Agents In Acute Coronary Syndromes Research Articles

Heart rate lowering agents in acute coronary syndrome

Background: Heart rate is a key indicator of cardiovascular mortality, with ACS having the highest mortality risk when heart rate is elevated. With a target heart rate of <70 bpm, it is crucial to evaluate the effects of medications that lowers heart rate. Methods: In this prospective observational study, 45 patients with ACS were studied, and it was determined whether or not the patients' heart rates at discharge from the hospital were within goal range. Additionally, we looked at demographics, drug-related issues, vitals and then statistical tests were performed. Results: The demographic of 45 patients showed mean adult age was 47 years and most observed ACS was STEMI (53.3%). Patients prescribed with HRLA showed lower mean HR, SBP and DBP at discharge. Evaluated Optimal HR ≤70 bpm with HRLA therapy at discharge of the inpatients was achieved in 26.6% (63.5±5.5 bpm). Conclusions: The current study showed HRLA therapy effectively reduced the heart rate at hospital discharge, but despite being on HRLA only 1/4th of patients achieved the optimal heart rate.

Impact of the rs73598374 polymorphism of the adenosine deaminase gene on platelet reactivity and long-term outcomes among patients with acute coronary syndrome treated with ticagrelor

BackgroundThe positive interaction of ticagrelor with the metabolism of adenosine has been claimed for the large antithrombotic and antiischemic benefits of this antiplatelet agent in acute coronary syndromes (ACS). Adenosine catabolism is regulated by the activity of the adenosine deaminase enzyme (ADA), for which several polymorphisms have been identified. Therefore, the aim of our study was to explore the impact of the rs73598374 polymorphism of ADA gene on platelet reactivity in ACS patients treated with ticagrelor. MethodsWe included consecutive patients receiving ASA and ticagrelor after an ACS and coronary intervention. Platelet reactivity was evaluated by impedance aggregometry at 30–90 days post-discharge. The genetic analysis was carried out by PCR and RFLP. Clinical endpoints were mortality, cardiovascular death, recurrent myocardial infarction or coronary revascularization at the maximum available follow-up. ResultsOur population is represented by 464 patients, of whom 33.4% were A-heterozygotes and 6 homozygotes. A-allele carriers showed a greater prevalence of renal failure (p = 0.02) and a lower rate of previous coronary artery bypass graft (p = 0.03) and statin treatment (p = 0.02). No differences in the mean values of platelet reactivity or HRPR on ticagrelor were found according to the ADA genotype (11.3%vs13.9%, p = 0.45; adjusted OR[95% CI] = 1.17[0.64–2.14], p = 0.61). At follow up, patients carrying the A-allele showed a non-significantly lower incidence of ACS and repeated unplanned revascularization, although with no effect on mortality. ConclusionsIn the present study the rs73598374 polymorphism of the ADA gene did not affect platelet reactivity or the long-term prognosis in patients with ACS receiving dual antiplatelet therapy with ASA and ticagrelor.

464 Comparison of Potent Anti-Platelet Agents in Acute Coronary Syndrome

464 Comparison of Potent Anti-Platelet Agents in Acute Coronary Syndrome

P3612Potential for Bruton's tyrosine kinase inhibitors as additional antiplatelet agents in acute coronary syndromes

P3612Potential for Bruton's tyrosine kinase inhibitors as additional antiplatelet agents in acute coronary syndromes

Antiplatelet Agents in Acute Coronary Syndromes

Abstract Under balanced conditions, hemostasis is maintained by a complex interaction between endothelium, platelets, and coagulation factors. Situations involving injury and discontinuation of the endothelial lining stimulate the adhesion, activation, and aggregation of platelets, culminating in the formation of arterial or venous thrombi. In this context, antiplatelet therapy occupies a prominent role in the management of pathologies arising from this process, notably acute coronary syndromes. The increased conceptual understanding of receptors, agonists, and antagonists of the pathophysiological cascades involved in this process has allowed the development of new drugs and refinement of the current therapy, demanding a complete knowledge of the arsenal of antiplatelet agents with respect to their indication, dosage, moment of administration, and duration of treatment. The objective of this review is to define the role of antiplatelet drugs in the management of acute coronary syndrome, revisiting aspects that have been already consolidated and addressing current and still controversial topics on the subject.

0084 : Adherence to antihypertensive agents in acute coronary syndrome: Moroccan experience

Antihypertensive (AH) agents have been shown to reduce the risk of cardiovascular events, including coronary artery disease. Nonadherence to AH agents may reduce their effectiveness. The aim was to determine the impact of better adherence to antihypertensive agents on patient's outcomes. We proceed to prospective study of 57 diabetic's patients with acute coronary syndrome (ACS), from January to June 2015 in Cardiology department of IBN ROCHD University Hospital of Casablanca (Morocco), after collecting general demographic characteristics, the assessment of adherence to the medical regime was by the Morisky Medication Adherence Scale (MMAS 4 – item version). In this period 57 patients with ACS were included (42% of total ACS). The mean patient age was 64±8 years, 43, 9% were male. Among these patients, level of compliance was 60% according to (MMAS 4). Compared with non compliant patients, lower adherence level was associated with a high risk on in-hospital mortality (p=0,037) and 30-day mortality (p=0,015). this study is among the first conducted in Morocco which suggests that better adherence to AH agents is associated with a risk reduction of ACS. Adherence to hypoglycemic agents needs to be improved so that patients can benefit from the full protective effects of hypoglycemic therapies. The author hereby declares no conflict of interest

Novel anti-platelet agents in acute coronary syndrome: mechanisms of action and opportunities to tailor therapy.

Dual anti-platelet therapy, most commonly aspirin and clopidogrel, has been the standard of care for over a decade in patients who have experienced acute coronary syndrome, particularly when treated with coronary stenting. However, residual risk in patients receiving dual anti-platelet therapy post-acute coronary syndrome raises an unmet need for alternative therapy to clopidogrel. Consequently, novel anti-platelets agents including the P2Y12 receptor antagonists, such as prasugrel and ticagrelor, have emerged. Furthermore, using new methods to assess genetic polymorphisms and functional phenotypic assessments of platelet reactivity may become important in the development of personalized medicine and in developing tailored approaches to individual treatment. While robust large-scale evidence for genotypic- and phenotypic-guided therapy in improving outcomes is currently lacking, tremendous interest from various stakeholders including researchers, funding agencies, and industry continues to spur research endeavors in this arena. Further investigation is required in this emerging field to potentially offer improved platelet inhibition that may optimize cardioprotection and minimize bleeding risk in patients with acute coronary syndrome.

Use of novel antiplatelet agents in acute coronary syndromes.

Acute coronary syndromes (ACS) encompass a broad spectrum of clinical presentations based on underlying pathology that results in myocardial ischemia and/or infarction. Despite advancements in invasive management and secondary preventive therapies, recurrent atherothrombotic coronary events remain a prevalent cause of death and recurrent cardiac events after ACS and, in those who survive, the root of long-standing cardiac comorbidities. Antiplatelet drug therapy has proven beneficial in the reduction of these events, and novel antiplatelet agents have resulted in significant improvement in clinical outcomes over the last decade. However, the balance of optimal platelet inhibition with minimal bleeding complications remains a clinical challenge. This review focuses on more recent advances in antiplatelet therapies used in the treatment of ACS.

Novel antiplatelet agents in acute coronary syndrome.

For more than 10 years, dual antiplatelet therapy with aspirin and clopidogrel has remained the cornerstone of treatment for patients with acute coronary syndrome (ACS). The novel oral P2Y purinoceptor 12 (P2Y12)-receptor inhibitors prasugrel and ticagrelor were approved by the FDA for clinical use in 2009 and 2011, respectively. These agents have a faster-acting, more-potent, and more-predictable antiplatelet effect than clopidogrel, which translates into improved clinical outcomes in patients with ACS, albeit at the expense of an increased risk of bleeding. However, some patients continue to experience adverse ischaemic events despite treatment with aspirin and a P2Y12-receptor antagonist, because platelets can remain activated via pathways not inhibited by these agents, such as the protease-activated receptor (PAR)-1 platelet activation pathway stimulated by thrombin. Emerging antiplatelet therapies that might address these limitations include intravenous P2Y12 antagonists, oral PAR-1 antagonists, and thromboxane-receptor inhibitors. In this Review, we provide an overview of these novel antiplatelet drugs, including newly approved agents and emerging compounds currently under clinical development, and also discuss evolving concepts and unmet needs related to antiplatelet therapy for the treatment of ACS.

Review of Newer Anticoagulants and Anti-platelet Agents in Acute Coronary Syndrome and Cardiovascular Diseases

In the last few years three new oral anticoagulants-Dabigatran, Rivaroxaban and Apixaban and two new antiplatelet agents Prasugrel and Ticagrelor have been approved for use. Dabigatran, Rivaroxaban and Apixaban have been approved for the prevention of stroke and systemic embolism in non valvular Atrial Fibrillation in the United States. Rivaroxaban is also approved for the prevention and treatment of venous thromboembolism, including pulmonary embolism. These drugs have been shown to be non-inferior to Warfarin. These drugs do not need monitoring and have lesser drug interactions compared to Warfarin. The newer antiplatelet agents Prasugrel and Ticagrelor are more potent than Clopidogrel and are more effective in patients with CYP2 C19 enzyme deficiency. Both of these drugs are approved in acute coronary syndrome and Prasugrel is approved only in acute coronary syndrome with percutaneous coronary intervention.

Subgroup analyses with special reference to the effect of antiplatelet agents in acute coronary syndromes

Controlled trials estimate treatment effects averaged over the reference population of subjects. However, physicians are interested in whether the treatment effect varies across subgroups (effect heterogeneity) in order to target specific subgroups to maximise the benefit of treatment and minimise harm. Therefore, large clinical trials of antiplatelet agents include subgroup analyses that examine whether treatment effects differ between subgroups of subjects identified by baseline characteristics. Reporting subgroup is pervasive and often accompanied by claims of difference of treatment effects between subgroups with potential important implications for clinical practice. However, subgroup-specific analyses of clinical trial data have inherent limitations that reduce their reliability. These include reduced statistical power, failure to specify the subgroups of interest a priori, failure to account for examining large numbers of subgroups, lack of strong rationale for biological response modification, and performing analyses based on variables measured post randomisation or in trials showing no overall difference between treatments. Rules for interpretation of subgroup findings in subgroups have been suggested but are frequently not applied. In this article we draw attention to the pitfalls of subgroup analyses in the context of recent trials of antiplatelet agents.

Any room left for new antiplatelet agents in acute coronary syndrome?

This editorial refers to ‘Effect of vorapaxar on myocardial infarction in the thrombin receptor antagonist for clinical event reduction in acute coronary syndrome (TRA·CER) trial’[†][1], by S. Leonardi et al. , on page 1723 Over the past two decades, the combination of aspirin and clopidogrel has been the gold standard antiplatelet strategy to prevent recurrent ischaemic events after an acute coronary syndrome (ACS). Several new pharmacological options have been evaluated since then. This includes more potent dual antiplatelet therapy (DAPT) with the new generation of P2Y12 inhibitors, and triple oral antithrombotic therapy (TOAT), a combination of aspirin and clopidogrel with either oral low dose Xa inhibition or oral platelet thrombin receptor blockade. Selecting the most favourable strategy for the post-ACS period warrants a careful evaluation of the risks and benefits for each patient. Although the one size fits all strategy is not ideal, the strategy of selecting drugs and doses according to patient characteristics remains challenging. Indeed, the ischaemic risk decreases over time, and the benefit of a prolonged and stronger antiplatelet treatment is so far unknown, especially in fragile patients who deserve more protection against ischaemic events but are also exposed to more severe bleeding on treatment. A more aggressive P2Y12 receptor blockade has consistently improved clinical outcome of ACS patients as compared with clopidogrel. Shorter and stronger platelet inhibition has also become an option in percutaeous coronary intervention (PCI) with the superiority of cangrelor over clopidogrel in the CHAMPION PHOENIX trial, although even a treatment limited to the time of PCI was associated with more bleeding complications.1 The benefit of stronger P2Y12 inhibition is particularly clear in patients with ST elevation myocardial infarction (STEMI) undergoing … [1]: #fn-2

Anticoagulant agents for Acute Coronary Syndromes

The classical recommendations for efficient and safe use of fibrinolytic agents have been described in detail in The Bangkok Medical Journal; February 2012, Volume 3. This article is an up to date description of how to use anticoagulant agents in acute coronary syndrome.

High on-treatment platelet reactivity - why should we be concerned?

High on-treatment platelet reactivity - why should we be concerned?

THIENOPYRIDINES: PLATELET ADP RECEPTOR ANTAGONIST

Atherothrombotic disease is the result of atherosclerosis progression, and its clinical manifestations [acute coronary syndromes (ACS), stroke, etc). These events are mostly secondary to atherosclerotic plaque disruption and subsequent thrombus formation. Atherosclerosis prevention is mainly focused on the management of the so-called ‘cardiovascular risk factors’; whereas thrombosis-related complications are mainly prevented and/or treated by antithrombotic therapies. The central role of platelets in the pathophysiology of arterial vascular disease has focused attention on the development of effective platelet inhibitor modalities to mitigate the clinical consequences of atherothrombotic disease. Aspirin has been the mainstay; the thienopyridines provide new opportunities for those patients who are intolerant, resistant or have failed aspirin, and for those who can derive greater benefit from combined therapy. Thienopyridines (ticlopidine, clopidogrel etc.) are a class of ADP receptor/P2Y12 inhibitors used for their anti-platelet activity. The co-administration aspirin-clopidogrel results in enhancement of platelet inhibition, since they act via different platelet receptors. This article reviews the current antiplatelet agents in ACSs and role of thienopyridines as antiplatelet agents in management.

Pharmacogenetics Testing: Implications for Cardiovascular Therapeutics with Clopidogrel and Warfarin

The recent US Food and Drug Administration (FDA) boxed warning [1] for the antiplatelet agent clopidogrel urging caution that poor metabolizers may not derive the full potential protection from heart attacks, stroke, and cardiovascular death is the latest in a series of recent developments that highlight the possible future role of pharmacogenetics testing in clinical decision making. The FDA advisory also states that “healthcare professionals consider alternative dosing of Plavix for these patients, or consider using other antiplatelet medications. Tests are available to assess CYP2C19 genotype to determine if a patient is a poor metabolizer.” Several large clinical trials such as CURE [2] and CAPRIE [3] have shown the therapeutic benefit of clopidogrel in reducing cardiovascular events in at-risk cohorts. It is now established as a therapeutic agent in acute coronary syndromes (ACSs) in various European and American guidelines [4,5] with loading doses up to 600 mg in clinical use. Clopidogrel is a prodrug that requires primarily cytochrome (CYP) P450 2C19 enzyme for its activation with its subsequent mechanism of action being the inhibition of the P2Y12 ADP receptor on the platelet surface and consequent platelet inhibition. There has been recent recognition that genetic polymorphism can influence the level of 2C19 activity [6,7]. Carriers of the ∗2, ∗3, ∗4, and ∗5 alleles have reduced enzymatic activity and therefore reduced levels of clopidogrel-induced platelet inhibition. According to a study by Mega et al., among clopidogrel-treated subjects in the TRITON-TIMI 38 trial, carriers of these alleles had a relative increase of 53% in the composite primary efficacy outcome of the risk of death from cardiovascular causes, myocardial infarction, or stroke, as compared with noncarriers (12.1% vs. 8.0%; P = 0.01) and an increase by a factor of 3 in the risk of stent thrombosis (2.6% vs. 0.8%; P = 0.02) [8]. Conversely, carriers of the ∗17 allele have a higher level of CYP2C19 activity and therefore platelet inhibition [6]. As the frequency of these variants differs widely in different populations, the efficacy of clopidogrel is likely to vary depending on the ethnic mix of the study population. Proton pump inhibitors (PPIs) are often coprescribed with clopidogrel for gastroprotection but these two

Antiplatelet Agents in Acute Coronary Syndromes

The platelet plays an essential role in atherothrombosis. Clinically, platelet-rich thrombi underlie acute coronary syndromes (ACSs). Current therapies have improved outcomes, however, often at the expense of increased risk of bleeding. With the increase in our understanding of the underlying pathophysiology of ACSs, newer targets for antiplatelet therapies continue to emerge. Novel antiplatelet agents may provide even greater reductions in ischemic events with the potential for less bleeding. This article reviews the evidence for current antiplatelet agents in ACSs as well as for the newer agents in later phases of clinical testing.

New antithrombotic agents in acute coronary syndromes

Acute coronary syndromes still account for high mortality in many countries. Antithrombotic therapy represents a cornerstone in the therapy of acute coronary syndromes. Recent research has focussed on improving anti-ischemic potency and reducing bleeding complications as well as improving predictability of antithrombotic efficacy. New antithrombotic drugs such as the factor Xa antagonists and the direct thrombin inhibitors have been developed and evaluated in clinical trials. Fondaparinux and bivalirudin are approved for clinical use in acute coronary syndromes. They improve the risk/benefit ratio and make routine control of their antithrombotic effect unnecessary. Other agents are being developed to further improve and facilitate antithrombotic therapy in acute coronary syndromes. Antithrombotic therapy is essential in acute coronary syndrome. New drugs are being developed to enter clinical practice and improve efficacy and safety of this therapeutic strategy.

Evaluation of a novel anti-ischemic agent in acute coronary syndromes: Design and rationale for the Metabolic Efficiency with Ranolazine for Less Ischemia in Non–ST-elevation acute coronary syndromes (MERLIN)-TIMI 36 trial

Despite advances in antithrombotic therapies and invasive technology, the risk of recurrent ischemic complications in patients with non-ST-elevation acute coronary syndromes (NSTE-ACSs) remains substantial. Ranolazine is a novel agent that inhibits the late sodium current thereby reducing cellular sodium and calcium overload and has been shown to reduce ischemia in patients with chronic stable angina. MERLIN-TIMI 36 is a phase III, randomized, double-blind, parallel-group, placebo-controlled, multinational clinical trial to evaluate the efficacy and safety of ranolazine during long-term treatment of patients with NSTE-ACS receiving standard therapy (N = 6500). Eligible patients are randomized 1:1 to ranolazine or matched placebo, initiated as 200 mg intravenously over 1 hour, followed by an 80-mg/h infusion (40 mg/h for patients with severe renal insufficiency) for up to 96 hours and oral ranolazine ER 1000 mg BID or matched placebo until the end of study. The primary end point is the time to first occurrence of any element of the composite of cardiovascular death, myocardial infarction, or recurrent ischemia. Secondary end points include ischemia on Holter monitoring, hospitalization for new or worsening heart failure, quality of life measures, and exercise performance. The evaluation of long-term safety will include death from any cause and symptomatic documented arrhythmia. Recruitment began in October 2004. The trial will continue until 730 major cardiovascular events and 310 deaths are recorded with expected completion in 24 to 28 months. MERLIN-TIMI 36 will evaluate the role of ranolazine in the acute and chronic management of patients presenting with NSTE-ACS.

Improving selection of αIIbβ3-binding phage antibodies with increased reactivity derived from immunized donors

Although many studies of the immune response in polytransfused Glanzmann thrombasthenia (GT) patients and in autoimmune thrombocytopenic purpura (AITP) have demonstrated the frequent development of Abs directed against the αIIbβ3 integrin, little is known about the induced anti-αIIbβ3 autoantibodies at the molecular level. Phage display is a powerful technology for selecting and engineering mAbs expressed on the surface of filamentous bacteriophage. Combinatorial libraries of single-chain IgG were constructed from splenocytes from two patients with AITP and one patient with GT. In a previous study, activated platelets or αIIbβ3-expressing CHO cells selection was performed to isolate human IgG anti-αIIbβ3 binding fragments using combinatorial libraries created from the B cells of a GT and an AITP patient. However, we have experienced practical problems such as enrichment of truncated antibodies during selection. We decided to test prolonged treatments with elution agents after screening on the purified form of the αIIbβ3 integrin activated with the RGD peptide. We obtained a higher percentage of clones with full-size antibody fragments as well as an enrichment of more specific αIIbβ3-binding phage-Abs. Some of them, recognizing the activated form of the integrin, would be interesting to further study as potential diagnostic or therapeutic agents in acute coronary syndromes. Sequencing of selected phage-Abs revealed that they used different VH and VL genes with, for the majority of them, a high level of extensive hypermutations in the complementarity determining regions, indicating the diversity of the antigen-driven immune response that occurred in GT and AITP patients.