Details

Autor(en) / Beteiligte

• ANDERSON, Jeffrey L
• HOME, Benjamin D
• HUNTINGHOUSE, John A
• ROLLO, Jeffrey S
• SILER, Dustin
• BAIR, Tami L
• KNIGHT, Stacey
• MUHLESTEIN, Joseph B
• CARLQUIST, John F
• STEVENS, Scott M
• WOLLER, Scott C
• SAMUELSON, Kent M
• MANSFIELD, Justin W
• ROBINSON, Michelle
• BARTON, Stephanie
• BRUNISHOLZ, Kim
• MOWER, Chrissa P

Titel

A Randomized and Clinical Effectiveness Trial Comparing Two Pharmacogenetic Algorithms and Standard Care for Individualizing Warfarin Dosing (CoumaGen-II)

Ist Teil von

• Circulation (New York, N.Y.), 2012-04, Vol.125 (16), p.1997-2005

Ort / Verlag

Hagerstown, MD: Lippincott Williams & Wilkins

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• Warfarin is characterized by marked variations in individual dose requirements and a narrow therapeutic window. Pharmacogenetics (PG) could improve dosing efficiency and safety, but clinical trials evidence is meager. A Randomized and Clinical Effectiveness Trial Comparing Two Pharmacogenetic Algorithms and Standard Care for Individualizing Warfarin Dosing (CoumaGen-II) comprised 2 comparisons: (1) a blinded, randomized comparison of a modified 1-step (PG-1) with a 3-step algorithm (PG-2) (N=504), and (2) a clinical effectiveness comparison of PG guidance with use of either algorithm with standard dosing in a parallel control group (N=1866). A rapid method provided same-day CYP2C9 and VKORC1 genotyping. Primary outcomes were percentage of out-of-range international normalized ratios at 1 and 3 months and percentage of time in therapeutic range. Primary analysis was modified intention to treat. In the randomized comparison, PG-2 was noninferior but not superior to PG-1 for percentage of out-of-range international normalized ratios at 1 month and 3 months and for percentage of time in therapeutic range at 3 months. However, the combined PG cohort was superior to the parallel controls (percentage of out-of-range international normalized ratios 31% versus 42% at 1 month; 30% versus 42% at 3 months; percentage of time in therapeutic range 69% versus 58%, 71% versus 59%, respectively, all P<0.001). Differences persisted after adjustment for age, sex, and clinical indication. There were fewer percentage international normalized ratios ≥4 and ≤1.5 and serious adverse events at 3 months (4.5% versus 9.4% of patients, P<0.001) with PG guidance. These findings suggest that PG dosing should be considered for broader clinical application, a proposal that is being tested further in 3 major randomized trials. The simpler 1-step PG algorithm provided equivalent results and may be preferable for clinical application. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00927862.