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For almost two decades, 12-month dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) has been the only class I recommendation on DAPT in American and European guidelines, which has resulted in 12-month durations of DAPT therapy being the most frequently implemented in ACS patients undergoing percutaneous coronary intervention (PCI) across the globe. Twelve-month DAPT was initially grounded in the results of the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) trial, which, by design, studied DAPT versus no DAPT rather than the optimal DAPT duration. The average DAPT duration in this study was 9 months, not 12 months. Subsequent ACS studies, which were not designed to assess DAPT duration, rather its composition (aspirin with prasugrel or ticagrelor compared with clopidogrel) were further interpreted as supportive evidence for 12-month DAPT duration. In these studies, the median DAPT duration was 9 or 15 months for ticagrelor and prasugrel, respectively. Several subsequent studies questioned the 12-month regimen and suggested that DAPT duration should either be fewer than 12 months in patients at high bleeding risk or more than 12 months in patients at high ischemic risk who can safely tolerate the treatment. Bleeding, rather than ischemic risk assessment, has emerged as a treatment modifier for maximizing the net clinical benefit of DAPT, due to excessive bleeding and no clear benefit of prolonged treatment regimens in high bleeding risk patients. Multiple DAPT de-escalation treatment strategies, including switching from prasugrel or ticagrelor to clopidogrel, reducing the dose of prasugrel or ticagrelor, and shortening DAPT duration while maintaining monotherapy with ticagrelor, have been consistently shown to reduce bleeding without increasing fatal or nonfatal cardiovascular or cerebral ischemic risks compared with 12-month DAPT. However, 12-month DAPT remains the only class-I DAPT recommendation for patients with ACS despite the lack of prospectively established evidence, leading to unnecessary and potentially harmful overtreatment in many patients. It is time for clinical practice and guideline recommendations to be updated to reflect the totality of the evidence regarding the optimal DAPT duration in ACS.
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Síndrome Coronariana Aguda , Terapia Antiplaquetária Dupla , Inibidores da Agregação Plaquetária , Humanos , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/terapia , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Hemorragia/induzido quimicamente , Intervenção Coronária Percutânea , Fatores de Tempo , Resultado do Tratamento , Cloridrato de Prasugrel/uso terapêutico , Cloridrato de Prasugrel/administração & dosagem , Cloridrato de Prasugrel/efeitos adversos , Esquema de MedicaçãoRESUMO
AIM: The "2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease" provides recommendations to guide clinicians in the treatment of patients with lower extremity peripheral artery disease across its multiple clinical presentation subsets (ie, asymptomatic, chronic symptomatic, chronic limb-threatening ischemia, and acute limb ischemia). METHODS: A comprehensive literature search was conducted from October 2020 to June 2022, encompassing studies, reviews, and other evidence conducted on human subjects that was published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through May 2023 during the peer review process, were also considered by the writing committee and added to the evidence tables where appropriate. STRUCTURE: Recommendations from the "2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease" have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with peripheral artery disease have been developed.
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American Heart Association , Extremidade Inferior , Doença Arterial Periférica , Humanos , Doença Arterial Periférica/terapia , Doença Arterial Periférica/diagnóstico , Extremidade Inferior/irrigação sanguínea , Estados Unidos , Cardiologia/normasRESUMO
BACKGROUND AND AIMS: In patients with acute coronary syndrome (ACS), dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor is recommended for 12 months after drug-eluting stent (DES) implantation. Monotherapy with a potent P2Y12 inhibitor after short-term DAPT is an attractive option to better balance the risks of ischaemia and bleeding. Therefore, this study evaluated the efficacy and safety of ticagrelor monotherapy after short-term DAPT, especially in patients with ACS. METHODS: Electronic databases were searched from inception to 11 November 2023, and for the primary analysis, individual patient data were pooled from the relevant randomized clinical trials comparing ticagrelor monotherapy after short-term (≤3 months) DAPT with ticagrelor-based 12-month DAPT, exclusively in ACS patients undergoing DES implantation. The co-primary endpoints were ischaemic endpoint (composite of all-cause death, myocardial infarction, or stroke) and bleeding endpoint [Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding] at 1 year. RESULTS: Individual patient data from two randomized clinical trials including 5906 ACS patients were analysed. At 1 year, the primary ischaemic endpoint did not differ between the ticagrelor monotherapy and ticagrelor-based DAPT groups [1.9% vs. 2.5%; adjusted hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.56-1.13; P = .194]. The incidence of the primary bleeding endpoint was lower in the ticagrelor monotherapy group (2.4% vs. 4.5%; adjusted HR 0.54; 95% CI 0.40-0.72; P < .001). The results were consistent in a secondary aggregate data meta-analysis including the ACS subgroup of additional randomized clinical trials which enrolled patients with ACS as well as chronic coronary syndrome. CONCLUSIONS: In ACS patients undergoing DES implantation, ticagrelor monotherapy after short-term DAPT was associated with less major bleeding without a concomitant increase in ischaemic events compared with ticagrelor-based 12-month DAPT. STUDY REGISTRATION: PROSPERO (ID: CRD42023476470).
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BACKGROUND AND AIMS: This study aimed to evaluate clinical outcomes in patients developing post-operative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) and characterize variations in oral anticoagulation (OAC) use, benefits, and complications. METHODS: A systematic search identified studies on new-onset POAF after CABG and OAC initiation. Outcomes included risks of thromboembolic events, bleeding, and mortality. Furthermore, a meta-analysis was conducted on these outcomes, stratified by the use or non-use of OAC. RESULTS: The identified studies were all non-randomized. Among 1 698 307 CABG patients, POAF incidence ranged from 7.9% to 37.6%. Of all POAF patients, 15.5% received OAC. Within 30 days, thromboembolic events occurred at rates of 1.0% (POAF: 0.3%; non-POAF: 0.8%) with 2.0% mortality (POAF: 1.0%; non-POAF: 0.5%). Bleeding rates were 1.1% for POAF patients and 2.7% for non-POAF patients. Over a median of 4.6 years, POAF patients had 1.73 thromboembolic events, 3.39 mortality, and 2.00 bleeding events per 100 person-years; non-POAF patients had 1.14, 2.19, and 1.60, respectively. No significant differences in thromboembolic risks [effect size -0.11 (-0.36 to 0.13)] and mortality [effect size -0.07 (-0.21 to 0.07)] were observed between OAC users and non-users. However, OAC use was associated with higher bleeding risk [effect size 0.32 (0.06-0.58)]. CONCLUSIONS: In multiple timeframes following CABG, the incidence of complications in patients who develop POAF is low. The use of OAC in patients with POAF after CABG is associated with increased bleeding risk.
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Anticoagulantes , Fibrilação Atrial , Ponte de Artéria Coronária , Complicações Pós-Operatórias , Tromboembolia , Humanos , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etiologia , Ponte de Artéria Coronária/efeitos adversos , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Tromboembolia/prevenção & controle , Tromboembolia/epidemiologia , Tromboembolia/etiologia , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Feminino , Administração Oral , Masculino , IncidênciaRESUMO
Dual antiplatelet therapy (DAPT) with aspirin and a platelet P2Y12 receptor inhibitor is the standard antithrombotic treatment after percutaneous coronary interventions (PCI). Several trials have challenged guideline-recommended DAPT after PCI by testing the relative clinical effect of an aspirin-free antiplatelet approach-consisting of P2Y12 inhibitor monotherapy after a short course (mostly 1-3 months) of DAPT-among patients undergoing PCI without a concomitant indication for oral anticoagulation (OAC). Overall, these studies have shown P2Y12 inhibitor monotherapy after short DAPT to be associated with a significant reduction in the risk of bleeding without an increase in thrombotic or ischaemic events compared with continued DAPT. Moreover, the effects of the P2Y12 inhibitor monotherapy without prior DAPT or following a very short course of DAPT after PCI are being investigated in emerging studies, of which one has recently reported unfavourable efficacy results associated with the aspirin-free approach compared with conventional DAPT. Finally, P2Y12 inhibitor alone has been compared with aspirin alone as chronic therapy after DAPT discontinuation, thus challenging the historical role of aspirin as a standard of care for secondary prevention following PCI. A thorough understanding of study designs, populations, treatments, results, and limitations of trials testing P2Y12 inhibitor monotherapy vs. DAPT or vs. aspirin is required to consider adopting this treatment in clinical practice. This review addresses the use of aspirin-free antiplatelet strategies among patients undergoing PCI without a concomitant indication for OAC, providing an overview of clinical evidence, guideline indications, practical implications, ongoing issues, and future perspectives.
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Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Intervenção Coronária Percutânea/métodos , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Aspirina/uso terapêutico , Terapia Antiplaquetária Dupla , Quimioterapia Combinada , Resultado do TratamentoRESUMO
During the past 30â years, several developments have occurred in the antiplatelet field, including the role of aspirin in primary prevention of atherosclerotic cardiovascular disease. There have been several attempts to develop antiplatelet drugs more effective and safer than aspirin and a shift in emphasis from efficacy to safety, advocating aspirin-free antiplatelet regimens after percutaneous coronary intervention. Evidence supporting a chemopreventive effect of low-dose aspirin against colorectal (and other digestive tract) cancer has also strengthened. The aim of this article is to revisit the role of aspirin in the prevention of atherothrombosis across the cardiovascular risk continuum, in view of developments in the antiplatelet field. The review will offer a clinical perspective on aspirin's mechanism of action, pharmacokinetics, and pharmacodynamics. This will be followed by a detailed discussion of its clinical efficacy and safety.
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Aspirina , Aterosclerose , Inibidores da Agregação Plaquetária , Humanos , Aspirina/administração & dosagem , Inibidores da Agregação Plaquetária/administração & dosagem , Aterosclerose/prevenção & controle , Doenças Cardiovasculares/prevenção & controleRESUMO
Multivessel coronary artery disease is present in â¼50% of patients with acute coronary syndrome and, compared with single-vessel disease, entails a higher risk of new ischaemic events and a worse prognosis. Randomized controlled trials have shown the superiority of 'complete revascularization' over culprit lesion-only treatment. Trials, however, only included patients treated with percutaneous coronary intervention (PCI), and evidence regarding complete revascularization with coronary artery bypass graft (CABG) surgery after culprit lesion-only PCI ('hybrid revascularization') is lacking. The CABG after PCI is an open, non-negligible therapeutic option, for patients with non-culprit left main and/or left anterior descending coronary artery disease where evidence in chronic coronary syndrome patients points in several cases to a preference of CABG over PCI. This valuable but poorly studied 'PCI first-CABG later' option presents, however, relevant challenges, mostly in the need of interrupting post-stenting dual antiplatelet therapy (DAPT) for surgery to prevent excess bleeding. Depending on patients' clinical characteristics and coronary anatomical features, either deferring surgery after a safe interruption of DAPT or bridging DAPT interruption with intravenous short-acting antithrombotic agents appears to be a suitable option. Off-pump minimally invasive surgical revascularization, associated with less operative bleeding than open-chest surgery, may be an adjunctive strategy when revascularization cannot be safely deferred and DAPT is not interrupted. Here, the rationale, patient selection, optimal timing, and adjunctive strategies are reviewed for an ideal approach to hybrid revascularization in post-acute coronary syndrome patients to support physicians' choices in a case-by-case patient-tailored approach.
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Despite its significant clinical efficacy as a first-line treatment for advanced bladder cancer, cisplatin-based chemotherapy provides a limited benefit for patients with lymphovascular invasion (LVI), which is characterized by the presence of tumor emboli within blood vessels and associated with enhanced cisplatin resistance and metastatic potential. Notably, platelets, a critical component of LVI, hinder the delivery of chemotherapeutic agents to tumors and facilitate metastasis. Consequently, platelet function inhibition holds the potential to disrupt LVI formation, as well as augment the antitumor activity of cisplatin. Herein, we developed a tumor microenvironment-targeted nanodrug with lipid-coated mesoporous silica nanoparticles (silicasomes) that synergistically combines cisplatin with an antiplatelet agent, tirofiban, for bladder cancer treatment. The customized nanodrug can concurrently prevent LVI formation and enhance the chemotherapeutic efficacy without significant adverse effects. This study supports the integration of chemotherapy and antiplatelet therapy via a silicasome-based nanosystem as a highly promising strategy for bladder cancer management.
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Cisplatino , Nanopartículas , Dióxido de Silício , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Humanos , Dióxido de Silício/química , Cisplatino/farmacologia , Cisplatino/química , Cisplatino/uso terapêutico , Nanopartículas/química , Linhagem Celular Tumoral , Animais , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Microambiente Tumoral/efeitos dos fármacos , Camundongos , Invasividade Neoplásica/prevenção & controle , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Peptídeos Cíclicos/uso terapêutico , OligopeptídeosRESUMO
BACKGROUND: Indobufen is widely used in patients with aspirin intolerance in East Asia. The OPTION trial launched by our cardiac center examined the performance of indobufen based dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). However, the vast majority of patients with acute coronary syndrome (ACS) and aspirin intolerance were excluded. We aimed to explore this question in a real-world population. METHODS: Patients enrolled in the ASPIRATION registry were grouped according to the DAPT strategy that they received after PCI. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE) and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. Propensity score matching (PSM) was adopted for confounder adjustment. RESULTS: A total of 7135 patients were reviewed. After one-year follow-up, the indobufen group was associated with the same risk of MACCE versus the aspirin group after PSM (6.5% vs. 6.5%, hazard ratio [HR] = 0.99, 95% confidence interval [CI] = 0.65 to 1.52, P = 0.978). However, BARC type 2, 3, or 5 bleeding was significantly reduced (3.0% vs. 11.9%, HR = 0.24, 95% CI = 0.15 to 0.40, P < 0.001). These results were generally consistent across different subgroups including aspirin intolerance, except that indobufen appeared to increase the risk of MACCE in patients with ACS. CONCLUSIONS: Indobufen shared the same risk of MACCE but a lower risk of bleeding after PCI versus aspirin from a real-world perspective. Due to the observational nature of the current analysis, future studies are still warranted to further evaluate the efficacy of indobufen based DAPT, especially in patients with ACS. TRIAL REGISTRATION: Chinese Clinical Trial Register ( https://www.chictr.org.cn ); Number: ChiCTR2300067274.
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Síndrome Coronariana Aguda , Isoindóis , Intervenção Coronária Percutânea , Fenilbutiratos , Humanos , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/cirurgia , Aspirina/efeitos adversos , Quimioterapia Combinada , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação Plaquetária/efeitos adversos , Sistema de Registros , Resultado do TratamentoRESUMO
BACKGROUND: The optimal duration of dual antiplatelet therapy after currently available drug-eluting stent (DES) implantation to prevent stent thrombosis (ST) remains controversial. Delayed healing is frequently identified as a leading cause of ST in the early phase. However, a thorough pathological investigation into strut coverage after currently available DES implantation is lacking-a gap addressed in the current study. METHODS: From our autopsy registry of 199 stented lesions, 4,713 struts from 66 currently available DES-stented lesions with an implant duration ≤370 days were histologically evaluated. Endothelial coverage was defined as the presence of luminal endothelial cells overlying struts and an underlying smooth muscle cell layer. The stented lesions were classified into acute coronary syndrome (ACS) (nâ¯=â¯40) and chronic coronary syndrome (CCS) (nâ¯=â¯26) groups and were compared. Endothelial coverage predictors were identified through logistic analysis. RESULTS: Although ACS and CCS lesions presented comparable clinical characteristics, including age, sex, and cause of death, the latter exhibited a significantly higher prevalence of chronic kidney disease and hemodialysis than the former (33.3% vs. 65.2%; pâ¯=â¯0.02, 7.7% vs. 30.4%; pâ¯=â¯0.02). The poststent implant median duration was significantly shorter in ACS lesions than in CCS lesions (13 [IQR 5-26 days] vs. 40 [IQR 16-233 days]; p < 0.01). The endothelial coverage percentage was 3.5% at 30 days and 27.7% at 90 days after currently available DES implantation. Multivariable logistic regression analysis implicated implant duration of ≤90 days [odds ratio (OR), 0.009; 95% confidence interval (CI), 0.006-0.012; p < 0.01], superficial calcification (OR, 0.11; 95% CI, 0.07-0.17; p < 0.01), ACS culprit site (OR, 0.29; 95% CI, 0.09-0.94; pâ¯=â¯0.039), and circumferentially durable polymer-coated DES (OR, 0.32; 95% CI, 0.24-0.41; p < 0.01) as delayed endothelial coverage predictors. CONCLUSIONS: Endothelial coverage was limited at 90 days after currently available DES implantation, and the ACS culprit site and circumferentially durable polymer-coated DES were identified as independent predictors of delayed endothelial coverage. Our findings suggest the importance of underlying plaque morphology and stent technology for vessel healing after such implantation.
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Long-term outcomes of patients with advanced heart failure treated with durable left ventricular assist devices (LVADs) have been augmented due to improved durability and hemocompatibility on the backbone of pump engineering enhancements. The incidence of hemocompatibility-related adverse events (pump thrombosis, stroke and non-surgical bleeding events) are device-specific and vary by type of engineered pump. A fully magnetically levitated rotor containing LVAD in concert with use of antithrombotic therapy has successfully overcome an increased risk of thrombosis albeit with only modest reduction in bleeding events. Modifications to antithrombotic strategies have focused on reduced dose vitamin K antagonist use or use of direct oral anticoagulants with demonstration of safety, and progress in reduction of mucosal bleeding episodes with elimination of antiplatelet agents. This review outlines the current landscape of advances in anticoagulation management in LVAD patients, highlighting the need for ongoing research and cautious application of emerging therapies and technologies.
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BACKGROUND: In the last few years, percutaneous LAA occlusion (LAAO) has become a plausible alternative in atrial fibrillation (AF) patients with contraindications to anticoagulation therapy. Nevertheless, the optimal antiplatelet strategy following percutaneous LAAO remains to be defined. METHODS: Studies comparing single antiplatelet therapy (SAPT) versus dual antiplatelet therapy (DAPT) following LAAO were systematically searched and screened. The outcomes of interest were ischemic stroke, device-related thrombus (DRT) and major bleeding. A random-effect meta-analysis was performed comparing outcomes in both groups. The moderator effect of baseline characteristics on outcomes was evaluated by univariate meta-regression analyses. RESULTS: Sixteen observational studies with 3255 patients treated with antiplatelet therapy (SAPT, n = 1033; DAPT, n = 2222) after LAAO were included. Mean age was 74.5 ± 8.3 years, mean CHA2DS2-VASc and HAS-BLED scores were 4.3 ± 1.5 and 3.2 ± 1.0, respectively. At a weighted mean follow-up of 12.7 months, the occurrence of stroke (RR 1.33; 95% CI 0.64-2.77; p =.44), DRT (RR 1.52; 95% CI 0.90-2.58; p =.12), and the composite of stroke and DRT (RR 1.26; 95% CI 0.67-2.37; p =.47) did not differ significantly between SAPT and DAPT groups. The rate of major bleedings was also not different between groups (RR 1.41; 95% CI 0.64-3.12; p =.39). CONCLUSIONS: Among AF patients at high bleeding risk undergoing percutaneous LAAO, a post-procedural minimalistic antiplatelet strategy with SAPT did not significantly differ from DAPT regimens regarding the rate of stroke, DRT and major bleeding.
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Apêndice Atrial , Fibrilação Atrial , Terapia Antiplaquetária Dupla , Hemorragia , Inibidores da Agregação Plaquetária , Humanos , Apêndice Atrial/cirurgia , Inibidores da Agregação Plaquetária/uso terapêutico , Terapia Antiplaquetária Dupla/métodos , Hemorragia/induzido quimicamente , Idoso , Trombose/prevenção & controle , AVC Isquêmico/prevenção & controle , Acidente Vascular Cerebral/prevenção & controle , Estudos Observacionais como Assunto , Oclusão do Apêndice Atrial EsquerdoRESUMO
Background: The aim of this study was to investigate the impact of body mass index (BMI) and body weight on the concentrations of ticagrelor and the ticagrelor metabolite, AR-C124910XX, as well as the platelet aggregation rate (PAR) in a Chinese Han population with unstable angina (UA). Specifically, it focused on these parameters following the administration of dual antiplatelet therapy (DAPT) comprising aspirin and ticagrelor. Methods: A total of 105 patients with UA were included in the study. Measurement of the platelet aggregation rate induced by adenosine diphosphate (PAR-ADP) was performed before, as well as 3 and 30 days after DAPT treatment. The plasma concentrations of ticagrelor and AR-C124910XX were detected at 3 and 30 days after DAPT treatment. We conducted correlation analyses to assess the effects of BMI and body weight on the concentrations of ticagrelor and AR-C124910XX, on PAR-ADP, and on the inhibition of platelet aggregation induced by adenosine diphosphate (IPA-ADP) at both 3 and 30 days after DAPT treatment. Results: The BMI and body weight were positively correlated with baseline PAR-ADP (r = 0.205, p = 0.007; r = 0.122, p = 0.022). The PAR-ADP at 3 and 30 days after DAPT treatment were significantly lower than at baseline (61.56% ± 10.62%, 8.02% ± 7.52%, 12.90% ± 7.42%, p < 0.001). There was a negative correlation between body weight and the concentrations of ticagrelor and AR-C124910XX at 3 days following DAPT treatment (r = -0.276, p < 0.001; r = -0.337, p < 0.001). Additionally, BMI showed a similar negative correlation with the concentrations of ticagrelor and AR-C124910XX (r = -0.173, p = 0.009; r = -0.207, p = 0.002). At 30 days after treatment, both body weight and BMI were negatively correlated with ticagrelor (r = -0.256, p < 0.001; r = -0.162, p = 0.015) and its metabolite (r = -0.352, p < 0.001; r = -0.202, p = 0.002). Body weight was positively correlated with PAR-ADP (r = 0.171, p = 0.010) and negatively correlated with IPA-ADP (r = -0.163, p = 0.015) at 30 days after treatment. Similarly, BMI was positively correlated with PAR-ADP (r = 0.217, p = 0.001) and negatively correlated with IPA-ADP (r = -0.211, p = 0.001) at the same time point. Conclusions: BMI and body weight are key factors influencing the pharmacokinetics and pharmacodynamics of ticagrelor in Chinese Han patients with UA following DAPT treatment that includes ticagrelor. Both BMI and body weight were positively correlated with PAR-ADP at baseline and 30 days after DAPT treatment. Clinical Trial Registration: ChiCTR2100044938, https://www.chictr.org.cn/.
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BACKGROUND: During the transition from dual antiplatelet therapy (DAPT) to single antiplatelet therapy (SAPT), previous studies have raised concerns about a rebound effect. We compared platelet and inflammatory cell adhesion on different types of stents in the setting of clopidogrel presence and withdrawal. METHODS: In Experiment 1, three pigs were administered with DAPT, that is, clopidogrel and acetylsalicylic acid (ASA), for 7 days. Each animal underwent an extracorporeal carotid arteriovenous shunt model implanted with fluoropolymer-coated everolimus-eluting stent (FP-EES), biodegradable-polymer sirolimus-eluting stent (BP-SES), and biodegradable-polymer everolimus-eluting stents (BP-EES). In Experiment 2, two pigs were administered DAPT, clopidogrel was then withdrawn at day 7, and SAPT with ASA was continued for next 21 days. Then flow-loop experiments with the drawn blood from each time point were performed for FP-EES, BioLinx-polymer zotarolimus-eluting stents (BL-ZES), and BP-EES. The rebound effect was defined as the statistical increase of inflammation and platelet adhesion assessed with immunohistochemistry on the stent-strut level basis from baseline to day-14 or 28. RESULTS: Both experiments showed platelet adhesion value was highest in BP-EES, while the least in FP-EES during DAPT therapy. There was no increase in platelet or inflammatory cell adhesion above baseline values (i.e., no therapy) due to the cessation of clopidogrel on the stent-strut level. Monocyte adhesion was the least for FP-EES with the same trend observed for neutrophil adhesion. CONCLUSIONS: No evidence of rebound effect was seen after the transition from DAPT to SAPT. FP-EES demonstrated the most favorable antithrombotic and anti-inflammatory profile regardless of the different experimental designs.
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Aspirina , Clopidogrel , Stents Farmacológicos , Terapia Antiplaquetária Dupla , Everolimo , Adesividade Plaquetária , Inibidores da Agregação Plaquetária , Desenho de Prótese , Sirolimo , Trombose , Animais , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Agregação Plaquetária/efeitos adversos , Clopidogrel/administração & dosagem , Clopidogrel/farmacologia , Fatores de Tempo , Sirolimo/análogos & derivados , Sirolimo/administração & dosagem , Sirolimo/farmacologia , Everolimo/administração & dosagem , Everolimo/farmacologia , Trombose/prevenção & controle , Trombose/etiologia , Aspirina/administração & dosagem , Adesividade Plaquetária/efeitos dos fármacos , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Sus scrofa , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Esquema de Medicação , Modelos Animais de DoençasRESUMO
BACKGROUND: We aimed to evaluate the characteristics, clinical outcomes, and blood product transfusion (BPT) rates of patients undergoing cardiac transplant (CT) while receiving uninterrupted anticoagulation and antiplatelet therapy. METHODS: A retrospective, single-center, and observational study of adult patients who underwent CT was performed. Patients were classified into four groups: (1) patients without anticoagulation or antiplatelet therapy (control), (2) patients on antiplatelet therapy (AP), (3) patients on vitamin K antagonists (AVKs), and (4) patients on dabigatran (dabigatran). The primary endpoints were reoperation due to bleeding and perioperative BPT rates (packed red blood cells (PRBC), fresh frozen plasma, platelets). Secondary outcomes assessed included morbidity and mortality-related events. RESULTS: Of the 55 patients included, 6 (11%) received no therapy (control), 8 (15%) received antiplatelet therapy, 15 (27%) were on AVKs, and 26 (47%) were on dabigatran. There were no significant differences in the need for reoperation or other secondary morbidity-associated events. During surgery patients on dabigatran showed lower transfusion rates of PRBC (control 100%, AP 100%, AVKs 73%, dabigatran 50%, p = 0.011) and platelets (control 100%, AP 100%, AVKs 100%, dabigatran 69%, p = 0.019). The total intraoperative number of BPT was also the lowest in the dabigatran group (control 5.5 units, AP 5 units, AVKs 6 units, dabigatran 3 units; p = 0.038); receiving significantly less PRBC (control 2.5 units, AP 3 units, AVKs 2 units, dabigatran 0.5 units; p = 0.011). A Poisson multivariate analysis showed that only treatment on dabigatran reduces PRBC requirements during surgery, with an expected reduction of 64.5% (95% CI: 32.4%-81.4%). CONCLUSIONS: In patients listed for CT requiring anticoagulation due to nonvalvular atrial fibrillation, the use of dabigatran and its reversal with idarucizumab significantly reduces intraoperative BPT demand.
Assuntos
Anticoagulantes , Transplante de Coração , Inibidores da Agregação Plaquetária , Humanos , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Anticoagulantes/uso terapêutico , Seguimentos , Transplante de Coração/efeitos adversos , Prognóstico , Transfusão de Sangue , Fatores de Risco , Idoso , Adulto , Dabigatrana/uso terapêutico , Complicações Pós-Operatórias/prevenção & controleRESUMO
OBJECTIVE: Adherence to antiplatelet therapy is recommended but unexplored in patients with symptomatic lower extremity peripheral arterial disease (PAD). Therefore, this study aimed to determine adherence and persistence to antiplatelet therapy in patients with PAD, defined as intermittent claudication and chronic limb threatening ischaemia. DESIGN: Population based nationwide cohort study. METHODS: This study included all Danish citizens aged ≥ 40 years with a first inpatient or outpatient diagnosis of symptomatic PAD between 2010 - 2017, and who had at least one prescription claim for aspirin and/or clopidogrel within 90 days after diagnosis. Adherence was determined by the proportion of days covered (PDC) during the first year after diagnosis. Persistence was defined as no treatment gap ≥ 30 days between prescription renewals over three year follow up. RESULTS: A total of 39 687 patients were eligible for inclusion, of whom 23 279 (58.7%) claimed a prescription for aspirin and/or clopidogrel within 90 days of diagnosis. Among these, 12 898 (55.4%) were prevalent users, while the remainder comprised new users who initiated the therapy after the index PAD diagnosis. The mean PDC was 74.5% (SD 35.0%) for prevalent users and 60.5% (SD 30.5%) for new users. Adherence increased with age and number of concomitant drugs. The overall one year cumulative incidence treatment discontinuation was 13.0% (95% CI 12.5 - 13.4%) overall, 17.2% (CI 16.6 - 17.9%) for prevalent users, and 7.9% (CI 7.4 - 8.4%) for new users. At three year follow up, the cumulative incidence of discontinuation was 31.5% (CI 30.9 - 32.2%) overall, 44.6% (CI 43.7 - 45.4%) for prevalent users, and 14.6% (CI 13.9 - 15.3) for new users. CONCLUSION: Less than 60% of patients with newly diagnosed symptomatic PAD claimed a prescription for antiplatelet therapy within 90 days of diagnosis, and both adherence and persistence were moderate during the first year after diagnosis. These findings underscore the importance of efforts to improve the initiation and continuation of antiplatelet therapy in patients with PAD.
Assuntos
Aspirina , Clopidogrel , Extremidade Inferior , Adesão à Medicação , Doença Arterial Periférica , Inibidores da Agregação Plaquetária , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Doença Arterial Periférica/tratamento farmacológico , Doença Arterial Periférica/epidemiologia , Doença Arterial Periférica/diagnóstico , Masculino , Feminino , Dinamarca/epidemiologia , Idoso , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Extremidade Inferior/irrigação sanguínea , Idoso de 80 Anos ou mais , Fatores de Tempo , Claudicação Intermitente/tratamento farmacológico , Claudicação Intermitente/diagnóstico , Claudicação Intermitente/epidemiologia , Adulto , Isquemia/tratamento farmacológico , Isquemia/epidemiologia , Isquemia/diagnóstico , Resultado do TratamentoRESUMO
BACKGROUND: There has long been clinical disagreement over the resumption of antiplatelet therapy in patients with primary intracranial hemorrhage (ICH). This meta-analysis aimed to systematically evaluate the efficacy and safety of restarting antiplatelet therapy after ICH among different races and ethnicities. METHODS: All relevant medical studies involving adults with antiplatelet-associated ICH published in PubMed, The Cochrane Library and Chinese National Knowledge Infrastructure from inception to March 2024 were sourced. Outcome measures were thromboembolic events (stroke and myocardial infarction) and recurrence of ICH. After assessing study heterogeneity and publication bias, we performed a meta-analysis using random-effects model to assess the strength of association between resumption of antiplatelet therapy and our outcomes.The review was not registered and the review protocol was not prepared. RESULTS: Thirty-five studies were included, with 9758 ICH patients. Subgroup analysis revealed that restarting antiplatelet therapy was associated with a significantly higher risk of recurrence or aggravation of cerebral hemorrhage in Asians[OR = 1.48, 95% CI (1.13-1.94), P = 0.004]; in Caucasians, on the contrary, reinitiation of antiplatelet therapy was not associated with a significantly higher risk of recurrence or aggravation of cerebral hemorrhage [OR = 0.85, 95% CI (0.67-1.06), P = 0.149]. Reinitiation of antiplatelet therapy was associated with a significantly lower risk of cerebral infarction [OR = 0.61, 95% CI (0.39-0.96), P = 0.033]. Restarting antiplatelet therapy after cerebral hemorrhage was not associated with a higher incidence rate of mortality [OR = 0.79, 95% CI (0.57, 1.08), P = 0.138], myocardial infarction [OR = 2.40, 95%CI (0.53,10.79), P = 0.253], hemiparesis [OR = 0.38, 95%CI (0.03,4.81), P = 0.451], neurological deficit [OR = 0.86,95%CI(0.32,2.33),P = 0.766]. CONCLUSION: Reinstitution of antiplatelet therapy after ICH was associated with a lower risk of thromboembolic complications.Resumption of antiplatelet therapy was not associated with a higher incidence of cerebral hemorrhage in Caucasians, but may be associated with a higher risk of cerebral hemorrhage recurrence in Asian populations.
Assuntos
Hemorragias Intracranianas , Inibidores da Agregação Plaquetária , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/etnologia , Hemorragias Intracranianas/epidemiologia , Etnicidade , Povo Asiático/etnologiaRESUMO
BACKGROUND: Antiplatelet and anticoagulation drugs complicate acute gastrointestinal bleeding (GIB) patients. Limited data about the risk factors and patient management has been presented. This study explored the association between previous antiplatelet or anticoagulant drug usage and clinical outcomes in GIB patients to improve awareness further and optimize treatment. METHODS: We conducted a multicenter, non-interventional, real-world prospective study in 106 hospitals in 23 provinces in China. GIB patients confirmed in the emergency department were included and were grouped according to previous drug histories. Univariate analysis, multivariate logistic regression, and multivariate stratification models were performed separately to investigate the associations. RESULTS: A total of 2299 patients (57.23 ± 17.21 years old, 68.3% male) were included, of whom 20.1% and 2.9% received antiplatelet and anticoagulation therapy, respectively. The all-cause 28-day mortality rates in patients without antiplatelet or anticoagulants, patients undergoing antiplatelet treatment, and patients with anticoagulation therapy were 2.8%, 4.6%, and 10.5%, respectively. After adjusting for confounding factors, both antiplatelet [odd ratio (OR), 2.92; 95% confidence interval (CI), 1.48-5.76; p = 0.002] and anticoagulation therapy (OR, 8.87; 95% CI, 3.02-26.02; p < 0.001) were associated with higher 28-day mortality. In the subgroup analysis, blood transfusion, especially red blood cell transfusion, in patients undergoing antiplatelet and anticoagulation therapy was associated with a decreased death risk. CONCLUSION: We confirmed an association between concurrent antiplatelet or anticoagulation therapy in GIB patients and elevated 28-day mortality. Blood transfusions could improve poor outcomes in such patients.
Assuntos
Anticoagulantes , Hemorragia Gastrointestinal , Inibidores da Agregação Plaquetária , Humanos , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/terapia , Hemorragia Gastrointestinal/mortalidade , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Masculino , Pessoa de Meia-Idade , Feminino , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Estudos Prospectivos , Fatores de Risco , Idoso , China/epidemiologia , AdultoRESUMO
BACKGROUND: The safety and feasibility of using 1-month dual antiplatelet therapy (DAPT) followed by P2Y12inhibitor monotherapy for patients after percutaneous coronary intervention (PCI) with thin-strut biodegradable polymer drug-eluting stents (BP-DES) in daily clinical practice remain uncertain. METHODSâANDâRESULTS: The REIWA region-wide registry is a prospective study conducted in 1 PCI center and 9 local hospitals in northern Japan. A total of 1,202 patients who successfully underwent final PCI using BP-DES (Synergy: n=400; Ultimaster: n=401; Orsiro: n=401), were enrolled in the registry, and received 1-month DAPT followed by P2Y12inhibitor (prasugrel 3.75 mg/day or clopidogrel 75 mg/day) monotherapy. The primary endpoint was a composite of cardiovascular and bleeding events at 12 months, including cardiovascular death, myocardial infarction (MI), definite stent thrombosis (ST), ischemic or hemorrhagic stroke, and Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding. Based on the results of a previous study, we set the performance goal at 5.0%. Over the 1-year follow-up, the primary endpoint occurred in 3.08% of patients, which was lower than the predefined performance goal (Pnon-inferiority<0.0001). Notably, definite ST occurred in only 1 patient (0.08%) within 1 year (at 258 days). No differences were observed in the primary endpoint between stent types. CONCLUSIONS: The REIWA region-wide registry suggests that 1-month DAPT followed by P2Y12inhibitor monotherapy is safe and feasible for Japanese patients with BP-DES.
Assuntos
Implantes Absorvíveis , Clopidogrel , Stents Farmacológicos , Terapia Antiplaquetária Dupla , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária , Antagonistas do Receptor Purinérgico P2Y , Sistema de Registros , Humanos , Masculino , Idoso , Feminino , Intervenção Coronária Percutânea/efeitos adversos , Pessoa de Meia-Idade , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/administração & dosagem , Clopidogrel/uso terapêutico , Clopidogrel/efeitos adversos , Clopidogrel/administração & dosagem , Estudos Prospectivos , Japão , Terapia Antiplaquetária Dupla/métodos , Hemorragia/induzido quimicamente , Cloridrato de Prasugrel/administração & dosagem , Cloridrato de Prasugrel/uso terapêutico , Cloridrato de Prasugrel/efeitos adversos , Polímeros , Resultado do TratamentoRESUMO
BACKGROUND: Patients treated with drug-coated balloons (DCB) have the theoretical advantage of adopting a low-intensity antiplatelet regimen due to the absence of struts and polymers. Nevertheless, the optimal antiplatelet strategy for patients undergoing DCB-only treatment remains a topic of debate and has not been investigated in randomized trials. METHODS: The REC-CAGEFREE II is an investigator-initiated, prospective, open-label, multi-center, randomized, non-inferiority trial aimed to enroll 1908 patients from ≥ 40 interventional cardiology centers in China to evaluate the non-inferiority of an antiplatelet regimen consisting of Aspirin plus Ticagrelor for one month, followed by five months Ticagrelor monotherapy, and then Aspirin monotherapy for six months (Experimental group) compared to the conventional treatment of Aspirin plus Ticagrelor for 12 months (Reference group) in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) using paclitaxel-coated balloons (DCB) exclusively. Participants will be randomly assigned to the Experimental or Reference group in a 1:1 ratio. The randomization will be stratified based on the center and the type of lesion being treated (De novo or in-stent restenosis). The primary endpoint is net adverse clinical events (NACE) within 12 months of PCI, which includes the composite of all-cause death, any stroke, any myocardial infarction, any revascularization and Bleeding Academic Research Consortium (BARC) defined type 3 or 5 bleeding. The secondary endpoint, any ischemic and bleeding event, which includes all-cause death, any stroke, MI, BARC-defined type 3 bleeding, any revascularization, and BARC-defined type 2 bleeding events, will be treated as having hierarchical clinical importance in the above order and analyzed using the win ratio method. DISCUSSION: The ongoing REC-CAGEFREE II trial aims to assess the efficacy and safety of a low-intensity antiplatelet approach among ACS patients with DCB. If non-inferiority is shown, the novel antiplatelet approach could provide an alternative treatment for ACS patients with DCB. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04971356.