Current concepts on coronary revascularization in diabetic patients

Diabetic mellitus (DM) patients with coronary artery disease (CAD) are at higher risk of cardiovascular events compared with non-DM individuals. While aggressive cardiovascular prevention and adequate blood glucose control remain cornerstones of therapy, the decision when and how to proceed to coronary revascularization in an individual DM patient should be based on the extent of CAD, ischaemic burden, ventricular function, as well as comorbidities. While in patients with stable symptoms, moderate CAD on coronary angiography and preserved left ventricular function a conservative strategy may be a valuable initial strategy, in patients with acute coronary syndromes (ACS) an early invasive approach should be favoured. The revascularization strategy for DM patients with complex multivessel CAD should be discussed within a heart team consisting of cardiologists, cardiac surgeons, and anaesthesiologists. In general, the threshold for coronary artery bypass surgery (CABG) should be lower for DM than for non-DM individuals. In patients undergoing percutaneous coronary intervention, the use of drug-eluting stents (DES) and—in the setting of ACS—of potent platelet inhibitors, such as prasugrel or ticagrelor, should be favoured. In the near future, multiple strategies may further favourably impact the prognosis of DM patients undergoing coronary revascularization. These include alternative antiplatelet agents such as thromboxane receptor inhibitors, the broad use of second generation DES, and possibly the implantation of bioresorbable stents. Coronary artery bypass surgery outcomes may also further improve by wide implementation of arterial revascularization, reduction in perioperative stroke by avoiding clamping of the aorta, reduction in wound infection by minimally invasive techniques, and optimization of post-operative medical managemen

Aspirin-dependent effects on purinergic P2Y1 receptor express

Chronic treatment with aspirin in healthy volunteers (HVs) is associated with recovery of adenosine diphosphate (ADP)-induced platelet activation. The purinergic P2Y1 receptor exerts its effects via a Gq-protein, which is the same biochemical pathway activated by thromboxane-A2 receptor. We hypothesized that recovery of ADP-induced platelet activation could be attributed to increased P2Y1 expression induced by chronic aspirin exposure. We performed a multi-phase investigation which embraced both in vitro and in vivo experiments conducted in (1) human megakaryoblastic DAMI cells, (2) human megakaryocytic progenitor cell cultures, (3) platelets obtained from HVs treated with aspirin and (4) platelets obtained from aspirin-treated patients. DAMI cells treated with aspirin or WY14643 (PPARα agonist) had a significant up-regulation of P2Y1 mRNA, which was shown to be a PPARα-dependent process. In human megakaryocytic progenitors, in the presence of aspirin or WY14643, P2Y1 mRNA expression was higher than in mock culture. P2Y1 expression increased in platelets obtained from HVs treated with aspirin for 8 weeks. Platelets obtained from patients who were on aspirin for more than 2 months had increased P2Y1 expression and ADP-induced aggregation compared with patients on aspirin treatment for less than a month. Overall, our results suggest that aspirin induces genomic changes in megakaryocytes leading to P2Y1 up-regulation and that PPARα is the nuclear receptor involved in this regulation. Since P2Y1 is coupled to the same Gq-protein of thromboxane-A2 receptor, platelet adaptation in response to pharmacological inhibition seems not to be receptor specific, but may involve other receptors with the same biochemical pathway

Antiplatelet Therapy Considerations in Women

Coronary artery disease (CAD) is the leading cause of death worldwide, but because of several factors, one of which is antiplatelet therapy, the mortality rates have steadily declined. However, women continue to experience higher CAD mortality rates than men. This may be explained by differences in comorbidities, increased time to presentation, higher bleeding rates, and differences in management. There are numerous landmark trials in the field of antiplatelet therapy; however, women are consistently underrepresented in these trials. The results of these trials reveal that women experience the same benefit as men from antiplatelet therapy but experience higher bleeding rates; therefore bleeding-reduction strategies are imperative in this patient population. This review provides an overview of the available evidence on CAD in women and its implications for antiplatelet medications

Factor XI inhibitors in adjunct to antiplatelet therapy: the ultimate dual-pathway inhibition?

A strategy of oral anticoagulants (OAC) in addition to single or dual antiplatelet therapy, known as dual-pathway inhibition (DPI), has shown to reduce thrombotic events in patients with cardiovascular disease. However, despite its efficacy, its use in clinical practice has been hindered by the fact this strategy is also associated with increased bleeding, including major bleeding. The use of low dose direct oral anticoagulant (i.e. rivaroxaban 2.5 mg twice daily) on top of antiplatelet therapy has been associated with reduced bleeding, but some safety concerns still exists. The availability of a novel class of OACs selectively targeting the intrinsic coagulation pathway and potentially uncoupling thrombosis and hemostasis has sparked the interest towards the use of a new generation DPI strategy associated with enhanced safety. Several phase II trials using factor XI (FXI) inhibitors on top of antiplatelet therapy in patients with coronary artery or cerebrovascular disease have been recently published and others are under investigation. We here discuss the available evidence and future perspectives of DPI with FXI inhibitors in patients with cardiovascular disease

Factor XI inhibitors in adjunct to antiplatelet therapy: the ultimate dual-pathway inhibition?

A strategy of oral anticoagulants (OAC) in addition to single or dual antiplatelet therapy, known as dual-pathway inhibition (DPI), has shown to reduce thrombotic events in patients with cardiovascular disease. However, despite its efficacy, its use in clinical practice has been hindered by the fact this strategy is also associated with increased bleeding, including major bleeding. The use of low dose direct oral anticoagulant (i.e. rivaroxaban 2.5 mg twice daily) on top of antiplatelet therapy has been associated with reduced bleeding, but some safety concerns still exists. The availability of a novel class of OACs selectively targeting the intrinsic coagulation pathway and potentially uncoupling thrombosis and hemostasis has sparked the interest towards the use of a new generation DPI strategy associated with enhanced safety. Several phase II trials using factor XI (FXI) inhibitors on top of antiplatelet therapy in patients with coronary artery or cerebrovascular disease have been recently published and others are under investigation. We here discuss the available evidence and future perspectives of DPI with FXI inhibitors in patients with cardiovascular disease

Interindividual variability in platelet reactivity among individuals with or without antiplatelet therapy. Results from a large tertiary care hospital

Antiplatelet therapy is crucial for reducing thrombotic events in patients with atherosclerotic disease, but the response vary widely among individuals. The identification of patients at high (HPR), optimal (OPR) or low platelet reactivity (LPR) is dependent on high interlaboratory variability. We report results of a large dataset of patients to assess the gold standard light transmission aggregometry (LTA). A total of 11,913 patients who sequentially underwent LTA assessment using several stimuli (ADP-2 mu M, collagen-2 mu g/ml, arachidonic acid 0.5 mM, epinephrine 10 mu M) with a standardized methodology between 2004 and 2022 were screened. After application of inclusion-exclusion criteria, 5,901 patients were included and divided into five groups: healthy-volunteers (HV; N = 534); controls (CTR; N = 1073); aspirin-treated patients (ASA; 75-150 mg/die; N = 3280); clopidogrel-treated patients (CLOP; 75 mg/die; N = 495) and patients treated with dual antiplatelet therapy, ASA plus CLOP (DAPT; N = 519). The mean PA% in response to ADP 2 mu m was 72.4 +/- 33.3 in the CTR population, 40.6 +/- 29.9 in the ASA group, 25.1 +/- 35.1 in the CLOP group and 10.2 +/- 18.5 in the DAPT group. The mean PA% in response to collagen 2 ug/ml was 90.7 +/- 10.5 in the CTR population, 40.8 +/- 26.3 in the ASA group, 79.4 +/- 21.8 in the CLOP group and 17.9 +/- 19.9 in the DAPT group. The percentage of patients at OPR following ADP stimuli was 66%, 25%, and 26%, in the ASA, CLOP, and DAPT group, respectively. The percentage of patients at OPR following collagen stimuli was 56%, 22%, and 41%, in the ASA, CLOP, and DAPT group, respectively. LTA was significantly increased in response to ADP (72.4 +/- 33.3vs62.7 +/- 37.1; p < 0.001) and AA (90.7 +/- 15.6vs87.6 +/- 20.5; p < 0.001) in CTR compared to HV. Our findings support the concept that a significant proportion of individuals present a hyper- or hypo-reactive platelet phenotype potentially affecting the safety and efficacy of antiplatelet therapy. The variability in response to antiplatelet therapy was particularly evident in patients undergoing single as opposed to dual antiplatelet therapy regimens. These data support ongoing strategies of guided selection of antiplatelet therapy in patients with cardiovascular disease

Erratum to: Pharmacodynamic effects of EV-077 in patients with diabetes mellitus and coronary artery disease on aspirin or clopidogrel monotherapy: results of an in vitro pilot investigation

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Antiplatelet Therapy and Platelet Function Testing

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58558/1/20370_ftp.pd