5
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Oral Anticoagulant Therapy—When Art Meets Science

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Anticoagulant treatment is extremely important and frequently encountered in the therapy of various cardiovascular diseases. Vitamin K antagonists (VKA) are in use for the prevention and treatment of arterial and venous thromboembolism, despite the introduction of new direct-acting oral anticoagulants (NOAC). The VKA still have the clear recommendation in patients with a mechanical prosthetic heart valve replacement or moderate to severe mitral stenosis of the rheumatic origin, in deep vein thrombosis associated with congenital thrombophilia, and in cases where NOAC are prohibited by social condition (financial reason) or by comorbidities (extreme weight, severe renal or liver disease). VKA dosing required to reach the targeted therapeutic range varies largely between patients (inter-individual variability). This inter-individual variability depends on multiple environmental factors such as age, mass, diet, etc. but it is also influenced by genetic determinism. About 30 genes implicated in the metabolism coumarins derivatives were identified, the most important being CYP2C9 and VKORC, each with several polymorphisms. Herein, we review the data regarding genetic alterations in general and specific populations, highlight the diagnosis options in particular cases presenting with genetic alteration causing higher sensitivity and/or resistance to VKA therapy and underline the utility of NOAC in solving such rare and difficult problems.

          Related collections

          Most cited references106

          • Record: found
          • Abstract: not found
          • Article: not found

          2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism.

            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Diagnosis and Management of the Antiphospholipid Syndrome

              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              A pharmacogenetic versus a clinical algorithm for warfarin dosing.

              The clinical utility of genotype-guided (pharmacogenetically based) dosing of warfarin has been tested only in small clinical trials or observational studies, with equivocal results. We randomly assigned 1015 patients to receive doses of warfarin during the first 5 days of therapy that were determined according to a dosing algorithm that included both clinical variables and genotype data or to one that included clinical variables only. All patients and clinicians were unaware of the dose of warfarin during the first 4 weeks of therapy. The primary outcome was the percentage of time that the international normalized ratio (INR) was in the therapeutic range from day 4 or 5 through day 28 of therapy. At 4 weeks, the mean percentage of time in the therapeutic range was 45.2% in the genotype-guided group and 45.4% in the clinically guided group (adjusted mean difference, [genotype-guided group minus clinically guided group], -0.2; 95% confidence interval, -3.4 to 3.1; P=0.91). There also was no significant between-group difference among patients with a predicted dose difference between the two algorithms of 1 mg per day or more. There was, however, a significant interaction between dosing strategy and race (P=0.003). Among black patients, the mean percentage of time in the therapeutic range was less in the genotype-guided group than in the clinically guided group. The rates of the combined outcome of any INR of 4 or more, major bleeding, or thromboembolism did not differ significantly according to dosing strategy. Genotype-guided dosing of warfarin did not improve anticoagulation control during the first 4 weeks of therapy. (Funded by the National Heart, Lung, and Blood Institute and others; COAG ClinicalTrials.gov number, NCT00839657.).
                Bookmark

                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                21 October 2019
                October 2019
                : 8
                : 10
                : 1747
                Affiliations
                [1 ]Department of Cardiology, Heart Institute, 40001 Cluj Napoca, Romania; pcimpan@ 123456gmail.com
                [2 ]Internal Medicine Department, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; mihaela.mocan@ 123456gmail.com (M.M.); ancafarcas@ 123456yahoo.com (A.D.F.)
                [3 ]Emergency Clinical County Hospital, 40006 Cluj Napoca, Romania
                Author notes
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-0831-1642
                https://orcid.org/0000-0002-8400-5938
                https://orcid.org/0000-0001-5906-8024
                Article
                jcm-08-01747
                10.3390/jcm8101747
                6832236
                31640208
                d98a6509-23d3-4d44-8123-60ca0e921123
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 16 September 2019
                : 16 October 2019
                Categories
                Review

                anticoagulant,cyp2c9,vkorc1
                anticoagulant, cyp2c9, vkorc1

                Comments

                Comment on this article