Patients presenting with acute coronary syndrome (ACS) are frequently treated with the P2Y12-inhibitor ticagrelor. Some patients prematurely discontinue ticagrelor, but the incidence of reasons for and clinical implications of treatment modification are relatively unknown.Data from 4,278 ACS patients (mean age: 63.6 years, 26.1% women) who were discharged on ticagrelor and enrolled in the FORCE-ACS registry between 2015 and 2020 were used. Treatment modifications were categorized as physician-recommended discontinuation, alteration, interruption, or disruption and occurred in 26.7, 20.1, 2.8, and 3.1% of patients within 12 months of follow-up (VISUAL SUMMARY: ). Underlying reasons for treatment modification differed per type of modification. Overall, the rate of ischemic events defined as all-cause death, myocardial infarction, or stroke was 6.6% at 12 months of follow-up. Cox regression analysis using time-updated modification variables as independent variables showed that treatment interruption (adjusted hazard ratio [HR]: 2.93, 95% confidence interval [CI]: 1.48-5.79, p < 0.01) and disruption (adjusted HR: 2.33, 95% CI: 1.07-5.07, p = 0.03) were associated with an increased risk of ischemic events even after adjustment for relevant confounders. Discontinuation and alteration were not associated with increased ischemic risk.In clinical practice, treatment modifications in ACS patients discharged on ticagrelor are common, although type and reasons for modification are heterogeneous. Treatment interruption and disruption are associated with excess cardiovascular risk.

Major bleedings following coronary artery bypass grafting (CABG) have significant implications on outcomes in acute coronary syndrome (ACS) patients. Owing fears of fatal bleedings in case of urgent CABG, current guidelines recommend a cessation of P2Y12 receptor antagonists (P2Y12-RA) before cardiac surgery and opt against routine pre-treatment with a P2Y12-RA before coronary angiography (CA). However, sparse information exists outside randomized trials on the frequency of urgent CABG and the consequences of inappropriately long cessation of P2Y12-RA treatment in patients presenting with ACS.

In this observational single-center study, ACS patients presenting to an emergency department requiring a CABG were recruited consecutively during a 2-year enrolment period. Baseline characteristics, CABG-related bleedings and all-cause mortality were collected from electronical medical records and related to the timing of CABG and P2Y12-RA cessation.

A total of 1,502 ACS patients were included, herein 102 (6.8%) underwent urgent CABG. The majority (76.5%) received a routine P2Y12-RA pre-treatment predominantly ticagrelor in addition to low-dose aspirin before CA. 31 (30.4%) developed a CABG-related bleeding event. Bleeding probability was highest (HR: 4.77, 95%CI 2.20-10.37, p = 0.0001) when CABG was performed within 24 h after administration of dual anti-platelet therapy (DAPT). Despite high utilization rates of DAPT pre-treatment and high prevalence of CABG-related major bleedings, no fatal bleedings occurred.

Need of urgent CABG in ACS is infrequent and does not result in an excess of mortality. However, cessation of ticagrelor for at least 48 h before CABG is recommended to minimize rates of CABG-related bleedings.

Antiplatelet therapy has been studied for its potential benefits in various cardiovascular conditions, but its role in sepsis remains less clear. This review aims to systematically analyse the available evidence on the effects of antiplatelet therapy in sepsis to assess its potential benefits and risks.

The studies published until 01st April 2024 from PubMed, Embase and Scopus databases were searched. Pooled effect sizes were reported as relative risks (RR) or weighted mean difference (WMD) with corresponding 95% confidence intervals (CI). Outcomes included mortality, length of intensive care unit (ICU) stay, hospital stay, and the risk of complications. The certainty of evidence was evaluated using GRADE.

Twenty-one studies were included. Antiplatelet therapy was associated with significantly lower risk of in-hospital mortality (RR 0.76, 95% CI: 0.67, 0.87), and mortality at one (RR 0.77, 95% CI: 0.66, 0.90) and three months (RR 0.77, 95% CI: 0.66, 0.90) follow up. Risk of complications was comparable in all patients (RR 1.01, 95% CI: 0.84, 1.21). ICU stay (in days) (WMD -0.23, 95% CI: -0.53, 0.07; N=7, I2=97.2%) and overall duration of hospital stay (in days) (WMD 0.63, 95% CI: -0.66, 1.92; N=6, I2=93.2%) was also statistically similar among patients who received and did not receive antiplatelet drugs. The certainty of evidence for the outcomes ranged from "low to very low".

Antiplatelet therapy appears safe and significantly lowers the risk of short-term mortality in septic patients. While antiplatelet therapy did not impact the duration of ICU or overall hospital stay, our findings underscore the potential of antiplatelet agents as a beneficial adjunctive therapy in sepsis management.

Perioperative bleeding is a major concern in patients receiving ticagrelor for acute coronary syndromes (ACS) when coronary artery bypass graft (CABG) surgery is required.

To evaluate whether early CABG surgery at 2 to 3 days after ticagrelor cessation is noninferior to waiting 5 to 7 days.

RAPID CABG was a noninferiority, open-label randomized trial with 6 months of follow-up. Participants were patients with ACS who had received ticagrelor and required CABG. Patients were enrolled in tertiary centers in Canada between January 2016 and March 2021. Data were analyzed from March 2021 to December 2023.

Early or delayed CABG.

The primary outcome was based on noninferiority comparison of class 3 or 4 universal definition of perioperative bleeding (UDPB). Noninferiority was prespecified as 8% between groups. Twelve-hour chest tube drainage was reported as a noninferiority comparison. Other bleeding, ischemic, and length-of-stay outcomes were assessed for superiority.

Among 143 randomized patients, the median (IQR) age was 65 (58-72) years; there were 117 male patients (82%) and 26 female (18%). Of these, 123 patients (86.0%) underwent surgery in the allocated time frame (per protocol). The median (IQR) time to surgery was 3 (2-3) days in the early group and 6 (5-7) days in the delayed group (P < .001). In a per-protocol analysis, severe or massive UDPB occurred in 3 of 65 early-group patients (4.6%) and 3 of 58 patients (5.2%) in the delayed group (between-group difference, -0.6%; 95% CI, -8.3% to 7.1%; P = .03 for noninferiority). Median (IQR) chest tube drainage was 470 (330-650) mL vs 495 (380-610) mL (between-group difference -25 mL; 95% CI, -111.25 to 35; P = .01 for noninferiority). Median (IQR) hospital stay was 9 (7-13) days and 12 (10-15) days for the early and delayed groups (P < .001).

This study found that an early surgical strategy, 2 to 3 days after ticagrelor cessation, was noninferior in incurring perioperative bleeding. The data support a reduction in the delay between ticagrelor cessation and CABG surgery and may decrease hospital length of stay.

ClinicalTrials.gov Identifier: NCT02668562.

American Society of Regional Anesthesia and Pain Medicine guidelines recommend holding most antiplatelet therapy before inserting an epidural catheter; however, guidance for patients acutely initiated on antiplatelet therapy with a catheter in situ is limited. Here, we describe the management of 2 cases of patients with indwelling epidural catheters for pain management who developed acute myocardial infarctions necessitating emergent antiplatelet therapy. Established pharmacokinetics demonstrate maximal platelet inhibition occurs within 30 minutes in ticagrelor and 4 to 6 hours in clopidogrel, suggesting early removal results in decreased the risk of epidural hematoma.

Perioperative management of antithrombotic agents requires practical and medical considerations. Discontinuing antithrombotic therapies increases the risk of thrombotic adverse events including cerebrovascular accidents, myocardial infarction, pulmonary embolism, deep vein thrombosis, and retinal artery occlusion. Conversely, continuation of antithrombotic therapy during surgical procedures has associated bleeding risks. Currently, no guidelines exist regarding management of antithrombotic agents in the perioperative period for cutaneous surgeries and practice differs by surgeon. Here, we review the data on antithrombotic medications in patients undergoing cutaneous surgery including medication-specific surgical and postoperative bleeding risk if the medications are continued, and thromboembolic risk if the medications are interrupted. Specifically, we focus on vitamin K antagonist (warfarin), direct-acting oral anticoagulants (rivaroxaban, apixaban, edoxaban, dabigatran), antiplatelet medications (aspirin, clopidogrel, prasugrel, ticagrelor, dipyridamole), unfractionated heparin, low molecular weight heparin (enoxaparin and dalteparin), fondaparinux, bruton tyrosine kinase inhibitors (ibrutinib, acalabrutinib), and dietary supplements (ie, garlic, ginger, gingko).

Patients with both acute coronary syndrome (ACS) and chronic kidney disease (CKD) face heightened risks of adverse cardiovascular events and bleeding. An optimal antiplatelet strategy for this patient population is needed.

We conducted a systematic review and meta-analysis to evaluate comparative advantages of clopidogrel vs. ticagrelor in the choice of dual antiplatelet therapy (DAPT) strategies for patients with ACS combined with CKD, while also exploring the appropriate duration of DAPT in the presence of CKD. Relevant studies were retrieved from PubMed, Embase, Cochrane Library, and Web of Science. The primary outcomes were all-cause mortality, major adverse cardiovascular events (MACE), and major bleeding. Data were analyzed using RevMan 5.4.1, and STATA 14 was used to assess publication bias. This study was registered with PROSPERO (CRD42024593764).

Six studies involving 9,947 patients met the inclusion criteria. Compared with clopidogrel, ticagrelor was associated with a reduced risk of MACE (RR: 0.89, 95% CI: 0.80-0.99; P = 0.04) and stroke (RR: 0.66, 95% CI: 0.45-0.96; P = 0.03) in patients receiving DAPT. No significant differences were observed in all-cause mortality, major bleeding, cardiovascular death, or acute myocardial infarction. Three studies on DAPT duration showed a consistent trend, indicating that shortening DAPT duration did not benefit patients.

In patients with ACS combined with CKD, ticagrelor-based DAPT has advantages over clopidogrel-based DAPT, which is associated with a lower incidence of MACE. And shortening the duration of DAPT does not improve clinical outcomes.

Aging has recently been associated with increased basal platelet activation and platelet hyperreactivity in response to adenosine diphosphate (ADP) but with decreased platelet response to thrombin receptor stimulation in individuals without antiplatelet therapy.

To investigate platelet response to agonist stimulation in elderly patients (≥70 years) on dual antiplatelet therapy with potent P2Y12 inhibitors.

Platelet aggregation in response to arachidonic acid (AA), ADP, collagen, the protease-activated receptor-1 agonist SFLLRN, and the protease-activated receptor-4 agonist AYPGKF was assessed by multiple electrode aggregometry in 79 prasugrel- and 77 ticagrelor-treated patients 3 days after acute percutaneous coronary intervention.

In the overall study population (N = 156), patients aged ≥70 years (n = 33) had lower platelet aggregation in response to AA, ADP, and SFLLRN than younger patients (all P < .05). In prasugrel-treated patients (n = 79), those aged ≥70 years (n = 13) showed lower platelet aggregation in response to all agonists than younger patients (all P < .05). In contrast, in ticagrelor-treated patients (n = 77), those aged ≥70 years (n = 20) only had lower ADP-inducible platelet aggregation than younger patients (P = .03), whereas platelet aggregation in response to AA, collagen, SFLLRN, and AYPGKF was similar between elderly and younger patients (all P > .05). Among patients aged ≥70 years, prasugrel-treated patients showed lower platelet aggregation in response to AA, collagen, and AYPGKF than those receiving ticagrelor (all P < .05).

Patients aged ≥70 years on potent P2Y12 inhibitors exhibit increased inhibition of ADP-inducible platelet aggregation. In addition, elderly patients on prasugrel show a lower response to AA, collagen, SFLLRN and AYPGKF than younger patients.

Ticagrelor is contraindicated in combination with cytochrome P450 3A4 and 3A5 enzyme (CYP3A4/5) inducers due to increased clearance, causing diminished antiplatelet effects. The emergent nature of acute coronary syndromes (ACS) may preclude scrutinization of home medications before P2Y12 inhibitor administration. The purpose of this case series is to establish the temporal impact of CYP3A4/5 enzyme induction on ticagrelor's pharmacodynamic effect by utilizing VerifyNow platelet aggregation studies. This was a retrospective case series of three patients who were taking a CYP3A4/5-inducing medication and loaded with ticagrelor for ACS. The duration of ticagrelor's antiplatelet effect was dramatically shortened in the presence of background CYP3A4/5 induction. The offset of antiplatelet effect, defined by platelet reactivity units (PRU), was 10-24 hours in the presence of CYP3A4/5 enzyme induction compared to the anticipated 36-48 hours. This was consistent across CYP3A4/5-inducing medications including carbamazepine, phenobarbital, and phenytoin. This study demonstrates rapid return of platelet function after a ticagrelor loading dose in the presence of CYP3A4/5-inducing medications. Monitoring of PRU every 6-12 hours with subsequent loading with clopidogrel or prasugrel should be considered. Larger scale studies are warranted to confirm these results.

Hemorrhagic complications associated with regional anesthesia are extremely rare. The fifth edition of the American Society of Regional Anesthesia and Pain Medicine's Evidence-Based Guidelines on regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy reviews the published evidence since 2018 and provides guidance to help avoid this potentially catastrophic complication.The fifth edition of the American Society of Regional Anesthesia and Pain Medicine's Evidence-Based Guidelines on regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy uses similar methodology as previous editions but is reorganized and significantly condensed. Therefore, the clinicians are encouraged to review the earlier texts for more detailed descriptions of methods, clinical trials, case series and pharmacology. It is impossible to perform large, randomized controlled trials evaluating a complication this rare; therefore, where the evidence is limited, the authors continue to maintain an 'antihemorrhagic' approach focused on patient safety and have proposed conservative times for the interruption of therapy prior to neural blockade. In previous versions, the anticoagulant doses were described as prophylactic and therapeutic. In this version, we will be using 'low dose' and 'high dose,' which will allow us to be consistent with other published guidelines and more accurately describe the dose in the setting of specific patient characteristics and indications. For example, the same 'high' dose may be used in one patient as a treatment for deep venous thrombosis (DVT) and in another patient as prophylaxis for recurrent DVT. Due to the increasing ability to obtain drug-specific assays, we have included suggestions for when ordering these tests may be helpful and guide practice. Like previous editions, at the end of each recommendation the authors have clearly noted how the recommendation has changed from previous editions.

Despite advancements in coronary artery disease (CAD) management, major adverse cardiovascular events persist. Vitamin K antagonists and direct oral anticoagulants present bleeding risks. Low-dose rivaroxaban (2.5 mg) is approved by the European Society of Cardiology and the US Food and Drug Administration for CAD. The survival advantage and risk-benefit profile of combining low-dose rivaroxaban with aspirin for CAD patients remain uncertain. This meta-analysis aims to compare the efficacy of low-dose rivaroxaban plus aspirin versus aspirin monotherapy in CAD patients.

We systematically searched databases for randomized controlled trials exploring low-dose rivaroxaban with aspirin in CAD patients. Of the 6220 studies screened, five met the inclusion criteria. Primary outcomes included myocardial infarction, stroke, major bleeding events, and all-cause mortality. The analysis employed a fixed-effects model, calculating hazard ratios (HRs) and 95% confidence intervals (CIs).

Five randomized controlled trials involving 41,351 participants were included. Rivaroxaban (2.5 mg) significantly reduced all-cause mortality (HR, 0.88; 95% CI, 0.81-0.95; P = 0.002), myocardial infarction (HR, 0.81; 95% CI, 0.70-0.94; P = 0.006), and stroke (HR, 0.61; 95% CI, 0.49-0.76; P < 0.00001) compared to aspirin alone. However, it increased major bleeding risk (HR, 1.66; 95% CI, 1.40-1.97; P < 0.01). Meta-regression revealed no dose-dependent impact on all-cause mortality.

Low-dose rivaroxaban demonstrates survival benefits and reduces myocardial infarction and stroke risks in CAD patients, albeit with an increased risk of major bleeding. Consideration of patient bleeding risk is crucial when adding rivaroxaban to antiplatelet therapy. Further research is warranted to compare its effectiveness and safety with dual antiplatelet therapy or P2Y12 inhibitors.

We analyzed The Society of Thoracic Surgeons Database to investigate risks and optimal timing for coronary artery bypass grafting (CABG) after clopidogrel administration.

Patients were categorized based on clopidogrel use within 5 days and further stratified by days from the last dose (0 to 5 days). Controls were patients who did not receive clopidogrel within 5 days of surgery. The primary outcome was operative mortality, and secondary outcomes included mediastinal reexploration for bleeding and blood product use.

Among 148,317 isolated CABG, 19,553 patients (13.2%) received clopidogrel within 5 days. Minimal differences in operative mortality (2.8% vs 2.1%, P < .001), but higher rates of mediastinal reexploration (3.5% vs 2.1%, P < .001) and blood product utilization (72.7% vs 56.8%, P < .001) were observed in the clopidogrel group. The adjusted odds ratio of operative mortality peaked on the day of clopidogrel administration but was comparable to controls thereafter. The odds of reexploration were highest on day 0, decreasing gradually to a plateau after day 3. Patients who underwent operations on day 3 after clopidogrel administration had similar odds of operative mortality and mediastinal reexploration for bleeding and shorter total and preoperative lengths of stay but higher blood product use compared with day 5.

CABG within 5 days from clopidogrel is associated with a modest increase in operative mortality and reexploration for bleeding and a substantial increase in blood product use. Risks decreased with increasing time from discontinuation, plateauing after 3 days from clopidogrel. CABG at 3 days yields comparable outcomes as 5 days, reducing the waiting period.

Acute coronary syndromes (ACS) are a leading cause of morbidity and mortality worldwide, with approximately 1.2 million hospitalizations annually in the U.S. This review aims to explore the contemporary evidence regarding revascularization strategies, including percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), in ACS patients. It also addresses the unresolved questions concerning the optimal procedural aspects of surgery and antithrombotic therapy for secondary prevention postsurgery.

Recent studies highlight that while PCI is generally preferred for its timeliness in high-risk non-ST-elevation ACS (NSTE-ACS) patients, CABG offers a benefit in terms of cardiovascular events in those with multivessel disease, particularly in the presence of diabetes and higher coronary disease complexity. For ST-elevation myocardial infarction (STEMI), CABG is less frequently utilized due to the preference for primary PCI, but it remains crucial for patients with complex anatomy or failed PCI. Furthermore, the optimal timing and type of antiplatelet therapy post-CABG remain controversial, with current evidence supporting the use of dual antiplatelet therapy (DAPT) to reduce ischemic events but necessitating careful management to balance bleeding risks.

In patients with ACS, the choice between PCI and CABG depends on the complexity of coronary disease and patient comorbidities. CABG is particularly beneficial for multivessel disease in NSTE-ACS and specific STEMI cases where PCI is not feasible. The management of antiplatelet therapy postsurgery requires a nuanced approach to minimize bleeding risks while preventing thrombotic complications. Further randomized clinical trials are needed to solidify these findings and guide clinical practice.

The left main (LM) coronary artery disease poses high risks for its special anatomical characteristics. Optimal antiplatelet therapy is still controversial in this disease. We aimed to investigate the efficacy and safety of ticagrelor and clopidogrel in patients with stent implantation in the LM coronary artery.

We analyzed 3221 patients with stent implantation in the LM coronary artery from January 2011 to June 2022. Patients were separated into two groups: the ticagrelor group (n = 1550) and the clopidogrel group (n = 1671). Baseline data were balanced by propensity score matching. The primary endpoint was all-cause mortality, and secondary endpoints included cardiovascular death, myocardial infarction, stroke, stent thrombosis, or target vessel revascularization. The primary safety endpoint was major bleeding, defined as BARC 3, 5 bleeding.

After propensity score matching (n = 1228 in each group), ticagrelor was linked to a lower incidence of all-cause mortality compared with clopidogrel after a three-year follow-up (5.7% vs. 8.5%; HR:0.728; 95%CI:0.537-0.985, P = 0.040). Ticagrelor treatment reduced target lesion revascularization (3.3% vs. 6.4%; HR: 0.542; 95%CI: 0.371-0.791, P = 0.001) and stent thrombosis (1.6% vs. 3.7%; HR: 0.459; 95%CI: 0.271-0.776, P = 0.004). There was no significant difference in major bleeding between the two groups. Multivariate COX analysis suggested that age, heart rate, diabetes, prior myocardial infarction, hemoglobin, serum creatinine, ticagrelor, DAPT duration, LM true-bifurcation, LM stent diameters, and IVUS were independent predictive parameters of all-cause death.

Ticagrelor was associated with lower all-cause mortality and no increased risk of major bleeding compared to clopidogrel in LM stenting patients. Thus, ticagrelor can be considered a viable substitute for clopidogrel in LM disease.

Thromboembolic complications are one of the major periprocedural complications following neuroendovascular procedures. Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel remain the principal agents for prevention of thromboembolic complications. However, clopidogrel resistance is associated with higher risk of thromboembolic complications. This study investigated the safety and efficacy of DAPT with ticagrelor and aspirin in patients undergoing intracranial stenting procedures.

This retrospective study was based on patients with intracranial aneurysms who undergoing intracranial stenting procedures at our institution between August 2017 and July 2020. These patients received DAPT with ticagrelor and aspirin were included. DAPT with 90 mg ticagrelor twice daily and aspirin 100 mg daily was continued for 3 months after the intracranial stenting procedure and aspirin continued for 1 year.

In this study, 151 patients were identified. The most common aneurysm location was the internal carotid artery with 127 (71.8%) patients. Of the 151 cases with 160 treated aneurysms, 30 (18.8%) patients were treated by flow diverters (FDs), and 130 (81.2%) by stent-assisted coiling. Five (3.3%) patients had thromboembolic complications. Intraprocedural aneurysmal rupture was observed in one patient because of coil extrusion during coil insertion. None of the patients showed a newly DAPT-related intracerebral hemorrhage. Two patients developed dyspnea, and the symptom resolved without intervention. Furthermore, ecchymoma and gastrointestinal bleeding occurred in one patient respectively. DAPT-related thromboembolic and hemorrhagic complications were not significantly different between the FD group and stent-assisted coiling group.

In our study, DAPT combining ticagrelor and aspirin seems to be a safe and efficient treatment for preventing thromboembolic complications in patients with intracranial aneurysms, without any increase in hemorrhagic complications. Ticagrelor may be an effective alternative for patients undergoing neurointervention.

Antiplatelet therapy involving aspirin and a P2Y12 receptor inhibitor is fundamental in managing patients with atherothrombotic disease. Switching between P2Y12 inhibitors is frequently observed in clinical settings for various reasons, such as safety, efficacy, patient adherence, or cost concerns. Although it occurs often, the optimal method for switching remains a concern owing to potential drug interactions, which can result in either inadequate platelet inhibition and subsequent thrombotic events or low platelet reactivity and increased bleeding risks due to therapy overlap. This review offers practical guidance on switching P2Y12 inhibitors, drawing from pharmacodynamic and clinical data.

Ticagrelor, used in acute coronary syndrome (ACS), can be administered via nasogastric tube when oral intake is impossible. We investigated platelet inhibition and pharmacokinetics in resuscitated ACS patients and those undergoing semi-urgent coronary artery bypass graft (CABG) surgery. Our study aimed to assess platelet inhibition with use of the Platelet Function Analyser (PFA) and measured plasma concentrations of ticagrelor and its active metabolite in these ACS patients.

We included resuscitated cardiac arrest patients (STEMI/NSTEMI) and semi-urgent CABG patients. Crushed ticagrelor tablets were administered using a nasogastric tube. PFA closure time (CT) was determined with CT longer than 113 s as reference range. Plasma concentrations of ticagrelor and its active metabolite were measured after protein precipitation, by using liquid chromatography with mass spectrometry detection.

In 20 resuscitated patients, 89% showed platelet inhibition at 24 h and 92% at day 4. For semi-urgent CABG patients, 85% exhibited platelet inhibition at 24 h and 84% at day 4. For ticagrelor in resuscitated patients, the median time to peak plasma concentration (Tmax) was 100 h [8; 100] for a median maximal concentration (Cmax) of 615.5 ng/mL [217.5; 1385.0]. For AR-C124910XX median Tmax was 100 h [8; 100] for a Cmax of 131.0 ng/mL [52.1; 177.7]. Among 20 patients undergoing semi-urgent CABG, Tmax for ticagrelor was 100 h [100; 100] for a median Cmax of 857.0 ng/ml [496.8; 1157.5]. For AR-C124910XX, median Tmax was 100 h [43; 100] for a Cmax of 251.0 ng/ml [173.0; 396.5].

Crushed ticagrelor via nasogastric tube achieved targeted platelet inhibition. Pharmacokinetics aligned with previous studies.EudraCT number: 2013-004191-35; Study protocol code: AGO/2013/011; EC/2014/1061; ClinicalTrial.gov identifier: NCT02341729.

Patients with atrial fibrillation (AF) undergoing elective procedures are at risk for Major Adverse Cardiovascular Events (MACE) and symptomatic bleeding. We aimed to identify risk factors to guide perioperative risk stratification.

We conducted a post-hoc analysis of the "Bridging Anticoagulation in Patients who Require Temporary Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgery" randomized trial. The primary outcomes were MACE and symptomatic bleeding. Our statistical approach encompassed standard univariate analysis, logistic stepwise regression, and Cox regression models. Additional interaction analyses evaluated the interplay between low-molecular-weight heparin bridge therapy and other identified risk factors.

Among a total of 1,813 participants (mean age 71.6 ± 8.8, 73.3 % male), MACE occurred in 25 (1.4 %) individuals, with pre-procedure clopidogrel use (adjusted hazard ratio [aHR] 7.73, 95 % CI 2.63-22.72, p < 0.001) and CHA2DS2-VASc score ≥ 5 (aHR 2.89, 95 % CI 1.26-6.63, p = 0.012) identified as risk factors. Symptomatic bleeding occurred in 57 (3.1 %) individuals, with bridge therapy (aHR 1.84, 95 % CI 1.07-3.19, p = 0.029), renal disease (aHR 2.50, 95 % CI 1.34-4.67, p = 0.004), post-procedure aspirin use (aHR 2.86, 95 % CI 1.66-4.91, p < 0.001), post-procedure nonsteroidal anti-inflammatory drug use excluding aspirin (aHR 3.40, 95 % CI 1.22-9.43, p = 0.019), and major surgery (aHR 3.94, 95 % CI 2.26-6.85, p < 0.001) identified as risk factors. The interactions between risk factors and bridging therapy on MACE and symptomatic bleeding outcomes were not significant (p > 0.05).

We identified predictors for MACE and symptomatic bleeding in AF patients undergoing elective procedures. These insights may help guide perioperative decisions to reduce the risk of adverse outcomes.

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) is indicated after percutaneous coronary intervention (PCI) to reduce the risk of atherothrombotic events. Approximately 30% of the US population has a CYP2C19 no-function allele that reduces the effectiveness of clopidogrel, but not prasugrel or ticagrelor, after PCI. We have shown improved outcomes with the integration of CYP2C19 genotyping into clinical care to guide the selection of prasugrel or ticagrelor in CYP2C19 no-function allele carriers. However, the influence of patient-specific demographic, clinical, and other genetic factors on outcomes with genotype-guided DAPT has not been defined. In addition, the impact of genotype-guided de-escalation from prasugrel or ticagrelor to clopidogrel in patients without a CYP2C19 no-function allele has not been investigated in a diverse, real-world clinical setting. The Precision Antiplatelet Therapy after Percutaneous Coronary Intervention (Precision PCI) Registry is a multicenter US registry of patients who underwent PCI and clinical CYP2C19 testing. The registry is enrolling a diverse population, assessing atherothrombotic and bleeding events over 12 months, collecting DNA samples, and conducting platelet function testing in a subset of patients. The registry aims to define the influence of African ancestry and other patient-specific factors on clinical outcomes with CYP2C19-guided DAPT, evaluate the safety and effectiveness of CYP2C19-guided DAPT de-escalation following PCI in a real-world setting, and identify additional genetic influences of clopidogrel response after PCI, with the ultimate goal of establishing optimal strategies for individualized antiplatelet therapy that improves outcomes in a diverse, real-world population.

To evaluate the association between guideline-conforming as compared to shorter than recommended withdrawal period of P2Y12 receptor inhibitors prior to isolated on-pump coronary artery bypass grafting (CABG) and the incidence of severe bleeding and ischaemic events. Randomized controlled trials are lacking in this field.

We searched PUBMED, Embase and other suitable databases for studies including patients on P2Y12 receptor inhibitors undergoing isolated CABG and reporting bleeding and postoperative ischaemic events from 2013 to March 2024. The primary outcome was incidence of Bleeding Academic Research Consortium type 4 (BARC-4) bleeding defined as any of the following: perioperative intracranial bleeding, reoperation for bleeding, transfusion of ≥5 units of red blood cells, chest tube output of ≥2 l. The secondary outcome was postoperative ischaemic events according to the Academic Research Consortium 2 Consensus Document. Patient-level data provided by each observational trial were synthesized into a single dataset and analysed using a 2-stage IPD-MA.

Individual data of 4837 patients from 7 observational studies were synthesized. BARC-4 bleeding, 30-day mortality and postoperative ischaemic events occurred in 20%, 2.6% and 5.2% of patients. After adjusting for EuroSCORE II and cardiopulmonary bypass time, guideline-conforming withdrawal was associated with decreased BARC-4 bleeding risk in patients on clopidogrel [adjusted odds ratio (OR) 0.48; 95% confidence intervals (CI) 0.28-0.81; P = 0.006] and a trend towards decreased risk in patients on ticagrelor (adjusted OR 0.48; 95% CI 0.22-1.05; P = 0.067). Guideline-conforming withdrawal was not significantly associated with 30-day mortality risk (clopidogrel: adjusted OR 0.70; 95% CI 0.30-1.61; ticagrelor: adjusted OR 0.89; 95% CI 0.37-2.18) but with decreased risk of postoperative ischaemic events in patients on clopidogrel (clopidogrel: adjusted OR 0.50; 95% CI 0.30-0.82; ticagrelor: adjusted OR 0.78; 95% CI 0.45-1.37). BARC-4 bleeding was associated with 30-day mortality risk (adjusted OR 4.76; 95% CI 2.67-8.47; P < 0.001).

Guideline-conforming preoperative withdrawal of ticagrelor and clopidogrel was associated with a 50% reduced BARC-4 bleeding risk when corrected for EuroSCORE II and cardiopulmonary bypass time but was not associated with increased risk of 30-day mortality or postoperative ischaemic events.

Ischemic etiology accounts for two thirds of all strokes in which platelet activation and aggregation play a major role. A variety of antiplatelet therapies have been tested for primary, secondary, and tertiary prevention, with certain patient subtypes benefiting more than others from a specific regimen.

This review aims at synthetizing current evidence on pharmacology of antiplatelet agents approved for primary, secondary, and tertiary stroke prevention and their application among possible patient subtypes that may benefit more from their administration.

Management of ischemic stroke has largely evolved over the past decades. A better understanding of stroke pathophysiology has allowed to identify patients who can benefit most from antiplatelet therapies, with varying degrees of benefit depending on whether these agents are being used for primary, secondary, or tertiary prevention. Importantly, the antiplatelet treatment regimens currently available have expanded and no longer limited to aspirin but include other drugs such as P2Y12 and phosphodiesterase inhibitors, also used in combination, as well as precision medicine approaches using genetic testing aiming at optimizing the safety and efficacy in this population.

This article discusses key considerations regarding ticagrelor's reported effect on heparin-induced thrombocytopenia functional assays, such as literature gaps and possible management strategies.

Limited data indicate that ticagrelor may induce false-negative results in functional assays used in the diagnosis of heparin-induced thrombocytopenia. False-negative functional assays for heparin-induced thrombocytopenia could have catastrophic consequences. The manufacturer labeling of ticagrelor now includes a warning for this potential drug-laboratory interaction. This article suggests areas that would benefit from further research and strategies in navigating this possible interaction.

Clinicians should exercise caution when evaluating functional assays for heparin-induced thrombocytopenia in patients receiving ticagrelor. This article offers suggestions for future areas of research and potential management strategies.

Myocardial necrosis following the successful reperfusion of a coronary artery occluded by thrombus in a patient presenting with ST-elevation myocardial infarction (STEMI) continues to be a serious problem, despite the multiple attempts to attenuate the necrosis with agents that have shown promise in pre-clinical investigations. Possible reasons include confounding clinical risk factors, the delayed application of protective agents, poorly designed pre-clinical investigations, the possible effects of routinely administered agents that might unknowingly already have protected the myocardium or that might have blocked protection, and the biological differences of the myocardium in humans and experimental animals. A better understanding of the pathobiology of myocardial infarction is needed to stem this reperfusion injury. P2Y12 receptor antagonists minimize platelet aggregation and are currently part of the standard treatment to prevent thrombus formation and propagation in STEMI protocols. Serendipitously, these P2Y12 antagonists also dramatically attenuate reperfusion injury in experimental animals and are presumed to provide a similar protection in STEMI patients. However, additional protective agents are needed to further diminish reperfusion injury. It is possible to achieve additive protection if the added intervention protects by a mechanism different from that of P2Y12 antagonists. Inflammation is now recognized to be a critical factor in the complex intracellular response to ischemia and reperfusion that leads to tissue necrosis. Interference with cardiomyocyte inflammasome assembly and activation has shown great promise in attenuating reperfusion injury in pre-clinical animal models. And the blockade of the executioner protease caspase-1, indeed, supplements the protection already seen after the administration of P2Y12 antagonists. Importantly, protective interventions must be applied in the first minutes of reperfusion, if protection is to be achieved. The promise of such a combination of protective strategies provides hope that the successful attenuation of reperfusion injury is attainable.

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is recommended for at least 6 and 12 months following percutaneous coronary intervention with drug-eluting stents among patients with stable ischemic heart disease and acute coronary syndrome, respectively. Additional exposure to antiplatelet therapy reduces ischemic events but also increases bleeding risk. Conversely, shorter durations of DAPT are preferred among those at high bleeding risk. Hence, decisions surrounding duration of DAPT after revascularization should include clinical judgment, assessment of the risk of bleeding and ischemic events, and time after revascularization.

Potent P2Y12 receptor antagonists have been used widely for patients undergoing percutaneous coronary intervention with different results. Benefits from different regimens various between trials. Randomized controlled trials (RCTs) have restrictive inclusion and exclusion criteria; thus, they may limit the generalizability of the findings to a broader population. This study was aimed to comprehensively investigate the outcomes of potent P2Y12 inhibitors in patients undergoing PCI, including RCTs and real-world evidence (RWE) studies. Multiple electronic databases were systemically reviewed and searched on compared potent P2Y12 inhibitors with clopidogrel. The primary efficacy end point was composite ischemic cardiovascular event and primary safety endpoint was major bleeding. Overall estimates of proportions and incidence rates with 95 % confidence intervals (CI) were calculated using fixed-effects models. Total 24 studies (140,986 patients) underwent coronary intervention were included in this meta-analysis, including 18 RCTs and 6 large cohort studies with propensity score matching. The potent P2Y12 inhibitors including cangrelor, prasugrel, and ticagrelor, significantly decreased the risk of composite adverse cardiovascular ischemic events (95 % CI 0.89-0.96, p < 0.001), but increased major bleeding (95 % CI 1.15-1.33, p < 0.001) or any bleeding (95 % CI 1.21-1.33, p < 0.001) compared with Clopidogrel. This meta-analysis merges RCTs and RWE studies and comprehensively evidences newer potent P2Y12 inhibitors are significantly more effective than clopidogrel in reduction of composite adverse thrombotic events, but the incidence of major or any bleeding was higher compared with clopidogrel.

This is a sub-analysis of the Personalized Antithrombotic Therapy for Coronary Heart Disease after PCI (PATH-PCI) trial in China to explore the relationship between smoking and outcomes following personalized antiplatelet therapy (PAT) in chronic coronary syndrome (CCS) patients undergoing percutaneous coronary intervention (PCI).

As a single-center, prospective, randomized controlled and open-label trial, the PATH-PCI trial randomized CCS patients undergoing PCI into standard group or personalized group guided by a novel platelet function test (PFT), from December 2016 to February 2018. All patients were divided into smokers and nonsmokers according to their smoking status. Subsequently, we underwent a 180-day follow-up evaluation. The primary endpoint was the net adverse clinical events (NACE).

Regardless of smoking status, in the incidence of NACE, there was a reduction with PAT but that the reductions are not statistically significant. In the incidence of bleeding events, we found no statistically significant difference between two groups (smokers: 2.0% vs. 1.4%, HR = 1.455, 95% confidence interval [CI]: 0.595-3.559, p = .412; nonsmokers: 2.2% vs. 1.8%, HR = 1.228, 95% CI: 0.530-2.842, p = .632). In smokers, PAT reduced major adverse cardiac and cerebrovascular events (MACCE) by 48.7% (3.0% vs. 5.9%, HR = 0.513, 95% CI: 0.290-0.908, p = .022), compared with standard antiplatelet therapy (SAT). PAT also reduced the major adverse cardiovascular events (MACE) but there was no statistically difference in the reductions (p > .05). In nonsmokers, PAT reduced MACCE and MACE by 51.5% (3.3% vs. 6.7%, HR = 0.485, 95% CI: 0.277-0.849, p = .011) and 63.5% (1.8% vs. 4.9%, HR = 0.365, 95% CI: 0.178-0.752, p = .006), respectively. When testing p-values for interaction, we found there was no significant interaction of smoking status with treatment effects of PAT (pint-NACE  = .184, pint-bleeding  = .660).

Regardless of smoking, PAT reduced the MACE and MACCE, with no significant difference in bleeding. This suggests that PAT was an recommendable regimen to CCS patients after PCI, taking into consideration both ischemic and bleeding risk.

Antiplatelet therapy (APT) is the foundation of treatment and prevention of atherothrombotic events in patients with atherosclerotic cardiovascular disease. Selecting the optimal APT strategies to reduce major adverse cardiovascular events, while balancing bleeding risk, requires ongoing review of clinical trials. Appended, the focused update of the Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology guidelines for the use of APT provides recommendations on the following topics: (1) use of acetylsalicylic acid in primary prevention of atherosclerotic cardiovascular disease; (2) dual APT (DAPT) duration after percutaneous coronary intervention (PCI) in patients at high bleeding risk; (3) potent DAPT (P2Y12 inhibitor) choice in patients who present with an acute coronary syndrome (ACS) and possible DAPT de-escalation strategies after PCI; (4) choice and duration of DAPT in ACS patients who are medically treated without revascularization; (5) pretreatment with DAPT (P2Y12 inhibitor) before elective or nonelective coronary angiography; (6) perioperative and longer-term APT management in patients who require coronary artery bypass grafting surgery; and (7) use of APT in patients with atrial fibrillation who require oral anticoagulation after PCI or medically managed ACS. These recommendations are all on the basis of systematic reviews and meta-analyses conducted as part of the development of these guidelines, provided in the Supplementary Material.

Inflammation is a complex pathophysiological process underlying many clinical conditions. Platelets contribute to the thrombo-inflammatory response. Platelet P2Y12 receptors amplify platelet activation, potentiating platelet aggregation, degranulation and shape change. The contents of platelet alpha granules, in particular, act directly on leucocytes, including mediating platelet-leucocyte aggregation and activation via platelet P-selectin. Much evidence for the role of platelet P2Y12 receptors in inflammation comes from studies using antagonists of these receptors, such as the thienopyridines clopidogrel and prasugrel, and the cyclopentyltriazolopyrimidine ticagrelor, in animal and human experimental models. These suggest that antagonism of P2Y12 receptors decreases markers of inflammation with some evidence that this reduces incidence of adverse clinical sequelae during inflammatory conditions. Interpretation is complicated by pleiotropic effects such as those of the thienopyridines on circulating leucocyte numbers and of ticagrelor on adenosine reuptake. The available evidence suggests that P2Y12 receptors are prominent mediators of inflammation and P2Y12 receptor antagonism as a potentially powerful strategy in a broad range of inflammatory conditions. LINKED ARTICLES: This article is part of a themed issue on Platelet purinergic receptor and non-thrombotic disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.4/issuetoc.

Prior studies have not determined whether the effect of dual antiplatelet therapy (DAPT) cessation on the subsequent risk of major adverse cardiac events (MACE) varies by the choice of P2Y12-inhibitor after acute coronary syndrome (ACS).

We performed a prespecified subanalysis of a multicenter, prospective registry of ACS patients discharged on ticagrelor or clopidogrel between 2015 and2019. Nonadherence to DAPT was categorized as physician-guided discontinuation and disruption due to adverse effects, nonadherence, or bleeding. The association between DAPT cessation and 1-year MACE was analyzed using multivariate time-updated Cox models with inverse probability of censoring weighted estimators.

Out of 2180 patients, 174 (8.3%) prematurely discontinued DAPT (physician-guided, n=126; disruption, n=48). Nonadherent patients were older and had more comorbidities than those on DAPT. Compared with physician-guided discontinuation, disruption occurred earlier after discharge and was more frequent with ticagrelor than with clopidogrel. In time-varying analysis, DAPT cessation was associated with an increased risk of MACE (adjusted HR, 1.32, 95%CI, 1.10-1.76), largely driven by disruption (adjusted HR, 1.47, 95%CI, 1.22-1.73). There was an exponential increase in MACE risk after DAPT cessation within 90 days after ACS, especially after disruption of ticagrelor compared with clopidogrel (Pinteraction<.001). After adjustment for DAPT duration, this interaction was not statistically significant on the additive scale (relative excess risk due to interaction 0.12, 95%CI,-0.99-1.24).

In this all-comers registry, 1 in 12 patients prematurely discontinued DAPT within 1 year after ACS. Compared with physician-recommended discontinuation, disruption resulted in a significantly higher risk of MACE. After adjustment for DAPT duration, this association was not moderated by the choice of P2Y12-inhibitor. Clinical trial registered at ClinicalTrials.gov (Identifier: NCT02500290).

Ticagrelor is a novel receptor antagonist that selectively binds to the P2Y12 receptor, thereby inhibiting adenosine diphosphate (ADP)-mediated platelet aggregation. Compared to clopidogrel, ticagrelor has the advantages of a fast onset, potent effects, and a reversible platelet inhibition function, which make this drug clinically suitable for treating acute coronary syndrome (ACS), especially acute ST-segment elevation myocardial infarction (STEMI).

This review was performed to determine the basic characteristics, clinical effects, and adverse reactions of ticagrelor.

Relevant trials and reports were obtained from the MEDLINE, Embase, and Cochrane Library databases.

Ticagrelor is rapidly absorbed by the body after oral administration, exhibits inherent activity without requiring metabolic activation, and binds reversibly to the P2Y12 receptor. Ticagrelor has been recommended in ACS treatment guidelines worldwide due to its advantageous pharmacological properties and significant clinical benefits. Ticagrelor inhibits platelet aggregation, inhibits inflammatory response, enhances adenosine function, and has cardioprotective effects. However, ticagrelor also causes adverse reactions such as bleeding tendency, dyspnea, ventricular pause, gout, kidney damage, and thrombotic thrombocytopenic purpura in clinical treatment. Therefore, it is necessary to pay attention to risk assessments when using ticagrelor.

Ticagrelor is a promising drug for the effective treatment of ACS. When using ticagrelor, individualized treatment should be provided based on the specific conditions of the patients to avoid serious adverse events.

There are dated and conflicting data about the optimal timing of initiation of P2Y12 inhibitors in elective percutaneous coronary intervention (PCI). Peri-PCI myocardial necrosis is associated with poor outcomes. We aimed to assess the impact of the P2Y12 inhibitor loading time on periprocedural myocardial necrosis in the population of the randomized Assessment of Loading With the P2Y12 Inhibitor Ticagrelor or Clopidogrel to Halt Ischemic Events in Patients Undergoing Elective Coronary Stenting (ALPHEUS) trial, which compared ticagrelor with clopidogrel in high-risk patients who received elective PCI.

The ALPHEUS trial divided 1809 patients into quartiles of loading time. The ALPHEUS primary outcome was used (type 4 [a or b] myocardial infarction or major myocardial injury) as well as the main secondary outcome (type 4 [a or b] myocardial infarction or any type of myocardial injury).

Patients in the first quartile group (Q1) presented higher rates of the primary outcome (P = 0.01). When compared with Q1, incidences of the primary outcome decreased in patients with longer loading times (adjusted odds ratio [adjOR], 0.70 [0.52.-0.95]; P = 0.02 for Q2; adjOR 0.65 [0.48-0.88]; P < 0.01 for Q3; adjOR 0.66 [0.49-0.89]; P < 0.01 for Q4). Concordant results were found for the main secondary outcome. There was no interaction with the study drug allocated by randomization (clopidogrel or ticagrelor). Bleeding complications (any bleeding ranging between 4.9% and 7.3% and only 1 major bleeding at 48 hours) and clinical ischemic events were rare and did not differ among groups.

In elective PCI, administration of the oral P2Y12 inhibitor at the time of PCI could be associated with more frequent periprocedural myocardial necrosis than an earlier administration. The long-term clinical consequences remain unknown.