242 research outputs found
Interaction between clopidogrel and proton-pump inhibitors and management strategies in patients with cardiovascular diseases
No full textPaul A Gurbel1, Udaya S Tantry1, Dean J Kereiakes21Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, Baltimore, MD, USA; 2The Christ Hospital Heart and Vascular Center/The Lindner Research Center at The Christ Hospital, Cincinnati, OH, USAAbstract: Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin has been successful in reducing ischemic events in a wide range of patients with cardiovascular diseases. However, the anti-ischemic effects of DAPT may also be associated with gastrointestinal (GI) complications including ulceration and bleeding particularly in ‘high risk’ and elderly patients. Current guidelines recommend the use of proton-pump inhibitors (PPIs) to reduce the risk of GI bleeding in patients treated with DAPT. However, pharmacodynamic studies suggest an effect of PPIs on clopidogrel metabolism with a resultant reduction in platelet inhibitory effects. Similarly, several observational studies have demonstrated reduced clopidogrel benefit in patients who coadministered PPIs. Although recent US Food and Drug Administration and European Medicines Agency statements discourage PPI (particularly omeprazole) and clopidogrel coadministration, the 2009 AHA/ACC/SCAI PCI guidelines do not support a change in current practice in the absence of adequately powered prospective randomized clinical trial data. The data regarding pharmacologic and clinical interactions between PPI and clopidogrel therapies are herein examined and treatment strategies are provided.Keywords: cardiovascular disease, gastrointestinal, proton-pump inhibitor, antiplatelet therap
Role of proprotein convertase subtilisin/kexin type 9 inhibitors in patients with coronary artery disease undergoing percutaneous coronary intervention
No full textAlthough novel therapies have improved outcomes in PCI patients, a sizeable number of patients still remain at high cardiovascular risk for recurrent event. There is therefore an unmet need for novel therapies that can improve clinical outcomes, with an associated satisfactory safety profile. Proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme is a novel lipid-lowering target with a potential to impact high-cardiovascular risk populations including patients with coronary artery disease (CAD), undergoing the percutaneous coronary intervention (PCI). A number of canonical and non-canonical pathways of PCSK9 action, including inflammation and platelet activation, as well as their inhibition, are undergoing intense investigation. Areas covered: This review will discuss the currently available evidence on PCSK9 inhibitors, pathways of PCSK9 enzyme action and results or its inhibition, the potential role of PCSK9 inhibitors in specific populations undergoing PCI, and completed and ongoing studies in patients with CAD. Expert commentary: PCSK9 inhibitors clinical outcomes in high risk cardiovascular disease patients and have the potential to function as powerful adjunctive therapy in patients undergoing PCI by a twofold mechanism on both lipid lowering and platelet/inflammation pathways
Efficacy and Safety of P2Y12 monotherapy vs standard DAPT in patients undergoing percutaneous coronary intervention: meta-analysis of randomized trials
No full textPharmacosimulation of delays and interruptions during administration of tirofiban: a systematic comparison between EU and US dosage regimens.
Full text linkTirofiban is a glycoproteine (GP) IIb/IIIa receptor antagonist, which inhibits platelet-platelet aggregation and is a potential adjunctive antithrombotic treatment in patients with acute coronary syndromes (ACS) or high-risk percutaneous coronary interventions (PCI). It is administered intravenously as a bolus followed by continuous infusion. However, the dosage recommendations in the United States (US) and European Union (EU) differ considerably. Furthermore, in routine clinical practice, deviations from the recommendations may occur. The objective of the present study was to investigate the impact of different alterations on tirofiban plasma concentrations in US and EU administration regimens and to give suggestions for delay management in clinical practice. We therefore mathematically simulated the effects of different bolus-infusion delays and infusion interruptions in different scenarios according to the renal function. Here, we provide a systematic assessment of concentration patterns of tirofiban in the US versus EU dosage regimens. We show that differences between the two regimens have important effects on plasma drug levels. Furthermore, we demonstrate that deviations from the proper administration mode affect the concentration of tirofiban. Additionally, we calculated the optimal dosage of a second bolus to rapidly restore the initial concentration without causing overdosage. In conclusion, differences in tirofiban dosing regimens between the U.S and EU and potential infusion interruptions have important effects on drug levels that may impact on degrees of platelet inhibition and thus antithrombotic effects. Thus, the findings of our modelling studies may help to explain differences in clinical outcomes observed in previous clinical trials on tirofiban
Acceptance of High Platelet Reactivity as a Risk Factor Now, What Do We Do About It?⁎⁎Editorials published in JACC: Cardiovascular Interventions reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Interventions or the American College of Cardiology.
No full textGEMINI-ACS-1: toward unearthing the antithrombotic therapy cornerstone for acute coronary syndromes
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