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.

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 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

Long-Term Risk of Major Adverse Cardiovascular Events in Patients With Acute Coronary Syndrome: Prognostic Role of Complete Blood Cell Count

Angiology ◽  
2020 ◽  
Vol 71 (9) ◽  
pp. 831-839
Author(s):  
Nuccia Morici ◽  
Valentina Molinari ◽  
Silvia Cantoni ◽  
Andrea Rubboli ◽  
Laura Antolini ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
High Risk ◽  
Blood Cell ◽  
Cardiovascular Events ◽  
Major Adverse Cardiovascular Events ◽  
Blood Cell Count ◽  
Prognostic Role ◽  
Coronary Syndrome

Individual parameters of complete blood count (CBC) have been associated with worse outcome in patients with acute coronary syndrome (ACS). However, the prognostic role of CBC taken as a whole has never been evaluated for long-term incidence of major adverse cardiovascular events (MACEs). Patients were grouped according to their hematopoietic cells’ inflammatory response at different time points during hospital stay. Patients with admission white blood cell count >10 × 109/L, discharge hemoglobin <120 g/L, and discharge platelet count >250 × 109/L were defined as “high-risk CBC.” Among 1076 patients with ACS discharged alive, 129 (12%) had a “high-risk CBC” and 947 (88%) had a “low-risk CBC.” Patients with “high-risk CBC” were older and had more comorbidities. Over a median follow-up of 665 days, they experienced a higher incidence of MACE compared to “low-risk CBC” patients (18.6% vs 8.1%). After adjustment for age, age-adjusted Charlson comorbidity index, female sex, cardiac arrest, suboptimal discharge therapy, coronary artery bypass, and ejection fraction, a high-risk CBC was significantly associated with increased MACE occurrence (adjusted hazard ratio 1.80; 95% CI: 1.09-3.00). The CBC was a prognostic marker in patients with ACS, and its evaluation at admission and discharge could better classify patient’s risk and improve therapeutic management.

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 Concomitant Use of Proton Pump Inhibitors and Dual Antiplatelet Therapy: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Hongzhou Guo ◽  
Zhishuai Ye ◽  
Rongchong Huang
Keyword(s):  
Antiplatelet Therapy ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Cardiovascular Events ◽  
Observational Studies ◽  
Dual Antiplatelet Therapy ◽  
Meta Analysis ◽  
Gi Bleeding ◽  
Coronary Syndrome ◽  
All Cause Mortality

Background: The safety and efficacy associated with the use of proton pump inhibitors (PPIs) by patients with coronary artery disease receiving dual antiplatelet therapy (DAPT) remain unclear.Methods: The evaluated outcomes included combined major adverse cardiovascular events (MACEs), myocardial infarction (MI), all-cause mortality, and gastrointestinal (GI) bleeding. A random effects meta-analysis, stratified by study design, was performed and heterogeneity was assessed using the I2 statistic.Results: In total, 6 randomized controlled trials (RCTs) (6930 patients) and 16 observational studies (183,546 patients) were included. Analysis of RCTs showed that there were no significant differences in the incidences of MACEs (risk ratio [RR] = 0.89 [95% confidence interval (CI) = 0.75–1.05]), MI (RR = 0.93 [95% CI = 0.76–1.15]), and all-cause mortality (RR = 0.79 [95% CI = 0.50–1.23]) in the PPI groups vs. the non-PPI groups. Pooled data from observational studies revealed an inconsistent association between the use of each PPI subtype and the increased risks of MACEs during clopidogrel treatment. There was no increased risk of MACEs or all-cause mortality associated with the use of PPIs (as a class) and other P2Y12 inhibitors. Both the RCTs and observational studies revealed that the use of PPIs significantly reduced the risks of GI bleeding.Conclusion: The use of PPIs was associated with a reduced risk of GI bleeding in patients treated with DAPT after percutaneous coronary intervention or acute coronary syndrome. There was no clear evidence of an association between the use of PPIs and adverse cardiovascular events.Clinical Trial Registration: identifier [CRD42020190315]

Effects of Edoxaban on the Cellular and Protein Phase of Coagulation in Patients with Coronary Artery Disease on Dual Antiplatelet Therapy with Aspirin and Clopidogrel: Results of the EDOX-APT Study

2019 ◽  
Vol 120 (01) ◽  
pp. 083-093 ◽  
Author(s):  
Francesco Franchi ◽  
Fabiana Rollini ◽  
Emilio Garcia ◽  
Jose Rivas Rios ◽  
Andrea Rivas ◽  
...  
Keyword(s):  
Phase I ◽  
Antiplatelet Therapy ◽  
Phase Ii ◽  
Low Dose ◽  
Dual Antiplatelet Therapy ◽  
High Dose ◽  
Once Daily ◽  
Daily Group ◽  
Group A ◽  
Group B

AbstractIn patients requiring dual antiplatelet therapy (DAPT) who also have an indication to be treated with oral anticoagulant (OAC) drugs, aspirin withdrawal reduces the risk of bleeding. There is limited data on the pharmacodynamic effects associated with adding a nonvitamin K antagonist OAC on a background of aspirin and a P2Y12 inhibitor as well as dropping aspirin. Seventy-five patients on DAPT (aspirin plus clopidogrel) were randomized to DAPT plus high-dose edoxaban (60 mg once daily, Group A), DAPT plus low-dose edoxaban (30 mg once daily, Group B), or DAPT only (Group C) for 10 ± 2 days (Phase I). Afterwards, Groups A and B interrupted aspirin and maintained clopidogrel plus edoxaban for 10 ± 2 days, while patients in Group C maintained DAPT (Phase II). Platelet aggregation and clot kinetics were assessed at baseline, end of Phase I, and end of Phase II using thrombelastography (TEG), light transmittance aggregometry (LTA), VerifyNow P2Y12, and serum thromboxane-B2. The primary endpoint was the comparison of maximum amplitude (MA) measured by TEG, a measure of clot strength, between patients on DAPT plus high-dose edoxaban and patients on DAPT only. Edoxaban prolonged in a dose-dependent manner speed of thrombin generation (TEG R; Group A: 7.7 [6.8–8.7] vs. Group B: 7.4 [6.4–8.5] vs. Group C: 6.3 [5.7–7.0]; p = 0.05) but did not affect other markers of clot kinetics, including TEG MA (Group A: 63 [61–64] vs. Group B: 65 [63–67] vs. Group C: 64 [63–65]; p = 0.10). After aspirin discontinuation, platelet reactivity assessed by LTA using thrombin receptor activating peptide as agonist increased to a greater extent with low-dose edoxaban. Stopping aspirin did not affect markers of P2Y12 reactivity and had no or marginal effects on clot kinetics, but increased markers sensitive to cyclooxygenase-1 blockade.

scholarly journals Preliminary Data from a Study on Polymorphism RS4244285 of P4502c19 Cytochrome Gene in Patients with Acute Coronary Syndrome, Undergoing Treatment with Dual Antiplatelet Therapy With Clopidogrel and Aspirin

2016 ◽  
Vol 9 (1) ◽  
pp. 65-71
Author(s):  
Katya S. Kovacheva ◽  
Petya A. Nikolova ◽  
Valentin V. Hristov ◽  
Diana I. Pendicheva ◽  
Sotir T. Marchev ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Antiplatelet Therapy ◽  
Preliminary Data ◽  
Dual Antiplatelet Therapy ◽  
Coronary Intervention ◽  
Major Adverse Cardiovascular Events ◽  
Individual Response ◽  
Coronary Syndrome ◽  
High Prevalence ◽  
The Individual

Summary Administration of antiplatelet therapy Aspirin and Clopidogrel (CLP) is a corner stone inpatients with Acute Coronary Syndrome (ACS) undergoing Percutaneous Coronary Intervention (PCI) with/without stent implantation. The CYP2C19*2 allele is the most important genetic variant determining response to CLP. We aim to investigate frequency of CYP2C19*2 polymorphism in patients with ACS and significance for the individual response to CLP therapy. The preliminary data of a study including a total of 120 patients with ACS undergoing PCI with stent placement and treated with dual antiplatelet therapy (CLP and Aspirin) are presented. So far 18 patients (41-81 year age) are tested for CYP2C19*l/*2 polymorphisms. The genotype CYP2C19*1/*1; CYP2C19*l/*2 and CYP2C19*2/*2 is demonstrated in 50%, 33%, 17% respectively, of the patients. The established frequency of CYP2C 19*2 allele (33%) is significantly higher (x2=5.220; p=0.022) than in healthy Bulgarian individuals (16%). In-stent thrombosis have developed 3 (17%) of patients: 2 are C YP2C19* l/*2 carriers, and 1 - homozygous CYP2C19*2/*2. The preliminary data demonstrate high prevalence of CYP2C19*2 polymorphism in patients with ACS and point to significance of the variant for CLP therapy. Further extension of the study with larger samples and monitoring of the patients are required to determine the effects of the polymorphism on the prognosis for major adverse cardiovascular events.

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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