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New drugs for thromboprophylaxis in atrial fibrillation

2011; Elsevier BV; Volume: 23; Issue: 1 Linguagem: Inglês

10.1016/j.ejim.2011.11.007

1879-0828

Pier Mannuccio Mannucci, Alessandro Nobili, Silvio Garattini,

Antiplatelet Therapy and Cardiovascular Diseases

The progressively increasing age of the general population in Europe and other continents makes more and more cogent the impact and burden of atrial fibrillation (AF) on health care systems, because 10% of the people over the age of 80 years (predicted to be almost 40 million by 2050 in North America and Europe) develop this heart arrhythmia. In patients with AF, the main clinical complication is cardioembolic stroke, a dramatic event because approximately 20% of patients die in the acute phase, 50% during the first year and 60% develop severe disability. Anticoagulant therapy with vitamin K antagonists (VKAs) such as warfarin and related oral drugs is the most efficacious form of thromboprophylaxis, reducing by at least 60% the risk of stroke, whereas aspirin is of more limited efficacy (risk reduction no greater than 20%, and mainly in patients at low risk of thromboembolism) [ 1 Hart R.G. Benavente O. McBride R. Pearce L.A. Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis. Ann Intern Med. 1999; 131: 492-501 Crossref PubMed Scopus (1500) Google Scholar , 2 Connolly S. Pogue J. Hart R. Pfeffer M. Hohnloser S. Chrolavicius S. et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet. 2006; 367: 1903-1912 Abstract Full Text Full Text PDF PubMed Scopus (1714) Google Scholar , 3 Camm A.J. Kirchhof P. Lip G.Y. Schotten U. Savelieva I. Ernst S. et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010; 31: 2369-2429 Crossref PubMed Scopus (4116) Google Scholar ]. Yet, this highly efficacious thromboprophylaxis is far from being optimally implemented, because no more than 50% of patients with AF at high risk of stroke according to the widely used CHADS2 scoring system [ [4] Gage B.F. Waterman A.D. Shannon W. Boechler M. Rich M.W. Radford M.J. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA. 2001; 285: 2864-2870 Crossref PubMed Scopus (4122) Google Scholar ] are actually treated with warfarin or related drugs [ 5 Ogilvie I.M. Newton N. Welner S.A. Cowell W. Lip G.Y. Underuse of oral anticoagulants in atrial fibrillation: a systematic review. Am J Med. 2010; 123: 638-645 Abstract Full Text Full Text PDF PubMed Scopus (751) Google Scholar , 6 Pugh D. Pugh J. Mead G.E. Attitudes of physicians regarding anticoagulation for atrial fibrillation: a systematic review. Age Ageing. 2011; 40: 675-683 Crossref PubMed Scopus (206) Google Scholar ]. The main reason for this suboptimal implementation is the perceived risk of bleeding, particularly in the central nervous system and other critical sites (the gastrointestinal tract, the retroperitoneal space), advanced age and the presence of multimorbidity and/or polypharmacy [ [7] Marcucci M. Iorio A. Nobili A. Tettamanti M. Pasina L. Marengoni A. et al. Factors affecting adherence to guidelines for antithrombotic therapy in elderly patients with atrial fibrillation admitted to internal medicine wards. Eur J Intern Med. 2010; 21: 516-523 Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar ]. Other reasons are the need for regular and repeated laboratory controls by means of the prothrombin time (expressed in International Normalized Ratio, INR), a test necessary to tailor individually the dosage of warfarin and related VKAs; the instability and vagaries of this therapy, witnessed by the fact that in clinical practice most patients are kept for no more than 50% of their time within a therapeutically efficacious INR range (between 2.0 and 3.0) [ [8] Rosendaal F.R. Cannegieter S.C. van der Meer F.J. Briet E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost. 1993; 69: 236-239 PubMed Google Scholar ]; the concern about interference of several commonly used drugs, food and genetic variants on the anticoagulant effect of VKA; and the difficulties that many frail elderly patients are tackling to attend and follow regularly anticoagulation monitoring.