the primary endpoint. Results Of the 15,968 randomized patients, 805 out of 7,980 (10.1%) in experimental group and 537 out of 7,988 (6.7%) in control group were classified as protocol deviators and artificially censored by month 12, not contributing events in the second year. The events for the adherence-adjusted analysis were 279 in experimental group and 325 in control group (25 and 24 less than in ITT analysis, respectively). The estimated adherence-adjusted RR was 0.87 (95% CI: 0.74–1.02; p=0.09), comparable to the ITT RR (0.87; 95% CI: 0.75–1.01; p=0.07). Conclusion At per-protocol analysis, ticagrelor monotherapy after 1 month of DAPT was not superior to conventional treatment, in line with the previously reported ITT effect. Similar per-protocol and ITT effects can be accounted for similar per-protocol and ITT populations, as a substantial proportion of patients were non-adherent due to clinically grounded reasons (anticipated in the protocol) and, accordingly, not considered as protocol deviators. Funding Acknowledgement Type of funding source: Other. Main funding source(s): GLOBAL LEADERS was sponsored by the European Clinical Research Institute, which received funding from Biosensors International, AstraZeneca, and the Medicines Company.

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Benefits and risks of longer-than-1-year dual antiplatelet therapy in TWLIGHT-like patients with high risk of ischemic or bleeding events after drug-eluting stents implantation

European Heart Journal ◽

10.1093/ehjci/ehaa946.1308 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

H.Y Wang ◽

K.F Dou ◽

B Xu ◽

R.L Gao ◽

A Kirtane

Keyword(s):

High Risk ◽

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Target Lesion ◽

Funding Source ◽

Medical Sciences ◽

Bleeding Events ◽

Index Procedure ◽

Drug Eluting

Abstract Background Dual-antiplatelet therapy (DAPT) exceeding 1 year may increase a bleeding risk despite reducing the risk of ischemic events. The benefits and harms of prolonging DAPT with aspirin and clopidogrel beyond 1 year after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation for TWLIGHT-like patients with high-risk for bleeding or an ischemic event remain unknown. Method Between January 2013 and December 2013, all consecutive patients undergoing PCI were prospectively included in the China Fuwai PCI Registry. We evaluated 7521 patients who were at high risk for ischemic or hemorrhagic complications and were events free (no death, myocardial infarction [MI], stroke, stent thrombosis [ST], any revascularization, or major bleeding) at 1 year after the index procedure. Subjects were divided into 2 groups: DAPT>1-year group (n=5252) and DAPT≤1-year group (n=2269). Patients at high-risk for ischemic or bleeding events were defined as having at least one additional clinical feature and one angiographic feature according to TWILIGHT trial criteria. The clinical criteria for high risk were age≥65 years, female sex, troponin-positive ACS, established vascular disease, diabetes mellitus that was being treated with medication, and CKD. Angiographic criteria included multivessel coronary artery disease, total stent lengthd≥30 mm, a thrombotic target lesion, a bifurcation lesion treated with two stents, an obstructive left main or proximal left anterior descending lesion, and a calcified target lesion treated with atherectomy. The primary outcome was major adverse cardiac and cerebrovascular events [MACCE] (a composite of all-cause death, MI, or stroke). Results During a median follow-up of 30 months after the index procedure, DAPT>1-year was associated with a reduction in risk for MACCE compared with DAPT≤1-year (1.5% vs. 3.8%; adjusted hazard ratio [HR]: 0.36; 95% confidence interval [CI]: 0.27–0.50; P<0.001) after multivariable adjustment. This difference was largely driven by a lower risk of all-cause mortality. In contrast, the risk of BARC type 2, 3 or 5 bleeding was statistically similar between the 2 groups (1.0% vs. 1.1%; adjusted HR: 0.81; 95% CI: 0.50–1.30; P=0.373). After propensity score matching, incidence of MACCE was still lower in the DAPT>1-year group than the DAPT≤1-year group (1.6% versus 4.5%; HR, 0.34; 95% CI, 0.22–0.52; P<0.001) and the rates of BARC type 2, 3 or 5 bleeding was not different between the 2 groups (1.1% versus 0.9%; adjusted HR, 1.12; 95% CI, 0.57–2.18; P=0.744). In subgroup analysis, the treatment effect of prolonged DAPT was consistent across subgroups regardless of ACS, DAPT score, or type of used DES. Conclusions DAPT continuation with aspirin and clopidogrel beyond 1-year after DES implantation resulted in a significantly lower rate of MACCE, with no higher risk of clinically relevant bleeding in TWLIGHT-like patients who were at high-risk for ischemic or bleeding events. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Natural Science Foundation of China

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Urgent percutaneous coronary intervention leads to a decrease in serum concentrations of soluble CD40 ligand

Vojnosanitetski pregled ◽

10.2298/vsp1009732r ◽

2010 ◽

Vol 67 (9) ◽

pp. 732-740

Author(s):

Nenad Ratkovic ◽

Radoslav Romanovic ◽

Aleksandra Jovelic ◽

Branko Gligic ◽

Saso Rafajlovski ◽

...

Keyword(s):

Percutaneous Coronary Intervention ◽

Angina Pectoris ◽

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Coronary Intervention ◽

Cd40 Ligand ◽

Control Group ◽

Soluble Cd40 Ligand ◽

Percutaneous Coronary ◽

Experimental Group

Background/Aim. Inflammation as a consequence of vascular injury after percutaneous coronary intervention (PCI) is a pathological substrate of restenosis and of its complications. The aim of the study was to examine perprocedural inflammatory response expressed by soluble CD40 ligand (sCD40L) and C-reactive protein (CRP) in patients treated with PCI and dual antiplatelet therapy. Methods. The experimental group included 52 patients (80.8% men, age 60 ? 9 years) with angina pectoris treated by PCI (22 urgent PCI) with stent implantation, and dual antiplatelet therapy (tienopiridins and aspirin), according to the current recommendations for the execution of the intervention. The control group consisted of 8 patients (70.5% men, age 59 ? 7 years) with angina pectoris, who had undergone coronarography taking aspirin 3 days prior to it. In all the patients 24 hours before and after the PCI concentrations of CRP and sCD40L in the blood were determined. Results. In the experimental group, the concentration of sCD40L was lower as compared to the control (p < 0.02). In 34 (65%) patients postprocedural decrease in sCD40L was recorded, in 18 (34.6%) of them increase, while in 50 (96%) patients there was a rise in CRP. The patients with postprocedural fall in sCD40L hod greater preprocedural concentration of sCD40L (p < 0.001), and less postprocedural concentration of sCD40L (p < 0.001), compared to the group with an increase in sCD40L after the PCI, while CRP levels tients treated with emergency PCI compared to elective patietns had a postprocedural decrease in sCD40L (p = 0.02). Increase in the level of CRP was higher in the group with emergency PCI in relation to elective PCI (p < 0.01). Conclusion. Emergency PCI procedures in the treatment of patients with unstable angina pectoris lead to a postprocedural fall in the serum concentration of sCD40L. Dual antiplate therapy with tienopiridins and aspirin inhibits the release of sCD40L. Regardless a clinical presentation of coronary disease PCI leads to an postprocedural increase in concentrations of CRP in the serum.

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Benefit-risk profile of longer-than-1-year dual antiplatelet therapy in TWLIGHT-like patients with high risk of ischemic or bleeding events after drug-eluting stents implantation

European Heart Journal ◽

10.1093/ehjci/ehaa946.2496 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

H.Y Wang ◽

R Gao ◽

B.O Xu ◽

K Dou ◽

A Kirtane

Keyword(s):

High Risk ◽

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Target Lesion ◽

Clinical Feature ◽

Funding Source ◽

Bleeding Events ◽

Index Procedure ◽

Drug Eluting

Abstract Background Dual-antiplatelet therapy (DAPT) exceeding 1 year may increase a bleeding risk despite reducing the risk of ischemic events. The benefits and harms of prolonging DAPT with aspirin and clopidogrel beyond 1 year after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation for TWLIGHT-like patients with high-risk for bleeding or an ischemic event remain unknown. Method Between January 2013 and December 2013, all consecutive patients undergoing PCI were prospectively included in the Fuwai PCI Registry. We evaluated 7521 patients who were at high risk for ischemic or hemorrhagic complications and were events free (no death, myocardial infarction [MI], stroke, stent thrombosis [ST], any revascularization, or major bleeding) at 1 year after the index procedure. Subjects were divided into 2 groups: DAPT >1-year group (n=5252) and DAPT ≤1-year group (n=2269). Patients at high-risk for ischemic or bleeding events were defined as having at least one additional clinical feature and one angiographic feature according to TWILIGHT trial criteria. The clinical criteria for high risk were age ≥65 years, female sex, troponin-positive ACS, established vascular disease, diabetes mellitus that was being treated with medication, and CKD. Angiographic criteria included multivessel coronary artery disease, total stent length ≥30 mm, a thrombotic target lesion, a bifurcation lesion treated with two stents, an obstructive left main or proximal left anterior descending lesion, and a calcified target lesion treated with atherectomy. The primary outcome was major adverse cardiac and cerebrovascular events [MACCE] (a composite of all-cause death, MI, or stroke). Results During a median follow-up of 30 months after the index procedure, DAPT >1-year was associated with a reduction in risk for MACCE compared with DAPT ≤1-year (1.5% vs. 3.8%; adjusted hazard ratio [HR]: 0.36; 95% confidence interval [CI]: 0.27–0.50; P<0.001) after multivariable adjustment. This difference was largely driven by a lower risk of all-cause mortality. In contrast, the risk of BARC type 2, 3 or 5 bleeding was statistically similar between the 2 groups (1.0% vs. 1.1%; adjusted HR: 0.81; 95% CI: 0.50–1.30; P=0.373). After propensity score matching, incidence of MACCE was still lower in the DAPT >1-year group than the DAPT ≤1-year group (1.6% versus 4.5%; HR, 0.34; 95% CI, 0.22–0.52; P<0.001) and the rates of BARC type 2, 3 or 5 bleeding was not different between the 2 groups (1.1% versus 0.9%; adjusted HR, 1.12; 95% CI, 0.57–2.18; P=0.744). In subgroup analysis, the treatment effect of prolonged DAPT was consistent across subgroups regardless of ACS, DAPT score, or type of used DES. Conclusions DAPT continuation with aspirin and clopidogrel beyond 1-year after DES implantation resulted in a significantly lower rate of MACCE, with no higher risk of clinically relevant bleeding in TWLIGHT-like patients who were at high-risk for ischemic or bleeding events. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Natural Science Foundation of China

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Rationale and design of the Web-basEd soCial media tecHnology to improvement in Adherence to dual anTiplatelet Therapy following Drug-Eluting Stent Implantation (WECHAT): protocol for a randomised controlled study

BMJ Open ◽

10.1136/bmjopen-2019-033017 ◽

2020 ◽

Vol 10 (1) ◽

pp. e033017

Author(s):

Guo-li Sun ◽

Li Lei ◽

Liwei Liu ◽

Jin Liu ◽

Yibo He ◽

...

Keyword(s):

Social Media ◽

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Intervention Group ◽

Antiplatelet Drug ◽

Controlled Study ◽

Drug Eluting Stent ◽

Control Group ◽

Web Based ◽

Drug Eluting

BackgroundDual antiplatelet therapy (DAPT) is frequently discontinued after drug-eluting stent (DES) implantation, which could increase the risk of major adverse cardiovascular events (MACEs). Few studies have attempted to improve DAPT adherence through web-based social media.ObjectiveTo explore the effect of social media on DAPT adherence following DES implantation.Methods/designThe WeChat trial is a multicentre, single-blind, randomised study (1:1). It will recruit 760 patients with DES who require 12 months of DAPT. The control group will only receive usual care and general educational messages on medical knowledge. The intervention group will receive a personalised intervention, including interactive responses and medication and follow-up reminders beyond the general educational messages. The primary endpoint will be the discontinuation rate which is defined as the cessation of any dual antiplatelet drug owing to the participants’ discretion within 1 year of DES implantation. The secondary endpoints will include medication adherence and MACEs. Both groups will receive messages or reminders four times a week with follow-ups over 12 months.Ethics and disseminationEthical approval was granted by Ethics Committee of Guangdong Provincial People’s Hospital (GDREC2018327H). Results will be disseminated via peer-reviewed publications and presentations at international conferences.Trial registration numberNCT03732066

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A Randomized Comparison of CLOpidogrel Monotherapy Versus Extended Dual-antiplatelet Therapy Beyond 12 Months After Implantation of Drug-eluting StEnts in High-risk Lesions or Patients; A-CLOSE Trial

Case Medical Research ◽

10.31525/ct1-nct03947229 ◽

2019 ◽

Author(s):

Keyword(s):

High Risk ◽

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Drug Eluting Stents ◽

Drug Eluting

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Comparative Efficacy and Safety of Duration of Dual Antiplatelet Therapy in Patients with CAD Undergoing Drug-eluting Stent Implantation: A Systematic Review and Network Meta-analysis

Current Pharmaceutical Design ◽

10.2174/1381612826666200625110349 ◽

2020 ◽

Vol 26 (44) ◽

pp. 5739-5745

Author(s):

Jieqiong Guan ◽

Wenjing Song ◽

Pan He ◽

Siyu Fan ◽

Hong Zhi ◽

...

Keyword(s):

Antiplatelet Therapy ◽

Major Bleeding ◽

Dual Antiplatelet Therapy ◽

Meta Analysis ◽

Cochrane Library ◽

Drug Eluting Stent ◽

Efficacy And Safety ◽

Risk Of Bleeding ◽

Increased Risk ◽

Drug Eluting

Objective: The aim was to evaluate the efficacy and safety of duration of dual antiplatelet therapy (DAPT) for patients who received percutaneous coronary intervention (PCI) with a drug-eluting stent. Background: The optimal duration of DAPT to balance the risk of ischemia and bleeding in CAD patients undergoing drug-eluting stent (DES) implantation remains controversial. Methods: PubMed, Cochrane Library, Web of Science, Clinicaltrials.gov, CNKI and Wanfang Databases were searched for randomized controlled trials of comparing different durations of DAPT after DES implantation. Primary outcomes were major adverse cardiac and cerebrovascular events (MACCE), and major bleeding, and were pooled by Bayes network meta-analysis. Net adverse clinical and cerebral events were used to estimate the surface under the cumulative ranking (SUCRA) curves. The subgroup analysis based on clinical status, follow-up and area was conducted using traditional pairwise meta-analysis. Results: A total of nineteen trials (n=51,035) were included, involving six duration strategies. The network metaanalysis showed that T2 (<6-month DAPT followed by aspirin, HR:1.51, 95%CI:1.02-2.22), T3 (standard 6-month DAPT, HR:1.47, 95%CI:1.14-1.91), T4 (standard 12-month DAPT, HR:1.41, 95%CI:1.15-1.75) and T5 (18-24 months DAPT, HR:1.47, 95%CI:1.09-1.97) was associated with significantly increased risk of MACCE compared to T6 (>24-month DAPT). However, no significant difference was found in MACCE risk between T1 (<6-month DAPT followed by P2Y12 monotherapy) and T6. Moreover, T5 was associated with significantly increased risk of bleeding compared to T1(RR:3.94, 95%CI:1.66-10.60), T2(RR:3.65, 95%CI:1.32-9.97), T3(RR:1.93, 95%CI:1.21-3.50) and T4(RR:1.89, 95%CI:1.15-3.30). The cumulative probabilities showed that T6(85.0%), T1(78.3%) and T4(44.5%) were the most efficacious treatment compared to the other durations. In the ACS (<50%) subgroup, T1 was observed to significantly reduce the risk of major bleeding compared to T4, but not in the ACS (≥50%) subgroup. Conclusions: Compared with other durations, short DAPT followed by P2Y12 inhibitor monotherapy showed non-inferiority, with a lower risk of bleeding and not associated with an increased MACCE. In addition, the risk of major bleeding increased significantly, starting with DAPT for 18-month. Compared with the short-term treatment, patients with ACS with the standard 12-month treatment have a better prognosis, including lower bleeding rate and the decreased risk of MACCE. Due to study's limitations, the results should be verified in different risk populations.

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