prasugrel-hydrochloride and Heart-Diseases

Antiplatelet therapy, the cornerstone of post coronary stenting antithrombotic therapy, reduces the rate of hard clinical endpoints in patients treated both conservatively and invasively following an acute coronary syndrome, as well as in those patients with chronic stable coronary disease who receive a coronary stent. The development of newer antiplatelet and direct anticoagulant agents provides new options in the antithrombotic management of patients with coronary artery disease, enabling different therapeutic combinations to be tailored to an individual patient's bleeding and ischemic risk profile. In this review, we will summarize the history of dual antiplatelet therapy, discuss the latest evidence and future perspectives in treating patients with coronary artery disease.

Topics: Acute Coronary Syndrome; Anticoagulants; Clopidogrel; Coronary Artery Disease; Drug-Eluting Stents; Dual Anti-Platelet Therapy; Heart Diseases; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Risk Assessment; Ticagrelor

Ticagrelor and prasugrel have shown superiority over clopidogrel. However, it remains unclear if one is superior to another regarding on-treatment platelet reactivity.. To compare the impact of ticagrelor and prasugrel on high on-treatment platelet reactivity (HTPR).. The PubMed and Cochrane databases were searched for eligible studies in December 2014. Studies were eligible if they compared ticagrelor and prasugrel regarding high on-treatment platelet reactivity (HTPR). Pooled estimates were calculated by using a random-effects model with 95% confidence intervals.. We included 14 studies and 1822 patients: 805 and 1017 in the ticagrelor and prasugrel groups, respectively. The rate of HTPR was significantly lower in the ticagrelor group: 1.5% vs. 9.8% (RR = 0.27 [0.14-0.50]). The pre-specified analysis focusing on randomized trials (n = 10) showed consistent results (RR = 0.27 [0.12-0.60]).. Our results suggest that ticagrelor allows a higher platelet reactivity inhibition as compared with prasugrel and leads to a further decrease in the rate of HTPR.

Topics: Adenosine; Blood Platelets; Chi-Square Distribution; Drug Resistance; Heart Diseases; Humans; Odds Ratio; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Predictive Value of Tests; Risk Factors; Ticagrelor; Treatment Outcome

Acute coronary syndromes (ACS) are common and carry a high risk of death and serious complications. Over the past three decades, the international cardiology community has collaborated in numerous large, well-designed randomized trials evaluating promising new treatments leading to important improvements in care for patients with ACS. Industry has funded most of the ACS trials of new pharmacologic treatments, but there are many independently funded trials evaluating treatment strategies such as percutaneous coronary intervention. Improvements in ACS care have led to challenges in demonstrating the efficacy of new treatments and many current trials are comparing one active treatment against another, although new paradigms including anti-inflammatory treatments and stem cell infusions are being tested against placebo. Developing new drugs for ACS is a very expensive process with many trials not showing any benefit, and much of this expense is related to the cost of large multicenter phase 3 trials. Reducing the administrative burden and associated costs of ACS trials is an important immediate goal if the strong tradition of large collaborative trials is to continue, as well as the need for health care providers to engage more actively in the clinical research process and support large multinational independently funded trials. We discuss methodologic issues of ACS trials with recent examples and provide some perspectives for the future.

Topics: Acute Coronary Syndrome; Adenosine; Aspirin; Clinical Trials as Topic; Clopidogrel; Cyclic N-Oxides; Eptifibatide; Heart Diseases; Humans; Peptides; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Pyridines; Research Design; Research Support as Topic; Risk Factors; Sample Size; Thiophenes; Ticagrelor; Ticlopidine; United Kingdom

A unique dose of prasugrel has been approved exclusively for Japanese patients, but real-world data for prasugrel at that dose in patients with ischemic heart disease (IHD) are limited. Therefore, large-scale, real-world data are needed. Methods and Results: A 2-year observational study of Japanese patients with IHD undergoing percutaneous coronary intervention and being treated with prasugrel to evaluate safety and effectiveness. This report is an interim analysis of data from case report forms (CRFs) after 3 months. CRFs were collected from 4,270 patients, 4,157 of whom were eligible for the safety and effectiveness analysis sets (mean age, 68.3 years; male, 76.5%). The median treatment period was 112 days, and 92.3% of patients continued treatment with prasugrel. The incidence of non-coronary artery bypass grafting-related bleeding adverse events (AEs) was 3.1%, of which Thrombolysis in Myocardial Infarction (TIMI) major and minor bleeding accounted for 0.5% and 0.6%, respectively. The most common bleeding AEs were gastrointestinal disorders, which accounted for 43.2% of the sum of "TIMI major and minor bleeding AEs". The incidence of major adverse cardiovascular events (MACE) was 1.0%, and the cumulative incidence of MACE was 1.4%. The incidence of stent thrombosis was 0.2%.. Interim study results indicated that prasugrel was safe and effective during the early phase of treatment in Japanese patients with IHD in real-world clinical settings.

Topics: Aged; Drug Evaluation; Female; Heart Diseases; Hemorrhage; Humans; Japan; Male; Middle Aged; Myocardial Ischemia; Prasugrel Hydrochloride; Product Surveillance, Postmarketing; Treatment Outcome

Selective intensification of platelet inhibition may improve high on treatment platelet reactivity (HPR). We evaluated the efficacy of dual-antiplatelet therapy, including clopidogrel (CPG), compared to new P2Y12-receptor antagonists in patients with HPR undergoing percutaneous coronary intervention, regarding the outcome of composite major adverse cardiac events (MACEs, including death, acute coronary syndrome [ACS], and stent restenosis). The presence of HPR (71 of 181 patients) almost doubled the risk of MACEs. The new antiplatelet agent reduced MACEs (45.8%, 26%, and 16.7% for CPG, prasugrel, and ticagrelor [TGL]; RR 0.36; 0.13-0.98, P = .03, TGL), specifically in patients with ACS. Failure to reduce HPR after the antiplatelet change and diabetes were independent predictors for MACEs. The HPR was early and effectively reduced after changing the antiplatelet therapy, but the intensity of this reduction did not significantly decrease the risk of MACEs. These findings support the benefit of HPR-guided intensification of platelet inhibition. Whether the intensity of this reduction improves the patient's clinical outcomes deserves further investigation.

Topics: Aged; Clopidogrel; Female; Heart Diseases; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Prasugrel Hydrochloride; Receptors, Purinergic P2Y12; Ticlopidine

Identification of factors affecting platelet reactivity (PR) and high PR (HPR) or high platelet inhibition (HPI) rates while on prasugrel maintenance dose (MD) might be helpful in avoiding ischemic or bleeding complications. We retrospectively analyzed all patients (n=233) treated in our institution between April 2010 and November 2012 who had platelet function assessment pre-prasugrel and following prasugrel 10 mg MD for at least 5 days, using the Verify Now P2Y12 platelet function assay. Multiple linear regression and logistic regression models were applied to identify independent factors affecting post-prasugrel PR level, HPR and HPI status. The amount of variance in PR under prasugrel MD that could be explained by the model was 25.9% (adjusted R²), p<0.001. Pre-prasugrel treatment PR, acute coronary syndrome (ACS), prasugrel loading and smoking uniquely accounted for 10.8%, 1.3%, 3.5% and 1.2% of the observed variance, respectively. HPR and HPI were observed in 7.7% and 13.7% of the cases, respectively. On multivariate analysis, pre-prasugrel PR in the upper quartile (>313 PRU) was the only independent factor associated with HPR under prasugrel MD. In contrast, pre-prasugrel PR in the lower quartile (<242 PRU) and prasugrel loading emerged as the only independent predictors of HPI. In patients under different clinical settings receiving prasugrel 10 mg MD a significant amount of the PR variability in response to prasugrel may be explained by pre- treatment PR level, ACS, prasugrel loading and smoking status. A high pre- treatment PR is associated with HPR, while a low pre-treatment PR and prasugrel loading predict HPI.

Topics: Acute Coronary Syndrome; Aged; Blood Platelets; Cohort Studies; Drug Resistance; Female; Heart Diseases; Hemorrhage; Humans; Maintenance Chemotherapy; Male; Middle Aged; Models, Biological; Myocardial Ischemia; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation; Platelet Aggregation Inhibitors; Postoperative Complications; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Smoking; Thiophenes