Pharmacokinetics and Pharmacodynamics of Approved and Investigational P2Y12 Receptor Antagonists

AbstractCoronary artery disease remains the major cause of mortality worldwide. Antiplatelet drugs such as acetylsalicylic acid and P2Y12 receptor antagonists are cornerstone treatments for the prevention of thrombotic events in patients with coronary artery disease. Clopidogrel has long been the gold standard but has major pharmacological limitations such as a slow onset and long duration of effect, as well as weak platelet inhibition with high inter-individual pharmacokinetic and pharmacodynamic variability. There has been a strong need to develop potent P2Y12 receptor antagonists with more favorable pharmacological properties. Prasugrel and ticagrelor are more potent and have a faster onset of action; however, they have shown an increased bleeding risk compared with clopidogrel. Cangrelor is highly potent and has a very rapid onset and offset of effect; however, its indication is limited to P2Y12 antagonist-na ïve patients undergoing percutaneous coronary intervention. Two novel P2Y12 receptor antagonists are currently in clinical development, namely vicagrel and selatogrel. Vicagrel is an analog of clopidogrel with enhanced and more efficient formation of its active metabolite. Selatogrel is characteriz ed by a rapid onset of action following subcutaneous administration and developed for early treatment of a suspected acute myocardial infarction. This review article describes the clinical pharmacology profile of marketed P2Y12 receptor antagonists and those under dev...
Source: Clinical Pharmacokinetics - Category: Drugs & Pharmacology Source Type: research

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Conclusion: In adults with AF after PCI, dual therapy reduces risk for bleeding compared with triple therapy, whereas its effects on risks for death and ischemic end points are still unclear. Primary Funding Source: None. PMID: 32176890 [PubMed - as supplied by publisher]
Source: Annals of Internal Medicine - Category: Internal Medicine Authors: Tags: Ann Intern Med Source Type: research
Conclusions: DPI compared with aspirin produced consistent reductions in MACE and mortality but with increased major bleeding with or without prior PCI. Among those with prior PCI one- year and beyond, effects on MACE and mortality were consistent irrespective of time since last PCI. Clinical Trial Registration: URL: www.ClinicalTrials.gov Unique Identifier: NCT01776424. PMID: 32178526 [PubMed - as supplied by publisher]
Source: Circulation - Category: Cardiology Authors: Tags: Circulation Source Type: research
Abstract BACKGROUND: The transradial approach is reportedly associated with reduced bleeding complications and mortality after percutaneous coronary intervention (PCI). It is unknown whether the clinical benefits of transradial vs. transfemoral PCI differ between high bleeding risk (HBR) and non-HBR patients.Methods and Results:After excluding patients with acute myocardial infarction, dialysis, and a transbrachial approach from the 13,087 patients undergoing first PCI in the CREDO-Kyoto Registry Cohort-2, 6,828 patients were eligible for this study. Patients were divided into 2 groups according to bleeding ri...
Source: Circulation Journal - Category: Cardiology Authors: Tags: Circ J Source Type: research
we found of interest the paper by Lu et al. on the outcome after percutaneous coronary intervention in patients with cirrhosis.1 In these patients they observed a much higher frequency of overall adverse events (44.7% vs 17.7%); most importantly, gastrointestinal bleeding was increased more than five times (15.3% vs 2.7%).1 We believe this paper should gain wide diffusion among practicing gastroenterologists, and cardiologists, as acute myocardial infarction is increasing among cirrhosis patients, also in the USA.
Source: The American Journal of Cardiology - Category: Cardiology Authors: Source Type: research
AbstractPatients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) have traditionally received triple antithrombotic therapy (TAT) consisting of aspirin and a P2Y12 inhibitor plus an oral anticoagulant (OAC) to reduce atherothrombotic events, even though this strategy is associated with a high risk of severe bleeding. Recent trials have indicated that dual antithrombotic therapy (DAT), consisting of a P2Y12 inhibitor plus an OAC, may be superior to TAT in terms of bleeding risk; however, the  trade-off regarding ischemic complications may be questionable. Patients who have had a myocard...
Source: American Journal of Cardiovascular Drugs - Category: Cardiology Source Type: research
Conclusions Neither perioperative aspirin nor clonidine have significant long-term effects after noncardiac surgery. Perioperative aspirin in patients with previous percutaneous coronary intervention showed persistent benefit at 1 yr, a plausible sub-group effect.Editor ’s PerspectiveWhat We Already Know about This TopicThe Perioperative Ischemic Evaluation-2 study (POISE-2) authors previously reported that neither aspirin nor clonidine reduced a 30-day composite of nonfatal myocardial infarction or death. Aspirin caused perioperative bleeding, and clonidine provoked hypotension and bradycardia.In a subgroup analysis...
Source: Anesthesiology - Category: Anesthesiology Source Type: research
AbstractGuidelines advice against dual antiplatelet therapy (DAPT) discontinuation less than 12  months after percutaneous coronary intervention with drug-eluting stents (DES-PCI). However, any delay of necessary surgery in patients with descending thoracic (DTA) or abdominal aortic aneurysm (AAA), treated by DES-PCI, increases the risk of aneurysm rupture/dissection. We evaluated the safety of 8-week waiting time between DES-PCI and endovascular aortic repair (EVAR). 1152 consecutive patients with coronary artery disease (CAD) needing elective DTA or AAA repair were enrolled and divided into two groups. Group A inclu...
Source: Updates in Surgery - Category: Surgery Source Type: research
Conclusions: In the setting of STEMI, the DRA could be a feasible alternative access route for primary PCI. PMID: 32122114 [PubMed - as supplied by publisher]
Source: The Korean Journal of Internal Medicine - Category: Internal Medicine Authors: Tags: Korean J Intern Med Source Type: research
AbstractPurposeThe aim of this study was to explore the safety and efficacy of bivalirudin in elderly patients undergoing percutaneous coronary intervention (PCI).MethodsAn electronic search was conducted for randomized controlled trials with outcomes of interest in the elderly ( ≥ 65 years of age). Pooled risk ratios (RR) and 95% confidence interval (CI) using random effects Der Simonian–Laird models were calculated. Primary outcomes were net adverse clinical events (NACE) and major bleeding events at 30 days. Secondary outcomes were major adverse cardiac events (MA CE) at 30 days. MACE, all...
Source: Cardiovascular Drugs and Therapy - Category: Cardiology Source Type: research
In conclusion, the effects of 1-month DAPT for the primary and major secondary endpoints were consistent in HBR and non-HBR patients without any significant interactions. The benefit of 1-month DAPT in reducing major bleeding was numerically greater in HBR patients.Clinical trial registration Short and optimal duration of dual antiplatelet therapy after everolimus-eluting cobalt –chromium stent-2 [STOPDAPT-2]; NCT02619760.
Source: Cardiovascular Intervention and Therapeutics - Category: Cardiology Source Type: research
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