Risk of colonoscopic post-polypectomy bleeding in patients on single antiplatelet therapy: systematic review with meta-analysis

Background It was not yet fully established whether the use of antiplatelet agents (APAs) is associated with an increased risk of colorectal post-polypectomy bleeding (PPB). Temporarily, discontinuation of APAs could reduce the risk of PPB, but at the same time, it could increase the risk of cardiovascular disease recurrence. This study aimed to assess the PPB risk in patients using APAs compared to patients without APAs or anticoagulant therapy who had undergone colonoscopy with polypectomy. Methods A systematic electronic search of the literature was performed using PubMed/MEDLINE, Scopus, and CENTRAL, to assess the risk of bleeding in patients who do not interrupt single antiplatelet therapy (P2Y12 inhibitors or aspirin) and undergone colonoscopy with polypectomy. Results Of 2417 identified articles, 8 articles (all of them were non-randomized studies of interventions (NRSI); no randomized controlled trials (RCT) were available on this topic) were selected for the meta-analysis, including 1620 patients on antiplatelet therapy and 13,321 controls. Uninterrupted APAs single therapy was associated with an increased risk of PPB compared to the control group (OR 2.31; CI 1.37–3.91). Patients on P2Y12i single therapy had a higher risk of both immediate (OR 4.43; CI 1.40–14.00) and delayed PPB (OR 10.80; CI 4.63–25.16) compared to the control group, while patients on aspirin single therapy may have a little to no difference increase in the number of both immediate and delayed PPB events. Conclusions Uninterrupted single antiplatelet therapy may increase the risk of PPB, but the evidence is very uncertain. The risk may be higher in delayed PPB. However, in deciding to discontinue APAs before colonoscopy with polypectomy, the potential higher risk of major adverse cardiovascular events should always be assessed.

The Effect of Periprocedural Clinical Factors Related to the Course of STEMI in Men and Women Based on the National Registry of Invasive Cardiology Procedures (ORPKI) between 2014 and 2019

Background: There are several sex-related differences in the course, management, and outcomes of ST-elevation myocardial infarction (STEMI). This study aimed to identify the risk factors that may affect the odds of procedure-related death in patients with STEMI. Methods: The observational cohort study group consisted of 118,601 participants recruited from the National Registry of Invasive Cardiology Procedures (ORPKI). Results: Procedure-related death occurred in 802 (1.0%) men and in 663 (1.7%) women. The odds of procedure-related death among women were significantly higher than among men (OR, 1.76; 95% CI, 1.59–1.95; p < 0.001). The probability of procedure-related mortality was highest in both men and women with cardiac arrest in the cath lab, critical stenosis of the left main coronary artery, and direct transfer to the cath lab. The factors that reduced the probability of procedure-related mortality in both men and women were thrombolysis in myocardial infarction (TIMI) flow grade and the use of P2Y12 inhibitors in the peri-infarct period. Psoriasis was associated with increased odds of procedure-related death among men, whereas cigarette smoking reduced the odds among women. Conclusions: Procedure-related deaths occurred more frequently in women than men with STEMI. Additional scrutiny needs to be undertaken to identify factors influencing survival regarding gender differences.

Monotherapy with P2Y12 receptor inhibitors in patients treated by percutaneous coronary intervention

Since the mid-1990s, the dual antiplatelet therapy, consisting of the association between acetylsalicylic acid and a platelet P2Y12 receptor inhibitor, is the core of thrombosis prevention after coronary stent implantation, regardless of the models used. It is also used to prevent the occurrence of atherothrombotic events in the late phase after the intervention. The clinical presentation of coronary artery disease influences the duration of dual therapy, which tends to be longer in treated cases of acute coronary syndrome (usually for one year), when compared to cases of chronic coronary disease (often for up to 6 months). After this period, the P2Y12 inhibitor is usually discontinued, and monotherapy with aspirin is maintained. However, in the last two decades, it has been observed that prolonged use of two associated antiplatelet agents predisposes treated cases to bleeding complications, with potentially severe consequences – including increased mortality. Thus, alternatives that minimize this risk have been considered and evaluated, such as early discontinuation of acetylsalicylic acid (between 1 and 3 months after discharge), or the so-called monotherapy with P2Y12 inhibitors, aiming to reduce bleeding without compromising prevention of ischemic events. In the last decade, a series of randomized clinical trials evaluated this hypothesis, generally resulting in reduced bleeding complications, although not necessarily of those classified as major, with no significant increase in the most relevant cardiovascular events. This review discusses the main results of these clinical trials and their potential clinical implications for routine cardiology practice.

817 Potent P2Y12 inhibitors in elderly population, insigth from praise registry

Background The safety and efficacy of potent P2Y12 inhibitors (Ticagrelor and Prasugrel) in dual antiplatelet therapy (DAPT) with aspirin in elderly patients with acute coronary syndrome (ACS) remains unclear. Methods All ACS patients aged 75 years and older treated with Percutaneous Coronary Intervention (PCI) from PRAISE dataset were included. The safety and efficacy of Ticagrelor vs Clopidogrel was evaluated with inverse probability of treatment weighting (IPTW). Sensitivity analysis was performed for patients older or equal than 85 years old. All-cause mortality was the primary endpoint, while myocardial infarction (MI), Bleeding Academic Research Consortium (BARC) 3-5 bleedings and Major and Net Adverse Clinical and Cardiac Events (MACE and NACE) were the secondary ones. Results 4287 patients were included, 3197 treated with Clopidogrel and 1090 with Ticagrelor. After 16±3 months, Ticagrelor showed neutral effect on NACE and mortality (HR 0.98; 0.63-1.52, p=0.94 and HR 0.38; 0.14-1.04, p=0,06), reduced risk of MACE and MI (HR 0.82; 0.23-0.91, p=0.03 and HR 0.43; 0.14-0.89, p=0.04) and increased risk of BARC 3-5 bleeding (HR 2.14; 1.19-3.85, p=0.001). In very elderly patients (≥85 years) Ticagrelor decreased risk of MI and increased risk of bleeding (HR 0.69; 0.22-0.95, p=0.04 and HR 2.36; 1.02-5.52, p=0.04, all 95%CI) with neutral effect on NACE and MACE. Conclusions In elderly ACS patients treated with PCI, Ticagrelor was associated with neutral effect on all-cause mortality, lower risk MACE and MI compared with Clopidogrel. Such benefit was counterbalanced by increased risk of major bleedings. These results were consistent among patients aged 85 years and older. 817 Figure 1

P2Y12 receptor as a new target for electroacupuncture relieving comorbidity of visceral pain and depression of inflammatory bowel disease

Background The P2Y12 receptor is a kind of purinoceptor that is engaged in platelet aggregation, and P2Y12 inhibitors have been used in clinical antithrombotic therapy. The P2Y12 receptor in microglia induces interleukin-1β (IL-1β) expression, which is a key mediator of depression in the brain. Although peripheral P2Y12 is involved in neuropathic pain, whether P2Y12 expression in the medial prefrontal cortex (mPFC) is associated with comorbidities of visceral pain and depression remains unclear. Accumulating evidence suggests that electroacupuncture (EA) is effective in treating inflammatory bowel disease (IBD), but its mechanism is unknown. This study aimed to determine whether P2Y12 expression in the mPFC is associated with comorbidities of visceral pain and depression in IBD and whether EA treats IBD by targeting the P2Y12 receptor. Methods We used 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced IBD mice. P2Y12 short hairpin RNA (shRNA) was stereotaxically injected into the bilateral mPFC. EA was performed on bilateral “Dachangshu” (BL25) acupoints once a day for 7 days. Von Frey filaments and colorectal distension were used to detect the mechanical pain threshold and visceral pain sensitivity. The sucrose preference test, tail suspension test and forced swimming test were used to evaluate depression in mice. Western blotting was used to test the expression of P2Y12 and IL-1β. Immunofluorescence staining was used to assess microglial activity. Results We found that IBD mice presented visceral pain and depression associated with increased P2Y12 expression in the mPFC. P2Y12 shRNA significantly attenuated visceral pain and depression in IBD mice. P2Y12 shRNA significantly downregulated IL-1β expression and inhibited the activation of microglia in the mPFC of IBD mice. Meanwhile, EA played a similar role of P2Y12 shRNA. EA significantly downregulated P2Y12 expression, weakened the activation of microglia, and then inhibited IL-1β expression in the mPFC, thus relieving visceral pain and depression in IBD mice. Conclusion The present study provided new ideas that the P2Y12 receptor in the mPFC could be a new target for the treatment of comorbid visceral pain and depression by EA. This may not only deepen our understanding of the analgesic and antidepressant mechanisms of EA but also promote the application of EA to treat IBD.

205 Dual antiplatelet therapy with third generation P2Y12 inhibitors in STEMI patients: impact of body mass index on high on-treatment platelet reactivity

Aims High on-treatment platelet reactivity (HTPR) has been associated with high risk of ischaemic events in STEMI patients. Body mass index (BMI) and specifically overweight and obesity are risk factors for increased platelet reactivity in different series of patients; however, data regarding their relationship with pharmacodynamic response to oral 3rd generation P2Y12 inhibitors is still lacking. This study aims to assess the association between BMI and HTPR 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 &lt;25 vs. ≥25 kg/m2). A propensity score matching (1:1) was performed to balance potential confounders in baseline patients 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. HTPR was defined as a platelet reactivity unit values ≥ 208 units. Results Mean age was 62 ± 12 years, and males were 75%. Patients with a BMI ≥25 were younger (61 ± 12 vs. 64 ± 11, P= 0.006), with a higher prevalence of male gender (78% vs. 68%, P = 0.035), and they were less frequently treated with morphine before PCI (30% vs. 42%; P=0.018). After propensity score matching, patients with BMI ≥25 had similar values of baseline platelet reactivity [T0: 308 (285–342) vs. 300 (281–330), P= 0.396], while they had higher level of platelet reactivity at 1 and 2 h after the LD [T1: 285 (200–308) vs. 265 (196–320), P= 0.047; T2: 241 (87–305) vs. 200 (56–256), P= 0.004] and higher rate of HRPT [T1: (66% vs. 47%, P= 0.004); T2: (40% vs. 24%, P= 0.006)]. Furthermore, multivariable analysis demonstrated that BMI ≥25 was an independent predictor of HTPR at 2 h (OR 2.01, 95% CI 1.18–3.42; P=0.009). Conversely, starting from 4 h after the LD, platelet reactivity values [T3: 68 (7–173) vs. 15 (6–71), P = 0.76; T4: 38 (4–104) vs. 44 (4–82), P=0.958] and HRPT rates (T3: 13% vs. 10%, P = 0.595; T4: 1% vs. 1%, P= 0.320) were comparable among the two study groups. Conclusions A BMI ≥25 kg/m2 is associated with decelerated pharmacodynamic response to oral 3rd generation P2Y12 inhibitors LD, and it is a strong predictor of HRPT in STEMI patients treated by dual antiplatelet therapy with ticagrelor or prasugrel.

Clopidogrel or ticagrelor alongside dabigatran in acute coronary syndrome and indication for NOAC: a study rationale

The combination of oral anticoagulants with platelet inhibitors has been widely investigated in patients with coronary stenting and concomitant atrial fibrillation. In these patients, default therapy after percutaneous coronary intervention in acute coronary syndrome is clopidogrel plus non–vitamin K antagonist oral anticoagulant, omitting aspirin. However, in view of the high thromboembolic risk associated with acute coronary syndrome and the number of poor metabolizers for clopidogrel, investigation of alternative P2Y12-inhibitors is mandatory. This prospective, multicenter, open-label, registry-based, randomized, controlled trial aims to show the non-inferiority of dabigatran plus ticagrelor versus dabigatran plus clopidogrel in patients on chronic anticoagulants who undergo percutaneous coronary intervention in acute coronary syndrome. The primary end point is major bleeding as defined by the Bleeding Academic Research Consortium bleeding definition. Trial registration number: NL75644.096.21

Global Thrombosis Test: Occlusion is attributable to shear-induced platelet thrombus formation.

Herein, we set out a rebuttal to the publication by Claveria and co-workers published in TH Open this month entitled “Global Thrombosis Test: Occlusion by Coagulation or SIPA?” We strongly believe that the conclusions of their paper, suggesting that occlusion (OT) in the Global Thrombosis Test (GTT) is due to coagulation, rather than shear-induced platelet thrombus formation, is incorrect and the evidence and arguments they present are fundamentally flawed, with major errors both in the experimental approach and in the interpretations of the results. The evidence which they demonstrate, shows that occlusion in the GTT is, in fact, caused by high shear induced platelet thrombus formations. We set out herein the evidence for that, based on histology of the thrombus from the GTT in earlier work using electron microscopy showing large platelet aggregates, the very brief timescale of OT in the GTT compared to coagulation time and the sensitivity of the OT in the GTT to the effects of heparin, t-PA and P2Y12 inhibitors. In addition, we revisit the known pathomechanism of high shear-mediated platelet aggregation to underpin our rationale and show that the modifications to the instrument proposed by Claveria and co-authors would render the technique unphysiological. We highlight several methodological concerns and apparent misinterpreted of the data obtained. We present evidence predominantly from the authors’ own data, together with our earlier published data and evidence from the literature, showing that occlusion in the GTT occurs do to shear-induced platelet aggregation.