New antiplatelet agents for cardiovascular disease

Chua, Doson; Nishi, Cesilia

doi:10.1503/cmaj.130033

Cited by 9 publications

(6 citation statements)

References 37 publications

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“…In general, the rates of major bleeding are in the range of 2%-3% when ASA is used in combination with a second antiplatelet agent. 9 The benefits of prasugrel and ticagrelor relative to clopidogrel must be weighed against the increase in the risk of bleeding. Prasugrel was associated with significant increases in major, life-threatening and fatal bleeding in the total study population and increased intracranial bleeding in those with a history of cerebrovascular disease.…”

Section: Adverse Effects Of Antiplatelet Agentsmentioning

confidence: 99%

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A pharmacist’s guide to the 2012 update of the Canadian Cardiovascular Society Guidelines for the Use of Antiplatelet Therapy

et al. 2015

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Section: Adverse Effects Of Antiplatelet Agentsmentioning

confidence: 99%

“…Rates of major bleeding on dual-antiplatelet therapy are reported to be in the range of 2% to 3%. 9 Patients should seek medical attention if they develop any unexpected, prolonged or excessive bleeding complications such as hematuria, melena, epistaxis or hematemesis.…”

Section: Patient Educationmentioning

confidence: 99%

A pharmacist’s guide to the 2012 update of the Canadian Cardiovascular Society Guidelines for the Use of Antiplatelet Therapy

et al. 2015

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“…Platelet activation is a key event in thrombus formation, chronic inflammation and atherosclerosis, which are all multicellular processes involved in the development of cardiovascular diseases. Currently, anti-platelet agents such as aspirin and clopidogrel are widely used alone or in combination to reduce the incidence of ischemic stroke and to prevent arterial thrombosis [ 1 ]. Despite the efficacy of dual anti-aggregation therapy, growing evidence of drug resistance for aspirin and clopidogrel [ 2 ] highlight the need to search for novel anti-platelet agents to reduce the incidence of cardiovascular diseases; which are the globally leading causes of death and disability [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

The norpurpureine alkaloid from Annona purpurea inhibits human platelet activation in vitro

et al. 2018

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BackgroundThe leaves of Annona purpurea have yielded several alkaloids with anti-aggregation activities against rabbit platelets. This is promising in the search for agents that might act against platelets and reduce the incidence of cardiovascular diseases. Since significant differences in platelet function have been reported between human and animal platelets, a study focusing on the effect of A. purpurea extracts against human platelet activation is necessary.MethodsThe compounds in an A. purpurea ethanolic extract underwent bio-guided fractionation and were used for in vitro human platelet aggregation assays to isolate the compounds with anti-platelet activity. The bioactive compounds were identified by spectroscopic analysis. Additional platelet studies were performed to characterize their action as inhibitors of human platelet activation.ResultsThe benzylisoquinoline alkaloid norpurpureine was identified as the major anti-platelet compound. The IC50 for norpurpureine was 80 μM against platelets when stimulated with adenosine 5′-diphosphate (ADP), collagen and thrombin. It was pharmacologically effective from 20 to 220 μM. Norpurpureine (220 μM) exhibited its in vitro effectiveness in samples from 30 healthy human donors who did not take any drugs during the 2 weeks prior to the collection. Norpurpureine also gradually inhibited granule secretion and adhesion of activated platelets to immobilized fibrinogen. At the intra-platelet level, norpurpureine prevented agonist-stimulated calcium mobilization and cAMP reduction. Structure–activity relationship analysis indicates that the lack of a methyl group at the nitrogen seems to be key in the ability of the compound to interact with its molecular target.ConclusionNorpurpureine displays a promising in vitro pharmacological profile as an inhibitor of human platelet activation. Its molecular target could be a common effector between Ca2+ and cAMP signaling, such as the PLC-PKC-Ca2+ pathway and PDEs. This needs further evaluation at the protein isoform level.Electronic supplementary materialThe online version of this article (10.1186/s11658-018-0082-4) contains supplementary material, which is available to authorized users.

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“…Chua and Nishi 1 did not reference the US Food and Drug Administration (FDA) medical review of ticagrelor. 2 This comprehensive review considered both published and unpublished data from the PLATO trial. The FDA reviewers identified that the reduction in mortality reported by Chua and Nishi 1 was present only in the non-US population, thus limiting the generalizability of this finding.…”

mentioning

confidence: 99%

“…The authors respond O'Sullivan and Tejani 1 provide an interesting perspective on our CMAJ review article. 2 Because of geographic differences in the efficacy of ticagrelor, the FDA delayed approval of the drug twice and requested further data and analysis. 3,4 Although the FDA document does identify some concerns, the manufacturer responses, an exhaustive review of additional data and reanalysis proved satisfactory for the FDA to finally approve ticagrelor in July 2011.…”

mentioning

confidence: 99%