Antiplatelet therapy in acute coronary syndromes

Menozzi, Alberto; Lina, Daniela; Conte, Giulio; Mantovani, Francesco; Ardissino, Diego

doi:10.1517/14656566.2012.642862

Cited by 4 publications

(3 citation statements)

References 99 publications

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“…Numerous antiplatelet therapies have been developed; however, currently available agents are still associated with inadequate efficacy, risk of bleeding, and variability in individual response 4 . Dual Antiplatelet therapy with Aspirin and P2Y12 inhibitors, drugs from thienopyridine class (Ticlopidine, Clopidogrel, and Prasugrel) is therefore the cornerstone of medical management in patients with ACS, those undergoing percutaneous coronary Intervention (PCI), prevention of stent thrombosis and is necessary in both the acute phase and long-term maintenance therapy [5][6][7] . Despite these benefits, many patients continue to have recurrent atherothrombotic events while receiving standard dual antiplatelet therapy 8 .…”

Section: Introductionmentioning

confidence: 99%

“…It has been established that not all of the patients receiving Clopidogrel benefit to the same extent, and it has been shown that patients with a Poor Metabolizers (PM) genotype status for CYP2C19 are at increased risk of ischemic events after percutaneous coronary intervention 5,14 suggesting that CYP2C19 polymorphism is a clinically relevant determinant of response to Clopidogrel. In 2010, the USFDA had imposed a box warning on Clopidogrel bisulfate tablets (Plavix) stating that "Effectiveness of Clopidogrel bisulfate depends on conversion to an active metabolite by the cytochrome P450 (CYP) system, principally CYP2C19 enzyme.…”

Section: Introductionmentioning

confidence: 99%

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A Phase 1 Study of Novel Antiplatelet Agent to Overcome Pharmacogenomic Limitations of Clopidogrel

Pareek,

Chandurkar,

Raut

et al. 2024

Preprint

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Background: Clopidogrel is the most commonly prescribed thienopyridine as part of dual antiplatelet therapy for the treatment of cardiovascular diseases. However, Clopidogrel responsiveness shows variability based on CYP2C19 polymorphism. Therefore, we planned a study with an objective of evaluating safety, tolerability, pharmacodynamics and pharmacokinetics of a novel thienopyridine antiplatelet agent AT-10 in healthy Indian subjects in comparison with standard dosage regimen of Clopidogrel based on their CYP2C19 genotyping. Methods: Two CYP2C19 genotype-based groups were identified i.e., Poor Metabolizer and Extensive Metabolizers with 20 subjects in each group (N=40) for participating in a randomized, two period, cross-over study. Each study period lasted 6 days including administration of loading and maintenance doses of AT-10 (40mg/10mg) or Clopidogrel (300mg/75mg). The pharmacokinetics and pharmacodynamics were assessed on day 1 and day 6 at several time intervals. Results: Overall result of pharmacodynamic parameters showed that, mean % Inhibition of Platelet Aggregation between AT-10 and Clopidogrel in all subjects at post-dose 6hr (loading dose) (AT-10: Clopidogrel; 73.30% vs. 18.53%) and post-dose 6 hr on Day 6 (maintenance dose) (AT-10: Clopidogrel; 83.41% vs. 51.19 %) obtained from the AT-10 group was significantly higher than the Clopidogrel group. Further, %inhibition of platelet aggregation from AT-10 treatment in poor metabolizer group was significantly higher than the Clopidogrel treatments in extensive metabolizer group. Overall pharmacokinetic comparison in all subjects indicates that AT-10 gives greater exposure to active Metabolite MP-H4 than Clopidogrel. Conclusion: AT-10 may emerge as a promising anti-platelet drug and can be further developed in clinical studies for the unmet medical needs of cardiovascular diseases.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Phase 1 Study of Novel Antiplatelet Agent to Overcome Pharmacogenomic Limitations of Clopidogrel

Pareek,

Chandurkar,

Raut

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Thrombus occlusion of a coronary artery, which may result in an acute myocardial infarction, is the proximate cause of acute coronary syndrome (ACS). With platelets thus playing a central role in atherothrombosis and consequent pathologies, antiplatelet therapy has emerged as a cornerstone of treatment for ACS patients .…”

Section: Introductionmentioning

confidence: 99%

Projected inhibition of platelet aggregation with ticagrelor twice daily vs. clopidogrel once daily based on patient adherence data (the TWICE project)

Vrijens¹,

Claeys

Legrand

et al. 2014

Brit J Clinical Pharma

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AIMTwice daily dosing is often perceived as inferior to once daily dosing due to a higher likelihood of missing a dose. However, more important is the extent to which drug action is maintained when doses are delayed or missed. We compared the estimated inhibition of platelet aggregation (eIPA) for ticagrelor twice daily and clopidogrel once daily, based on their pharmacokinetic/ pharmacodynamic relationships and patient dosing history data. METHODSDrug dosing histories of 5014 patients prescribed cardiovascular medications (primarily antihypertensive medicines) were extracted from an electronically compiled dosing history database. eIPA levels were simulated for 677 twice daily and 677 once daily dosing histories over a 30 day period, based on published onset/offset models for ticagrelor and clopidogrel IPA characteristics. RESULTSWhile many patients treated twice daily missed at least one dose in 30 days, only 25.7% missed two consecutive doses. By comparison, 46.8% of patients treated once daily missed at least one dose. Simulations based on patient adherence over time showed that the average mean eIPA for ticagrelor twice daily remained significantly higher than for clopidogrel once daily (81.1% vs. 55.0%, P < 0.001). Ticagrelor twice daily patients had an eIPA below 10% for 0.20% of the 30 day period compared with 2.05% for clopidogrel once daily (P = 0.0001). CONCLUSIONSThe projected level of platelet inhibition remained higher for ticagrelor twice daily than clopidogrel once daily, mainly due to the higher eIPA level achieved with ticagrelor and the relatively low likelihood of missing two consecutive twice daily doses. This modelling and simulation study suggests a therapeutic benefit of ticagrelor over clopidogrel when taking into account the most common dosing omissions.

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Acute cardiac syndromes, investigations and interventions

Power¹

2014

Oh's Intensive Care Manual

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Antiplatelet therapy in acute coronary syndromes

Cited by 4 publications

References 99 publications

A Phase 1 Study of Novel Antiplatelet Agent to Overcome Pharmacogenomic Limitations of Clopidogrel

A Phase 1 Study of Novel Antiplatelet Agent to Overcome Pharmacogenomic Limitations of Clopidogrel

Projected inhibition of platelet aggregation with ticagrelor twice daily vs. clopidogrel once daily based on patient adherence data (the TWICE project)

Acute cardiac syndromes, investigations and interventions

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