Management of patients on antithrombotic therapy with severe infections: a joint clinical consensus statement of the ESC Working Group on Thrombosis, the ESC Working Group on Atherosclerosis and Vascular Biology, and the International Society on Thrombosis and Haemostasis.

Patients with severe infections and a pre-existing indication for antithrombotic therapy, i.e. antiplatelet agents, anticoagulant drugs, or their combinations, require integrated clinical counselling among coagulation, infectious disease, and cardiology specialists, due to sepsis-induced coagulopathy that frequently occurs. Bacterial and viral pathogens constitute an increasing threat to global public health, especially for patients with ongoing antithrombotic treatment who have a high risk of thrombotic recurrences and high susceptibility to severe infections with increased morbidity and mortality. Similarly, sepsis survivors are at increased risk for major vascular events. Coagulopathy, which often complicates severe infections, is associated with a high mortality and obligates clinicians to adjust antithrombotic drug type and dosing to avoid bleeding while preventing thrombotic complications. This clinical consensus statement reviews the best available evidence to provide expert opinion and statements on the management of patients hospitalized for severe bacterial or viral infections with a pre-existing indication for antithrombotic therapy (single or combined), in whom sepsis-induced coagulopathy is often observed. Balancing the risk of thrombosis and bleeding in these patients and preventing infections with vaccines, if available, are crucial to prevent events or improve outcomes and prognosis.

A Multicenter, Phase 2, Randomized, Placebo-Controlled, Double-Blind, Parallel-Group, Dose-Finding Trial of the Oral Factor XIa Inhibitor Asundexian to Prevent Adverse Cardiovascular Outcomes After Acute Myocardial Infarction.

BACKGROUND: Oral activated factor XI (FXIa) inhibitors may modulate coagulation to prevent thromboembolic events without substantially increasing bleeding. We explored the pharmacodynamics, safety, and efficacy of the oral FXIa inhibitor asundexian for secondary prevention after acute myocardial infarction (MI). METHODS: We randomized 1601 patients with recent acute MI to oral asundexian 10, 20, or 50 mg or placebo once daily for 6 to 12 months in a double-blind, placebo-controlled, phase 2, dose-ranging trial. Patients were randomized within 5 days of their qualifying MI and received dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor. The effect of asundexian on FXIa inhibition was assessed at 4 weeks. The prespecified main safety outcome was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding comparing all pooled asundexian doses with placebo. The prespecified efficacy outcome was a composite of cardiovascular death, MI, stroke, or stent thrombosis comparing pooled asundexian 20 and 50 mg doses with placebo. RESULTS: The median age was 68 years, 23% of participants were women, 51% had ST-segment-elevation MI, 80% were treated with aspirin plus ticagrelor or prasugrel, and 99% underwent percutaneous coronary intervention before randomization. Asundexian caused dose-related inhibition of FXIa activity, with 50 mg resulting in >90% inhibition. Over a median follow-up of 368 days, the main safety outcome occurred in 30 (7.6%), 32 (8.1%), 42 (10.5%), and 36 (9.0%) patients receiving asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian versus placebo: hazard ratio, 0.98 [90% CI, 0.71-1.35]). The efficacy outcome occurred in 27 (6.8%), 24 (6.0%), 22 (5.5%), and 22 (5.5%) patients assigned asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian 20 and 50 mg versus placebo: hazard ratio, 1.05 [90% CI, 0.69-1.61]). CONCLUSIONS: In patients with recent acute MI, 3 doses of asundexian, when added to aspirin plus a P2Y12 inhibitor, resulted in dose-dependent, near-complete inhibition of FXIa activity without a significant increase in bleeding and a low rate of ischemic events. These data support the investigation of asundexian at a dose of 50 mg daily in an adequately powered clinical trial of patients who experienced acute MI. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04304534; URL: https://www.clinicaltrialsregister.eu/ctr-search/search; Unique identifier: 2019-003244-79.

Assessment and mitigation of bleeding risk in atrial fibrillation and venous thromboembolism: A Position Paper from the ESC Working Group on Thrombosis, in collaboration with the European Heart Rhythm Association, the Association for Acute CardioVascular Care and the Asia-Pacific Heart Rhythm Society.

Whilst there is a clear clinical benefit of oral anticoagulation (OAC) in patients with atrial fibrillation (AF) and venous thromboembolism (VTE) in reducing the risks of thromboembolism, major bleeding events (especially intracranial bleeds) may still occur and be devastating. The decision to initiate and continue anticoagulation is often based on a careful assessment of both the thromboembolism and bleeding risk. The more common and validated bleeding risk factors have been used to formulate bleeding risk stratification scores, but thromboembolism and bleeding risk factors often overlap. Also, many factors that increase bleeding risk are transient and modifiable, such as variable international normalized ratio values, surgical procedures, vascular procedures, or drug-drug and food-drug interactions. Bleeding risk is also not a static 'one off' assessment based on baseline factors but is dynamic, being influenced by ageing, incident comorbidities, and drug therapies. In this Consensus Document, we comprehensively review the published evidence and propose a consensus on bleeding risk assessments in patients with AF and VTE, with the view to summarizing 'best practice' when approaching antithrombotic therapy in these patients. We address the epidemiology and size of the problem of bleeding risk in AF and VTE, review established bleeding risk factors, and summarize definitions of bleeding. Patient values and preferences, balancing the risk of bleeding against thromboembolism are reviewed, and the prognostic implications of bleeding are discussed. We propose consensus statements that may help to define evidence gaps and assist in everyday clinical practice.

Multicenter and all-comers validation of a score to select patients for manual thrombectomy, the DDTA score.

BACKGROUND: Routine manual thrombectomy (MT) is not recommended in primary percutaneous coronary intervention (P-PCI) but it is performed in many procedures. The objective of our study was validating the DDTA score, designed for selecting patients who benefit most from MT. METHODS: Observational and multicenter study of all consecutive patients undergoing P-PCI in five institutions. Results were compared with the design cohort and the performance of the DDTA was analyzed in all patients. Primary end-point of the analyses was TIMI 3 after MT; secondary endpoints were final TIMI 3, no-reflow incidence, in-hospital mortality and in-hospital major cardiovascular events (MACE). In-hospital prognosis was assessed by the Zwolle risk score. RESULTS: Three hundred forty patients were included in the validation cohort and no differences were observed as compared to the design cohort (618 patients) except for lower use of MT and higher IIb/IIIa inhibitors or drug-eluting stents. The probability of TIMI 3 after MT decreased as delay to P-PCI was higher. If DDTA score, MT was associated to TIMI 3 after MT (OR: 4.11) and final TIMI 3 (OR: 2.44). There was a linear and continuous relationship between DDTA score and all endpoints. DDTA score ≥ 4 was independently associated to lower no-reflow, in-hospital MACE or mortality. The lowest incidence of in-hospital mortality or MACE was in patients who had DDTA score ≥ 4 and Zwolle risk score 0-3. CONCLUSIONS: MT is associated to higher rate of final TIMI3 in patients with the DDTA score ≥ 4. Patients with DDTA score ≥ 4 had lower no-reflow and in-hospital complications.

Late onset prosthetic joint infection caused by Parvimonas micra.

Parvimonas micra (P.micra) is a difficult to culture gram positive anaerobic microorganism, typically found in the human microbiota, specially in the oral cavity. There are limited cases in literature reporting prosthetic joint infection due to this bacteria, although its isolation has been reported in different settings in later years. We present the case of a late onset knee prosthetic joint infection caused by Parvimonas micra in an 87 year old woman treated with antibiotics and two-step surgery with prosthetic material removal, antibiotic-loaded cement spacer placement and new prosthetic material replacement after 2 weeks of intravenous antimicrobial therapy followed by 6 weeks of oral therapy.

Role of New Antiplatelet Drugs on Cardiovascular Disease: Update on Cangrelor.

Dual therapy with a P2Y12 receptor antagonist in addition to aspirin is the antiplatelet treatment of choice in patients with acute coronary syndromes or undergoing percutaneous coronary intervention (PCI). However, available oral P2Y12 antagonists have several limitations, mostly due to their pharmacological profile, which can affect outcomes in certain clinical settings. Cangrelor is an intravenous, direct-acting, potent P2Y12 inhibitor with rapid onset and offset of action, which has been recently approved for clinical use in patients undergoing PCI. In clinical trials, cangrelor has demonstrated greater efficacy than clopidogrel with a favorable safety profile among PCI patients not receiving pretreatment with oral P2Y12 antagonists. However, its definitive role in contemporary practice is yet to be determined. This review aims to provide a comprehensive overview of the current status of knowledge on cangrelor, focusing on its pharmacological properties, clinical development, and the potential applications of this newly available agent.

Platelet reactivity over time in coronary artery disease patients treated with a bioabsorbable everolimus-eluting scaffold.

Everolimus-eluting bioabsorbable scaffolds (BVSs) have exhibited similar long-term clinical outcomes compared to its everolimus-eluting metallic counterparts. However, reports from earlier studies have shown a signal for an increased rate of stent thrombosis. The aim of the current investigation is to describe the platelet reactivity profiles over time in patients treated with everolimus-eluting BVS in comparison to everolimus-eluting metallic stents. This is a pilot study in which patients on aspirin and clopidogrel with at least 1 everolimus-eluting BVS were included (n = 24). Patients with at least 1 everolimus-eluting metallic stent implanted were included as control group (n = 25). Blood samples were taken at time of discharge and at 3- and 6-month follow-up. Platelet function tests included VerifyNow (VN-P2Y12), multiplate aggregometry (MEA), and light transmission aggregometry (LTA). There was no difference in platelet reactivity at discharge, 3- and 6-month visits (unadjusted p = 0.733 and p = 0.582; p = 0.432 and p = 0.899 after adjusting for discharge value platelet reactivity0, respectively) using VN-P2Y12. Similar findings were observed with LTA. However, patients with BVS showed significantly higher platelet reactivity than patients with metallic stents at 3 and 6 months in the crude analysis (p = 0.003) and after adjusting for discharge value (p = 0.013) measured with ADP-MEA. There were no differences in platelet reactivity mediated by the T × A2 pathway between both groups. Finally, there is no statistical difference in high on-clopidogrel platelet reactivity (HPR) rate between both groups. The results of this pilot study suggest that BVS might have different platelet reactivity profiles, and warrants further investigation in dedicated clinical studies.

Impact of sex differences on the feasibility and safety of distal radial access for coronary procedures: a multicenter prospective observational study.

BACKGROUND: Conventional transradial access in women is associated with a lower success rate and a higher incidence of spasm compared to men. To date, the effect of sex on the performance of distal radial access (DRA) has not been fully elucidated. The aim of this study was to assess the impact of sex on catheterization success and other performance parameters of DRA procedures. METHODS: This is a prospective three-center observational study. From August 2020 to September 2022, data from all consecutive patients who underwent DRA for coronary procedures were collected. RESULTS: A total of 868 procedures were registered and stratified into two groups according to sex: women (n = 258) and men (n = 610). Female patients had less favorable baseline characteristics than male patients in terms of absent or weak pulse (29% vs. 17%; P  < 0.001), distal radial diameter (2.2 ±â€…0.3 vs. 2.4 ±â€…0.4 mm; P  < 0.001) and proximal radial diameter (2.5 ±â€…0.7 vs. 2.7 ±â€…0.7 mm; P  = 0.001). No differences in success rates were found in women compared to men (94.2% vs. 96.6%; P  = 0.135), with a higher presence of arterial spasm in women (5.8% vs. 3.0%; P  = 0.044). The preprocedural ultrasound evaluation was the only predictor of DRA success [odds ratio = 20.0 (4.739-83.333); P  < 0.001]. CONCLUSION: In patients undergoing coronary procedures, the success rate of DRA was high regardless of sex, with a higher incidence of arterial spasm in women.

Everolimus-eluting stent versus bare metal stent in proximal left anterior descending ST-elevation myocardial infarction: insights from the EXAMINATION trial.

BACKGROUND: ST-elevation myocardial infarctions (STEMI) caused by proximal left-anterior descending (LAD) lesions have more myocardium at risk and worse outcomes than those located in other segments. The aim is to compare outcomes of patients with STEMI and proximal-LAD lesions treated with bare-metal stents (BMS) versus everolimus-eluting stents (EES). METHODS: The EXAMINATION trial randomized 1498 STEMI patients to BMS versus EES. The primary end point was the patient-oriented combined of all-cause death, any-recurrent myocardial infarction (MI) and any-revascularization. The secondary end point included the device-oriented combined of cardiac death, target-vessel MI and target-lesion revascularization (TLR). RESULTS: STEMI with a proximal-LAD occlusion was observed in 290 patients (BMS = 132 and EES = 158). Both groups were similar except for diabetes (12.9% vs 24.1%; P = .016). At 1 year, the primary end point was observed in 18.9% and 9.5% of patients treated with BMS and EES, respectively (P = .023). The secondary end point was observed in 11.4% and 5.1%, respectively (P = .053). There were no differences in cardiac death (4.5% vs 3.8%; P = .750) and MI (1.5% vs 0%; P = .121). BMS had higher rate of TLR compared to EES (6.8% vs 1.3%; P = .014). Patients with proximal-LAD STEMI had higher mortality than patients with non proximal-LAD STEMI (5.5% vs 2.9%; P = .027). Proximal-LAD lesions treated with BMS tended to increase the risk of the primary end point compared with other segments (18.9% vs 13.0%; P = .079). However, EES implanted in proximal-LAD had similar outcomes compared with other locations (9.5% vs 12.0%; P = .430). Adjusting for confounders, the interaction between BMS and proximal-LAD location was associated with the primary end point. CONCLUSION: Patients with STEMI and proximal-LAD lesions treated with EES have better outcomes compared with BMS at 1 year. Although further investigations are required, it seems reasonable to consider EES for proximal-LAD STEMI-lesions.

Pharmacodynamic effects of adjunctive cilostazol therapy in patients with coronary artery disease on dual antiplatelet therapy: impact of high on-treatment platelet reactivity and diabetes mellitus status.

BACKGROUND: In patients on dual antiplatelet therapy with aspirin and clopidogrel, the adjunctive use of cilostazol is associated with enhanced platelet inhibition. However, if cilostazol exerts different pharmacodynamic (PD) effects according to levels of on-treatment platelet reactivity remains unknown. This study aimed to determine the PD effects of cilostazol in patients with and without high on-clopidogrel platelet reactivity (HPR) according to diabetes mellitus (DM) status. METHODS: This is a post-hoc analysis derived from patients (n = 79) enrolled in a prospective, randomized, double-blind, double-dummy, crossover study comparing cilostazol with placebo in stable coronary artery disease patients on aspirin and clopidogrel therapy. In the present analysis, patients were divided according to the presence or absence of HPR (HPR and non-HPR). HPR was defined as a P2Y12 units (PRU) > 240 as assessed by the VerifyNow P2Y12 assay. The PD effects of cilostazol were evaluated in patients with and without HPR according to DM status. RESULTS: Significant absolute changes in PRU values were observed after adjunctive cilostazol in both HPR [53.4 (95% CI 24.7-82.1), P = 0.001] and non-HPR [40.8 (95% CI 28.7-52.8), P < 0.0001] patients. This difference was statistically significant in HPR patients with DM (P = 0.001), but not without DM (P = 0.24), and in non-HPR patients with and without DM (P = 0.0001 for both). The greatest mean reduction in PRU was observed in HPR patients with DM (72.9; 95% CI 33.7-112.0). Thrombin generation was not affected by cilostazol, irrespective of HPR status. CONCLUSION: Cilostazol reduces platelet reactivity both in HPR and non-HPR patients, although these PD effects are enhanced in HPR patients with DM. Nevertheless, larger studies are needed to better evaluate possible differential effects of cilostazol on platelet reactivity by diabetes status.

Impact of renal function on clopidogrel-induced antiplatelet effects in coronary artery disease patients without diabetes mellitus.

Diabetes mellitus (DM) is the most important predictor of chronic kidney disease (CKD), and pharmacodynamic (PD) studies have shown that DM patients with impaired renal function are characterized by reduced clopidogrel response. However, post-hoc PD studies conducted in unselected cohorts, composed of both DM and non-DM patients, have reached controversial findings on the effects of CKD on clopidogrel response, likely attributed to patient heterogeneity. The impact of renal function on clopidogrel response in non-DM patients remains unexplored and represented the aim of this prospective investigation. We conducted a prospective PD investigation in non-DM patients with and without CKD defined as an estimated glomerular filtration rate (eGFR) below or above 60 mL/min, respectively. All patients had known coronary artery disease and were on maintenance aspirin therapy. PD assessments were assessed at baseline and 2 and 24 h after a 600 mg loading dose of clopidogrel. PD assays included light transmission aggregometry (LTA) using 5 and 20 µmol ADP with and without PGE1 and flow cytometric assessment of the phosphorylation status of the vasodilator-stimulated phosphoprotein (VASP) to determine the platelet reactivity index. A total of 60 patients were studied (n = 30 eGFR ≥60 mL/min; n = 30 eGFR <60 mL/min). At baseline there were no differences between groups. Following clopidogrel loading dose administration, levels of on-treatment platelet reactivity were similar between groups at 2 and 24 h as measured with LTA and VASP. Accordingly, there were no differences in rates of high on-treatment platelet reactivity between groups. In non-DM patients with CAD, the presence of impaired renal function is not associated with differences in clopidogrel-induced antiplatelet effects compared with patients with preserved renal function.

European practice patterns for antiplatelet management in NSTE-ACS patients: Results from the REal-world ADoption survey focus on Acute antiPlatelet Treatment (READAPT) survey.

BACKGROUND: The 2020 European Society of Cardiology (ESC) guidelines for the diagnosis and management of patients with non-ST elevation-acute coronary syndrome (NSTE-ACS) recommend early invasive coronary angiography in high-risk patients and no routine pre-treatment with oral P2Y12 receptor inhibitor in NSTE-ACS patients prior to defining coronary anatomy. OBJECTIVE: To assess the implementation of this recommendation in the real-life setting. METHODS: A web-survey in 17 European countries collected physician profiles and their perceptions of the diagnosis, medical and invasive management of NSTE-ACS patients at their hospital. A sample size of at least 1100 responders permitted the estimation of proportions with a precision of at least ±3.0%. RESULTS: Among the 3024 targeted participants, 1154 provided valid feedback defined as a 50% response rate of answers to the survey questions. Overall, >60% of the participants declared full implementation of the guidelines at their institution. The time delay from admission to coronary angiography and PCI was reported to be <24 h in over 75% of the hospitals while pre-treatment was intended in >50% of NSTE-ACS patients. Ad-hoc percutaneous coronary intervention (PCI) was performed in >70% of the cases while intravenous platelet inhibition was rarely used (<10%). Between countries differences in practice patterns for antiplatelet management for NSTE-ACS were observed, suggesting heterogeneous implementation of the guidelines. CONCLUSIONS: This survey indicates that the implementation of 2020 NSTE-ACS guidelines on early invasive management and pre-treatment is heterogeneous, potentially due by local logistical constraints.

Outcomes Prediction in Complex High-Risk Indicated Percutaneous Coronary Interventions in the Older Patients.

Complex high-risk indicated percutaneous coronary intervention (CHIP-PCI) is a poorly defined concept, which has not been validated in an older population before. This study aimed to evaluate the predictive value of the CHIP-PCI score in a large cohort of elderly patients and to identify potential further risk factors. This is a pooled analysis of 3 registries that included patients aged ≥75 years who underwent percutaneous coronary intervention from 2012 to 2019: the multicenter prospective EPIC05-Sierra 75 study, the multicenter retrospective PACO-PCI (EPIC-15) registry, and the single-center, prospective Elderly-HCD registry. A total of 2,725 patients with a mean age of 81 ± 4 years were included in the study; 269 patients (10%) met the primary end point of 1-year major adverse cardiac and cerebrovascular events (MACCEs), and 51 patients (2%) had in-hospital MACCEs. Of the 12 investigated original CHIP-PCI score variables, 5 were independent predictors: previous myocardial infarction, left ventricular ejection fraction <30%, chronic kidney disease, left main coronary artery percutaneous coronary intervention, and nonradial access. Furthermore, diabetes mellitus, anemia, and severe calcification showed to be significant predictors of MACCEs. The additional variables improved the discriminatory value of the CHIP-PCI score for 1-year MACCEs (modified CHIP-PCI score: area under the curve [AUC] 0.647 vs original CHIP-PCI score: AUC 0.598, p = 0.02) and in-hospital MACCEs (AUC 0.729 vs 0.657, p = 0.003, respectively). In conclusion, the CHIP-PCI score retains its prognostic value in older patients for in-hospital MACCEs; however, it is of limited value at 1-year follow-up. The modified CHIP-PCI score, including the 5 patient-related and 3 procedure-related factors, significantly improved its discriminatory potential.

Treatment of Slow-Flow After Primary Percutaneous Coronary Intervention With Flow-Mediated Hyperemia: The Randomized RAIN-FLOW Study.

Background ST-segment-elevation myocardial infarction complicated with no reflow after primary percutaneous coronary intervention is associated with adverse outcomes. Although several hyperemic drugs have been shown to improve the Thrombolysis in Myocardial Infarction flow, optimal treatment of no reflow remains unsettled. Saline infusion at 20 mL/min via a dedicated microcatheter causes (flow-mediated) hyperemia. The objective is to compare the efficacy of pharmacologic versus flow-mediated hyperemia in patients with ST-segment-elevation myocardial infarction complicated with no reflow. Methods and Results In the RAIN-FLOW (Treatment of Slow-Flow After Primary Percutaneous Coronary Intervention With Flow-Mediated Hyperemia) study, 67 patients with ST-segment-elevation myocardial infarction and no reflow were randomized to receive either pharmacologic-mediated hyperemia with intracoronary adenosine or nitroprusside (n=30) versus flow-mediated hyperemia (n=37). The angiographic corrected Thrombolysis in Myocardial Infarction frame count and the minimal microcirculatory resistance, as assessed with intracoronary pressure-thermistor wire, dedicated microcatheter, and thermodilution techniques, were compared after study interventions. Both Thrombolysis in Myocardial Infarction frame count(40.2±23.1 versus 39.2±20.7; P=0.858) and minimal microcirculatory resistance (753.6±661.5 versus 993.3±740.8 Wood units; P=0.174) were similar between groups. Thrombolysis in Myocardial Infarction 3 flow was observed in 26.7% versus 27.0% (P=0.899). Flow-mediated hyperemia showed 2 different thermodilution patterns during saline infusion indicative of the severity of the no reflow phenomenon. In-hospital death and nonfatal heart failure were observed in 10.4% and 26.9%, respectively. Conclusions Both treatments showed similar (and limited) efficacy restoring coronary flow. Flow-mediated hyperemia with thermodilution pattern assessment allowed the simultaneous characterization of the no reflow degree and response to hyperemia. No reflow was associated with a high rate of adverse outcomes. Further research is warranted to prevent and to treat no reflow in patients with ST-segment-elevation myocardial infarction. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04685941.

De-escalation or abbreviation of dual antiplatelet therapy in acute coronary syndromes and percutaneous coronary intervention: a Consensus Statement from an international expert panel on coronary thrombosis.

Conventional dual antiplatelet therapy (DAPT) for patients with acute coronary syndromes undergoing percutaneous coronary intervention comprises aspirin with a potent P2Y purinoceptor 12 (P2Y12) inhibitor (prasugrel or ticagrelor) for 12 months. Although this approach reduces ischaemic risk, patients are exposed to a substantial risk of bleeding. Strategies to reduce bleeding include de-escalation of DAPT intensity (downgrading from potent P2Y12 inhibitor at conventional doses to either clopidogrel or reduced-dose prasugrel) or abbreviation of DAPT duration. Either strategy requires assessment of the ischaemic and bleeding risks of each individual. De-escalation of DAPT intensity can reduce bleeding without increasing ischaemic events and can be guided by platelet function testing or genotyping. Abbreviation of DAPT duration after 1-6 months, followed by monotherapy with aspirin or a P2Y12 inhibitor, reduces bleeding without an increase in ischaemic events in patients at high bleeding risk, particularly those without high ischaemic risk. However, these two strategies have not yet been compared in a head-to-head clinical trial. In this Consensus Statement, we summarize the evidence base for these treatment approaches, provide guidance on the assessment of ischaemic and bleeding risks, and provide consensus statements from an international panel of experts to help clinicians to optimize these DAPT approaches for individual patients to improve outcomes.

Reduction or de-escalation of dual antiplatelet therapy intensity or duration in patients with acute coronary syndromes undergoing percutaneous coronary intervention: A mini-review.

Current guidelines for patients with acute coronary syndrome (ACS) recommend dual antiplatelet therapy (DAPT) for 12 months. Since bleeding is the main Achilles' heel of DAPT, in recent years several randomized controlled trials have evaluated the safety and efficacy of de-escalation of DAPT with respect to ischaemic and bleeding endpoints. These trials can be broadly divided into studies evaluating a shorter duration of DAPT, and those studies in which DAPT that includes a potent P2Y12 inhibitor, such as prasugrel or ticagrelor, is compared to less intense DAPT, mainly clopidogrel or reduced-dose prasugrel. We sought to evaluate the studies assessing de-escalation of DAPT in patients with ACS undergoing PCI. We review the studies evaluating the strategies of de-escalation of DAPT intensity and those evaluating a strategy of de-escalation of DAPT duration in ACS patients undergoing PCI. We summarize the limitations of studies to date, gaps in evidence and make recommendations for future studies.

Antiplatelet efficacy of ticagrelor versus clopidogrel in Mediterranean patients with diabetes mellitus and chronic coronary syndromes: A crossover pharmacodynamic investigation.

Introduction: Patients with diabetes mellitus (DM) have augmented platelet reactivity and diminished responsiveness to clopidogrel. Ticagrelor, a more potent P2Y12 inhibitor, is clinically superior to clopidogrel in acute coronary syndromes, although its role in chronic coronary syndromes (CCS) is still the subject of debate. The aim of this investigation was to compare the pharmacodynamic effectiveness of ticagrelor and clopidogrel in Mediterranean DM patients with CCS. Materials and methods: In this prospective, randomized, crossover study, patients (n = 20) were randomized (1:1) to receive, on top of aspirin therapy, either ticagrelor 180 mg loading dose (LD)/90 mg maintenance dose (MD) b.i.d. or clopidogrel 600 mg LD/75 mg MD o.d. for 1 week in a crossover fashion with a 2-4 week washout period between regimens. Platelet function measurements were performed at 4 timepoints in each period (baseline, 2 h and 24 h after LD, and 1 week), including light transmission aggregometry (LTA, primary endpoint), VASP assay, Multiplate and VerifyNow P2Y12. Results: The ticagrelor LD achieved greater platelet inhibitory effect than clopidogrel LD, assessed with LTA (20 µM ADP as agonist), at 2 h (34.9 ± 3.9% vs. 63.6 ± 3.9%; p < 0.001) and 24 h (39.4 ± 3.5% vs. 52.3 ± 3.8%; p = 0.014). After 1 week of therapy, platelet reactivity was again significantly inferior with ticagrelor compared to clopidogrel (30.7 ± 3.0% vs. 54.3 ± 3.0%; p < 0.001). The results were consistent with the other platelet function assays employed. Conclusion: In Mediterranean patients with DM and CCS, ticagrelor provides a more potent antiplatelet effect than clopidogrel after the LD and during the maintenance phase of therapy. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT02457130].

Assessment and Mitigation of Bleeding Risk in Atrial Fibrillation and Venous Thromboembolism: Executive Summary of a European and Asia-Pacific Expert Consensus Paper.

While there is a clear clinical benefit of oral anticoagulation in patients with atrial fibrillation (AF) and venous thromboembolism (VTE) in reducing the risks of thromboembolism, major bleeding events (especially intracranial bleeds) may still occur and be devastating. The decision for initiating and continuing anticoagulation is often based on a careful assessment of both thromboembolism and bleeding risk. The more common and validated bleeding risk factors have been used to formulate bleeding risk stratification scores, but thromboembolism and bleeding risk factors often overlap. Also, many factors that increase bleeding risk are transient and modifiable, such as variable international normalized ratio values, surgical procedures, vascular procedures, or drug-drug and food-drug interactions. Bleeding risk is also not a static "one-off" assessment based on baseline factors but is dynamic, being influenced by aging, incident comorbidities, and drug therapies. In this executive summary of a European and Asia-Pacific Expert Consensus Paper, we comprehensively review the published evidence and propose a consensus on bleeding risk assessments in patients with AF and VTE, with a view to summarizing "best practice" when approaching antithrombotic therapy in these patients. We address the epidemiology and size of the problem of bleeding risk in AF and VTE, and review established bleeding risk factors and summarize definitions of bleeding. Patient values and preferences, balancing the risk of bleeding against thromboembolism, are reviewed, and the prognostic implications of bleeding are discussed. We propose consensus statements that may help to define evidence gaps and assist in everyday clinical practice.

Antithrombotic Therapy in Elderly Patients with Acute Coronary Syndromes.

The treatment of acute coronary syndrome (ACS) in elderly patients continues to be a challenge because of the characteS.G.B.ristics of this population and the lack of data and specific recommendations. This review summarizes the current evidence about critical points of oral antithrombotic therapy in elderly patients. To this end, we discuss the peculiarities and differences reported referring to dual antiplatelet therapy (DAPT) in ACS management in elderly patients and what might be the best option considering these population characteristics. Furthermore, we analyze antithrombotic strategies in patients with atrial fibrillation (AF), with a particular focus on those cases that also present coronary artery disease (CAD). It is imperative to deepen our knowledge regarding the management of these challenging patients through real-world data and specifically designed geriatric studies to help resolve the questions remaining in their disease management.