ticagrelor and Drug-Related-Side-Effects-and-Adverse-Reactions

Our aim was to examine clinical trials, provide guidance to practitioners and estimate the efficacy and safety of two agents by comparing low dose ticagrelor with standard dose clopidogrel in patients with acute coronary syndrome. We systematically looked through Pubmed, Embase, the Cochrane Library, Wanfang data and CNKI for trials comparing low dose ticagrelor with standard dose clopidogrel for the treatment of patients with ACS since the database was created. The primary endpoint for efficacy was the rate of major adverse cardiac events (MACEs). The primary endpoint for safety was the rate of major bleeding events. We also evaluated platelet function between low dose ticagrelor and standard dose clopidogrel in ACS patients. From 6744 articles, 16 studies including 1629 patients met the inclusion criteria. In contrast with standard dose clopidogrel, low dose ticagrelor significantly reduced MACEs (OR 0.39, 95% CI 0.26, 0.58) and the difference was statistically significant (p<0.01). No difference was noted for major bleeding events (OR 1.16, 95% CI 0.43, 3.08) between the two agents (p=0.77). In addition, low dose ticagrelor showed lower platelet aggregation rate than clopidogrel (standardised mean difference (SMD) -0.68, 95% CI -0.83 to 0.53) (p<0.01). Platelet reaction units for low dose ticagrelor were much lower than those for standard dose clopidogrel (SMD -2.46, 95% CI -2.85 to -2.07) (p<0.01). In comparison with standard dose clopidogrel, low dose ticagrelor significantly lowered the incidence of MACEs, improved left ventricular ejection fraction, decreased left ventricular end diastolic dimension and did not expand the risk of major bleeding events or minor or minimal bleeding events in ACS patients with a considerable safety and efficacy profile. In addition, low dose ticagrelor was associated with dramatically lower platelet aggregation compared with standard dose clopidogrel.

Topics: Acute Coronary Syndrome; Clopidogrel; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Humans; Off-Label Use; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

Ticagrelor is a reversible P2Y

Topics: Acute Coronary Syndrome; Drug Costs; Drug-Related Side Effects and Adverse Reactions; Global Health; Humans; Incidence; Purinergic P2Y Receptor Antagonists; Ticagrelor

 The clinical benefit of anti-platelet agents in patients with chronic kidney disease (CKD) is uncertain. In addition, the risk-benefit ratio of potent oral P2Y12-adenosine diphosphate (ADP) receptor antagonists (PPAs), namely, prasugrel and ticagrelor, compared with clopidogrel in CKD patients suffering from acute coronary syndrome (ACS) remains unknown..  We performed a meta-analysis of all studies comparing the clinical outcomes of PPA and clopidogrel therapy in CKD patients suffering from ACS..  We searched PubMed, the Cochrane library, Google Scholar, Clinical trial.org and the abstracts of international cardiology congresses from April 2000 to October 2017. Clinical studies comparing PPA with clopidogrel in ACS patients with CKD were selected. Our literature research identified five studies which were included in the meta-analysis. The primary endpoint was a composite of major adverse cardiovascular events (MACEs) at the latest follow-up available. Secondary endpoint included bleedings..  Compared with clopidogrel, PPAs were associated with a reduced rate of MACE without increased bleedings in CKD patients with ACS. Among invasively managed patients, this benefit from PPA included a reduction in mortality.

Topics: Acute Coronary Syndrome; Administration, Oral; Clopidogrel; Drug-Related Side Effects and Adverse Reactions; France; Hemorrhage; Humans; Odds Ratio; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Survival Analysis; Ticagrelor; Treatment Outcome

Like all antithrombotic drugs, antiplatelet agents expose to a risk of bleeding complications. Clinical research has extensively focused on the efficacy of these drugs to reduce ischemic events. The bleeding risk associated with them was solely considered as an inevitable and acceptable complication. When two new potent P2Y12-receptor inhibitors, prasugrel and ticagrelor, were marketed, the risk of major bleeding increased. These new agents have modified the balance between the absolute risk reduction in ischemic events and the absolute risk increase in bleeding events. This paper is an update on the bleeding risk assessment associated with antiplatelet agents. It discusses the place of platelet function monitoring, and the optimal management of bleeding complications. It addresses the challenging issue of reversal of antiplatelet therapy, focusing especially on ticagrelor, which pharmacodynamics complicate bleeding management.

Topics: Adenosine; Aspirin; Clopidogrel; Drug-Related Side Effects and Adverse Reactions; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Risk Factors; Ticagrelor; Ticlopidine

Dual antiplatelet therapy with aspirin and a platelet adenosine diphosphate P2Y(12) receptor blocker reduces the risk of major adverse cardiovascular events following percutaneous coronary intervention or an acute coronary syndrome. Clopidogrel is the most widely used P2Y(12) receptor blocker, but has suboptimal speed of onset of action and maximal platelet inhibition, as well as variability in the inhibition of platelet aggregation achieved. Therefore, novel P2Y(12) receptor blockers have been developed to address these limitations, including prasugrel and ticagrelor. This article describes the pharmacokinetic and pharmacodynamic evaluation of ticagrelor, which has been demonstrated to have significantly faster onset, faster offset, greater maximal inhibition of platelet aggregation and less variability in response compared with clopidogrel. These detailed Phase II data helped guide the design of the large landmark clinical trial Platelet Inhibition and Patient Outcomes (PLATO; n = 18,624 patients with acute coronary syndrome) in which ticagrelor was associated with a 16% relative risk reduction in the primary composite end point of cardiovascular death, myocardial infarction or stroke at 12 months (9.8 vs 11.7%; hazard ratio: 0.84; 95% CI: 0.77-0.92; p < 0.001). Ongoing trials are evaluating the clinical value of individualizing therapy according to on-treatment residual platelet activity, genetic polymorphism (loss-of-function allele status) and by improved safety/efficacy risk stratification.

Topics: Adenosine; Clinical Trials as Topic; Drug-Related Side Effects and Adverse Reactions; Humans; Ticagrelor; Time Factors

Topics: Adenosine Monophosphate; Aged; Anxiety; Chest Pain; Coronary Angiography; Coronary Occlusion; Drug Substitution; Drug-Eluting Stents; Drug-Related Side Effects and Adverse Reactions; Dyspnea; Electrocardiography; Humans; Inferior Wall Myocardial Infarction; Male; Percutaneous Coronary Intervention; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome; Withholding Treatment

Topics: Adenosine; Adverse Drug Reaction Reporting Systems; Cardiovascular Diseases; Clinical Trials as Topic; Drug-Related Side Effects and Adverse Reactions; Humans; Purinergic P2Y Receptor Antagonists; Ticagrelor; United States; United States Food and Drug Administration