Warfarin Pharmacogenetics: A Rising Tide for its Clinical Value.

Circulation. 2012 Mar 19;

Authors: Johnson JA

Abstract
Warfarin has been in clinical use for nearly 60 years, and in 2010 there were over 25 million prescriptions for warfarin in the U.S. While warfarin is highly efficacious, it has a narrow therapeutic window to achieve desired anticoagulation without excess risk of bleeding. Anticoagulation status is monitored with the International Normalized Ratio (INR), where the most common target INR is 2 to 3. Not only does warfarin exhibit a narrow therapeutic index, but there can be 10 to 20-fold differences in the warfarin dose required to achieve target INR. Thus the early period after warfarin therapy initiation requires frequent INR monitoring to determine the proper dose for the patient, is often associated with multiple dose adjustments, and many patients experience prolonged periods of over- or under-anticoagulation while the appropriate dose is identified. These challenges lead warfarin to be a leading cause of emergency room visits and hospitalizations for an adverse drug reaction, and lead to significant underuse of the drug in patients for whom it is strongly indicated, particularly those with atrial fibrillation.(1) (SELECT FULL TEXT TO CONTINUE).

PMID: 22431866 [PubMed - as supplied by publisher]

Short- Versus Long-term Duration of Dual Antiplatelet Therapy After Coronary Stenting: A Randomized Multicentre Trial.

Circulation. 2012 Mar 21;

Authors: Valgimigli M, Campo G, Monti M, Vranckx P, Percoco G, Tumscitz C, Castriota F, Colombo F, Tebaldi M, Fucà G, Kubbajeh M, Cangiano E, Minarelli M, Scalone A, Cavazza C, Frangione A, Borghesi M, Marchesini J, Parrinello G, Ferrari R

Abstract
BACKGROUND: The optimal duration of dual antiplatelet therapy and the risk-benefit ratio for long-term dual antiplatelet therapy after coronary stenting remain poorly defined. We evaluated the impact of up to 6 versus24 month duration of dual antiplatelet therapy in a broad all comer patient population receiving a balanced proportion of Food and Drug Administration-approved drug-eluting or bare metal stents. METHODS AND RESULTS: We randomly assigned 2,013 patients to receive bare metal, zotarolimus-eluting, paclitaxel-eluting or everolimus-eluting stent implantation. At 30 days, patients in each stent group were randomly allocated to receive up to 6 or 24 months clopidogrel therapy on top of aspirin. The primary endpoint was a composite of death from any cause, myocardial infarction or cerebrovascular accident. The cumulative risk of the primary outcome at 2 years was 10.1% with the 24-month dual antiplatelet therapy, as compared to 10.0% with the 6-month dual antiplatelet therapy (hazard ratio, 0.98; 95% CI, 0.74 to 1.29; P = 0.91). The individual risks of death, myocardial infarction, cerebrovascular accident or stent thrombosis did not differ between the study groups. However, there was a consistent greater risk of haemorrhage in the 24-month clopidogrel group according to all prespecifed bleeding definitions including the recently proposed Bleeding Academic Research Consortium classification. CONCLUSIONS: A 24-month clopidogrel therapy in patients who had received a balanced mixture of drug-eluting or bare-metal stents was not significantly more effective than a 6-month clopidogrel regimen in reducing the composite of death for any cause, myocardial infarction or cerebrovascular accident. CLINICAL TRIAL REGISTRATION INFORMATION: clinicaltrials.gov; Identifier: NCT00611286.

PMID: 22438530 [PubMed - as supplied by publisher]