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The P2Y12 receptor plays a central role in platelet activation, secretion, and procoagulant activity. The CURE (clopidogrel in unstable angina to prevent recurrent events) trial, conducted in 2001, was the first to effectively demonstrate the benefit of dual anti-aggregation therapy with aspirin and clopidogrel in patients with acute coronary syndromes (ACS) undergoing invasive treatment. Since then, the field of interventional cardiology has changed considerably. The introduction of drug-eluting stents (DES) and the development of new, potent P2Y12 inhibitors such as ticagrelor, prasugrel and cangrelor have revolutionized the treatment of ACS. Nevertheless, ST-elevation myocardial infarction (STEMI) remains a critical condition that requires rapid and effective intervention. The use of P2Y12 receptor antagonists as part of the pretreatment strategy is an interesting topic to optimize outcomes in STEMI patients. This review summarizes the existing evidence on the efficacy and safety of pretreatment with P2Y12 receptor antagonists in STEMI, and emphasizes the importance of making pretreatment decisions based on individual clinical characteristics. The review also looks to the future, pointing to the potential role of artificial intelligence (AI) in improving STEMI diagnosis and treatment decisions, suggesting a future where technology could improve the accuracy and timeliness of care for STEMI patients. [ABSTRACT FROM AUTHOR]

Platelet-fibrin clot formation is a key process in acute arterial thrombosis. The relationship between thrombin-induced platelet-fibrin clot strength (P-FCS) and fibrinogen levels in patients with cardiovascular disease (CVD) and COVID-19 has not been studied. In thhe current study, the contribution of fibrinogen to P-FCS has been explored in healthy subjects (n=157), patients hospitalized with COVID-19 (n=116), and patients with CVD (n=93) using thrombelastography (TEG 6s) with citrate cartridge. We found that thrombin-induced P-FCS, fibrin clot strength (F-CS) and fibrinogen levels (FLEV) were higher among patients with CVD and COVID-19 compared to HS (p<0,05 for all) and highest among patients with COVID-19. P-FCS, an established risk factor for post-PCI ischemic event occurrences, was associated with both F-CS and FLEV (R2=0.67, p<0.001 for both comparisons. These data indicate that fibrinogen levels strongly influence the viscoelastic strength of the platelet-fibrin clot, fibrinogen may be an important driving factor for arterial thrombosis in the presence of potent platelet inhibition and may be as equally important a risk factor as high platelet reactivity. Since P-FCS is significantly associated with fibrinogen levels, the role of fibrinogen as a risk factor for arterial ischemic event occurrences should be further studied to improve antithrombotic therapy personalization. [ABSTRACT FROM AUTHOR]

This article is co-authored by a patient with acute coronary syndrome (ACS) who is receiving long-term antiplatelet therapy in the USA and a cardiologist who routinely treats patients with ACS. The patient describes his experience from diagnosis to the present day and discusses his concerns regarding treatment and management of the condition, including the balance between the benefits and risks of antiplatelet therapy. The patient also describes his work as an advocate for cardiac health. The physician perspective on treating and managing patients with ACS is provided by a cardiologist based in the USA who is and was not involved in this patient's care. The physician reviews the benefits and risks of antiplatelet therapies for the treatment of patients with ACS and discusses his own clinical experience of managing these patients, including how issues such as treatment adherence, as well as the potential inertia to prescribing certain medications that may be seen among physicians, could be overcome. Plain Language Summary: Antiplatelet therapies are commonly prescribed to patients who have experienced events termed "acute coronary syndrome" (ACS), such as a heart attack, to prevent further cardiovascular events. However, these medicines come with potential risks, such as bleeding. This article provides perspectives from a patient and a cardiologist on managing ACS, and the benefits and risks of antiplatelet therapies. Platelet inhibitors, which aim to prevent blood clots from forming, are the standard treatment for ACS. Different types of platelet inhibitors are used, including treatments known as P2Y12 inhibitors as well as treatments referred to as platelet aggregation inhibitors. Clinical trials have tested different combinations and durations of antiplatelet therapies, and some trials have shown that changing to P2Y12 inhibitor treatment alone after receiving a combination of platelet inhibitors can reduce the risk of cardiovascular events without increasing the risk of bleeding. Treatment guidelines recommend at least 12 months of platelet inhibitors for patients with ACS; however, treatment decisions should be individualized based on the patient's risk profile. Despite the evidence supporting their benefits, some physicians remain reluctant to prescribe potent P2Y12 inhibitors, preferring older, less potent options. Treatment adherence is also challenging, and is influenced by factors such as bleeding, education level, and cost. Improved education about the benefits and risks of antiplatelet therapies may help to address these issues and improve outcomes for patients with ACS. The perspectives of both the patient and the physician contribute to an increased understanding of ACS management and the challenges faced by patients and health care providers. [ABSTRACT FROM AUTHOR]

Abstract Background Sepsis is a life-threatening disease accompanied by disorders of the coagulation and immune systems. P2Y12 inhibitors, widely used for arterial thrombosis prevention and treatment, possess recently discovered anti-inflammatory properties, raising potential for improved sepsis prognosis. Method We conducted a retrospective analysis using the data from Medical Information Mart for Intensive Care-IV database. Patients were divided into an aspirin-alone group versus a combination group based on the use of a P2Y12 inhibitor or not. Differences in 30-day mortality, length of stay (LOS) in intensive care unit (ICU), LOS in hospital, bleeding events and thrombotic events were compared between the two groups. Result A total of 1701 pairs of matched patients were obtained by propensity score matching. We found that no statistically significant difference in 30-day mortality in aspirin-alone group and combination group (15.3% vs. 13.7%, log-rank p = 0.154). In addition, patients received P2Y12 inhibitors had a higher incidence of gastrointestinal bleeding (0.5% vs. 1.6%, p = 0.004) and ischemic stroke (1.7% vs. 2.9%, p = 0.023), despite having a shorter LOS in hospital (11.1 vs. 10.3, days, p = 0.043). Cox regression showed that P2Y12 inhibitor was not associated with 30-day mortality (HR = 1.14, 95% CI 0.95–1.36, p = 0.154). Conclusion P2Y12 inhibitors did not provide a survival benefit for patients with sepsis 3 and even led to additional adverse clinical outcomes.

The P2Y12 receptor plays a central role in platelet activation, secretion, and procoagulant activity. The CURE (clopidogrel in unstable angina to prevent recurrent events) trial, conducted in 2001, was the first to effectively demonstrate the benefit of dual anti-aggregation therapy with aspirin and clopidogrel in patients with acute coronary syndromes (ACS) undergoing invasive treatment. Since then, the field of interventional cardiology has changed considerably. The introduction of drug-eluting stents (DES) and the development of new, potent P2Y12 inhibitors such as ticagrelor, prasugrel and cangrelor have revolutionized the treatment of ACS. Nevertheless, ST-elevation myocardial infarction (STEMI) remains a critical condition that requires rapid and effective intervention. The use of P2Y12 receptor antagonists as part of the pretreatment strategy is an interesting topic to optimize outcomes in STEMI patients. This review summarizes the existing evidence on the efficacy and safety of pretreatment with P2Y12 receptor antagonists in STEMI, and emphasizes the importance of making pretreatment decisions based on individual clinical characteristics. The review also looks to the future, pointing to the potential role of artificial intelligence (AI) in improving STEMI diagnosis and treatment decisions, suggesting a future where technology could improve the accuracy and timeliness of care for STEMI patients.

Background Although age and body mass index (BMI) significantly affect platelet reactivity units and clinical outcomes after percutaneous coronary intervention, there are limited data on the relationship between high on‐treatment platelet reactivity (HPR) and clinical outcomes on age and BMI differences. Thus, we investigated the association of HPR with clinical outcomes according to age and BMI. Methods and Results The study analyzed 11 714 patients who underwent platelet function tests after percutaneous coronary intervention. The primary end point was the occurrence of major adverse cardiac and cerebrovascular events (MACCEs), whereas the secondary end point was major bleeding. HPR was defined as platelet reactivity units ≥252. Patients were categorized by age (22.6 kg/m2). Patients 22.6 kg/m2 had increases in MACCEs (adjusted HR, 1.387 [95% CI, 1.140–1.688]; P=0.001). No differences were shown in major bleeding. Conclusions HPR was linked to an increase in MACCEs or a decrease in major bleeding in patients after percutaneous coronary intervention, depending on age and BMI. This study is the first to observe that clinical outcomes in patients with HPR after percutaneous coronary intervention may vary based on age and BMI. Because the study is observational, the results should be viewed as hypothesis generating and emphasize the need for randomized clinical trials.

Evidence to support immediate P2Y 12 inhibitor loading in ST-segment elevation myocardial infarction (STEMI) is limited. This study sought to compare outcomes of STEMI patients receiving immediate or delayed P2Y 12 inhibitor treatment. Using data from the prospective Bern-PCI registry between 2016 and 2020, we stratified STEMI patients undergoing percutaneous coronary intervention according to time periods with different institutional recommendations regarding P2Y 12 inhibitor pretreatment. In cohort 1 (October 2016-September 2018), immediate P2Y 12 inhibitor treatment was recommended. In cohort 2 (October 2018-September 2020), P2Y 12 inhibitor treatment was recommended after coronary anatomy was confirmed. The primary endpoint was a composite of major adverse cardiac or cerebrovascular events (MACCEs) defined as all-cause death, recurrent myocardial infarction, stroke, or definite stent thrombosis at 30 days. Sensitivity analysis included only patients in whom these recommendations were followed. Cohort 1 included 1,116 patients; pretreatment was actually given in 708 (63.4%). Cohort 2 included 847 patients; pretreatment was withheld in 798 (94.2%). The mean age was 65 ± 13 years, and 24% were female. Baseline characteristics were well-balanced between groups. The median difference for P2Y 12 loading to angiography was 52 minutes between cohort 1 and 2 and 100 minutes between patients receiving vs not receiving pretreatment. Rates of MACCEs were similar between cohort 1 and cohort 2 (10.1% vs 8.1%; adjusted HR: 0.91; 95% CI: 0.65-1.28; P = 0.59) and between patients receiving vs not receiving pretreatment (7.1% vs 8.4%; adjusted HR: 1.17; 95% CI: 0.78-1.74; P = 0.45). In this cohort study of patients with STEMI undergoing primary percutaneous coronary intervention, P2Y 12 inhibitor pretreatment was not associated with improved MACCEs. [Display omitted] [ABSTRACT FROM AUTHOR]

The antithrombotic management of patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) poses numerous challenges. Triple antithrombotic therapy (TAT), which combines dual antiplatelet therapy (DAPT) with oral anticoagulation (OAC), provides anti-ischemic protection but increases the risk of bleeding. Therefore, TAT is generally limited to a short phase (1 week) after PCI, followed by aspirin withdrawal and continuation of 6–12 months of dual antithrombotic therapy (DAT), comprising OAC plus clopidogrel, followed by OAC alone. This pharmacological approach has been shown to mitigate bleeding risk while preserving adequate anti-ischemic efficacy. However, the decision-making process remains complex in elderly patients and those with co-morbidities, significantly influencing ischemic and bleeding risk. In this review, we discuss the available evidence in this area from randomized clinical trials and meta-analyses for post-procedural antithrombotic therapies in patients with non-valvular AF undergoing PCI. [ABSTRACT FROM AUTHOR]

Introduction: Patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) require dual antiplatelet therapy (DAPT). However, the response to treatment can vary considerably. Certain platelet microRNAs (miRs) are suspected to predict DAPT response and influence platelet function. This study aimed to analyze selected miRs' expressions and compare them among patients treated with different P2Y12 inhibitors while assessing their association with platelet activity and turnover parameters. Materials and methods: We recruited 79 ACS patients post-PCI treated with clopidogrel, ticagrelor, or prasugrel, along with 18 healthy volunteers. Expression levels of miR-126-3p, miR223-3p, miR-21-5p, miR-197-3p, and miR-24-3p, as well as immature platelet fraction (IPF) and ADP-induced platelet reactivity, were measured and compared between groups. Results: Analyses revealed significantly lower expressions of miR-126-3p, miR-223-3p, miR-21-5p, and miR-197-3p in patients treated with ticagrelor, compared to clopidogrel (fold changes from −1.43 to −1.27, p-values from 0.028 to 0.048). Positive correlations were observed between platelet function and the expressions of miR-223-3p (r = 0.400, p = 0.019) and miR-21-5p (r = 0.423, p = 0.013) in patients treated with potent drugs. Additionally, miR-24-3p (r = 0.411, p = 0.012) and miR-197-3p (r = 0.333, p = 0.044) showed correlations with IPF. Conclusions: The identified platelet miRs hold potential as biomarkers for antiplatelet therapy. (ClinicalTrials.gov number, NCT06177587). [ABSTRACT FROM AUTHOR]

Aspirin has for some time been used as a first-line treatment for acute coronary syndromes, including ST-elevation myocardial infarction, for secondary prevention of established coronary disease, and for primary prevention in patients at risk of coronary artery disease. Although aspirin has been in use for decades, the available evidence for its efficacy largely predates the introduction of other drugs, such as statins and P2Y12 inhibitors. Based on recent trials, the recommendation for aspirin use as primary prevention has been downgraded. In addition, P2Y12 inhibitors given as a single antiplatelet therapy have been associated with a lower incidence of bleeding than dual antiplatelet therapy in combination with aspirin in patients with stable and unstable coronary artery disease. The aim of this review is to discuss the role of aspirin considering the available evidence for primary prevention, secondary prevention for stable coronary artery disease or acute coronary syndromes, and after percutaneous coronary intervention or coronary artery bypass revascularization. [ABSTRACT FROM AUTHOR]

Antiplatelet therapy is a cornerstone of secondary prevention of cardiovascular diseases (CVDs). However, current guidelines are based on data derived primarily from men, as women are generally underrepresented in trials. Consequently, there are insufficient and inconsistent data on the effect of antiplatelet drugs in women. Sex differences were reported in platelet reactivity, patient management, and clinical outcomes after treatment with aspirin, P2Y12 inhibitor, or dual antiplatelet therapy. To evaluate whether sex-specific antiplatelet therapy is needed, in this review we discuss (i) how sex affects platelet biology and response to antiplatelet agents, (ii) how sex and gender differences translate into clinical challenges and (iii) how the cardiological care in women might be improved. Finally, we highlight the challenges faced in clinical practice regarding the different needs and characteristics of female and male patients with CVD and address issues requiring further investigation. [ABSTRACT FROM AUTHOR]

Cangrelor, a potent intravenous P2Y12 platelet inhibitor, has demonstrated effectiveness in reducing ischemic events without a corresponding increase in severe bleeding during percutaneous coronary intervention, as evidenced by the CHAMPION-PHOENIX trial. Its off-label role as a bridging antiplatelet agent for patients facing high thrombotic risks who must temporarily stop oral P2Y12 inhibitor therapy further underscores its clinical utility. This is the first case series to shed light on the application of cangrelor in cancer patients needing to pause dual antiplatelet therapy for a range of medical interventions, marking it as a pioneering effort in this domain. The inclusion of patients with a variety of cancer types and cardiovascular conditions in this series underlines the adaptability and critical role of cangrelor in managing the dual challenges of bleeding risk and the need for uninterrupted antiplatelet protection. By offering a bridge for high-risk cancer patients who have recently undergone percutaneous coronary intervention and need to halt oral P2Y12 inhibitors temporarily, cangrelor presents a practical solution. Early findings indicate it can be discontinued safely 2-4 h before medical procedures, allowing for the effective reintroduction of oral P2Y12 inhibitors without adverse effects. This evidence calls for expanded research to validate and extend these preliminary observations, emphasizing the importance of further investigation into cangrelor's applications in complex patient care scenarios.

(1) Background: Little prospective data exist regarding the perioperative management and long-term prognosis of elderly patients receiving treatment with antithrombotic drugs and undergoing urgent surgery for a hip fracture. (2) Methods: The study included patients who required hip surgery and were receiving warfarin, DOAc or P2Y12 antiplatelet agents at the moment of trauma. Ongoing antithrombotic treatment was managed according to existing recommendations. The endpoints of the study were the time to surgery, perioperative bleeding, the need for transfusion and, finally, mortality, major cardiovascular events and re-hospitalization at 6 and 12 months. (3) Results: The study included a total of 138 patients. The mean age was 86 years; 75.4% were female. Eighty-two received DOAc, thirty-six received warfarin and twenty received P2Y12 inhibitors. The controls were 283 age- and sex-matched patients who did not receive antithrombotic treatment. A total of 38% of patients receiving warfarin underwent surgery <48 h, 52% receiving DOAc, 55% receiving P2Y12 inhibitors and, finally, 82% in the control group. Perioperative bleeding and the need for transfusion were not different between the four groups. Mortality at 6 months was higher in patients receiving warfarin and P2Y12 inhibitors (30% and 25%) in comparison to DOAc and the control group (11.6% and 10% p < 0.0001). Similarly, the other endpoints were more frequent in patients receiving warfarin and P2Y12 inhibitors. The trend was maintained for 12 months. No significant differences in mortality were found between early (<48 h) and late (>48 h) surgery independent of the type of treatment. (4) Conclusions: Our study confirmed that anticoagulants delay surgery in patients with hip fractures; however, intervention > 48 h is not associated with a poorer prognosis. This finding is relevant as it underlines that, in patients at high risk of postoperative cardiovascular complications, the careful management of anticoagulation before surgery may compensate for the delay of surgery with a very low in-hospital mortality rate (<1%). One-year survival was significantly lower in patients receiving warfarin, probably related to their worse risk profile at the moment of trauma survival. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to assess the association between body mass index (BMI) and platelet reactivity in STEMI patients treated with oral 3rd generation P2Y12 inhibitors. Methods: Overall, 429 STEMI patients were enrolled in this study. Patients were divided into two groups according to BMI (BMI < 25 vs ≥ 25 kg/m2). A propensity score matching (1:1) was performed to balance potential confounders in patient baseline characteristics. Platelet reactivity was assessed by VerifyNow at baseline and after 3rd generation P2Y12 inhibitor (ticagrelor or prasugrel) loading dose (LD). Blood samples were obtained at baseline (T0), 1 h (T1), 2 h (T2), 4–6 h (T3), and 8–12 h (T4) after the LD. High on-treatment platelet reactivity (HTPR) was defined as a platelet reactivity unit value ≥ 208 units. Results: After propensity score matching, patients with BMI ≥ 25 had similar values of baseline platelet reactivity, while they had higher level of platelet reactivity at 1 and 2 h after the LD and higher rate of HRPT. Furthermore, multivariate analysis demonstrated that BMI ≥ 25 was an independent predictor of HTPR at 2 h (OR 2.01, p =.009). Conversely, starting from 4 h after the LD, platelet reactivity values and HRPT rates were comparable among the two study groups. Conclusions: A BMI ≥ 25 kg/m2 is associated with delayed pharmacodynamic response to oral 3rd generation P2Y12 inhibitor LD, and it is a strong predictor of HTPR in STEMI patients treated by dual antiplatelet therapy with ticagrelor or prasugrel. [ABSTRACT FROM AUTHOR]

There is still a debate about the safety and efficacy of an aspirin free strategy after percutaneous coronary intervention (PCI). Hence, we performed a meta-analysis comparing aspirin free strategy to dual antiplatlets therapy (DAPT). Randomized trials (RCTs) comparing aspirin free strategy to DAPT in patients who received PCI were included. The primary outcome of interest was bleeding, defined per the Bleeding Academic Research Consortium (BARC). Secondary outcomes included major adverse cardiovascular and cerebrovascular events (MACE); defined as all-cause mortality, myocardial infarction or stroke, the individual component of MACE and stent thrombosis. A total of 4 RCTs with 29,089 patients were included. There was significant reduction in BARC 2,3 or 5 bleeding events in patients who were treated with aspirin free strategy versus DAPT (HR 0.61, 95% CI 0.39-, p = 0.03, I2 = 89%). Moreover, although there was a trend of reduced major bleeding (BARC 3 or 5) outcomes in the aspirin free strategy group compared to the DAPT group, this did not achieve statistical significance (HR 0.63, 95% CI 0.37-1.06, p = 0.08, I2 = 795). Additionally, there was no difference between the aspirin free strategy and DAPT in term of MACE (HR 0.92, 95% CI 0.82-1.03, p = 0.13, I2 = 0%), all-cause mortality (HR 0.89, 95% CI 0.77-1.04, p = 0.15, I2 = 0%), MI (HR 0.89, 95% CI 0.74-1.08, p = 0.24, I2 = 0%), stroke (HR 1.13, 95% CI 0.65-1.99, p = 0.66, I2 = 60%) or stent thrombosis (HR 0.1.01, 95% CI 0.83-1.22, p = 0.93, I2 = 0%). Aspirin free strategy is as effective as DAPT in reducing MACE with better safety profile in term of bleeding.

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Cardiovascular disease, particularly coronary artery disease (CAD), remains the leading cause of mortality and morbidity in industrialized countries. Platelet activation and aggregation at the site of endothelial injury play a key role in the processes ultimately resulting in thrombus formation with vessel occlusion and subsequent end-organ damage. Consequently, antiplatelet therapy has become a mainstay in the pharmacological treatment of CAD. Several drug classes have been developed over the last decades and a broad armamentarium of antiplatelet agents is currently available. This review portrays the evolution of antiplatelet therapy, and provides an overview on previous and current antiplatelet drugs and strategies. [ABSTRACT FROM AUTHOR]

Purpose: Acute myocardial ischaemia triggers a non-specific inflammatory response of remote myocardium through the increase of plasma concentrations of acute-phase proteins, which causes myocardial oedema. As ticagrelor has been shown to significantly decrease circulating levels of several pro-inflammatory cytokines in patients after acute myocardial infarction with ST-elevation (STEMI), we sought to investigate a potential suppressive effect of ticagrelor over prasugrel on cardiac magnetic resonance (CMR) T1 and T2 values in remote myocardium. Methods: Ninety STEMI patients were prospectively included and randomised to receive either ticagrelor or prasugrel maintenance treatment after successful primary percutaneous coronary intervention. Patients underwent CMR after 2–7 days. The protocol included long and short axis cine imaging, T1 mapping, T2 mapping and late gadolinium enhancement imaging. Results: After excluding 30 patients due to either missing images or insufficient quality of the T1 or T2 maps, 60 patients were included in our analysis. Of those, 29 patients were randomised to the ticagrelor group and 31 patients to the prasugrel group. In the remote myocardium, T1 values did not differ between groups (931.3 [919.4–950.4] ms for ticagrelor vs. 932.6 [915.5–949.2] ms for prasugrel (p = 0.94)), nor did the T2 values (53.8 ± 4.6 ms for ticagrelor vs. 53.7 ± 4.7 ms for prasugrel (p = 0.86)). Also, in the infarcted myocardium, T1 and T2 values did not differ between groups. Conclusion: In revascularised STEMI patients, ticagrelor maintenance therapy did not show superiority over prasugrel in preventing early remote myocardial inflammation as assessed by CMR T1 and T2 mapping. [ABSTRACT FROM AUTHOR]

The continuation of antiplatelet agents in the periprocedural period around carotid stenting (CAS) procedures is felt to be mandatory to minimize the risk of periprocedural stroke. However, the optimal antiplatelet regimen is unclear, with some advocating dual antiplatelet therapy, and others supporting the use of P2Y 12 inhibitors alone. The objective of this study was to evaluate the periprocedural effect of P2Y 12 inhibitors for CAS. The Vascular Quality Initiative was used from years 2007 to 2020. All transcarotid artery revascularization (TCAR) and transfemoral carotid artery stenting (TF-CAS) procedures were included. Patients were stratified based on perioperative use of P2Y 12 inhibitors as well as symptomatic status. Primary end points were perioperative neurological events (strokes and transient ischemic attacks). Secondary end points were mortality and myocardial infarction. A total of 31,036 CAS procedures were included for analysis, with 49.8% TCAR and 50.2% TF-CAS cases; 63.8% of patients were male and 82.3% of patients were on a P2Y 12 inhibitor. P2Y 12 inhibitor use was more common in males, asymptomatic patients, those older than 70 years, and concurrent statin use. P2Y 12 inhibitors were more likely to be used in TCAR cases than in TF-CAS cases (87.3% vs 76.8%; P <.001). The rate of periprocedural neurological events in the whole cohort was 2.6%. Patients on P2Y 12 inhibitors were significantly less likely to experience a periprocedural neurological event (2.3% vs 3.9%; P <.001) and mortality (0.6% vs 2.1%; P <.001) than those who were not on a P2Y 12 inhibitor. There was no effect on the rates of myocardial infarction. On multivariate analysis, both symptomatic and asymptomatic patients on P2Y 12 inhibitors were significantly less likely to develop perioperative neurological events. Additionally, the use of P2Y 12 inhibitors demonstrated an independent significant effect in reducing of the rate of perioperative stroke (odds ratio, 0.29; 95% confidence interval, 0.25-0.33). Finally, additional analysis of the types of P2Y 12 inhibitors used revealed that all seemed to be equally effective in decreasing the periprocedural neurological event rate. The use of perioperative P2Y 12 inhibitors seems to markedly decrease the perioperative neurological event rate with TCAR and TF-CAS in both symptomatic and asymptomatic patients and should be strongly considered. Patients with contraindications to P2Y 12 inhibitors may not be appropriate candidates for any CAS procedure. Additionally, alternative types of P2Y 12 inhibitors seem to be equally effective as clopidogrel. Finally, an analysis of the Vascular Quality Initiative demonstrates that, even for TCAR cases, only 87.3% of patients seem to be on P2Y 12 inhibitors in the periprocedural period, leaving room for significant improvement. [ABSTRACT FROM AUTHOR]

Platelet reactivity (PR) has been indicated as a pathophysiological key element for ST-Elevation Myocardial Infarction (STEMI) development. Patients with not-high before-treatment platelet reactivity (NHPR) have been poorly studied so far. The aim of this study is to investigate the prevalence, clinical characteristics, response to therapy and outcomes of baseline prior to treatment NHPR among patients with STEMI undergoing primary PCI. We analyzed the data from 358 STEMI patients with assessment of PR by VerifyNow before P2Y12 inhibitor loading dose (LD). Blood samples were obtained at baseline, and after 1 hour, 2 hours, 4–6 hours and 8–12 hours after LD. High platelet reactivity (HPR) was defined as Platelet Reactivity Unit values ≥208, while patients with values

It remains unclear whether P2Y 12 inhibitor monotherapy preserves ischemic protection while limiting bleeding risk compared with dual antiplatelet therapy (DAPT) after complex percutaneous coronary intervention (PCI). We sought to assess the effects of P2Y 12 inhibitor monotherapy after 1-month to 3-month DAPT vs standard DAPT in relation to PCI complexity. We pooled patient-level data from randomized controlled trials comparing P2Y 12 inhibitor monotherapy and standard DAPT on centrally adjudicated outcomes after coronary revascularization. Complex PCI was defined as any of 6 criteria: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or chronic total occlusion. The primary efficacy endpoint was all-cause mortality, myocardial infarction, and stroke. The key safety endpoint was Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding. Of 22,941 patients undergoing PCI from 5 trials, 4,685 (20.4%) with complex PCI had higher rates of ischemic events. The primary efficacy endpoint was similar between P2Y 12 inhibitor monotherapy and DAPT among patients with complex PCI (HR: 0.87; 95% CI: 0.64-1.19) and noncomplex PCI (HR: 0.91; 95% CI: 0.76-1.09; P interaction = 0.770). The treatment effect was consistent across all the components of the complex PCI definition. Compared with DAPT, P2Y 12 inhibitor monotherapy consistently reduced BARC 3 or 5 bleeding in complex PCI (HR: 0.51; 95% CI: 0.31-0.84) and noncomplex PCI patients (HR: 0.49; 95% CI: 0.37-0.64; P interaction = 0.920). P2Y 12 inhibitor monotherapy after 1-month to 3-month DAPT was associated with similar rates of fatal and ischemic events and lower risk of major bleeding compared with standard DAPT, irrespective of PCI complexity. (PROSPERO [P2Y12 Inhibitor Monotherapy Versus Standard Dual Antiplatelet Therapy After Coronary Revascularization: Individual Patient Data Meta-Analysis of Randomized Trials]; CRD42020176853) [Display omitted] [ABSTRACT FROM AUTHOR]

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Antiplatelet medications interfere with hemostasis which can contribute to increased risk of hematoma expansion and potentially worse outcomes in patients presenting with intracranial hemorrhages (ICH). Current Neurocritical Care Society guidelines recommend desmopressin (DDAVP) in patients with antiplatelet-associated ICH with evidence limited by small cohorts. Patients were included in our multi-center, retrospective study if they had computed tomographic (CT) scan confirmed ICH and were taking antiplatelet medications. Patients were excluded if hospital length of stay was <24 h, administered DDAVP dose was <0.3 μg/kg, no follow-up head CT scan was performed within the first 24 h after baseline, major neurosurgical intervention was performed in between CT scans, or the injury was an acute on chronic ICH. The primary outcome was incidence of hematoma expansion (defined as >20 % increase from baseline). Secondary outcomes were incidence of thrombotic complications within 7 days, largest absolute decrease in serum sodium within the first 24 h, and patient disposition. Among the 209 patients included in the study, 118 patients received DDAVP while 91 did not. The frequency of hematoma expansion was similar between patients who received DDAVP and those who did not (16.1 % vs 17.6 %; P = 0.78). No difference in secondary outcomes was observed between the two groups. These findings in conjunction with recently published literature may suggest minimal benefit or harm with DDAVP treatment. However, further study could elucidate any potential impact on long-term function outcomes. • This study sought to analyze the safety and efficacy of DDAVP in patients with antiplatelet-associated ICH. • Primary outcome of hematoma expansion incidence was determined by review of CT scans within 24 hours of the baseline scan. • Administration of DDAVP did not reduce incidence of hematoma volume expansion in patients with antiplatelet-associated ICH. • Future prospective randomized controlled studies are needed to evaluate the efficacy of DDAVP in antiplatelet associated ICH. [ABSTRACT FROM AUTHOR]

Dual antiplatelet therapy with aspirin and the oral P2Y 12 inhibitor clopidogrel as the cornerstone of treatment for patients with an acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) was firstly established in 2001. Soon thereafter, the newer-generation P2Y 12 inhibitors prasugrel and ticagrelor became commercially available. The clinical management of ACS patients undergoing PCI has evolved significantly in the last 2 decades, with a shift toward more rapid invasive management, broader use of drug-eluting stents, and the increasing recognition that major bleeding due to antiplatelet therapy is detrimental. In this ever-changing scenario, numerous studies have addressed 4 main questions regarding P2Y 12 inhibition in ACS patients undergoing PCI: timing, selection, modulation, and duration. This paper reviews the latest evidence surrounding these topical questions, with a focus on efficacy and safety data, practice guidelines, and residual areas of uncertainty. [Display omitted] • The rationale for pretreatment with P2Y 12 inhibitors in patients with ACS is weak in the era of quick access to early invasive coronary angiography. • Prasugrel and ticagrelor are first-line options for DAPT combinations with aspirin, but clopidogrel reduces the risk of bleeding, which may be useful in some patients at risk. • The duration of P2Y 12 inhibition on a background of aspirin must be tailored to the individual risks of thrombotic/ischemic and bleeding complications. • Strategies of P2Y 12 inhibitor monotherapy with no aspirin or de-escalation from a more potent to a less potent P2Y 12 inhibitor intensity are emerging. [ABSTRACT FROM AUTHOR]

Liver fibrosis results from an imbalance between extracellular matrix formation and degradation. The background of liver fibrosis is chronic inflammation and subsequent microcirculation disturbance including microthrombosis. Platelets actively participate in liver fibrosis not only as a part of the clotting system but also by releasing granules containing important mediators. In fact, platelets may play a dual role in the pathophysiology of liver fibrosis as they are able to stimulate regeneration as well as aggravate the destruction of the liver. Recent studies revealed that antiplatelet therapy correlates with inhibition of liver fibrosis. However, liver impairment is associated with extensive coagulation disorders thus the safety of antiplatelet therapy is an area for detailed exploration. In this review, the role of platelets in liver fibrosis and accompanying hemostatic disorders are discussed. Additionally, results of animal and human studies on antiplatelet drugs in liver disorders and their potential therapeutic utility are presented.

Background: Currently, there is a paucity of data concerning the safety and effectiveness of P2Y12 inhibitors in the acute coronary syndrome (ACS) with chronic kidney disease (CKD) population. The aim of this study is to compare the different oral P2Y12 inhibitors in terms of efficacy and safety, focusing exclusively on patients with CKD who were treated for ACS. Methods: We systematically searched PubMed, CENTRAL, and Web of Science to identify studies that compared different oral P2Y12 inhibitors (clopidogrel, prasugrel, and ticagrelor) in patients with ACS with CKD. Efficacy outcomes included the major adverse cardiovascular events composite outcome and safety outcomes included major bleedings and major or minor bleedings combined. We performed a frequentist network meta-analysis. Results: Twelve studies were included in the systematic review, 7 CKD subgroup analyses of RCTs (8878 patients) and 5 observational studies (20175 patients). After the exclusion of studies with conservative management, prasugrel resulted in significant primary endpoint reduction versus clopidogrel (HR 0.80 and 95% CI 0.64 - 0.99), while ticagrelor did not (HR 0.88 and 95% CI 0.73 - 1.06). Major bleedings did not differ between the interventions. Ticagrelor resulted in more major or minor bleedings than clopidogrel (HR 1.21 and 95% CI 1.06 - 1.38), whereas prasugrel did not (HR 1.12 and 95% CI 0.84 - 1.49). Conclusion: In patients with ACS with underlying CKD, who are intended to receive invasive management, there may be a significant reduction of the primary efficacy outcome with prasugrel as compared to clopidogrel but not with ticagrelor as compared to clopidogrel. There probably exists no difference among interventions in the major bleedings. Dedicated RCTs are needed to confirm these results.

Dual antiplatelet therapy (DAPT) is the gold standard for the antithrombotic management of patients with an acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). Implementation of intensified or prolonged DAPT regimens has proven to lower the risk of ischemic events but at the expense of increased bleeding. Importantly, bleeding is a predictor of poor prognosis. Risk stratification and selection of tailored antiplatelet strategies to maximize the net clinical benefit in individual patients with ACS or undergoing PCI is therefore potentially beneficial. Recently, novel approaches including DAPT de-escalation or escalation have been proposed as possible alternatives to standard DAPT. These strategies, which are generally based on patient's risk profile, genetics, and/or platelet function have been proposed to offer more tailored treatments in patients with ACS or PCI, with the ultimate goal of providing adequate ischemic protection while mitigating the risk of bleeding. This review summarizes the available evidence on DAPT de-escalation or escalation (both guided and unguided) and discusses the practical implications of these strategies in the contemporary management of patients with ACS and/or undergoing PCI. [ABSTRACT FROM AUTHOR]

Objectives: To compare angiographic findings between diabetic and non-diabetic patients with acute coronary syndrome (ACS) along with feasibility of P2Y12 inhibitors withholding approach for urgent coronary artery bypass grafting (CABG) in diabetic (DM) patients with severe lesions. Methodology: Consecutive ACS patients were included. P2Y12 inhibitors was hold in a certain number of diabetic patients with either left main (LM) or multi-vessel disease (MVD) on baseline angiogram, at the discretion of primary physician. Angiographic diseases severity was compared between diabetic and non-diabetics. The clinical management and outcomes of diabetic patients were further compared based on the deferred P2Y12 inhibitors approach. Results: Out of 205 patients, 149 were males and 40.9% were diabetic. Involved vessel was LM in 19.8% vs. 16.6%; p=0.566, left anterior descending artery (LAD) in 62.8% vs. 39.3%; p=0.001, and right coronary artery in 27.3% vs. 45.2%; p=0.008 with MVD in 42.1% vs. 28.6%, p=0.047 of the diabetic and non-diabetic patients, respectively. P2Y12 inhibitors was hold in 59 diabetic patients who undergone urgent CABG with hospital stay of <5 days. In remaining 62 diabetic patients, 50 undergo coronary intervention and 12 undergo delayed CABG with hospital stay of >5 days due to P2Y12 administration. Conclusion: The presence of DM showed a significant association with the involvement of the LAD artery. Most participants showed presence of MVD. By holding P2Y12 inhibitors reduces the perioperative bleeding and hospital stay. [ABSTRACT FROM AUTHOR]

Background: Superiority of potent P2Y12 inhibitors over clopidogrel after an acute coronary syndrome (ACS) has been well established, however potent P2Y12 inhibition is responsible for more adverse events, which may influence patient adherence to treatment. Aim of the present study is to investigate the adherence to the prescribed P2Y12 inhibitor (P2Y12i) in patients on dual antiplatelet therapy (DAPT) after an ACS.Methods: In an IDEAL-LDL trial substudy, we included 344 patients after ACS discharged on DAPT. The primary outcome was the difference between potent P2Y12i and clopidogrel in terms of adherence, as well as other predictors of adherence to the antiplatelet regimen. Secondary outcomes included the prevalence of DAPT continuation and its predictors and the antiplatelet regimen selection after DAPT.Results: Adherence to the potent P2Y12i and to clopidogrel was observed in 140/178 (78.7%) and 111/166 (66.9%) patients (p = 0.016), respectively. In the multivariate model, after adjustment for P2Y12i switching during the first year of therapy, there was no difference observed in adherence between potent P2Y12i and clopidogrel (odds ratio [OR] = 0.98, 95% confidence interval [CI] = 0.55-1.74). Significant predictors included history of cardiovascular disease (CVD) (OR = 0.51, 95% CI = 0.31-0.86) and percutaneous coronary intervention (PCI) index event treatment (OR = 2.58, 95% CI = 1.38-4.82). Of patients, 72% continued DAPT >12 months and female gender was a negative predictor of DAPT prolongation (adjusted OR = 0.43, 95% CI = 0.21-0.90). DAPT was continued until the end of follow-up in 42.7%, while 54.6% resumed with single antiplatelet regimen.Conclusions: Adherence to DAPT was not affected by the P2Y12i potency, whereas history of CVD and PCI treatment were associated with reduced and increased adherence, respectively.Clinical Trial Registration: NCT02927808, https://clinicaltrials.gov/ct2/show/NCT02927808. [ABSTRACT FROM AUTHOR]

Abstract Background Despite the advances of potent oral P2Y12 inhibitors, their onset of action is delayed, which might have a negative impact on clinical outcome in patients undergoing percutaneous coronary intervention (PCI). Trials conducted in the United States of America have identified cangrelor as a potent and rapid-acting intravenous P2Y12 inhibitor, which has the potential of reducing ischemic events in these patients without an increase in the bleeding. As cangrelor is rarely used in The Netherlands, we conducted a nationwide registry to provide an insight into the use of cangrelor in the management of patients with suboptimal platelet inhibition undergoing (primary) PCI (the Dutch Cangrelor Registry). Study design The Cangrelor Registry is a prospective, observational, multicenter, single-arm registry with cangrelor administered pre-PCI in: (1) P2Y12 naive patients with ad-hoc PCI, (2) patients with STEMI/NSTEMI with suboptimal P2Y12 inhibition including (3) stable resuscitated/defibrillated patients with out-of-hospital cardiac arrest (OHCA) due to acute ischemia and (4) STEMI/NSTEMI patients with a high thrombotic burden. Primary endpoint is 48 h Net Adverse Clinical Events (NACE), which is a composite endpoint of all-cause death, recurrent myocardial infarction (MI), target vessel revascularization (TVR), stroke, stent thrombosis (ST) and BARC 2-3-5 bleeding. Summary The Dutch Cangrelor Registry will assess the feasibility and safety of cangrelor in patients with suboptimal P2Y12 inhibition undergoing (primary) PCI in the setting of acute coronary syndrome (ACS) and stable coronary artery disease (CAD) in the Netherlands.

Abstract Background Oral antiplatelet therapy is the cornerstone of treatment for acute myocardial infaction (AMI). However, detailed usage data on oral antiplatelet therapy are lacking. Methods Using data from a nationally representative sample of patients with AMI, the detailed usage of oral antiplatelet therapy was analyzed in 40,202 consecutive eligible patients. Results The proportions of patients with AMI taking loading doses of aspirin and P2Y12 inhibitors were relatively low (62.2% and 63.6%, respectively), whereas approximately 90% of patients received maintenance doses of aspirin, P2Y12 inhibitors, and dual antiplatelet therapy. The proportions of patients taking loading doses of aspirin and P2Y12 inhibitors gradually decreased with age. Male sex, an educational level of at least college, an interval from onset to treatment of

Different pathological conditions, including viral infections and cancer, can have a massive impact on the endoplasmic reticulum (ER), causing severe damage to the cell and exacerbating the disease. In particular, coronavirus infections, including SARS coronavirus-2 (SARS-CoV-2), responsible for COVID-19, cause ER stress as a consequence of the enormous amounts of viral glycoproteins synthesized, the perturbation of ER homeostasis and the modification of ER membranes. Therefore, ER has a central role in the viral life cycle, thus representing one of the Achilles' heels on which to focus therapeutic intervention. On the other hand, prolonged ER stress has been demonstrated to promote many pro-tumoral attributes in cancer cells, having a key role in tumor growth, metastasis and response to therapies. In this report, adopting a repurposing approach of approved drugs, we identified the antiplatelet agent ticlopidine as an interferent of the unfolded protein response (UPR) via sigma receptors (SRs) modulation. The promising results obtained suggest the potential use of ticlopidine to counteract ER stress induced by viral infections, such as COVID-19, and cancer. [ABSTRACT FROM AUTHOR]

We assessed the impact on periprocedural myocardial injury of a ticagrelor loading dose given <6 or >6 hours before percutaneous coronary intervention (PCI) in non–ST‐elevation myocardial infarction (NSTEMI) patients at high risk. All consecutive patients pretreated with ticagrelor and undergoing PCI for a high‐risk NSTEMI have been included in the present analysis. Propensity‐score matching was performed to compare the outcomes between patients pretreated with ticagrelor for >6 hours or ≤6 hours. The primary outcome was the rate of periprocedural myocardial injury after PCI. We also recorded clinical outcomes, including major adverse cardiovascular events and major bleedings at 1 month. A total of 1216 patients with NSTEMI were deemed eligible for the study: 481 received a ticagrelor loading dose ≤6 hours (mean time, 4.3 ± 1.2 h) and 735 >6 hours (16.1 ± 8.4 hours) before PCI. Patients pretreated with ticagrelor for >6 hours presented more risk factors and comorbidities compared to others. In patients pretreated with ticagrelor for >6 hours, the rate of periprocedural myocardial injury was significantly lower compared to the other group, in the overall population (19.6% vs 37.8%; P <.0001) and in the matched cohort of 644 patients (18.9% vs 33.5%; P <.0001). The rate of major adverse cardiovascular events and major bleeding events did not differ between the two groups, in both unmatched and matched populations. The present study suggests that ticagrelor pretreatment reduces periprocedural myocardial injury in high‐risk patients with NSTEMI undergoing PCI with expected time intervals >6 hours. [ABSTRACT FROM AUTHOR]

Objective: To study the use of CYP2C19 genotyping to guide P2Y12 inhibitor selection to maximize efficacy, and attenuate risk in appropriate patients who underwent PCI for CAD. Methods: We performed a retrospective analysis of 868 patients with CAD who received CYP2C19 genotyping after PCI and changed P2Y12 inhibitor based on the results. Patients were divided into two groups based on clopidogrel metabolizer status. Group I: Intermediate (IM) and poor metabolizers (PM). Group II: Ultra-rapid (UM), rapid (RM) and normal metabolizers (NM). Each group was then categorized to one of two treatment arms guided by CYP2C19 genotype. Category 1: IM/PM started on clopidogrel, switched to ticagrelor or prasugrel; 2:IM/PM started on ticagrelor/prasugrel, continued these medications; 3: UM/RM/NM started on ticagrelor/prasugrel, switched to clopidogrel; 4: UM/RM/NM started on clopidogrel, continued clopidogrel. Death due to cardiac causes, bleeding events, non-fatal MI, target vessel revascularization (TVR), and MACE in all four categories were considered at 1, 6 and 12 months. Results: We did not observe significant difference between phenotypes for MACE at 1 (p = 0.274), 6 (p = 0.387), and 12 months (p = 0.083). Death due to cardiac causes, MI, and bleeding events were not significant at 1, 6, and 12 months. There was no significant difference in TVR at 6 (p = 0.491), and 12 months (p = 0.423) except at 1 month (p = 0.012). Conclusion: CYP2C19 genotype-based intervention can be implemented effectively and reliably to guide selection of P2Y12 inhibitor to optimize patient quality and safety when appropriate in post PCI patients.

BackgroundCYP2C19 loss-of-function (LOF) alleles reduce the effectiveness of clopidogrel and are associated with high rates of clinical events in patients undergoing percutaneous coronary intervention (PCI) and stenting in Northeast Asians. However, the prevalence and influence of CYP2C19 LOF alleles in Southeast Asians remain unclear.ObjectivesThis study aims to retrospectively investigate the prevalence of CYP2C19 LOF alleles and clinical outcomes in East Asian patients taking clopidogrel and undergoing PCI.MethodsBetween June 2019 and June 2020, volunteer participants in a single medical center were consecutively selected. The genetic data of CYP2C19 were derived from the Taiwan Precision Medicine Initiative (TPMI). Patients receiving clopidogrel while undergoing PCI with stenting were retrospectively analyzed.ResultsA total of 999 patients (62.4 ± 11.1 years old, 83.7% men) were enrolled; 39.3% without the CYP2C19 LOF allele (normal metabolizers + rapid metabolizers, NM + RM); 44.9% with one LOF allele (intermediate metabolizers, IM); 15.7% with two LOF alleles (poor metabolizers, PM). The incidence of stroke was higher in the PM subgroup compared to the NM + RM subgroup or IM subgroup in patients presenting with acute myocardial infarction (AMI). The 1-year major adverse cardiac and cerebrovascular events (MACCE)-free survival rates in all participants were similar among the three groups. However, in the AMI group, the 1-year MACCE-free survival rates were significantly lower in the PM subgroup compared to the NM + RM subgroup or IM subgroup.ConclusionIn East Asians presenting with AMI, CYP2C19 PM was associated with deleterious cardiovascular outcomes and stroke. Our results reinforce the crucial role of preemptive CYP2C19 genotyping in East Asian AMI patients receiving clopidogrel treatment.

Indeed, tailoring antiplatelet treatment regimens to an individual patient to optimize their safety and efficacy has represented a field of extensive investigation over the past decade [[6]]. Bedside testing of CYP2C19 vs. conventional clopidogrel treatment to guide antiplatelet therapy in ST-segment elevation myocardial infarction patients. Keywords: Pharmacogenetics; percutaneous coronary intervention; clinical trial; antiplatelet therapy; P2Y12 inhibitors EN Pharmacogenetics percutaneous coronary intervention clinical trial antiplatelet therapy P2Y12 inhibitors 383 385 3 05/23/23 20230501 NES 230501 1. In patients undergoing PCI, oral P2Y SB 12 sb inhibitors are generally used in addition to aspirin therapy, a regimen known as dual antiplatelet therapy (DAPT) [[1]]. [Extracted from the article]

Irene Lizano-Díez,1 Silvia Paz Ruiz2 1Ferrer, Barcelona, Spain; 2SmartWorking4U SLU, Benicàssim, SpainCorrespondence: Irene Lizano-DíezFerrer, Av Diagonal 549, Barcelona 08029, SpainTel +34 93 600 37 00Email ilizano@ferrer.comPurpose: Cangrelor is an intravenous, direct-acting, reversible P2Y12 inhibitor indicated for the reduction of thrombotic cardiovascular events in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) in whom oral P2Y12 inhibitors are not feasible or desirable. The objective was to assess the financial impact of introducing cangrelor into the hospital formulary in Spain.Patients and Methods: A budget impact model was developed to calculate the cost difference between two scenarios (without and with cangrelor) to treat CAD patients undergoing PCI in whom oral P2Y12 inhibitors are not feasible or desirable, over 3 years. Intravenous P2Y12 inhibitor (cangrelor), oral P2Y12 inhibitors (clopidogrel, prasugrel, and ticagrelor), and glycoprotein IIb-IIIa inhibitors (GPIs) for bail-out use were considered. Epidemiological, efficacy (thrombotic events including cardiac death), safety (bleeding events), and costs (€, 2019) data were based on Spanish registries, clinical trials, and meta-analyses. One-way sensitivity analysis established the effect of uncertainty on results.Results: For years 1, 2, and 3, the target population to receive cangrelor was 607, 1,822, and 3,340 patients, and cangrelor uptake was 23.70%, 58.30%, and 51.30%, respectively. The 3-year budget impact was 1,021,717€ varying from 50,245€ in year 1 to 599,272€ in year 3. The results were sensitive to the number of patients treated with GPIs in Spanish hospitals.Conclusion: Based on our results, the financial effort needed to introduce the use of cangrelor in patients undergoing PCI in whom antiplatelet therapy with oral P2Y12 inhibitors is not feasible or desirable barely exceeds one million € over three years, in Spain.Keywords: P2Y12 inhibitors, cangrelor, percutaneous coronary intervention, budget impact

Aspirin and P2Y12 inhibitors remain commonly prescribed antiplatelet drugs in the treatment of atherothrombotic conditions. Despite established benefits of dual antiplatelet therapy (DAPT) in the setting of acute coronary syndromes, there remains residual ischemic risk in this group and the problem of bleeding complications is an ongoing issue. DAPT with aspirin and ticagrelor has now been studied in other patient groups such as those with concurrent diabetes and stable coronary artery disease, and those undergoing elective percutaneous coronary intervention (PCI). Recent trials of ticagrelor monotherapy have suggested this may have benefits over standard-of-care in some settings, such as PCI, but not in others such as peripheral arterial disease or stroke. A novel subcutaneously administered P2Y12 inhibitor, selatogrel, has shown powerful, rapid and consistent effect in a phase 2 study. Aspirin dosing remains an area of investigation, particularly in the setting of DAPT. A novel regimen of very-low-dose twice-daily aspirin has hypothetical advantages in pharmacodynamic and pharmacokinetic effects, maintaining antiplatelet effect whilst reducing potentially harmful peak-trough variation.