scholarly journals Thrombotic vs. Bleeding Events of Interruption of Dual Antiplatelet Therapy within 12 Months among Patients with Stent-Driven High Ischemic Risk Definition following PCI

2022 ◽  
Vol 2022 ◽  
pp. 1-15
Author(s):  
Hao-Yu Wang ◽  
Bo Xu ◽  
Chen-Xi Song ◽  
Chang-Dong Guan ◽  
Li-Hua Xie ◽  
...  
Keyword(s):  
High Risk ◽  
Propensity Score ◽  
Antiplatelet Therapy ◽  
Cardiovascular Events ◽  
Dual Antiplatelet Therapy ◽  
Cox Regression ◽  
Major Adverse Cardiovascular Events ◽  
Bleeding Events ◽  
Risk Criteria ◽  
Clinical Events

Background. There is a paucity of real-world data regarding the clinical impact of dual antiplatelet therapy (DAPT) interruption (temporary or permanent) among patients at high ischemic risk. The aim of this study was to assess the risk of cardiovascular events after interruption of DAPT in high-risk PCI population. Methods. This study used data from the Fuwai PCI registry, a large, prospective cohort of consecutive patients who underwent PCI. We assessed 3,931 patients with at least 1 high ischemic risk criteria of stent-related recurrent ischemic events proposed in the 2017 ESC guidelines for focused update on DAPT who were free of major cardiac events in the first 12 months. The primary ischemic endpoint was 30-month major adverse cardiac and cerebrovascular events, and the key safety endpoints were BARC class 2, 3, or 5 bleeding and net adverse clinical events. Results. DAPT interruption within 12 months occurred in 1,122 patients (28.5%), most of which were due to bleeding events or patients’ noncompliance to treatment. A multivariate Cox regression model, propensity score (PS) matching, and inverse probability of treatment weighting (IPTW) based on the propensity score demonstrated that DAPT interruption significantly increased the risk of primary ischemic endpoint compared with prolonged DAPT (3.9% vs. 2.2%; Cox-adjusted hazard ratio (HR): 1.840; 95% confidence interval (CI): 1.247 to 2.716; PS matching-HR: 2.049 [1.236–3.399]; IPTW-adjusted HR: 1.843 [1.250–2.717]). This difference was driven mainly by all-cause death (1.8% vs. 0.7%) and MI (1.3% vs. 0.5%). Furthermore, the rate of net adverse clinical events (4.9% vs. 3.2%; Cox-adjusted HR: 1.581 [1.128–2.216]; PS matching-HR: 1.639 [1.075–2.499]; IPTW-adjusted HR: 1.554 [1.110–2.177]) was also higher in patients with DAPT interruption (≤12 months), whereas no significant differences between groups were observed in terms of BARC 2, 3, or 5 bleeding. These findings were consistent across various stent-driven high-ischemic risk subsets with respect to the primary ischemic endpoints, with a greater magnitude of harm among patients with diffuse multivessel diabetic coronary artery disease. Conclusions. In patients undergoing high-risk PCI, interruption of DAPT in the first 12 months occurred infrequently and was associated with a significantly higher adjusted risk of major adverse cardiovascular events and net adverse clinical events. 2017 ESC stent-driven high ischemic risk criteria may help clinicians to discriminate patient selection in the use of long-term DAPT when the ischemic risk certainly overcomes the bleeding one.

scholarly journals Rationale and design of “Can Very Low Dose Rivaroxaban (VLDR) in addition to dual antiplatelet therapy improve thrombotic status in acute coronary syndrome (VaLiDate-R)” study

2019 ◽  
Vol 49 (2) ◽  
pp. 192-198
Author(s):  
Ying X. Gue ◽  
Rahim Kanji ◽  
David M. Wellsted ◽  
Manivannan Srinivasan ◽  
Solange Wyatt ◽  
...  
Keyword(s):  
High Risk ◽  
Antiplatelet Therapy ◽  
Cardiovascular Events ◽  
Large Scale ◽  
Low Dose ◽  
Dual Antiplatelet Therapy ◽  
Major Adverse Cardiovascular Events ◽  
Daily Group ◽  
Coronary Syndrome ◽  
Endogenous Fibrinolysis

AbstractImpaired endogenous fibrinolysis is novel biomarker that can identify patients with ACS at increased cardiovascular risk. The addition of Very Low Dose Rivaroxaban (VLDR) to dual antiplatelet therapy has been shown to reduce cardiovascular events but at a cost of increased bleeding and is therefore not suitable for all-comers. Targeted additional pharmacotherapy with VLDR to improve endogenous fibrinolysis may improve outcomes in high-risk patients, whilst avoiding unnecessary bleeding in low-risk individuals. The VaLiDate-R study (ClinicalTrials.gov Identifier: NCT03775746, EudraCT: 2018-003299-11) is an investigator-initiated, randomised, open-label, single centre trial comparing the effect of 3 antithrombotic regimens on endogenous fibrinolysis in 150 patients with ACS. Subjects whose screening blood test shows impaired fibrinolytic status (lysis time > 2000s), will be randomised to one of 3 treatment arms in a 1:1:1 ratio: clopidogrel 75 mg daily (Group 1); clopidogrel 75 mg daily plus rivaroxaban 2.5 mg twice daily (Group 2); ticagrelor 90 mg twice daily (Group 3), in addition to aspirin 75 mg daily. Rivaroxaban will be given for 30 days. Fibrinolytic status will be assessed during admission and at 2, 4 and 8 weeks. The primary outcome measure is the change in fibrinolysis time from admission to 4 weeks follow-up, using the Global Thrombosis Test. If VLDR can improve endogenous fibrinolysis in ACS, future large-scale studies would be required to assess whether targeted use of VLDR in patients with ACS and impaired fibrinolysis can translate into improved clinical outcomes, with reduction in major adverse cardiovascular events in this high-risk cohort.

Abstract 14325: Pooled Analysis of Bleeding, Major Adverse Cardiovascular Events and Mortality in Clinical Trials of Time-constrained Dual-antiplatelet Therapy After Percutaneous Coronary Intervention

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jennifer Ramsay ◽  
John McClure ◽  
Colin Berry
Keyword(s):  
Antiplatelet Therapy ◽  
Cardiovascular Events ◽  
Dual Antiplatelet Therapy ◽  
Pooled Analysis ◽  
Major Adverse Cardiovascular Events ◽  
Bleeding Events ◽  
P2y12 Inhibitor ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Reduced Risk

Introduction: The net clinical benefit of dual antiplatelet therapy (DAPT) reflects the paradoxical effects of an increased risk of bleeding and a reduced risk of major adverse cardiovascular events (MACE). A time-constrained approach to DAPT has been recently investigated in five multicenter trials including GLOBAL LEADERS, STOP-DAPT2, SMART-CHOICE, TWIGHLIGHT and TICO. Methods: We undertook a pooled analysis of these trials to assess the overall associations between time-constrained P2Y12 inhibitor monotherapy (“aspirin free regimen”) for bleeding events, MACE and all-cause mortality as compared to standard care with DAPT for at least 12 months post-PCI. We implemented a DerSimonian and Laird random effects meta-analysis using the metafor package in R. Results: 32,361 randomized trial participants, including 16,898 (52.2%) with a history of ACS, underwent PCI and had outcome data available. P2Y12 inhibitor monotherapy from 1 - 3 months was associated with a reduced risk for bleeding (hazard ratio (HR) (95% confidence interval (CI)) 0.60 (0.45, 0.81); p=0.024), including in the ACS group in which the magnitude of risk reduction was greatest (HR (95% CI) 0.50 (0.41, 0.61). The estimates of the effect of P2Y12 inhibitor monotherapy on the hazard were also favorable for MACE (0.88 (0.77, 1.02)) and all-cause mortality (95% CI 0.85 (0.71, 1.03)). Conclusions: Compared with DAPT for 12 months post-PCI, P2Y12 inhibitor monotherapy from 1-3 months substantially reduces the risk of major and fatal bleeding and, in addition, potentially protective effects, for MACE and all-cause mortality. Considering patient safety, the results support a strategy of DAPT for 1-3 months followed by ‘aspirin free’ P2Y12 inhibitor monotherapy.

TWILIGHT: A Randomized Trial of Ticagrelor Monotherapy Versus Ticagrelor Plus Aspirin Beginning at 3 Months in High-risk Patients Undergoing Percutaneous Coronary Intervention

2020 ◽  
Vol 14 ◽  
Author(s):  
Johny Nicolas ◽  
Usman Baber ◽  
Roxana Mehran
Keyword(s):  
Percutaneous Coronary Intervention ◽  
High Risk ◽  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Coronary Intervention ◽  
Bleeding Events ◽  
High Risk Patients ◽  
Risk Of Death ◽  
Percutaneous Coronary ◽  
Risk Patients

A P2Y12 inhibitor-based monotherapy after a short period of dual antiplatelet therapy is emerging as a plausible strategy to decrease bleeding events in high-risk patients receiving dual antiplatelet therapy after percutaneous coronary intervention. Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention (TWILIGHT), a randomized double-blind trial, tested this approach by dropping aspirin at 3 months and continuing with ticagrelor monotherapy for an additional 12 months. The study enrolled 9,006 patients, of whom 7,119 who tolerated 3 months of dual antiplatelet therapy were randomized after 3 months into two arms: ticagrelor plus placebo and ticagrelor plus aspirin. The primary endpoint of interest, Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, occurred less frequently in the experimental arm (HR 0.56; 95% CI [0.45–0.68]; p<0.001), whereas the secondary endpoint of ischemic events was similar between the two arms (HR 0.99; 95% CI [0.78–1.25]). Transition from dual antiplatelet therapy consisting of ticagrelor plus aspirin to ticagrelor-based monotherapy in high-risk patients at 3 months after percutaneous coronary intervention resulted in a lower risk of bleeding events without an increase in risk of death, MI, or stroke.

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

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&gt;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&gt;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&lt;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&gt;1-year group than the DAPT≤1-year group (1.6% versus 4.5%; HR, 0.34; 95% CI, 0.22–0.52; P&lt;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

scholarly journals Plasma miR-142 predicts major adverse cardiovascular events as an intermediate biomarker of dual antiplatelet therapy

2018 ◽  
Vol 40 (2) ◽  
pp. 208-215 ◽  
Author(s):  
Qian-jie Tang ◽  
He-ping Lei ◽  
Hong Wu ◽  
Ji-yan Chen ◽  
Chun-yu Deng ◽  
...  
Keyword(s):  
Antiplatelet Therapy ◽  
Cardiovascular Events ◽  
Dual Antiplatelet Therapy ◽  
Major Adverse Cardiovascular Events

scholarly journals Clopidogrel Bisulfate: A Review of its Use in the Management of Acute Coronary Syndrome

2009 ◽  
Vol 1 ◽  
pp. CMT.S1170
Author(s):  
Roberta Rossini ◽  
Giuseppe Musumeci ◽  
Tamar Nijaradze ◽  
Antonello Gavazzi
Keyword(s):  
Antiplatelet Therapy ◽  
Cardiovascular Events ◽  
Dual Antiplatelet Therapy ◽  
Coronary Thrombosis ◽  
Bleeding Events ◽  
Percutaneous Coronary Angioplasty ◽  
Coronary Syndrome ◽  
Coronary Stent Implantation ◽  
Long Term Treatment

Antiplatelet therapy is the cornerstone in the modern therapy of patients with acute coronary syndromes (ACS), because of the unique role of platelets in coronary thrombosis. Clopidogrel in combination with aspirin is the current “gold standard” for reducing cardiovascular events in such patients, providing a synergistic platelet inhibition through different platelet activation pathways. Clopidogrel is a thienopyridine which inhibits ADP-induced platelet aggregation, with no direct effects on the metabolism of arachidonic acid. Due to a better safety profile with a similar antiplatelet effectiveness, it is preferred to ticlopidine. In patients with ACS without ST segment elevation (NSTEMI), clopidogrel plus aspirin is able to reduce the relative risk of adverse cardiovascular events by 20%, compared with aspirin alone. Clopidogrel plays a key role also in patients undergoing coronary stenting, in order to prevent stent thrombosis. Pretreatment and long-term treatment with clopidogrel reduces by about one-third the risk of cardiovascular death or myocardial infarction in NSTEMI ACS patients undergoing percutaneous coronary angioplasty (PCI). However, a long-term dual antiplatelet therapy is associated with a higher rate of bleeding events. Clinical practice guidelines currently recommend long-term dual antiplatelet therapy with aspirin and clopidogrel in patients with ACS and a pre-treatment with clopidogrel in every patient scheduled for PCI. The concept of clopidogrel resistance and the need for a pretreatment in patients undergoing coronary stent implantation led to the concept that an improved antiplatelet regimen with novel drugs is desirable.

scholarly journals Clinical outcomes of prolonged dual antiplatelet therapy after coronary drug-eluting stent implantation in dialysis patients

2020 ◽  
Vol 13 (5) ◽  
pp. 803-812
Author(s):  
Seokwoo Park ◽  
Yaerim Kim ◽  
Hyung Ah Jo ◽  
Soojin Lee ◽  
Mi-Sook Kim ◽  
...  
Keyword(s):  
Antiplatelet Therapy ◽  
Major Bleeding ◽  
Dual Antiplatelet Therapy ◽  
Cox Regression ◽  
Coronary Revascularization ◽  
Major Adverse Cardiovascular Events ◽  
Drug Eluting Stent ◽  
Cardiovascular Risks ◽  
Dialysis Patients ◽  
Drug Eluting

Abstract Background End-stage renal disease yields susceptibility to both ischemia and bleeding. The optimal duration of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation is not established in dialysis patients, who are usually excluded from randomized studies. Since recent studies implied the benefits of prolonged DAPT &gt;12 months in chronic kidney disease, we investigated the effectiveness and safety of prolonged DAPT in dialysis patients with higher cardiovascular risks. Methods In this nationwide population-based study, we analyzed dialysis patients who underwent DES implantation from 2008 to 2015. Continued DAPT was compared with discontinued DAPT using landmark analyses, including free-of-event participants at 12 (n = 2246), 15 (n = 1925) and 18 months (n = 1692) after DES implantation. The primary outcome was major adverse cardiovascular events (MACEs): a composite of mortality, nonfatal myocardial infarction, coronary revascularization and stroke. Major bleeding was a safety outcome. Inverse probability of treatment weighting Cox regression was performed. Results Mean follow-up periods were 278.3–292.4 days, depending on landmarks. Overall, incidences of major bleeding were far lower than those of MACE. Continued DAPT groups showed lower incidences of MACE and higher incidences of major bleeding, compared with discontinued DAPT groups. In Cox analyses, continued DAPT reduced the hazards of MACE at the 12- [hazard ratio (HR) = 0.74, 95% confidence interval (CI) 0.61–0.90; P = 0.003], 15- (HR = 0.78, 95% CI 0.64–0.96; P = 0.019) and 18-month landmarks (HR = 0.79, 95% CI 0.63–0.99; P = 0.041), but without a significant increase in major bleeding at 12 (HR = 1.39, 95% CI 0.90–2.16; P = 0.14), 15 (HR = 1.13, 95% CI 0.75–1.70; P = 0.55) or 18 months (HR = 1.27, 95% CI 0.83–1.95; P = 0.27). Conclusions Prolonged DAPT reduced MACE without significantly increasing major bleeding in patients who were event-free at 12 months after DES implantation. In deciding on DAPT duration, prolonged DAPT should be considered in dialysis patients.

scholarly journals Aspirin Versus Clopidogrel as Single Antithrombotic Therapy After Transcatheter Aortic Valve Replacement: Insight From the OCEAN-TAVI Registry

2021 ◽  
Vol 14 (5) ◽  
Author(s):  
Yusuke Kobari ◽  
Taku Inohara ◽  
Tetsuya Saito ◽  
Nobuhiro Yoshijima ◽  
Makoto Tanaka ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Propensity Score ◽  
Aortic Valve Replacement ◽  
Propensity Score Matching ◽  
Antiplatelet Therapy ◽  
Valve Replacement ◽  
Transcatheter Aortic Valve Replacement ◽  
Dual Antiplatelet Therapy ◽  
Bleeding Events ◽  
Transcatheter Aortic Valve

Background: Current guidelines recommend dual antiplatelet therapy for the first 1 to 6 months after transcatheter aortic valve replacement (TAVR); however, recent studies have reported better outcomes with single antiplatelet therapy than with dual antiplatelet therapy in the occurrence of bleeding events, while not increasing thrombotic events. However, no data exist about optimal single antiplatelet therapy following TAVR. Methods: Patients who underwent TAVR between October 2013 and May 2017 were enrolled from the OCEAN-TAVI Japanese multicenter registry (Optimized Transcatheter Valvular Intervention). After excluding 1759 patients, 829 who received aspirin (100 mg/d) or clopidogrel (75 mg/d) after TAVR were identified and stratified according to the presence or absence of anticoagulation. Propensity score matching was performed to adjust the baseline characteristics between the aspirin and clopidogrel groups. Outcomes of interest were all-cause and cardiovascular deaths, stroke, and life-threatening or major bleeding within 2 years following TAVR. Results: After propensity score matching, 98 and 157 pairs of patients without and with anticoagulation, respectively, were identified. Falsification end points of pneumonia, urinary tract infection, and hip fracture were evaluated, and their rates were not different between groups. All-cause deaths were not statistically different between the groups in patients with (aspirin, 17.5%; clopidogrel, 11.1%; log-rank P =0.07) and without (aspirin, 29.6%; clopidogrel, 20.1%; log-rank P =0.15) anticoagulation at 2 years post-TAVR, whereas clopidogrel was associated with a lower cardiovascular mortality at 2 years in patients with (aspirin, 8.5%; clopidogrel, 2.7%; log-rank P =0.03) and without (aspirin, 18.0%; clopidogrel, 5.2%; log-rank P =0.02) anticoagulation. Conclusions: We demonstrated that clopidogrel monotherapy was associated with a lower incidence of cardiovascular death compared with aspirin monotherapy during the 2-year follow-up after TAVR regardless of anticoagulation use. Registration: URL: https://upload.umin.ac.jp ; Unique identifier: UMIN000020423.

scholarly journals Efficacy and Safety of Antiplatelet Therapies in Symptomatic Peripheral Artery Disease: A Systematic Review and Network Meta-Analysis

2020 ◽  
Vol 18 ◽  
Author(s):  
Marco De Carlo ◽  
Giovanni Di Minno ◽  
Tobias Sayre ◽  
Mir Sohail Fazeli ◽  
Gaye Siliman ◽  
...  
Keyword(s):  
Antiplatelet Therapy ◽  
Cardiovascular Events ◽  
Dual Antiplatelet Therapy ◽  
Meta Analysis ◽  
Bleeding Risk ◽  
Major Adverse Cardiovascular Events ◽  
Limb Ischaemia ◽  
All Cause Mortality ◽  
Artery Disease ◽  
Randomised Controlled

Background: Clopidogrel monotherapy is guideline-recommended in symptomatic peripheral artery disease (PAD). The advent of new antithrombotic strategies prompts an updated analysis of available evidence on antiplatelet therapy for PAD. Methods: We searched MEDLINE, Embase and CENTRAL through January 2019 for randomised controlled trials and observational studies comparing antiplatelet therapies as monotherapy, dual therapy, or combination with anticoagulants. Efficacy (major adverse cardiovascular events, acute or chronic limb ischaemia, vascular amputation, peripheral revascularisation) and safety (all-cause mortality and overall bleeding) outcomes were evaluated via Bayesian network meta-analyses. Results: We analysed 26 randomised controlled trials. Clopidogrel (hazard ratio, HR, 0.78; 95% credible interval [CrI] 0.65- 0.93) and ticagrelor (HR 0.80; 95%CrI 0.65-0.98) significantly reduced major adverse cardiovascular events risk compared with aspirin. No significant difference was observed for dual antiplatelet therapy with clopidogrel and aspirin. Vorapaxar significantly reduced limb ischaemia and revascularisation compared with placebo, while dual antiplatelet therapy with clopidogrel and aspirin showed a trend for reduced risk of amputation compared with aspirin (risk ratio 0.68; 95%CrI 0.43- 1.04). For all-cause mortality, picotamide, vorapaxar, dipyridamole with aspirin, and ticlopidine showed significantly lower risk of all-cause mortality vs aspirin. Clopidogrel and ticagrelor showed similar overall bleeding risk vs aspirin, while dual antiplatelet therapy with clopidogrel and aspirin significantly increased bleeding risk. Conclusion: This updated network meta-analysis confirms that clopidogrel significantly decreases the risk of major adverse cardiovascular events compared with aspirin, without increasing bleeding risk. Clopidogrel should remain a mainstay of PAD treatment, at least in patients at higher bleeding risk.

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