ticagrelor and Body-Weight

The 3 main clinical manifestations of acute coronary syndrome (ACS) are unstable angina, non-ST-segment myocardial infarction, and ST-segment myocardial infarction. Together they comprise a major cause of emergency care and hospitalization in the United States. Consequently, all hospital-based physicians should be familiar with current recommendations regarding the diagnosis and management of ACS. Effective inhibition of platelet activation and aggregation is central to the treatment of ACS, and dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is recommended in all patients with ACS. Recently, the American Heart Association and American College of Cardiology Foundation published focused updates to their guidelines for the management of ACS patients. These updates included changes in antiplatelet therapy arising from the introduction of prasugrel and ticagrelor as alternatives to clopidogrel for the P2Y12 inhibitor component of dual antiplatelet therapy. Among the P2Y12 inhibitors recommended for each indication, the guidelines do not advocate any one P2Y12 inhibitor over another, but instead recommend that therapy is individualized based on each patient's demographic and clinical characteristics. This article presents a clinical case study to illustrate the hospital management of ST-segment myocardial infarction and unstable angina/non-ST-segment myocardial infarction with particular reference to the latest changes in antiplatelet therapy guidelines. This article outlines key differences in the indications and recommendations for P2Y12 inhibitors and summarizes clinical data from the pivotal studies of prasugrel and ticagrelor.

Topics: Acute Coronary Syndrome; Adenosine; Age Factors; Aspirin; Body Weight; Clopidogrel; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prasugrel Hydrochloride; Quality of Health Care; Randomized Controlled Trials as Topic; Thiophenes; Ticagrelor; Ticlopidine

Oral P2Y. This study sought to assess inhibition of platelet aggregation following subcutaneous administration of selatogrel in patients with AMI.. Patients with AMI were randomized to a single subcutaneous dose of selatogrel of 8 or 16 mg. The primary endpoint was response to treatment (P2Y. Forty-seven patients received selatogrel 8 mg (n = 24) or 16 mg (n = 23) followed by ticagrelor (n = 43) or clopidogrel (n = 1). The proportion of responders 30 min post-dose was 91% (one-sided 97.5% confidence interval [CI]: 80% to 100%) and 96% (97.5% CI: 87% to 100%) with 8 and 16 mg, respectively (p values for responders >85% target; p = 0.142 and p = 0.009, respectively). Response rates were independent from type of AMI presentation, age, or sex. A similar response rate was observed at 15 min (8 mg: 75% [97.5% CI: 58% to 100%]; 16 mg: 91% [97.5% CI: 80% to 100%]), which was sustained at 60 min post-dose (8 mg: 75% [97.5% CI: 58% to 100%]; 16 mg: 96% [97.5% CI: 87% to 100%]). At 15 min, median P2Y. Single-dose subcutaneous administration of selatogrel in patients with AMI was safe and induced a profound, rapid, and dose-related antiplatelet response. (A Medical Research Study to Evaluate the Effects of ACT-246475 in Adults With Heart Attack; NCT03487445, 2018-000765-36 [EudraCT]).

Topics: Adult; Aged; Aged, 80 and over; Body Weight; Clopidogrel; Drug Therapy, Combination; Female; Humans; Injections, Subcutaneous; Male; Middle Aged; Myocardial Infarction; Organophosphonates; Patient Safety; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prospective Studies; Pyrimidines; Ticagrelor; Treatment Outcome

The efficacy and safety of a reduced dose of prasugrel versus a standard dose of ticagrelor in elderly patients or those with a low body weight presenting with an acute coronary syndrome (ACS) are unknown.. To investigate the effect of an age- and weight-adapted dose of prasugrel versus a standard dose of ticagrelor in patients with ACS. (ClinicalTrials.gov: NCT01944800).. Prespecified analysis of the multicenter, randomized ISAR-REACT 5 trial.. 23 centers in Germany and Italy.. 3997 patients with ACS planned for invasive management.. Participants were randomly assigned to receive a standard dose of ticagrelor or prasugrel (reduced dose in the elderly or low-weight group and standard dose in the neither elderly nor low-weight group).. The efficacy end point was a composite of death, myocardial infarction, or stroke, and the safety end point was bleeding, both at 12 months.. In the elderly or low-weight group, the efficacy end point occurred in 12.7% of patients assigned to receive prasugrel and 14.6% of those assigned to receive ticagrelor (hazard ratio [HR], 0.82 [95% CI, 0.60 to 1.14]); in the neither elderly nor low-weight group, the efficacy end point occurred in 4.8% of patients assigned to receive prasugrel and 7.3% of those assigned to receive ticagrelor (HR, 0.65 [CI, 0.48 to 0.88];. The study is a subgroup analysis.. In elderly or low-weight patients with ACS, a reduced dose of prasugrel compared with the standard dose of ticagrelor is associated with maintained anti-ischemic efficacy while protecting these patients against the excess risk for bleeding.. German Center for Cardiovascular Research and Deutsches Herzzentrum München.

Topics: Acute Coronary Syndrome; Age Factors; Aged; Body Weight; Drug Dosage Calculations; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor; Treatment Outcome

The current standard of antiplatelet therapy for patients with myocardial infarction (MI) includes the P2Y12-receptor antagonist clopidogrel, prasugrel or ticagrelor. While it has been shown that platelet reactivity after clopidogrel administration depends on factors such as body weight, it is not known if these factors have an effect on the activity of prasugrel or ticagrelor. Thus, this study aimed to analyse factors associated with high residual platelet reactivity after administration of third generation P2Y12-antagonists compared to clopidogrel. In a single centre registry the antiplatelet effect of clopidogrel, prasugrel or ticagrelor was investigated by aggregometry in patients after MI. To assess the overall capacity of platelet aggregation whole blood was induced with thrombin receptor activating peptide (TRAP; 32 µM). To specifically quantify the effect of P2Y12-antagonists, blood was stimulated with 6.4 µM adenosine diphophosphate (ADP). Relative ADP induced aggregation (r-ADP-agg) was defined as the ADP-TRAP-ratio to reflect an individual degree of P2Y12-dependent platelet inhibition. Platelet function of 238 patients was analysed [clopidogrel (n = 58), prasugrel (n = 65), ticagrelor (n = 115)]. It was found that the r-ADP-agg correlated significantly with body weight in patients after clopidogrel administration (r = 0.423; p < 0.001). In contrast, this association was not present in patients after prasugrel (r = -0.117; p = 0.354) or ticagrelor (r = -0.082; p = 0.382) administration. Comparison of the correlation coefficients showed a significant difference (p = 0.003). In contrast to clopidogrel, platelet reactivity after administration of prasugrel or ticagrelor does not depend on body weight in patients after MI. Hence, our mechanistic data support the results of large clinical trials indicating that patients with high body weight do not need to be treated with increased doses of third generation P2Y12-antagonists to achieve sufficient platelet inhibition (registry for patients after myocardial infarction treated with antiplatelet agents; DRKS00003146).

Topics: Adenosine; Body Weight; Clopidogrel; Dose-Response Relationship, Drug; Drug Dosage Calculations; Humans; Platelet Activation; Platelet Aggregation; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine