Chaining trends in anti-coagulant therapies. Are heparins and oral anti-coagulants challenged?

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dc.authorwosidIqbal, Muhammad Omer/ABI-4539-2020
dc.contributor.authorFareed, J.
dc.contributor.authorIqbal, O.
dc.contributor.authorCunanan, J.
dc.contributor.authorDemir, M.
dc.contributor.authorWahi, R.
dc.contributor.authorClarke, A.
dc.contributor.authorAdiguzel, C.
dc.date.accessioned2024-06-12T11:03:07Z
dc.date.available2024-06-12T11:03:07Z
dc.date.issued2008
dc.departmentTrakya Üniversitesien_US
dc.description.abstractThe conventional management of thrombotic and cardiovascular disorders is based on the use of heparin, oral anticoagulants and aspirin. Despite progress in the sciences, these drugs still remain a challenge and mystery. The development of low molecular weight heparins (LMWHS) and the synthesis of heparinomimetics represent a refined use of heparin. Additional drugs will continue to develop. However, none of these drugs will ever match the polypharmacology of heparin. Aspirin still remains the leading drug in the management of thrombotic and cardiovascular disorders. The newer antiplatelet drugs such as adenosine diphosphate receptor inhibitors, GPIIb/IIIa inhibitors and other specific inhibitors have limited effects and have been tested in patients who have already been treated with aspirin. Warfarin provides a convenient and affordable approach in the long-term outpatient management of thrombotic disorders. The optimized use of these drugs still remains the approach of choice to manage thrombotic disorders. The new anticoagulant targets, such as tissue factor, individual clotting factors, recombinant forms of serpins (antithrombin, heparin co-factor II and tissue factor pathway inhibitors), recombinant activated protein C, thrombomodulin and site specific serine proteases inhibitors complexes have also been developed. There is a major thrust on the development of orally bioavailable anti-Xa and IIa agents, which are stated to replace oral anticoagulants. Both the anti-factor Xa and anti-IIa agents have been developed for oral use and have provided impressive clinical results. However, safety concerns related to liver enzyme elevations and thrombosis rebound have been reported with their use. For these reasons, the US Food and Drug Administration did not approve the orally active antithrombin agent Ximelagatran for several indications. The synthetic pentasaccharide (Fondaparinux) has undergone clinical development. Unexpectedly, Fondaparinux also produced major bleeding problems at minimal dosages. Fondaparinux represents only one of the multiple pharmacologic effects of heparins. Thus, its therapeutic index will be proportionately narrower. The newer antiplatelet drugs have added a new dimension in the management of thrombotic disorders. The favorable clinical outcomes with aspirin and clopidogrel have validated COX-I and P2Y(12) receptors as targets for new drug development. Prasugrel, a novel thienopyridine, Cangrelor and AZD 6140 represent newer P2Y12 antagonists. Cangrelor and AZD 6140 are direct inhibitors, whereas Prasugrel requires metabolic activation. While clinically effective, recent results have prompted a closure of a clinical trial with Prasugrel due to bleeding. The newer anticoagulant and antiplatelet drugs are attractive, however, none of these are expected to replace the conventional drugs in polytherapeutic approaches. Heparins, warfarin and aspirin will continue to play a major role in the management of thrombotic and cardiovascular disorders for years to come.en_US
dc.identifier.endpage192en_US
dc.identifier.issn0392-9590
dc.identifier.issue3en_US
dc.identifier.pmid18506123en_US
dc.identifier.startpage176en_US
dc.identifier.urihttps://hdl.handle.net/20.500.14551/21539
dc.identifier.volume27en_US
dc.identifier.wosWOS:000257933600002en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherEdizioni Minerva Medicaen_US
dc.relation.ispartofInternational Angiologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectHeparinen_US
dc.subjectWarfarinen_US
dc.subjectAspirinen_US
dc.subjectAntithrombinsen_US
dc.subjectPercutaneous Coronary Interventionen_US
dc.subjectMolecular-Weight Heparinen_US
dc.subjectTotal Hip-Replacementen_US
dc.subjectFactor-Xa Inhibitoren_US
dc.subjectElevation Myocardial-Infarctionen_US
dc.subjectDirect Thrombin Inhibitorsen_US
dc.subjectVenous Thromboembolismen_US
dc.subjectInduced Thrombocytopeniaen_US
dc.subjectArgatroban Anticoagulationen_US
dc.subjectRecombinant Hirudinen_US
dc.titleChaining trends in anti-coagulant therapies. Are heparins and oral anti-coagulants challenged?en_US
dc.typeReview Articleen_US

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