Antiplatelet Treatment Regimens Research Articles

Indian Perspective on De-escalation from Dual Antiplatelet Therapy to Single Antiplatelet Therapy Study: A Knowledge, Attitude, and Practice Study among Indian Interventional Cardiologists.

Coronary artery disease (CAD) management is one of the most significant facets of interventional cardiology. Evidence from several clinical trials has redefined the drug management of CAD, including optimizing the duration of antiplatelet treatment regimens in the management of CAD, which is an intricate clinical issue. The available evidence indicates that East Asians have a higher bleeding risk. However, the Indian phenotype differs from that of East Asians, making this data confounding when applied to clinical decision-making among Indian patients. There is a need for a close understanding of Indian interventional cardiologists' perceptions of complex decision-making pertaining to antiplatelet agents among Indian CAD patients in real-world clinical settings. This Indian Perspective on De-escalation from Dual Antiplatelet Therapy to Single Antiplatelet Therapy (INDEPTH) study aims to assess the perspective of Indian interventional cardiologists regarding de-escalating from dual antiplatelet therapy (DAPT) to single antiplatelet therapy (SAPT), approach to decision-making, barriers, and related challenges in CAD management. A cross-sectional knowledge, attitude, and practice (KAP) study survey was carried out among Indian interventional cardiologists practicing across different regions of India. A total of 209 responses were received. Descriptive statistics was used to summarize all the parameters. IBM Statistical Package for the Social Sciences (SPSS) statistics was used for biostatistical analysis. The study indicated that >90% of CAD patients received DAPT therapy immediately after percutaneous coronary intervention (PCI) (86.1%, p < 0.001). About 115 (55%) of the respondents reported using calculator-based scoring for evaluating bleeding risk in patients on DAPT therapy for the management of acute coronary syndrome (ACS) with post-PCI (p = 0.167). Regarding the usual duration of DAPT therapy post-ACS, nearly half of the respondents, 94 (45%), said that 6-12 months is the usual duration for DAPT therapy in post-ACS patients, followed by > 12 months 94 (45%) of the respondents; 17 (8.1%) of the respondents reported it is 3-6 months, and lastly up to 3 months as per four (1.9%) of the respondents (p < 0.001). A total of 128 (61%) of the respondents strongly believe that balancing bleeding with ischemic risk influenced the choice of antiplatelet agent when treating established CAD. As per interventional cardiologists surveyed, the perfect de-escalation time frame for Indian CAD patients with high bleeding risk (HBR) is up to 3 months (35.9%, p < 0.001), 6-12 months for medium bleeding risk (48.8%, p < 0.001), and >12 months for low bleeding risk (65.6%, p < 0.001). Regarding SAPT therapy, almost one-third of the respondents, 65 (31.1%), reported that they prescribed antiplatelet therapy other than aspirin in 20-40% of their SAPT-eligible patients. Furthermore, 69 (33%) of the respondents said that they preferred to prescribe clopidogrel in 50-75% of SAPT-eligible patients. While 64 (30.5%) prescribed in 25-50%, 53 (25.4%) prescribed in <25% and 23 (11%) of the respondents prescribed the drug in >75% of the SAPT-eligible patients. (p < 0.001). "Atorvastatin + clopidogrel" is the most preferred combination of SAPT primarily for the management of CAD among the majority of interventional cardiologists [33%, 95% confidence interval (CI): 1.97-2.24, p < 0.001]. The study respondents also indicated a need for Indian-specific guidelines on de-escalating from DAPT to SAPT in CAD management. The INDEPTH study indicated that the majority of CAD patients received DAPT immediately after PCI. The perfect de-escalation time frame for Indian CAD patients with "high-bleeding" risk is up to 3 and 6-12 months for "medium-bleeding" risk and >12 months for "low-bleeding" risk. One-third of respondents used clopidogrel as an antiplatelet agent in 50-75% of SAPT-eligible patients. Atorvastatin + clopidogrel is predominantly the most preferred combination of statin + SAPT for the management of CAD. Although the current international guidelines cover the Indian perspective to some extent, there is a need for Indian-specific guidelines on de-escalating from DAPT to SAPT.

Tirofiban combined with Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction (STRATEGY): protocol for a multicentre, randomised controlled trial

BackgroundPerforating artery territorial infarction (PAI) caused by branch atheromatous disease (BAD) is prone to recurrence and early progression without an effective and well-documented antiplatelet treatment regimen. Tirofiban, an adjunctive antiplatelet...

Novel Aspects Targeting Platelets in Atherosclerotic Cardiovascular Disease—A Translational Perspective

Platelets are important cellular targets in cardiovascular disease. Based on insights from basic science, translational approaches and clinical studies, a distinguished anti-platelet drug treatment regimen for cardiovascular patients could be established. Furthermore, platelets are increasingly considered as cells mediating effects "beyond thrombosis", including vascular inflammation, tissue remodeling and healing of vascular and tissue lesions. This review has its focus on the functions and interactions of platelets with potential translational and clinical relevance. The role of platelets for the development of atherosclerosis and therapeutic modalities for primary and secondary prevention of atherosclerotic disease are addressed. Furthermore, novel therapeutic options for inhibiting platelet function and the use of platelets in regenerative medicine are considered.

Propensity-score-matched analysis of dual antiplatelet treatment and alternative antiplatelet regimens after transcarotid revascularizations

ObjectiveDual antiplatelet therapy (DAPT) continues to be the preferred medication regimen after the placement of a carotid stent using the transcarotid revascularization (TCAR) technique despite a dearth of quality data. Therefore, this investigation was performed to define the risks associated with antiplatelet choice. MethodsWe queried all patients who underwent TCAR captured by the Vascular Quality Initiative from September 2016 to June 2022, to determine the association between antiplatelet choice and outcomes. Patients maintained on DAPT were compared with those receiving alternative regimens consisting of single antiplatelet, anticoagulation, or a combination of the two. A 1:1 propensity-score match was performed with respect to baseline comorbidities, functional status, anatomic/physiologic risk, medications, and intraoperative characteristics. In-hospital and 1-year outcomes were compared between the groups. ResultsDuring the study period, 29,802 procedures were included in our study population, with 24,651 (82.7%) receiving DAPT and 5151 (17.3%) receiving an alternative antiplatelet regimen. A propensity-score match with respect to 29 variables generated 4876 unique pairs. Compared with patients on DAPT, in-hospital ipsilateral stroke was significantly higher in patients receiving alternative antiplatelet regimens (1.7% vs 1.1%, odds ratio [95% confidence interval]: 1.54 [1.10-2.16], P = .01), whereas no statistically significant difference was noted with respect to mortality (0.6% vs 0.5%, 1.35 [0.72-2.54], P = .35). A composite of stroke/death was also more likely in patients receiving an alternative regimen (2.4% vs 1.7%, 1.47 [1.12-1.93], P = .01). Immediate stent thrombosis (2.75 [1.16-6.51]) and a nonsignificant trend toward increased return to the operating room were more common in the alternative patients. Conversely, the incidence of perioperative myocardial infarction was lower in the alternative regimen group (0.4% vs 0.7%, 0.53 [0.31-0.90], P = .02). At 1 year after the procedure, we observed an increased risk of mortality (hazard ratio [95% confidence interval]: 1.34 [1.11-1.63], P < .01) but not stroke (0.52 [0.27-0.99], P = .06) in patients treated with an alternative medication regimen. ConclusionsThis propensity-score-matched analysis demonstrates an increased risk of in-hospital stroke and 1-year mortality after TCAR in patients treated with an alternative medication regimen instead of DAPT. Further studies are needed to elucidate the drivers of DAPT failure in patients undergoing TCAR to improve outcomes for carotid stenting patients.

Impact of the Xinsorb Scaffold-Related Parameters on Platelet Reactivity in Patients with Single De Novo Coronary Artery Lesions Undergoing Clopidogrel Treatment.

This study aimed to assess the relationship between stent parameters and platelet function, as well as the platelet reactivity profiles over time in patients treated with the Xinsorb scaffold. Adenosine diphosphate-induced maximal amplitude was measured as clopidogrel on-treatment platelet reactivity using thrombelastography. High residual platelet reactivity was defined as MAADP > 47 mm. Platelet function testing was induced at baseline, discharge, and 6- and 12-month visits. A total of 40 individuals undergoing Xinsorb scaffold implantation and platelet function testing were included. No adverse events were recorded during follow-up. No correlation was observed among thrombelastography indices, stent diameters, and stent coverage surface area. Significant correlation was found between MAADP and lengths of stents (Spearman rank correlation = 0.324, P =.031). Multiple logistic regression analyses demonstrated that high levels of high-density lipoprotein cholesterol was an independent protective factor for high residual platelet reactivity (odds ratio = 0.049, 95% confidence interval = 0.011-0.296, P =.016). No significant risk factors were identified; MAADP presented to be 20.6 [13.1-36.2] mm, 26.8 [18.2-35.0] mm, and 30.0 [19.6-33.4] mm 48 hours, 6 months, and 12 months after procedure, respectively; 12-month MAADP was significantly higher than the 48-hour MAADP (P =.026). There was no obvious trend for platelet response status over time. Among patients on a clopidogrel-based dual antiplatelet treatment regimen following Xinsorb scaffold implantation, stent parameters had no significant effects on platelet reactivity. The high residual platelet reactivity phenotype is relatively stable over time. High residual platelet reactivity is more likely to occur in patients with lower high-density lipoprotein cholesterol levels.

Abstract 11054: Switching From Dual Antiplatelet Treatment Regimens With Aspirin Plus a P2Y 12 Inhibitor to Dual Pathway Inhibition With Low-Dose Rivaroxaban in Adjunct to Aspirin in Patients With Coronary Artery Disease: The SWAP-AC Study

Introduction: Dual antiplatelet therapy (DAPT) and dual pathway inhibition (DPI) are potential long-term antithrombotic strategies for patients with coronary artery disease (CAD). However, patients already on DAPT are most likely to remain on the same treatment regimen rather than switching. To date, there is no data on the feasibility of switching from DAPT to DPI and the pharmacodynamic (PD) effects of such approach. Methods: SWAP-AC was a prospective, randomized, PD study conducted in 90 patients with CAD on DAPT with aspirin (81mg/qd) plus a P2Y 12 inhibitor [clopidogrel (75 mg/qd; n=30), ticagrelor (90mg/bid; n=30), or prasugrel (10mg/qd; n=30)]. Patients in each cohort were randomized to maintain DAPT or switch to DPI (aspirin 81mg/qd plus rivaroxaban 2.5mg/bid). PD assessments included VerifyNow P2Y 12 reaction units (PRU), light transmittance aggregometry (LTA) using 20 μM ADP, tissue factor (TF), and a combination of collagen + 5 μM ADP + TF (CATF, a marker of platelet-mediated global thrombogenicity), and a thrombin generation (TG) assay. Assays were performed at baseline (on DAPT) and 30 days post-randomization [trough (before maintenance dose) and peak (2 hours after maintenance dose) levels]. Results: Switching from DAPT to DPI occurred without side effects. TG was reduced with DPI. In each cohort, DAPT was associated with lower PRU levels than DPI ( Figure ); LTA following ADP stimuli showed consistent results (data not shown). LTA following CATF stimuli (primary endpoint) showed no differences between DPI and DAPT in the ticagrelor and prasugrel, but not clopidogrel, cohorts ( Figure ). There were no differences in any of the cohorts with LTA using TF. Conclusions: SWAP-AC is the first study supporting the feasibility of switching to DPI patients with CAD on different maintenance DAPT regimens. Such approach was associated with increased P2Y 12 reactivity but reduced thrombin generation with a limited impact on platelet-mediated global thrombogenicity.

Circulating miRNAs as independent predictors of cardiovascular mortality in patients with type 2 diabetes mellitus

Abstract Background MicroRNAs (miRNAs, miR) are essential gene expression regulators involved in numerous biological processes and diseases including type 2 diabetes (DM). Purpose We aimed to determine the predictive value of selected circulating miRNAs for cardiovascular and all-cause mortality and their potential usefulness as biomarkers in DM patients. Method Two hundred fifty-two patients with diabetes were enrolled in the study. Among the patients included, 26 (10.3%) patients died during a median follow-up of 71 months (5.9 years). Plasma miR-191 and miR-16 expressions were assessed by quantitative real-time PCR and compared between the patients who survived and those who died. Results Patients who died from cardiovascular-related death had significantly higher expression of miR-191 and miR-16 as compared with patients who survived (p=0.003, p=0.001, respectively). The study population was divided into two subgroups by using ROC curve analysis for each miRNA, i.e., low or high value of single miRNAs. Kaplan Meier and Cox regression were performed for survival analysis. High expression levels of miRNAs were associated with cardiovascular mortality, when the models included one single miRNA and other covariates: miR-191 (HR = 4.793, 95% CI: 1.48–15.579; p=0.009) and miR-16 (HR = 4.66, 95% CI: 1.48–14.75; p=0.009). Furthermore, miRNAs expression between clopidogrel and the whole acetylsalicylic acid groups (i.e., 75 mg +150 mg), miR-191 expressions was significantly higher in the clopidogrel subgroup (p=0.010), whereas miR-16 did not differ (p=0.127). Conclusion To conclude, miR-191 and miR-16 expression are strong and independent predictors of cardiovascular and all-cause mortality in patients with T2DM. Moreover, miR-191 and miR-16 present significant interactions with antiplatelet treatment regimens and clinical outcomes. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Medical University of Warsaw

De-escalation of antiplatelet therapy in acute coronary syndromes: Why, how and when?

The synergistic blockade of the key platelet signaling pathways of cyclooxygenase-1 blockade and P2Y12 signaling by combining aspirin plus a potent P2Y12 inhibitor (prasugrel or ticagrelor), the so called dual antiplatelet treatment (DAPT), has represented the antithrombotic regimen of choice in patients with acute coronary syndrome (ACS) for nearly a decade. Nevertheless, the use of such antiplatelet treatment regimen, while reduced the risk of thrombotic complications, it is inevitably associated with increased bleeding and this risk may outweigh the benefit of a reduction of ischemic events in specific subgroup of patients. In light of the adverse prognostic implications of a bleeding complication, there has been a great interest in the development of antiplatelet regimens aimed at reducing bleeding without any trade-off in ischemic events. The fact that the ischemic risk is highest in the early phase after an ACS while the risk of bleeding remains relatively stable over time has represented the rationale for the implementation of a more intense antithrombotic regimen early after an ACS, followed by a less intense antithrombotic regimen thereafter. This practice, known as a “de-escalation” strategy, represents one of the more promising approaches for personalization of antithrombotic therapy in ACS. In this review we discuss the rationale, appraise the evidence and provide practical recommendations on the use of a de-escalation strategy of antiplatelet therapy in patients with an ACS.

Precision medicine in interventional cardiology: implications for antiplatelet therapy in patients undergoing percutaneous coronary intervention.

Precision medicine is a medical model that proposes the customization of medical treatments to the individual patient, as opposed to a one-drug-fits-all model. Such a "personalized medicine" approach has been widely adopted in several medical fields, such as cancer medicine, but the implementation of precision medicine in cardiovascular medicine has not been similarly straightforward. Because pharmacogenomics plays an important role in the safety and efficacy of cardiovascular drug therapy, there has been a great interest in the use of tools aiming at personalizing antiplatelet therapy. Moreover, antiplatelet therapy is essential for the treatment of cardiovascular patients to reduce the risk of thrombotic complications, particularly those undergoing percutaneous coronary intervention, but it is inevitably associated with increased bleeding risk. In this review, the authors discuss the rationale, summarize the evidence and discuss the current and future directions for the personalization of antiplatelet treatment regimens in patients undergoing percutaneous coronary intervention.

De-escalation strategies of dual antiplatelet therapy in patients undergoing percutaneous coronary intervention for acute coronary syndrome

Antiplatelet therapy is important for reducing systemic and local thrombotic events in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). Antiplatelet treatment regimens, along with dual antiplatelet therapy consisting of aspirin and a P2Y12 inhibitor for patients receiving PCI, have frequently changed over the years. With improvements in the understanding of the prognostic relevance of bleeding events in patients with PCI, as well as the safety and efficacy of drug-eluting stents, several randomized controlled trials (RCTs) have been conducted on antiplatelet treatment strategies associated with a more favorable balance between ischemic and bleeding risks. Several key RCTs for appropriate antiplatelet therapy in patients receiving PCI for ACS have been reported, and practical guidelines have been updated. This manuscript presents the results of major RCTs on de-escalation strategies of dual antiplatelet treatment in patients receiving PCI for ACS.

Antiplatelet therapy after percutaneous coronary intervention.

Antiplatelet therapy is key to reducing local thrombotic complications and systemic ischaemic events among patients undergoing percutaneous coronary interventions (PCI), but it is inevitably associated with increased bleeding. The continuous refinement in stent technologies, together with the high incidence of ischaemic recurrences after PCI and the understanding of prognostic implications associated with bleeding, have led to a substantial evolution in antiplatelet treatment regimens over the past decades. Numerous investigations have been conducted to better stratify patients undergoing PCI according to their ischaemic and bleeding risks and to implement antithrombotic regimens accordingly. Evidence from these investigations have resulted in a number of antithrombotic treatment options as recommended by recent guidelines. In this State-of-the-Art review we provide the rationale, summarise the evidence, and discuss current and future directions of antiplatelet treatment regimens after PCI.

The impact of antiplatelet and antithrombotic regimen after TAVI: Data from the VIenna CardioThOracic Aortic Valve RegistrY (VICTORY).

We compared the outcomes and adverse events of TAVI patients based on the discharge and long-term antiplatelet or anticoagulant treatment regimens (single antiplatelet [SAPT] vs. dual antiplatelet [DAPT] vs. anticoagulation [OAC] vs. no treatment [NT]). The outcome of 532 consecutive patients treated with TAVI was evaluated. As the main study endpoint, the 1-year all-cause mortality was chosen to compare the different discharge treatment regimens and the 3-year all-cause mortality to compare the different long-term treatment regimens. The secondary endpoints were adverse events as defined by the Valve Academic Research Consortium-II. One-year survival after TAVI was highest amongst patients treated with DAPT compared to SAPT (P<.001) and OAC (P=.003), and patients under OAC demonstrated improved 1-year survival over patients treated with SAPT (P=.006). Furthermore, there was a strong trend towards improved 3-year survival for patients in the OAC cohort treated with non-vitamin K antagonists compared to vitamin K antagonists (N-VKAs vs. VKA; log-rank P=.056). The lower all-cause mortality for DAPT within the first year and N-VKAs over VKA within the first 3years warrant considerable attention in further recommendations of antithrombotic and anticoagulation regimens after TAVI.

MiR-126 Is an Independent Predictor of Long-Term All-Cause Mortality in Patients with Type 2 Diabetes Mellitus.

MicroRNAs are endogenous non-coding RNAs that are involved in numerous biological processes through regulation of gene expression. The aim of our study was to determine the ability of several miRNAs to predict mortality and response to antiplatelet treatment among T2DM patients. Two hundred fifty-two patients with diabetes were enrolled in the study. Among the patients included, 26 (10.3%) patients died within a median observation time of 5.9 years. The patients were receiving either acetylsalicylic acid (ASA) 75 mg (65%), ASA 150 mg (15%) or clopidogrel (19%). Plasma miR-126, miR-223, miR-125a-3p and Let-7e expressions were assessed by quantitative real time PCR and compared between the patients who survived and those who died. Adjusted Cox-regression analysis was used for prediction of mortality. Differential miRNA expression due to different antiplatelet treatment was analyzed. After including all miRNAs into one multivariate Cox regression model, only miR-126 was predictive of future occurrence of long-term all-cause death (HR = 5.82, 95% CI: 1.3–24.9; p = 0.024). Furthermore, miR-126, Let-7e and miR-223 expressions in the clopidogrel group were significantly higher than in the ASA group (p = 0.014; p = 0.013; p = 0.028, respectively). To conclude, miR-126 expression is a strong and independent predictor of long-term all-cause mortality among patients with T2DM. Moreover, miR-223, miR-126 and Let-7e present significant interactions with antiplatelet treatment regimens and clinical outcomes.

Antiplatelet therapy in percutaneous coronary intervention: latest evidence from randomized controlled trials.

Antiplatelet therapy is key to reduce systemic and local thrombotic events among patients undergoing percutaneous coronary interventions (PCI). Antiplatelet treatment regimens have been subject to continuous changes over the years, with a dual antiplatelet therapy (DAPT), consisting of aspirin and a P2Y12 inhibitor representing the cornerstone of treatment in these patients. The need for less aggressive antithrombotic drugs to prevent local ischemic events with newer generation drug-eluting stent together with the increased understanding of the prognostic relevance of bleeding events in PCI patients, have prompted investigations aimed at identifying antiplatelet treatment regimens associated with a more favorable balance between ischemic and bleeding risks. Several key randomized controlled trials (RCTs) on antiplatelet regimens in patients undergoing PCI have been recently reported resulting in updates in practice guidelines. This manuscript provides an overview of the advancements in the field deriving from key RCTs on antiplatelet regimens in patients undergoing PCI.

Percutaneous dilatational tracheotomy in high-risk ICU patients

Abstract Funding Acknowledgements Type of funding sources: None. Background Percutaneous dilatational tracheotomy (PDT) has become an established procedure in cardiac intensive care units (ICU). However, the safety of this method has been under debate given the growing number of critically ill patients with high bleeding risk receiving anticoagulation, dual antiplatelet therapy (DAPT) or even a combination of both, i.e. triple therapy. There is a need for critical evaluation of these safety concerns. This is the first and largest international, multicenter study on PDT to date including such a high proportion of patients on antithrombotic therapy investigating whether PDT in high-risk ICU patients is associated with elevated procedural complications and analysing risk factors for bleeding occurring during and after PDT. Methods PDT interventions conducted in ICUs at 12 European sites between January 2016 and October 2019 were retrospectively analysed for procedural complications. For subgroup analyses, patient stratification into clinically relevant risk groups based on anticoagulation and antiplatelet treatment regimens was performed. Procedure-related complications for each risk group were analysed until hospital discharge. Additionally, predictors of bleeding occurrence were analysed by uni- and multivariable regression models. Results In total, 671 patients receiving PDT according to Ciaglia’s technique with accompanying bronchoscopy were included. Patients were stratified into seven clinically relevant antithrombotic treatment groups. Within the whole cohort, 74 (11%) bleedings were reported to be procedure-related, none of which required surgical intervention. In almost all cases bleedings were associated with skin bleedings from the entry site and could easily be treated with minimally invasive stitching. Subgroup analysis showed no increase in the rate of procedure-related complications in patients with elevated body mass index. In a multivariable regression model bleeding occurrence during and after PDT was independently associated with platelet count (Odds ratio [OR] 0.73, 95% confidence interval [95% CI] [0.56, 0.92], p = 0.009), chronic kidney disease (OR 1.75, 95% CI [1.01, 3.03], p = 0.047) and previous stroke (OR 2.13, 95% CI [1.1, 3.97], p = 0.02). Neither PTT (OR 1.01, 95% CI [0.99, 1.02], p = 0.32), nor DAPT (OR 1.11, 95% CI [0.56, 2.04], p = 0.75) nor triple therapy (OR 0.93, 95% CI [0.49, 1.66], p = 0.82) were associated with bleeding risk. Conclusion In this international, multicenter study bronchoscopy-guided PDT was a safe and low-complication airway management option, even in a cohort of high risk for bleeding on cardiovascular ICUs. Platelet count, chronic kidney disease and previous stroke were identified as independent risk factors of bleeding during and after PDT whereas DAPT and triple therapy had no influence on bleeding events.

Guided P2Y12 inhibitor therapy after percutaneous coronary intervention

Antiplatelet treatment regimens for patients after percutaneous coronary intervention (PCI) have undergone major changes and substantial improvements. Extensions or a shortening of treatment as well as the use of various scores have been assessed in numerous trials to maximise anti-ischaemic efficacy and minimise bleeding. 1 Collet JP Thiele H Barbato E et al. 2020 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2020; (published online Aug 29.)https://doi.org/10.1093/eurheartj/ehaa575 Crossref PubMed Scopus (122) Google Scholar , 2 Knuuti J Wijns W Saraste A et al. 2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020; 41: 407-477 Crossref PubMed Scopus (1634) Google Scholar The key limitation of these strategies is the inherent time delay in the implementation of any therapy adjustments. At the same time, several clinical trials have investigated tailored and guided antiplatelet treatment. 3 Sibbing D Aradi D Alexopoulos D et al. Updated expert consensus statement on platelet function and genetic testing for guiding P2Y12 receptor inhibitor treatment in percutaneous coronary intervention. JACC Cardiovasc Interv. 2019; 12: 1521-1537 Crossref PubMed Scopus (180) Google Scholar Unfortunately, the pioneering trials of tailored treatment did not meet their primary endpoints or show improvement in patients' outcomes. 4 Price MJ Berger PB Teirstein PS et al. Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA. 2011; 305: 1097-1105 Crossref PubMed Scopus (1130) Google Scholar , 5 Trenk D Stone GW Gawaz M et al. A randomized trial of prasugrel versus clopidogrel in patients with high platelet reactivity on clopidogrel after elective percutaneous coronary intervention with implantation of drug-eluting stents: results of the TRIGGER-PCI (Testing Platelet Reactivity in Patients Undergoing Elective Stent Placement on Clopidogrel to Guide Alternative Therapy with Prasugrel) Study. J Am Coll Cardiol. 2012; 59: 2159-2164 Crossref PubMed Scopus (521) Google Scholar Various explanations have been attributed to these disappointing results, including insufficient intensification of treatment in patients with low response to clopidogrel by limited use of potent P2Y12 inhibitors and preferential inclusion of low-risk patients. 3 Sibbing D Aradi D Alexopoulos D et al. Updated expert consensus statement on platelet function and genetic testing for guiding P2Y12 receptor inhibitor treatment in percutaneous coronary intervention. JACC Cardiovasc Interv. 2019; 12: 1521-1537 Crossref PubMed Scopus (180) Google Scholar To address these issues, a series of recent trials included patients at higher risk and investigated the use of platelet function testing (phenotyping) 6 Sibbing D Aradi D Jacobshagen C et al. Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial. Lancet. 2017; 390: 1747-1757 Summary Full Text Full Text PDF PubMed Scopus (295) Google Scholar or genetic testing (genotyping) 7 Claassens DMF Vos GJA Bergmeijer TO et al. A genotype-guided strategy for oral P2Y12 inhibitors in primary PCI. N Engl J Med. 2019; 381: 1621-1631 Crossref PubMed Scopus (212) Google Scholar , 8 Pereira NL Farkouh ME So D et al. Effect of genotype-guided oral P2Y12 inhibitor selection vs conventional clopidogrel therapy on ischemic outcomes after percutaneous coronary intervention: the TAILOR-PCI randomized clinical trial. JAMA. 2020; 324: 761-771 Crossref PubMed Scopus (93) Google Scholar as a strategy by including study groups with a clear distinction of testing versus no testing. Notably, these trials did not provide unequivocal results and were partly limited in sample size and sometimes underpowered to compare specific ischaemic and bleeding endpoints. Guided versus standard antiplatelet therapy in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysisGuided selection of antiplatelet therapy improved both composite and individual efficacy outcomes with a favourable safety profile, driven by a reduction in minor bleeding, supporting the use of platelet function or genetic testing to optimise the choice of agent in patients undergoing PCI. Full-Text PDF

Effect of ticagrelor with or without aspirin on vein graft outcome 1 year after on-pump and off-pump coronary artery bypass grafting.

BackgroundIn the present post hoc analysis of the DACAB trial, we evaluated the effects of ticagrelor with or without aspirin on 1-year vein graft outcomes after coronary artery bypass grafting (CABG) with and without cardiopulmonary bypass (CPB) (on-pump and off-pump).MethodsThe DACAB trial was a multicenter, randomized, open-label, parallel control study enrolling 500 patients with 1,460 vein grafts undergoing CABG. For current post-hoc study, all patients in the DACAB study were included in the analysis to compare the effects of different antiplatelet regimens under on/off pump. Patients were randomly assigned to 1 of 3 antiplatelet treatment regimens (ticagrelor plus aspirin, T + A; ticagrelor alone, T; or aspirin alone, A) within 24 hours after CABG, and were stratified into on-pump and off-pump subgroups. The primary outcome was 1-year vein graft patency rate.ResultsTotally 121 patients underwent on-pump CABG (39 with 121 vein grafts in T + A, 36 with 101 vein grafts in T, and 46 with 137 vein grafts in A) and 379 patients underwent off-pump CABG (129 with 336 vein grafts in T + A, 130 with 387 vein grafts in T, and 120 with 348 vein grafts in A). Compared with A, T + A showed a higher 1-year vein graft patency rate in both on-pump (adjusted OR for non-patency =0.62, 95% CI: 0.16–2.45) and off-pump (adjusted OR for non-patency =0.35, 95% CI: 0.20–0.62) subgroups, P interaction =0.647; whereas T did not in either on-pump (adjusted OR for non-patency = 0.92, 95% CI: 0.31–2.76) or off-pump (adjusted OR for non-patency =0.58, 95% CI: 0.34–1.00) subgroups, P interaction =0.430.ConclusionsIn the DACAB trial, for patients underwent either on-pump or off-pump CABG, ticagrelor plus aspirin showed consistent benefit for achieving 1-year vein graft patency, with particular benefit being seen in the off-pump.

A drug safety evaluation of apixaban for the treatment of atrial fibrillation, acute coronary syndrome, and percutaneous coronary intervention

ABSTRACTIntroduction: The non-vitamin K antagonist oral anticoagulants (NOACs) are changing the landscape for stroke prevention in atrial fibrillation (AF) and prevention or treatment of venous thromboembolism (VTE). In patients with AF and concomitant acute coronary syndrome (ACS), the treatment regimen of combined NOACs and P2Y12 inhibitors is gaining popularity.Areas covered: We conducted a review of safety evaluation and effectiveness of apixaban for AF and ACS treatment, both alone and in combination with different antiplatelet treatment regimens. The aim was to provide an overview of apixaban including mechanism of action, indications, adverse events and tolerability.Expert opinion: Apixaban is recommended as a safe, well tolerated and effective oral anticoagulant for reducing the risk of ischemic events among AF patients. It is of value in prevention and treatment of VTE and pulmonary embolism. Comparing to VKA, apixaban was superior in preventing stroke or systemic embolism with lower major bleeding events among AF patients. When combined with dual antiplatelet therapy apixaban may cause dose-related increase in bleeding which reduces the benefit of this treatment regimen among ACS patients but without AF. In those with ACS and concomitant AF, the combination of apixaban with P2Y12 inhibitor appears to be safe and effective.

Efficacy and Safety of Ticagrelor Monotherapy in Patients Undergoing Multivessel PCI

BackgroundData on optimal antiplatelet treatment regimens in patients who undergo multivessel percutaneous coronary intervention (PCI) are sparse. ObjectivesThis post hoc study investigated the impact of an experimental strategy (1-month dual antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) versus a reference regimen (12-month DAPT followed by 12-month aspirin monotherapy) according to multivessel PCI. MethodsThe GLOBAL LEADERS trial is a prospective, multicenter, open-label, randomized controlled trial, allocating all-comer patients in a 1:1 ratio to either the experimental strategy or the reference regimen. The primary endpoint was the composite of all-cause death or new Q-wave myocardial infarction at 2 years. The secondary safety endpoint was Bleeding Academic Research Consortium type 3 or 5 bleeding. ResultsAmong the overall study population (n=15,845), 3,576 patients (22.4%) having multivessel PCI experienced a significantly higher risk of ischemic and bleeding events at 2 years, compared to those having single-vessel PCI. There was an interaction between the experimental strategy and multivessel PCI on the primary endpoint (hazard ratio: 0.62; 95% confidence interval: 0.44 to 0.88; pinteraction = 0.031). This difference was largely driven by a lower risk of all-cause mortality. In contrast, the risk of Bleeding Academic Research Consortium type 3 or 5 bleeding was statistically similar between the 2 regimens (hazard ratio: 0.92; 95% confidence interval: 0.61 to 1.39; pinteraction = 0.754). ConclusionsLong-term ticagrelor monotherapy following 1-month DAPT can favorably balance ischemic and bleeding risks in patients with multivessel PCI. These findings should be interpreted as hypothesis-generating and need to be replicated in future dedicated randomized trials. (GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation; NCT01813435).

Influence of smoking on CYP2C19 genetic variants and clopidogrel efficacy in patients with minor stroke or transient ischaemic attack.

Studies suggest that smoking affects clopidogrel efficacy. However, whether it influences the association between CYP2C19 genetic variants and clopidogrel efficacy is not clear. In total, 2961 patients from the CHANCE trial were involved in this substudy and were successfully genotyped for two single-nucleotide polymorphisms of CYP2C19 (*2 and *3). The Cox proportional risk regression model was used to evaluate the interactions between CYP2C19*2 and CYP2C19*3 carrier status and clopidogrel efficacy stratified by smoking status. There were marginal significant interactions between CYP2C19*2 and CYP2C19*3 allele carrier status and antiplatelet treatment regimen for the risk of recurrent stroke and composite events (P=0.054, P=0.051, respectively) amongst smokers, but not in non-smokers. Amongst smokers, clopidogrel plus aspirin decreased the recurrence rate of stroke compared with aspirin alone in non-carriers (3.8% vs. 11.8%, hazard ratio 0.32, 95% confidence interval 0.15-0.65, P=0.002), but not in carriers. Similar results were also found for the recurrence rate of composite events in smokers. No significant difference was found for hemorrhage events in any group. Amongst patients with minor stroke or transient ischaemic attack, marginal significant interactions between CYP2C19*2 and CYP2C19*3 allele carrier status and clopidogrel efficacy were found in smokers but not in non-smokers. Amongst smokers, clopidogrel plus aspirin might decrease the recurrence rate of stroke in non-carriers of *2 and *3 alleles of CYP2C19 compared with aspirin alone. However, caution should be taken to interpret our findings in view of several limitations in our study.