Platelet Receptor Inhibition Research Articles

Impact of Levosimendan and Its Metabolites on Platelet Activation Mechanisms in Patients during Antiplatelet Therapy-Pilot Study.

Levosimendan is used for the short-term treatment of severe heart failure or other cardiac conditions. The area of existing clinical applications for levosimendan has increased significantly. This study aimed to assess whether levosimendan and its metabolites impact the mechanisms related to platelet activation. In this study, we included patients with coronary artery disease receiving antiplatelet therapy. We analyzed the pharmacodynamic profile using three independent methods to assess platelet activity. The results of the conducted studies indicate a mechanism of levosimendan that affects the function of platelets, causing higher inhibition of platelet receptors and, thus, their aggregation. It is essential to clarify whether levosimendan may affect platelets due to the need to maintain a balance between bleeding and thrombosis in patients treated with levosimendan. This is especially important in the case of perioperative bleeding. This study was conducted in vitro; the research should be continued and carried out in patients to check the complete pharmacokinetic and pharmacodynamic profile.

Ácido acetilsalicílico versus inibidores dos receptores P2Y12 para prevenção secundária em pacientes tratados por meio de intervenção coronária percutânea

Currently, percutaneous coronary intervention with a drug-eluting stent implantation is the main method of myocardial revascularization in tertiary care hospitals, regardless of the clinical presentation of coronary artery disease. It is well known that to be effective, it requires the use of a dual antiplatelet therapy, which is a combination of acetylsalicylic acid and a P2Y12 platelet receptor inhibitor, which plays a key role in preventing thromboses after endoprosthesis implantation and is also indicated to prevent atherothrombotic events in the late clinical course, regardless of the stent model used. After a variable period of time, depending on some factors, such as the clinical presentation of coronary artery disease and the type of stent implanted, this therapy is discontinued, and the main current guidelines recommend interrupting the P2Y12 receptor inhibitor and maintaining acetylsalicylic acid in the long term, as one of the main pharmacological measures for secondary prevention of atherosclerosis. However, recently, due to their greater antiplatelet potency and probable lower potential for significant bleeding, especially in the digestive tract, P2Y12 inhibitors have been considered a valid and attractive option as an antiplatelet agent for long-term use; but this alternative has not been endorsed by guidelines yet. This review discusses the details related to this important decision that must be made by cardiologists when discontinuing the different antithrombotic therapies initially used after percutaneous coronary intervention. In principle, the scarcity of conclusive and normative clinical studies, especially in the population treated by percutaneous intervention, means that acetylsalicylic acid is the only antiplatelet agent with class I indication for secondary prevention of atherosclerosis.

Acute coronary syndrome in a young patient with ECG presentation of acute inferior myocardial infarction and acute thrombosis of left main stem coronary artery

Introduction. The left main stem (MS) coronary artery (CA) (MSCA) thrombosis is a rare but potentially lethal manifestation of acute coronary syndrome. The standard approach in treating such patients is the primary percutaneous coronary intervention (pPCI) or CA bypass graft surgery. In some cases, depending on the morphological appearance of the thrombus, findings and flow rates assessed on coronary angiography (CAn), clinical conditions, and cardiologist?s experiences, another possible method of treatment can be the conservative approach using antithrombotic therapy. Case report. A 37-year-old male was admitted to the emergency room with symptoms of an acute myocardial infarction with an ST elevation in diaphragmal localization. Using an emergency CAn, we have visualized a thrombus at the ostial and proximal part of the left MSCA, with no complete obstruction of the blood flow. Initially, dual antithrombotic therapy (ticagrelor and acetylsalicylic acid) was applied, and in the further procedure, it was decided to introduce glycoprotein IIb/IIIa platelet receptor inhibitor (tirofiban) as an intracoronary bolus (0.3 ?g/kg) and later as a continuous infusion (0.1 ?g/kg/min). Four days later, a control CAn and intravascular echocardiography were performed, and it was decided to continue the treatment using conservative therapy without a pPCI procedure. The patient was discharged in good condition with no signs of illness on the eighth day after hospital admission for home recovery, with planned frequent follow-ups in the future. Conclusion. In the case of non-obstructive thrombotic masses without significant atherosclerotic stenotic lesions, conservative treatment modality with the use of aggressive antithrombotic therapy may be considered.

Polysaccharide extracted from Morchella esculenta inhibits carrageenan-induced thrombosis in mice

MCP prevented carrageenan-induced thrombosis in mice by reducing platelets activation, oxidative stress and monocytes adhesion to damaged endothelial cells. MCP has great potential to develop into a natural antithrombotic drug. Our study suggests a new application of Morchella esculenta , which can be used as food supplements and nutraceuticals to benefit human health. • Morchella esculenta Polysaccharide reduces thrombi formed in in mouse tissues. • Morchella esculenta Polysaccharide attenuates platelet activation. • Morchella esculenta Polysaccharide inhibits oxidative stress in platelets and endothelium cells. • Morchella esculenta Polysaccharide inhibits adhesion of monocytes to endothelium cells. Thrombosis is one of the leading causes of death worldwide and is associated with inflammation and oxidative stress. This study aims to investigate the effect of Morchella esculenta Polysaccharide (MCP) on thrombosis. Our results showed that MCP inhibited thrombi in blood vessels of mouse tail, liver and lung, which was contributed by the inhibition of collagen accumulation, tumor necrosis factor-α and P-selectin expression. In vitro , human platelet clot retraction test indicated that MCP inhibited platelet activation, which was related to inhibition of platelet receptors, AKT and ERK1/2 pathways. Additionally, MCP inhibited oxidative stress by inducing anti-oxidative enzymes in human platelets and human umbilical vein vascular endothelium cells (HUVECs). Moreover, MCP inhibited oxidized low-density lipoprotein or LPS-induced adhesion of monocytes to HUVECs by reducing adhesion molecules expression. Taken together, these data demonstrate MCP exhibits antithrombotic properties, indicating Morchella esculenta can be used as food supplements and nutraceuticals against thrombosis.

An Examination of Clopidogrel in the Treatment of Coronary Microvascular Disease.

The ability of clopidogrel (Plavix) to work in tandem with aspirin in a dual therapy strategy to boost the anti-platelet therapeutic impact and diminish platelet aggregation induced by platelet receptor inhibition is one of its many key advantages. The researchers discovered that the average reduction in risk of adverse cardiovascular events related to Plavix much outweighed any potential systemic effects. The analysis also revealed that, even though treatment results for diabetic patients with coronary microvascular disease (CMD) are poorer, the dosage and administration of clopidogrel for dual therapy are not modified to address this issue. Although it has been established that the current standard of care for microvascular disease decreases damage, more study is necessary to ensure that this standard is enhanced. It may become more usual in the future to include patient groups in trials who do not have diabetes as a criterion. Patients with diabetes often have higher low-density lipoprotein (LDL) cholesterol levels than the general population, therefore, it is possible that the research findings are flawed. To confirm or reject this assumption, further research is necessary.

Use of a p64 MW Flow Diverter with Hydrophilic Polymer Coating (HPC) and Prasugrel Single Antiplatelet Therapy for the Treatment of Unruptured Anterior Circulation Aneurysms: Safety Data and Short-term Occlusion Rates

PurposeTo assess the safety and short-term occlusion rates in procedures using the p64 MW hydrophilic polymer-coated (HPC) flow diverter (FD) with prasugrel single antiplatelet therapy (SAPT) for the treatment of anterior circulation saccular aneurysms.MethodsWe retrospectively identified patients who underwent treatment of one or more intracranial anterior circulation saccular aneurysms between March 2020 and December 2021 with a p64 MW HPC FD and prasugrel SAPT with verified P2Y12 platelet receptor inhibition. Patients diagnosed with fusiform, dissecting, or recently ruptured aneurysms were excluded. Periprocedural and postprocedural complications, clinical outcomes, and angiographic follow-up results were evaluated.ResultsOne hundred and two patients with 132 intracranial aneurysms met the inclusion criteria. Previous or concomitant treatments (e.g., coil occlusion) had been performed on 18 of these aneurysms. The technical success rate (i.e., implantation of the intended FD) was 100% with an average of 1.1 devices implanted per patient. Periprocedural and postprocedural complications occurred in 13.6% and 6.8% of these patients, respectively. No mortality or permanent clinical deterioration (i.e., modified Rankin scale score ≥ 3) were reported. Early follow-up digital subtraction angiography revealed aneurysmal occlusion rates of 72.6% and 83.8% at four and nine months, respectively.ConclusionsThe implantation of a p64 MW HPC FD with prasugrel SAPT is safe and results in rapid, reliable and effective aneurysmal occlusion.

No-reflow phenomenon and reperfusion injury. Mechanisms and treatment

Currently, one of the key methods of treating a patient with ST-elevation myocardial infarction is to restore blood flow to the infarct-related artery as quickly, completely and steadily as possible. However, in some cases, it is not possible to achieve adequate myocardial reperfusion, despite the restoration of coronary blood flow. This phenomenon was named no-reflow. Due to the lack of a unified approach to the diagnosis of no-reflow, its occurrence varies widely – from 2 to 44 %. Failure to achieve adequate myocardial perfusion leads to a higher mortality rate – from 7.4 to 30.3 %, as well as to more aggressive remodeling of the myocardium. For a long time, distal embolization in percutaneous coronary intervention was considered one of the leading mechanisms. However, the routine use of protective devices did not show a pronounced effect on the outcome and prognosis, although it is justified in certain clinical situations. Ischemic injury directly plays a significant role due to overload of cardiomyocytes with calcium, cellular edema, necrosis and apoptosis, which is significantly aggravated by myocardial reperfusion and forms obstruction at the level of the microcirculatory bed. More data is being accumulated about immune-mediated injury through activation of cellular immunity, intense inflammation and thrombosis in situ. Despite the success in the animal experiment, the clinical use of certain groups of drugs showed an ambiguous results. According to the latest recommendations European Society of Cardiology / European Association for Cardio-Thoracic Surgery (ESC / EACTS) 2018, GPIIb / IIIa platelet receptor inhibitors are recommended in the case of no-reflow. Besides this, according to the literature nicorandil and sodium nitroprusside, as well as IL-1β antagonists, seem to be promising. As a non-drug therapy, selective intracoronary hypothermia also has shown its effectiveness and safety in a pilot study. To date, it is clear that the no-reflow phenomenon is a manifestation of a complex cascade of reactions, including ischemic, reperfusion and immune-related injury, as well as distal embolization. Considering its significant contribution to the frequency of adverse outcomes and late complications, it seems necessary to introduce unified approaches to the diagnosis, prevention and treatment of no-reflow, which requires high-quality clinical studies.

Persistent risk of vascular complications and efficacy of prolonged dual antiplatelet therapy after myocardial infarction

The article discusses data on the duration of risk retention and the main cause of vascular complications in patients with acute coronary syndrome. Preconditions for prolonged use of dual antiplatelet therapy after myocardial infarction are presented. The authors consider the results of a large, prospective, randomized, placebo-controlled, multinational PEGASUS-TIMI 54 study evaluating the efficacy and safety of the long-term use of acetylsalicylic acid combined with ticagrelor (P2Y12 platelet receptor blocker) in patients with a high risk of thrombotic complications of atherosclerosis in the period from 1 to 3 years after myocardial infarction. The article presents an analysis of optimal approaches to prolonged double antiplatelet therapy after myocardial infarction, taking into account the results of the PEGASUS-TIMI 54 study, which laid the foundation for current clinical guidelines. The PEGASUS-TIMI 54 study demonstrated the benefits of prolonged dual antiplatelet therapy for at least 4 years after myocardial infarction in patients with a high risk of atherothrombotic complications and confirmed the expediency to reduce the dose of ticagrelor from 90 to 60 mg twice daily for 1 year after the onset of the disease to ensure the best balance of efficacy and safety of treatment. The possibility of prolonging double antiplatelet therapy using a combination of ASA and ticagrelor at a dose of 60 mg twice daily for 1 year after myocardial infarction is provided for in the guidelines for medical use of ticagrelor and is enshrined in existing clinical guidelines. Presently, ticagrelor is the only P2Y12 platelet receptor inhibitor approved in the Russian Federation as an adjunct to ASA for the long-term prevention of atherothrombotic cardiovascular events.

Platelet Aggregation Dysfunction in Sickle Cell Disease

Acute systemic painful vaso-occlusive crisis (VOC) is the predominant clinical event requiring sickle cell disease (SCD) patients to seek emergency medical care. VOC often serves as an antecedent to acute chest syndrome (ACS), which is a type of acute lung injury and the leading cause of mortality in SCD. Current treatments for ACS are primarily supportive, and there is a critical need for rescue strategies to prevent the progression of VOC to ACS. ACS involves thrombosis across pulmonary artery branches, but the pathophysiology of thrombosis in SCD is largely unknown. Adenosine diphosphate (ADP) released from lysed erythrocytes can activate platelets by stimulating the purinergic receptors P2Y1 and P2Y12, suggesting that blocking these receptors may prevent VOC. Surprisingly, P2Y12 receptor blockade was unsuccessful in preventing VOC in a recent DOVE trial, justifying the need for better understanding of purinergic signaling in SCD.We used a novel intravital microscopy enabled experimental model of vaso-occlusive pulmonary thrombosis in transgenic SCD mice triggered by an intravenous (IV) administration of ADP. This method allows real time in vivo visualization of platelet aggregation in the lung of live SCD mice using multi-photon-excitation based quantitative fluorescence intravital lung microscopy (qFILM). We discovered that vaso-occlusive thrombosis involves entrapment of large circulating platelet aggregates in the bottle-necks located between the pulmonary arterioles and capillaries. Surprisingly, the dose of ADP that led to the pulmonary vaso-occlusive thrombosis in control mice, failed to induce vaso-occlusive thrombosis in SCD mice. Remarkably, further in vivo and in vitro platelet aggregation studies confirmed that SCD mouse platelets were indeed refractory to ADP but not collagen.Our preliminary findings suggest that therapeutic inhibition of P2Y1 and P2Y12 platelet receptors will not be a successful therapy in SCD. Our findings also warrant the need for further studies to understand the role of purinergic signaling in SCD DisclosuresNo relevant conflicts of interest to declare.

Ticagrelor use and practice patterns among Canadian cardiac surgeons.

The P2Y12 platelet receptor inhibitor ticagrelor is widely used in patients following acute coronary syndromes or in those who have received coronary stents. Bentracimab is a monoclonal antibody-based reversal agent that is being formally evaluated in a Phase 3 clinical trial. Here, we probe the knowledge, attitudes, and practice patterns of cardiac surgeons regarding their perioperative management of ticagrelor and potential application of a ticagrelor reversal agent. A questionnaire was developed by a working group of cardiac surgeons to inquire into participants' practices and beliefs regarding ticagrelor and disseminated to practicing, Canadian-trained cardiac surgeons. A total of 70 Canadian-trained cardiac surgeons participated. Bleeding risk was identified as the most significant consideration when surgically revascularizing ticagrelor-treated patients (90%). There is variability in the duration of withholding ticagrelor before coronary artery bypass graft procedure in a stable patient; 44.3% wait 3 days and 32.9% wait 4 days or longer. Currently, 15.7% of cardiac surgeons prophylactically give platelet transfusions and fresh frozen plasma intraoperatively following protamine infusion in patients who have recently received ticagrelor. Interestingly, 47.1% of surveyed surgeons were aware of a reversal agent for ticagrelor, 91.4% of cardiac surgeons would consider utilizing a ticagrelor reversal agent if available, and 51.4% acknowledged that the introduction of such an agent would be a major advance in clinical practice. The present survey identified ticagrelor-related bleeding as a major concern for cardiac surgeons. Surgeons recognized the significant unmet need that a ticagrelor reversal agent would address.

Platelet reactivity in patients with coronary artery disease on treatment with ivabradine and clopidogrel: The PLATIVA study

The combination of aspirin and clopidogrel remains the most frequent dual antiplatelet therapy in patients with acute coronary syndrome or undergoing percutaneous coronary intervention. Clopidogrel, a P2Y12 adenosine diphosphate (ADP) platelet receptor inhibitor requires transformation by cytochrome P450 (CYP) in the liver to produce an active metabolite. On the other hand, ivabradine is an effective antianginal drug that is also metabolized by the CYP enzyme, acting as a weak inhibitor. Our aim is to evaluate the impact of ivabradine on platelet reactivity in patients receiving clopidogrel and to evaluate the possible pharmacodynamic interactions between them. This is a prospective, observational, post-authorization pharmacodynamic study including patients treated with aspirin and clopidogrel and initiating ivabradine. Patients with platelet abnormalities and those treated with anticoagulants or other CYP inhibitors were excluded. A platelet aggregation test was performed at baseline before the first dose of ivabradine and repeated after 4 weeks of treatment. The primary endpoint was inhibition of platelet aggregation (IPA) after 20 mM ADP stimulation. A total of 34 patients were initially recruited; eight patients were excluded, leaving 25 patients for final analysis. All patients had chronic ischemic heart disease. The maximum ivabradine dosage of 7.5 mg twice daily was achieved in seven patients (28%). After 4 weeks of treatment with ivabradine, no significant differences were found in maximal platelet aggregation from baseline, as assessed with 20 μM ADP stimulation. In addition, no significant difference in IPA from baseline was detected after stimulation with ADP 5 μM, arachidonic acid, thrombin receptor-activated peptide 25 μM, and platelet reactivity index. Ivabradine did not alter antiplatelet response to clopidogrel in patients treated concomitantly with both drugs.

Platelets Modulate IFN-γ Production against Candida albicans in Peripheral Blood Mononuclear Cells via Prostaglandins.

Platelets are known to have immunomodulatory properties. They modulate immune responses of leukocytes against various pathogens, including fungi. Candida albicans can cause systemic infection in immunocompromised individuals that is associated with a high mortality and morbidity. In the current study, we explored the role of platelets in antifungal host defense against C. albicans PBMCs were stimulated with heat-killed (HK) C. albicans in the presence or absence of isolated washed platelets. Cytokines were quantified from culture supernatants by ELISA. Inhibition of platelet receptors and cytokine pathways were used to elucidate the mechanisms involved in platelet-leukocyte interaction. In the presence of platelets, PBMCs produced less IFN-γ upon stimulation with HK C. albicans This effect was dependent on the direct contact between platelets and leukocytes but was independent of the platelet GPIb and P-selectin receptors. The attenuation of IFN-γ was not a direct effect on T cells but was dependent on the presence of APC and T cells. Platelets did not modulate the Th-1-polarizing cytokines IL-12 and IL-18. The addition of PG (PGE2) further diminished IFN-γ levels in PBMCs, and supplementation of cells with nonsteroidal anti-inflammatory drugs was able to restore the level of IFN-γ. Overall, we show that modulation of the Th1 response against C. albicans by platelets is dependent on PGs.

Возможности замены одного антиагрегантного препарата на другой у пациентов, получающих двойную антиагрегантную терапию

Therapeutic potential of replacement of one antiagregant by another one in patients receiving double antiaggregant therapy Double antiaggregant therapy reduces the risk of adverse cardiovascular events. There are currently several P2Y12 platelet receptor inhibitors available, which suggests that not only optimal therapy needs to be chosen, but a patient can also be switched from one drug to another. At present, there are limited research data, as well as guidelines based largely on the experts’ opinions on replacing one drug by another. The existing options for changing double antiaggregant therapy should be taken into account in order to achieve optimal treatment outcomes for each patient.

Abstract 250: Antiplatelet Therapy in Post-Acute Coronary Syndrome: Effect of Education on Physician Knowledge and Competence

Background: Decreasing hospital readmission rates resulting from suboptimal antiplatelet therapy requires education to diminish an gap in physician knowledge/competence. We sought to determine if online medical education could improve clinical knowledge/competence regarding dual antiplatelet therapy (DAPT) in post-acute coronary syndrome (ACS) patients among non-United States (US) cardiologists. Methods: The educational activity was a 30-minute online video discussion between 4 experts with synchronized slides. Educational effect was assessed using a 4-question repeated pairs pre-/post-assessment and McNemar’s chi-squared test. P values are shown as a measure of significance; P values <.05 are statistically significant. Cramer’s V statistic indicated the effect size (<0.05 no effect; 0.06-0.15 small effect, 0.16-0.30 medium effect, >0.30 large effect). The activity launched August 23, 2016; data were collected through December 20, 2016. Results: 117 non-US cardiologists completed the study. The change in correct responses from pre- to post-assessment achieved statistical significance (P<.05) for 2 of 3 questions. An average of 26% of cardiologists selected the best response at pre-assessment (range, 9% to 38%); this figure improved to an average of 35% at post-assessment (range, 22% to 55%). Specific improvements were observed in the following areas: The relationship between platelet reactivity and stent thrombosis with DAPT post-drug eluting stent implantation (90% improvement, 29%pre vs 55%post, P = <.001) Optimal treatment strategy with adenosine diphosphate platelet receptor (P2Y12) inhibition in patients with unstable angina or non-ST segment myocardial infarction (144% improvement, 9%pre vs 22%post, P =.007) Conclusion: Participation in a 30-minute online video discussion with synchronized slides resulted in statistically significant improvement in non-US cardiologists’ knowledge and competence regarding DAPT in patients with post-ACS.

Hemocoagulation Activity of Sulfur-Containing Pinane-Type Terpenoids

A series of pinane-type sulfides and sulfoxides were synthesized from (1S)-(–)-β-pinene. Their hemocoagulation activity in vitro on human blood plasma was studied. All tested compounds exhibited antiaggregation and anticoagulation activity. The most water-soluble sulfoxide with a mercaptoacetic acid moiety inhibited spontaneous platelet aggregation and that induced by collagen and arachidonic acid and also reduced the coagulation activity of human blood plasma. The hemocoagulation activity was due to selective inhibition of platelet receptors, decreased yield of thrombocytic microvesicles, and suppression of their activity.

Гемокоагуляционная активность серусодержащих терпеноидов пинанового ряда

Серия сульфидов и сульфоксидов пинанового ряда синтезирована на основе (1S)-(-)-β-пинена, изучена их гемокоагуляционная активность in vitro на плазме крови человека. Все полученные соединения обладают антиагрегационной и антикоагуляционной активностью. Наиболее водорастворимый сульфоксид с фрагментом меркаптоуксусной кислоты подавляет спонтанную и индуцированную коллагеном и арахидоновой кислотой агрегацию тромбоцитов, а также снижает коагуляционную активность плазмы крови человека. Гемокоагуляционная активность обусловлена селективным ингибированием рецепторов тромбоцитов, уменьшением выброса тромбоцитарных микровезикул и подавлением их активности.

Inhibidores del receptor plaquetario P2Y12. Parte 2 de 2: etiología, diagnóstico y manejo de la resistencia

Las enfermedades cardiovasculares, que comprenden las afecciones del corazón, del cerebro y de los vasos sanguíneos en general, representan la primera causa de muerte a nivel mundial con diecisiete millones y medio de muertes cada año, de los cuales una tercera parte se debe a eventos trombóticos. La antiagregación plaquetaria con diferentes agentes, incluidos los inhibidores del receptor plaquetario P2Y12, se ha convertido en la piedra angular de la prevención primaria y secundaria y del tratamiento de las enfermedades cardiovasculares, entre ellas el infarto agudo de miocardio, la apoplejía y las enfermedades trombóticas. Sin embargo, varios estudios de investigación han demostrado que algunos individuos presentan disminución en la respuesta in vivo a estas sustancias, la cual se expresa como resistencia. En el primer módulo se abordó el papel de las plaquetas en la enfermedad aterotrombótica y se describieron los seis inhibidores del receptor plaquetario P2Y12, disponibles para su uso clínico actual o a futuro: la ticlopidina, el clopidogrel, el prasugrel, el ticagrelor, el cangrelor y el elinogrel. En este segundo módulo se tratará el concepto de la resistencia a los inhibidores del receptor plaquetario P2Y12, en particular al clopidogrel, la etiología de la resistencia y el monitoreo de la antiagregación con inhibidores del receptor plaquetario P2Y12 mediante pruebas de función plaquetaria, como una manera de hacer una antiagregación personalizada; finalmente, se darán las pautas básicas para el manejo de la resistencia a los inhibidores del receptor plaquetario P2Y12.

A prospective, randomized, open-label trial of 6-month versus 12-month dual antiplatelet therapy after drug-eluting stent implantation in ST-elevation myocardial infarction: Rationale and design of the “DAPT-STEMI trial”

The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention with second-generation drug eluting stents (DESs) is unclear. Because prolonged DAPT is associated with higher bleeding risk and health care costs, establishing optimal DAPT duration is of paramount importance. No other randomized controlled trials have evaluated the safety of shorter DAPT duration in ST-elevation myocardial infarction (STEMI) patients treated with second-generation DESs and latest P2Y12 platelet receptor inhibitors. Six months of DAPT after Resolute Integrity stent implantation in STEMI patients is not inferior to 12 months of DAPT in clinical outcomes. The Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation In ST-elevation Myocardial Infarction (DAPT-STEMI) trial is a randomized, multicenter, international, open-label trial designed to examine the safety (noninferiority) of 6-month DAPT after Resolute Integrity stent implantation in STEMI patients compared with 12-month DAPT. Event-free patients on DAPT at 6month will be randomized (1:1 fashion) between single (aspirin only) versus DAPT for an additional 6 months and followed until 2 years after primary percutaneous coronary intervention. The primary end point is a patient-oriented composite endpoint of all-cause mortality, any myocardial infarction, any revascularization, stroke, and major bleeding (net adverse clinical events [NACE]) at 18 months after randomization. To achieve a power of 85% for a noninferiority limit of 1.66, a total of 1100 enrolled patients are required. The DAPT-STEMI trial aims to assess in STEMI patients treated with second-generation DESs whether discontinuation of DAPT after 6 months of event-free survival is noninferior to routine 12-month DAPT.

Thrombus composition in sudden cardiac death from acute myocardial infarction

Background and aimIt was hypothesized that the pattern of coronary occlusion (thrombus composition) might contribute to the onset of ventricular arrhythmia and sudden cardiac death (SCD) in myocardial infarction (MI). MethodsThe TIDE (Thrombus and Inflammation in sudden DEath) study included patients with angiographically-proven acute coronary occlusion as the cause of a ST elevation MI (STEMI) complicated by Sudden Cardiac Death (SCD group) or not (STEMI group). Thrombi were obtained by thrombo-aspiration before primary percutaneous coronary stenting and analyzed with a quantitative method using scanning electron microscopy. We compared the composition of the thrombi responsible for the coronary occlusion between the two groups and evaluated factors influencing its composition. ResultsWe included 121 patients and found that thrombus composition was not different between the SCD group (n=23) and the STEMI group (n=98) regarding content of fibrin fibers (60.3±18.4% vs. 62.4±18.4% respectively, p=0.68), platelets (16.3±19.2% vs. 15.616.7±%, p=0.76), erythrocytes (14.6±12.5% vs. 13±12.1%, p=0.73) and leukocytes (0.6±0.9% vs. 0.8±1.5%, p=0.93). Thrombus composition did not differ between patients receiving upstream-use of glycoprotein IIb/IIIa platelet receptor inhibitors (GPI) and patients free of GPI. The only factor found to influence thrombus composition was the ischemic time from symptom onset to primary PCI, with a decreased content in fibrin fibers (57.8±18.5% vs. 71.9±10.1%, p=0.0008) and a higher platelet content (19.2±19.1% vs. 7.9±5.7% p=0.014) in early presenters (<3h of ischemic time) vs. late presenters (>6h of ischemic time). ConclusionComposition of intracoronary thrombi in STEMI patients does not differ between those presenting with and without SCD. Time from symptom onset to coronary reperfusion seems to be the strongest factor influencing thrombus composition in MI.

Inhibidores del receptor plaquetario P2Y12. Parte 1 de 2: escenario de acción, farmacología, aplicación clínica y limitaciones de su uso

Las enfermedades cardiovasculares, incluidas las afecciones del corazón, del cerebro y de los vasos sanguíneos en general, representan la primera causa de muerte a nivel mundial, con diecisiete millones y medio de muertes cada año. La prevención primaria y secundaria de las enfermedades aterotrombóticas, como el infarto agudo de miocardio, el accidente cerebrovascular y las enfermedades trombóticas, además de las medidas generales para el control de los factores de riesgo tales como la obesidad, el sedentarismo, el tabaquismo, la hipertensión arterial y la diabetes, se han centrado en el control de la agregación plaquetaria. El antiagregante plaquetario por excelencia o universal, sobre todo en la prevención primaria, es la aspirina y la terapia dual con la combinación de aspirina y un inhibidor del receptor plaquetario P2Y12, principalmente el clopidogrel, es usada en la prevención secundaria y en los casos de resistencia a la aspirina. En el momento, se dispone para uso clínico de seis inhibidores del receptor plaquetario P2Y12: la ticlopidina, el clopidogrel, el prasugrel, el ticagrelor, el cangrelor y el elinogrel. En este primer módulo, de dos que serán presentados, se abordará el uso de los inhibidores del receptor plaquetario P2Y12 en la práctica del día a día en la prevención primaria y secundaria de las enfermedades aterotrombóticas, enfocado en el análisis del papel de las plaquetas en la fisiopatología de la enfermedad aterotrombótica y la descripción de los seis inhibidores del receptor plaquetario P2Y12 disponibles ahora y en el futuro. En un segundo módulo se hará una aproximación al concepto de la resistencia a los inhibidores del receptor plaquetario P2Y12, su diagnóstico desde el punto de vista del laboratorio y las diferentes alternativas de manejo cuando se presenta resistencia a uno de estos medicamentos.