Comparison of 3- to 6-Month Versus 12-Month Dual Antiplatelet Therapy After Coronary Intervention Using the Contemporary Drug-Eluting Stents With Ultrathin Struts: The HOST-IDEA Randomized Clinical Trial.

BACKGROUND: Limited data are available on short-term dual antiplatelet therapy (DAPT) after percutaneous coronary intervention using third-generation drug-eluting stents with ultrathin struts and advanced polymer technology. We investigated whether 3- to 6-month DAPT was noninferior to 12-month DAPT after implantation of drug-eluting stents with ultrathin struts and advanced polymer technology. METHODS: We performed an open-label, randomized trial at 37 centers in South Korea. We enrolled patients undergoing percutaneous coronary intervention using the Orsiro biodegradable-polymer sirolimus-eluting stents or the Coroflex ISAR polymer-free sirolimus-eluting stents. Patients with ST-segment-elevation myocardial infarction were excluded. Patients were randomly assigned to receive either 3- to 6-month or 12-month DAPT after percutaneous coronary intervention. The choice of antiplatelet medications was at the physician's discretion. The primary outcome was a net adverse clinical event, a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, stent thrombosis, or major bleeding, defined as Bleeding Academic Research Consortium type 3 or 5 at 12 months. The major secondary outcomes were target lesion failure, a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, and major bleeding. RESULTS: A total of 2013 patients (mean age, 65.7±10.5 years; 1487 males [73.9%]; 1110 [55.1%] presented with acute coronary syndrome) were randomly assigned to 3- to 6-month DAPT (n=1002) or 12-month DAPT (n=1011). The primary outcome occurred in 37 (3.7%) patients in the 3- to 6-month DAPT group and 41 (4.1%) in the 12-month DAPT group. The noninferiority of the 3- to 6-month DAPT group to the 12-month DAPT group was met (absolute risk difference, -0.4% [1-sided 95% CI, -∞% to 1.1%]; P<0.001 for noninferiority). There were no significant differences in target lesion failure (hazard ratio, 0.98 [95% CI, 0.56-1.71], P=0.94) or major bleeding (hazard ratio, 0.82 [95% CI, 0.41-1.61], P=0.56) between the 2 groups. Across various subgroups, the treatment effect of 3- to 6-month DAPT was consistent for net adverse clinical event. CONCLUSIONS: Among patients undergoing percutaneous coronary intervention using third-generation drug-eluting stents, 3- to 6-month DAPT was noninferior to 12-month DAPT for net adverse clinical event. Further research is needed to generalize this finding to other populations and to determine the ideal regimen for 3- to 6-month DAPT. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02601157.

Effect of Prehospital Crushed Prasugrel Tablets in Patients With ST-Segment-Elevation Myocardial Infarction Planned for Primary Percutaneous Coronary Intervention: The Randomized COMPARE CRUSH Trial.

BACKGROUND: Early treatment with a potent oral platelet P2Y12 inhibitor is recommended in patients presenting with ST-segment-elevation myocardial infarction scheduled to undergo primary percutaneous coronary intervention (pPCI). The impact on coronary reperfusion of crushed P2Y12 inhibitor tablets, which lead to more prompt and potent platelet inhibition, is unknown. METHODS: We conducted a randomized controlled, multicenter trial in the Netherlands, enrolling patients with ST-segment-elevation myocardial infarction scheduled to undergo pPCI. Patients were randomly allocated to receive in the ambulance, before transfer, a 60-mg loading dose of prasugrel either as crushed or integral tablets. The independent primary end points were thrombolysis in myocardial infarction (TIMI) 3 flow in the infarct-related artery at initial coronary angiography, and complete (≥70%) ST-segment resolution 1 hour after pPCI. The safety end points were TIMI major and Bleeding Academic Research Consortium ≥3 bleedings. Secondary end points included platelet reactivity and ischemic outcomes. RESULTS: A total of 727 patients were assigned to either crushed or integral tablets of prasugrel loading dose. The median time from study treatment to wire-crossing during pPCI was 57 (47-70) minutes. The primary end point TIMI 3 flow in the infarct-related artery before pPCI occurred in 31.0% in the crushed group versus 32.7% in the integral group (odds ratio, 0.92 [95% CI, 0.65-1.30], P=0.64). Complete ST-segment resolution 1 hour after pPCI was present in 59.9% in the crushed group versus 57.3% in the integral group (odds ratio, 1.11 [95% CI, 0.78-1.58], P=0.55). Platelet reactivity at the beginning of pPCI, measured as P2Y12 reactivity unit, differed significantly between groups (crushed, 192 [132-245] versus integral, 227 [184-254], P≤0.01). TIMI major and Bleeding Academic Research Consortium ≥3 bleeding occurred in 0% in the crushed group versus 0.8% in the integral group, and in 0.3% in the crushed group versus 1.1% in the integral group, respectively. There were no differences observed between groups regarding ischemic events at 30 days. CONCLUSIONS: Prehospital administration of crushed prasugrel tablets does not improve TIMI 3 flow in the infarct-related artery before pPCI or complete ST-segment resolution 1 h after pPCI in patients presenting with ST-segment-elevation myocardial infarction scheduled for pPCI. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03296540.

Ticagrelor or Prasugrel in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

BACKGROUND: Data on the comparative efficacy and safety of ticagrelor versus prasugrel in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention are limited. We assessed the efficacy and safety of ticagrelor versus prasugrel in a head-to-head comparison in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention. METHODS: In this prespecified subgroup analysis, we included 1653 patients with ST-segment-elevation myocardial infarction randomized to receive ticagrelor or prasugrel in the setting of the ISAR REACT-5 trial (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5). The primary end point was the incidence of death, myocardial infarction, or stroke at 1 year after randomization. The secondary end point was the incidence of bleeding defined as BARC (Bleeding Academic Research Consortium) type 3 to 5 bleeding at 1 year after randomization. RESULTS: The primary end point occurred in 83 patients (10.1%) in the ticagrelor group and in 64 patients (7.9%) in the prasugrel group (hazard ratio, 1.31 [95% CI, 0.95-1.82]; P=0.10). One-year incidence of all-cause death (4.9% versus 4.7%; P=0.83), stroke (1.3% versus 1.0%; P=0.46), and definite stent thrombosis (1.8% versus 1.0%; P=0.15) did not differ significantly in patients assigned to ticagrelor or prasugrel. One-year incidence of myocardial infarction (5.3% versus 2.8%; hazard ratio, 1.95 [95% CI, 1.18-3.23]; P=0.010) was higher with ticagrelor than with prasugrel. BARC type 3 to 5 bleeding occurred in 46 patients (6.1%) in the ticagrelor group and in 39 patients (5.1%) in the prasugrel group (hazard ratio, 1.22 [95% CI, 0.80-1.87]; P=0.36). CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, there was no significant difference in the primary end point between prasugrel and ticagrelor. Ticagrelor was associated with a significant increase in the risk for recurrent myocardial infarction. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01944800.

Current and Novel Antiplatelet Therapies for the Treatment of Cardiovascular Diseases.

Over the last decades, antiplatelet agents, mainly aspirin and P2Y12 receptor antagonists, have significantly reduced morbidity and mortality associated with arterial thrombosis. Their pharmacological characteristics, including pharmacokinetic/pharmacodynamics profiles, have been extensively studied, and a significant number of clinical trials assessing their efficacy and safety in various clinical settings have established antithrombotic efficacy. Notwithstanding, antiplatelet agents carry an inherent risk of bleeding. Given that bleeding is associated with adverse cardiovascular outcomes and mortality, there is an unmet clinical need to develop novel antiplatelet therapies that inhibit thrombosis while maintaining hemostasis. In this review, we present the currently available antiplatelet agents, with a particular focus on their targets, pharmacological characteristics, and patterns of use. We will further discuss the novel antiplatelet therapies in the pipeline, with the goal of improved clinical outcomes among patients with atherothrombotic diseases.

[Dual antiplatelet therapy after acute coronary syndrome or percutaneous coronary intervention: with what and for how long?] / Duale Thrombozytenhemmung nach akutem Koronarsyndrom oder perkutaner Koronarintervention ­ womit und wie lange?

Thrombotic complications following coronary interventions (PCI) used to be frequent specifically in acute coronary syndrome (ACS) patients. In recent years complication rates have significantly fallen due to improved stent technology, catheterisation techniques and intravascular visualisation. Therefore, the shortest necessary duration of dual antiplatelet therapy (DAPT) comprising aspirin and a P2Y12 inhibitor is constantly the subject of scientific investigations in order to avoid bleeding complications without allowing ischemic complications to occur. A DAPT duration of 12 months after PCI and ACS was accepted as a standard. Meanwhile a highly individualized approach in terms of therapy duration and choice of drugs that takes the patient's individual bleeding and ischemic risk into account is being practised. Prolonged DAPT (>12 months) is currently recommended for patients post myocardial infarction with a low bleeding risk, at high ischemic risk due to coronary triple vessel disease, following a high risk coronary intervention with an unsatisfactory result or a personal history of prior stent thrombosis. Alternatively, instead of prolonged DAPT, dual-pathway antithrombotic therapy of aspirin plus rivaroxaban (2.5 mg bid) is recommended to prevent future strokes, critical limb ischemia and to reduce mortality in cases with multiregional atherosclerosis. In the meantime, reduced-duration DAPT of 3-6 months is being recommended for most patients. Recent data show that in patients with a high bleeding risk, a DAPT treatment period of 4 weeks may be sufficient with a markedly reduced rate of bleeding and without evidence for more ischemic events. Following the early termination of DAPT, continuing antithrombotic monotherapy with the P2Y12 inhibitor ticagrelor may be indicated to prevent further ischemic events without the risk of bleeding complications comparable to DAPT.

Pretreatment with P2Y12 receptor antagonists in ST-elevation myocardial infarction: a report from the Swedish Coronary Angiography and Angioplasty Registry.

AIMS: Pretreatment of patients with ST-elevation myocardial infarction (STEMI) with P2Y12 receptor antagonists is supported by guidelines and is a common practice despite the lack of definite evidence for its benefit. METHODS AND RESULTS: Using data from the Swedish Coronary Angiography and Angioplasty Registry on procedures between 2005 and 2016, we stratified all patients who underwent primary percutaneous coronary intervention due to STEMI in Sweden by whether or not they were pretreated with P2Y12 receptor antagonists. We investigated associations between pretreatment with P2Y12 receptor antagonists and the risk of adverse outcomes using propensity score-adjusted mixed-effects logistic regression, which accounted for clustering of patients within hospitals. The primary endpoint was all-cause death within 30 days. Secondary endpoints were infarct-related artery (IRA) occlusion, 30-day stent thrombosis, in-hospital bleeding, neurological complications, and cardiogenic shock. In total, 44 804 patients were included. They were treated with clopidogrel (N = 26 136, 58.3%), ticagrelor (N = 15 792, 35.3%), or prasugrel (N = 2352, 5.3%); 37 840 (84.5%) were pretreated, and 30 387 (67.8%) had IRA occlusion. At 30 days, there were 2488 (5.6%) deaths and 267 (0.6%) stent thrombosis. Pretreatment was not associated with better survival at 30 days [odds ratio (OR) 1.08, 95% confidence interval (CI) 0.95-1.24; P = 0.313], reduced IRA occlusion (OR 0.98, 95% CI 0.92-1.05; P = 0.608), decreased stent thrombosis (OR 0.99, 95% CI 0.69-1.43; P = 0.932), higher risk of in-hospital bleeding (OR 1.05, 95% CI 0.89-1.26; P = 0.526), or neurological complications (OR 0.72, 95% CI 0.43-1.21; P = 0.210). CONCLUSION: Pretreatment of STEMI patients with P2Y12 receptor antagonists was not associated with improved clinical outcomes.

Is There a Role for Preoperative Platelet Function Testing in Patients Undergoing Cardiac Surgery During Antiplatelet Therapy?

Up to 11% of patients presenting with acute coronary syndromes undergo coronary artery bypass grafting. Guidelines largely recommend a one-size-fits-all preoperative discontinuation period for P2Y12 receptor blockers to avoid bleeding. These recommendations do not account for highly variable pharmacodynamic responsiveness and for variable recovery of platelet reactivity following discontinuation of P2Y12 receptor blockers. Several observational studies have demonstrated that an objective measurement of platelet function among these patients may reduce the waiting period while mitigating the risk of bleeding. Based on these findings, 2 recent guidelines included a Class IIa and IIb recommendation for platelet function testing in patients undergoing cardiac surgery. The following review article describes the rationale for discontinuation of dual antiplatelet therapy before cardiac surgery and the limitations with this approach, available platelet function assays to assess pharmacodynamic effects, and the association between platelet inhibition and other clinical factors with surgery-related bleeding. The information will assist the reader in determining which patients undergoing cardiac surgery might benefit from preoperative platelet function monitoring.

A brief review on resistance to P2Y12 receptor antagonism in coronary artery disease.

BACKGROUND: Platelet inhibition is important for patients with coronary artery disease. When dual antiplatelet therapy (DAPT) is required, a P2Y12-antagonist is usually recommended in addition to standard aspirin therapy. The most used P2Y12-antagonists are clopidogrel, prasugrel and ticagrelor. Despite DAPT, some patients experience adverse cardiovascular events, and insufficient platelet inhibition has been suggested as a possible cause. In the present review we have performed a literature search on prevalence, mechanisms and clinical implications of resistance to P2Y12 inhibitors. METHODS: The PubMed database was searched for relevant papers and 11 meta-analyses were included. P2Y12 resistance is measured by stimulating platelets with ADP ex vivo and the most used assays are vasodilator stimulated phosphoprotein (VASP), Multiplate, VerifyNow (VN) and light transmission aggregometry (LTA). DISCUSSION/CONCLUSION: The frequency of high platelet reactivity (HPR) during clopidogrel therapy is predicted to be 30%. Genetic polymorphisms and drug-drug interactions are discussed to explain a significant part of this inter-individual variation. HPR during prasugrel and ticagrelor treatment is estimated to be 3-15% and 0-3%, respectively. This lower frequency is explained by less complicated and more efficient generation of the active metabolite compared to clopidogrel. Meta-analyses do show a positive effect of adjusting standard clopidogrel treatment based on platelet function testing. Despite this, personalized therapy is not recommended because no large-scale RCT have shown any clinical benefit. For patients on prasugrel and ticagrelor, platelet function testing is not recommended due to low occurrence of HPR.

Personalizing antiplatelet therapies: What have we learned from recent trials?

Dual antiplatelet therapy with aspirin and a P2Y12 receptor antagonist is currently the standard of care for the prevention of ischemic events in patients with acute coronary syndrome or undergoing percutaneous coronary intervention. Several studies have shown that not all patients benefit from the treatment to the same degree and demonstrated that high on-treatment platelet reactivity may be associated with an increased risk of thrombotic events, while low on-treatment platelet reactivity may be linked to a higher risk of bleeding. Personalized antiplatelet treatment strategies based on platelet function monitoring and genetic testing constitute a promising tool for the prevention of both stent thrombosis and bleeding events, but conclusive evidence that such approaches can improve clinical outcomes is lacking. This review presents the most recent studies on tailored antiplatelet therapy in the management of coronary heart disease, with a focus on the prognosis value of platelet function testing.

GPIIb-IIIa Receptor Inhibitors in Acute Coronary Syndrome Patients Presenting With Cardiogenic Shock and/or After Cardiopulmonary Resuscitation.

BACKGROUND: Data on the use of GPIIb-IIIa receptor inhibitors (GPI) in acute coronary syndrome (ACS) patients presenting with cardiogenic shock and/or after cardiopulmonary resuscitation is sparse. The aim of the study was to establish the possible influence of the adjunctive use of GPI on 30-day and 1-year mortality in these high-risk patients. METHODS: Acute coronary syndrome patients (261), who presented with cardiogenic shock and/or were cardiopulmonary resuscitated on admission, were analysed. Groups receiving (170 patients) and not receiving (91 patients) GPI were compared regarding 30-day and 1-year mortality. RESULTS: The unadjusted all-cause 30-day and 1-year mortality were similar in patients receiving GPI and those not receiving GPI [79 patients (46.5%) vs 50 patients (54.9%) at 30 days; ns, 91 patients (53.5%) vs. 55 (61.1%) at 1 year; ns]. After the adjustment for baseline and clinical characteristics, the adjunctive usage of GPI was identified as an independent prognostic factor in lower 30-day mortality (adjusted OR: 0.41; 95%CI: 0.20 to 0.84; p=0.015) and 1-year mortality (HR 0.62; 95%CI 0.39-0.97; p=0.037). Age, left main PCI and major bleeding, were also identified as independent prognostic factors in worse 30-day and 1-year mortality. In addition, Thrombolysis in Myocardial Infarction (TIMI) flow 0/1 pre-percutaneous coronary intervention (PCI) predicted a worse 1-year outcome. Novel oral P2Y12 receptor antagonists predicted better 30-day and 1-year survival. CONCLUSION: Our study suggests that the adjunctive usage of GPI may be beneficial in this high-risk group of patients in whom a delayed onset of action of oral antiplatelet therapy would be expected.

Analgesic drug use in patients with STEMI: Current perspectives and challenges.

Therapy for patients with ST-elevation myocardial infarction (STEMI) has been a controversial topic since the introduction of thrombolytic agents in the 1980s. The use of morphine, fentanyl and lidocaine has increased substantially during this period. However, there is still limited evidence on their advantages and limitations. In this review, the clinical application, as well as future considerations of morphine, fentanyl and lidocaine in patients with ST segment elevation myocardial infarction were discussed.

Mind the Gap: Model-Based Switching from Selatogrel to Maintenance Therapy with Oral P2Y12 Receptor Antagonists.

Background: The P2Y12 receptor antagonist selatogrel is being developed for subcutaneous self-administration with a ready-to-use autoinjector at the onset of acute myocardial infarction (AMI) symptoms. The unique pharmacological profile of selatogrel (fast, potent, and short-acting) can bridge the time gap between the onset of AMI and first medical care. A clinical Phase 1 study showed a time-dependent pharmacodynamic interaction between selatogrel and loading doses of clopidogrel and prasugrel. As treatment switching is a common clinical practice, the assessment of subsequent switching from a clopidogrel loading dose to the first maintenance dose of oral P2Y12 receptor antagonists is highly relevant. Objectives: Model-based predictions of inhibition of platelet aggregation (IPA) for the drugs triggering pharmacodynamic interactions were to be derived to support clinical guidance on the transition from selatogrel to oral P2Y12 receptor antagonists. Methods: Scenarios with selatogrel 16 mg administration or placebo followed by a clopidogrel loading dose and, in turn, prasugrel or ticagrelor maintenance doses at different times of administration were studied. Population pharmacokinetic/pharmacodynamic modeling and simulations of different treatment scenarios were used to derive quantitative estimates for IPA over time. Results: Following selatogrel/placebo and a clopidogrel loading dose, maintenance treatment with ticagrelor or a prasugrel loading dose followed by maintenance treatment quickly achieved sustained IPA levels above 80%. Prior to maintenance treatment, a short time span from 18 to 24 h was identified where IPA levels were predicted to be lower with selatogrel than with placebo if clopidogrel was administered 12 h after selatogrel or placebo. Predicted IPA levels reached with placebo alone and a clopidogrel loading dose at 4 h were consistently lower than with selatogrel administration, followed by a clopidogrel loading dose at 12 h. If a clopidogrel loading dose is administered at 12 h, selatogrel maintains higher IPA levels up to 16 h. IPA levels are subsequently lower than on the placebo until the administration of the first maintenance dose. Conclusions: Model-based predictions informed the transition from selatogrel subcutaneous administration to oral P2Y12 therapy. The application of modeling techniques illustrates the value of employing pharmacokinetic and pharmacodynamic modeling for the simulation of various clinical scenarios of switching therapies.

Antiplatelet Therapy for Atherothrombotic Disease in 2022-From Population to Patient-Centered Approaches.

Antiplatelet agents, with aspirin and P2Y12 receptor antagonists as major key molecules, are currently the cornerstone of pharmacological treatment of atherothrombotic events including a variety of cardio- and cerebro-vascular as well as peripheral artery diseases. Over the last decades, significant changes have been made to antiplatelet therapeutic and prophylactic strategies. The shift from a population-based approach to patient-centered precision medicine requires greater awareness of individual risks and benefits associated with the different antiplatelet strategies, so that the right patient gets the right therapy at the right time. In this review, we present the currently available antiplatelet agents, outline different management strategies, particularly in case of bleeding or in perioperative setting, and develop the concept of high on-treatment platelet reactivity and the steps toward person-centered precision medicine aiming to optimize patient care.

P2Y12 Antagonists in Cardiovascular Disease-Finding the Best Balance Between Preventing Ischemic Events and Causing Bleeding.

Dual antiplatelet therapy comprising of aspirin and oral P2Y12 receptor antagonists are an established cornerstone of therapy in acute coronary syndromes and percutaneous coronary intervention. As a result, the platelet P2Y12 receptor remains a key therapeutic target in cardiovascular medicine since pharmacological antagonists were first developed in the 1990's. With a greater understanding of platelet biology and the role played by the P2Y12 receptor in the amplification of platelet activation and thrombus formation, there has been progressive refinement in the development of P2Y12 receptor antagonists with greater potency and consistency of antiplatelet effect. However, challenges remain in the utilization of these agents particularly in balancing the need for greater protection from ischemic events whilst minimizing the bleeding risk and present a real opportunity for the institution of individualized medicine. Future drug developments will provide clinicians with greater avenues to achieve this.

Ticagrelor is Not Superior to Clopidogrel in Patients With Acute Coronary Syndromes Undergoing PCI: A Report from Swedish Coronary Angiography and Angioplasty Registry.

Background Ticagrelor reduces ischaemic end points in acute coronary syndromes. However, outcomes of ticagrelor versus clopidogrel in real-world patients with acute coronary syndromes treated with percutaneous coronary intervention (PCI) remain unclear. We sought to examine whether treatment with ticagrelor is superior to clopidogrel in unselected patients with acute coronary syndromes treated with PCI. Methods and Results We used data from SCAAR (Swedish Coronary Angiography and Angioplasty Registry) for PCI performed in Västra Götaland County, Sweden. The database contains information about all PCI performed at 5 hospitals (∼20% of all data in SCAAR). All procedures between January 2005 and January 2015 for unstable angina/non‒ST-segment‒elevation myocardial infarction and ST-segment‒elevation myocardial infarction were included. We used instrumental variable 2-stage least squares regression to adjust for confounders. The primary combined end point was mortality or stent thrombosis at 30 days, secondary end points were mortality at 30 days and 1-year, stent thrombosis at 30 days, in-hospital bleeding, in-hospital neurologic complications and long-term mortality. A total of 15 097 patients were included in the study of which 2929 (19.4%) were treated with ticagrelor. Treatment with ticagrelor was not associated with a lower risk for the primary end point (adjusted odds ratio [aOR], 1.20; 95% CI, 0.87-1.61; P=0.250). Estimated risk of death at 30 days (aOR, 1.18; 95% CI, 0.88-1.64; P=0.287) and at 1-year (aOR, 1.28; 95% CI, 0.86-1.64; P=0.556) was not different between the groups. The risk of in-hospital bleeding was higher with ticagrelor (aOR, 2.88; 95% CI, 1.53-5.44; P=0.001). Conclusions In this observational study, treatment with ticagrelor was not superior to clopidogrel in patients with acute coronary syndromes treated with PCI.

Platelet function testing: dead or alive.

Essentials Pharmacodynamic response to antiplatelet medication is heterogeneous. Platelet reactivity to dual antiplatelet therapy was analyzed by three platelet function assays. The prevalence of high and low platelet reactivity differed significantly between assays. Future trials are needed to determine the best assay to analyze platelet function. SUMMARY: Background High on-treatment platelet reactivity (HTPR) to antiplatelet medication leads to ischemic events, whereas low on-treatment platelet reactivity (LTPR) increases bleeding risk. However, various trials have failed to demonstrate superiority of tailored antiplatelet regimens (ARCTIC, ANTARCTIC, Trigger-PCI, and GRAVITAS). TROPICAL-ACS was the first study that demonstrated the benefit of tailoring antiplatelet medication according to platelet function analysis. A potential reason may be that different platelet function assays were used in these trials. Objectives To evaluate whether the results of platelet function tests are comparable. Patients/Methods We tested three commonly used assays - light transmission aggregometry (LTA), (Multiplate impedance aggregometry [MP]), and vasodilator-stimulated phosphoprotein phosphorylation assay (VASP) - in 23 patients receiving dual antiplatelet therapy with aspirin and clopidogrel. Results With LTA, HTPR occurred in 57% of patients; with VASP, it occurred in 43% of patients; and with MP, it occurred in 13% of patients. According to LTA, only 35% of patients were in the therapeutic window; according to VASP, 57% of patients were in the therapeutic window; and according to MP, 48% of patients were in the therapeutic window. With LTA, LTPR occurred in 9% of patients; with VASP, it occurred in 0% of patients; and with MP, it occurred in 39% of patients. Therefore, the prevalences of HTPR and LTPR differed significantly between assays. Remarkably, in 17% of patients, one assay showed HTPR whereas another showed LTPR. Conclusions The results of different platelet function assays differ substantially. Up to now, only TROPICAL-ACS had demonstrated a benefit of tailoring antiplatelet medication according to platelet function analysis. Future trials are needed to evaluate whether the platelet function assay used in TROPICAL-ACS is the 'correct' one and revives platelet function testing.

Evaluating current and emerging antithrombotic therapy currently available for the treatment of acute coronary syndrome in geriatric populations.

INTRODUCTION: Acute coronary syndromes (ACS) represent one of the most perilous presentations of ischemic heart disease. Temporal trends clearly demonstrate that ACS occur later and later in life. Elderly patients with ACS comprise a populous and growing group, with more than half of individuals presenting with myocardial infarction being 75 years or older. Nevertheless, geriatric patients are greatly underrepresented in the landmark ACS trials evaluating innovative pharmacological strategies. AREAS COVERED: The authors critically summarize recently published research on contemporary and emerging antithrombotic therapy for the treatment of ACS in geriatric patients. EXPERT OPINION: Elderly ACS patients are characterized by simultaneously increased risk of cardiovascular events and bleeding. Very few studies assessing the efficacy and safety of novel ACS pharmacotherapy in geriatric patients are currently available. Guidelines on the treatment of ACS are based on the overall results of major randomized clinical trials (RCTs), and data supporting the recommended therapy in elderly mainly derive from subanalyses of these RCTs. Properly designed and powered RCTs are necessary to properly evaluate the net effect of current and emerging pharmacotherapy in geriatric patients. Until such data are available, elderly ACS patients should receive treatment according to the general recommendations.

Whole Blood Platelet Aggregation Test and Prediction of Hemostatic Difficulty After Tooth Extraction in Patients Receiving Antiplatelet Therapy.

When patients on antiplatelet therapy (APT) require minor invasive surgery, APT is usually continued to limit the risk of thrombosis. However, the possibility of hemostatic difficulties necessitates the monitoring of platelet aggregation to prevent unexpected bleeding. We examined whether whole blood aggregometry as a point-of-care testing (POCT) could be useful as a tool for predicting hemostatic difficulties. Sixty-five patients receiving APT and 15 patients who were not receiving APT were enrolled in the present study; all patients were scheduled to undergo a tooth extraction. Whole blood samples were obtained and were examined using multiple electrode aggregometry. The aggregometry was performed using arachidonic acid (AA), adenosine diphosphate (ADP), and thrombin receptor activating peptide. Hemostatic difficulty was defined as a need for more than 10 minutes of compression to achieve hemostasis. The AA test results were significantly lower in patients treated with aspirin (control: 97.7 [29.0] U, aspirin: 14.5 [7.2] U, P < .001). The ADP test results were also significantly lower in patients treated with a P2Y12 inhibitor (control: 77.7 [21.7] U, P2Y12 inhibitor: 37.3 [20.4] U, P < .01). Six of the examined cases exhibited hemostatic difficulties. The cutoff values for the prediction of hemostatic difficulty were 16.5 U for the AA test (sensitivity, 0.833; specificity, 0.508) and 21 U for the ADP test (sensitivity, 0.847; specificity, 0.500). Our study showed that whole blood aggregometry was useful as a POCT for the prediction of hemostatic difficulties after tooth extraction in patients receiving APT.

Relative efficacy and safety of ticagelor vs clopidogrel as a function of time to invasive management in non-ST-segment elevation acute coronary syndrome in the PLATO trial.

BACKGROUND: Guidelines suggest that "upstream" P2Y12 receptor antagonists should be considered in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). HYPOTHESIS: Early use of ticagrelor in patients managed with an invasive strategy would be more effective than clopidogrel because of its more rapid onset of action and greater potency. METHODS: In the PLATO trial, 6792 NSTE-ACS patients were randomized to ticagrelor or clopidogrel (started prior to angiography) and underwent angiography within 72 hours of randomization. We compared efficacy and safety outcomes of ticagrelor vs clopidogrel as a function of "early" (<3h) vs "late" (≥3h) time to angiography. Adjusted Cox proportional hazards models evaluated interaction between randomized treatment and time from randomization to angiography on subsequent outcomes. RESULTS: Overall, a benefit of ticagrelor vs clopidogrel for cardiovascular death/myocardial infarction/stroke was seen at day 7 (hazard ratio [HR]: 0.67, P = 0.002), day 30 (HR: 0.81, P = 0.042), and 1 year (HR: 0.80, P = 0.0045). There were no significant interactions in the <3h vs ≥3h groups at any timepoint. For major bleeding, overall there was no significant increase (HR: 1.04, 95% confidence interval: 0.85-1.27); but there was a significant interaction with no difference between ticagrelor and clopidogrel in the early group (HR: 0.79), but higher bleeding risk with ticagrelor in the late angiography group, at 7 days (HR: 1.51, Pint = 0.002). Patterns were similar at 30 days and 1 year. CONCLUSIONS: The benefit of ticagrelor over clopidogrel was consistent in those undergoing early and late angiography, supporting upstream use of ticagrelor.