A pharmacogenetic versus a clinical algorithm for warfarin dosing
Stephen E Kimmel, Benjamin French, Scott E Kasner, Julie A Johnson, Jeffrey L Anderson, Brian F Gage, Yves D Rosenberg, Charles S Eby, Rosemary A Madigan, Robert B McBane, Sherif Z Abdel-Rahman, Scott M Stevens, Steven Yale, Emile R Mohler 3rd, Margaret C Fang, Vinay Shah, Richard B Horenstein, Nita A Limdi, James A S Muldowney 3rd, Jaspal Gujral, Patrice Delafontaine, Robert J Desnick, Thomas L Ortel, Henny H Billett, Robert C Pendleton, Nancy L Geller, Jonathan L Halperin, Samuel Z Goldhaber, Michael D Caldwell, Robert M Califf, Jonas H Ellenberg, COAG Investigators, Robert D McBane, Kimberly Metzger, Nancy Lexvold, Amy Streichert-Blair, Waldemar Wysokinski, Terri Ransone, Jill Randolph, John Black, Dennis O'Kane, Philip Christiansen, Sherif Z Abdel-Rahman, Carlos A Clark, Leah E Snow, Hans vonMarrensdorff, Karl E Anderson, Ilona Nekhayeva, Csilla Kormos Hallberg, Christal Garcia, Kathleen J Albright, Cindy Mitchell, Scott M Stevens, Scott C Woller, Chrissa P Peterson, Amy R Butler, John F Carlquist, Steven Yale, Diane Kohnhorst, Sandra K Strey, James K Burmester, John Schmelzer, Michael Caldwell, Joseph J Mazza, Satay Bhupathi, Julie A Johnson, Larry Lopez, Marc Zumberg, Taimour Langaee, Hazem Elewa, Mohamed Shahin, Mohamed Mohamed, Shirley Shin-Wen Chang, Emile R Mohler 3rd, Elizabeth Medenilla, Giovanni Rivera, Vivianna van Deerlin, Margaret C Fang, Yimdriuska Magan, Jaekyu Shin, Loren Yglecias, Alan Wu, Vinay Shah, Scott Kaatz, Stacy Ellsworth, Helen Gikas, Dhananjay Chitale, Richard B Horenstein, Richard Y Zhao, Alan R Shuldiner, Jennifer Marron, Oladapo Fred-Omojole, Katie Kiser, Deborah Sturpe, Myounhee Lee, Nita A Limdi, Todd M Brown, John Alexander, Ludwine M Messiaen, Roberta Hill, Allyson Dudley, James A S Muldowney 3rd, Tami Neal, Darla Freehardt, Cindy Vnencak-Jones, Jaspal Gujral, Gyanendra Sharma, Carol Smith, Peggy Best, Hazem Elewa, Christina E Deremer, Kimble J Keller, Siyang Liu, Cong-Yi Wang, Patrice Delafontaine, Anand Irimpen, Gholam Ali, Salman Arain, Lawrence O'Meallie, Sheryl B Martin-Schild, Roberta McDuffie, Shanker Japa, Nana O Asafu-Adjaye, Suzanne Bowers, Sandra Eloby-Childress, Edward Morrison, Robert J Desnick, Jonathan L Halperin, Sarina van der Zee, Elizabeth Rothlauf, Ivy Cohen, Dana O Doheny, Leah Blanchard, Stuart Scott, Thomas L Ortel, Mary Ann Gleim, Patricia A Sexton, Sharon Hall, Lynn Jordan, Henny H Billett, Rizwan C Naeem, Clarice Maala-Gentolia, Brian F Gage, Elizabeth Do, Brett Venker, Robert C Pendleton, Lynnae Napoli, Matthew Rondina, Gwen McMillin, Robert M Califf, Sherif Z Abdel-Rahman, Jeffrey L Anderson, Henny H Billett, Ebony Bookman, Michael D Caldwell, Patrice Delafontaine, Robert J Desnick, Charles S Eby, Jonas H Ellenberg, Margaret C Fang, Benjamin French, Brian F Gage, Nancy L Geller, Suzanne Goldberg, Samuel Z Goldhaber, Jaspal Gujral, Robert G Hart, Lucia A Hindorff, Richard B Horenstein, Julie A Johnson, Stephen E Kimmel, Nita A Limdi, Robert D McBane, Teri A Manolio, Emile R Mohler 3rd, James A S Muldowney 3rd, Thomas Ortel, Robert C Pendleton, Yves D Rosenberg, Vinay Shah, Scott M Stevens, Dihua Xu, Steven Yale, Robert M Califf, Jeffrey L Anderson, Brian F Gage, Julie A Johnson, Stephen E Kimmel, Yves D Rosenberg, D George Wyse, Jack Ansell, Mark Crowther, Patricia Deverka, DeJuran Richardson, Russell Tracy, Stephen E Kimmel, Jonas H Ellenberg, Benjamin French, Scott E Kasner, Don A Baldwin, Shawn Ballard, Colleen Brensinger, Denise Cifelli, Marie Durborow, Steve Durborow, Henry A Glick, Christopher Helker, Jane Jaskowiak, Rosemary A Madigan, Kenneth Rockwell Jr, Xingmei Wang, Yanli Wang, Yves D Rosenberg, Suzanne Goldberg, Nancy L Geller, Yolanda Bursie, Ahmed Hasan, Erin Iturriaga, Dihua Xu, Ebony Bookman, Lucia A Hindoff, Teri A Manolio, Charles S Eby, Rhonda Porche-Sorbet, Cristi King, Scott E Kasner, Steven Messé, Samuel Z Goldhaber, Jonathan L Halperin, Scott M Stevens, Stephen E Kimmel, Benjamin French, Scott E Kasner, Julie A Johnson, Jeffrey L Anderson, Brian F Gage, Yves D Rosenberg, Charles S Eby, Rosemary A Madigan, Robert B McBane, Sherif Z Abdel-Rahman, Scott M Stevens, Steven Yale, Emile R Mohler 3rd, Margaret C Fang, Vinay Shah, Richard B Horenstein, Nita A Limdi, James A S Muldowney 3rd, Jaspal Gujral, Patrice Delafontaine, Robert J Desnick, Thomas L Ortel, Henny H Billett, Robert C Pendleton, Nancy L Geller, Jonathan L Halperin, Samuel Z Goldhaber, Michael D Caldwell, Robert M Califf, Jonas H Ellenberg, COAG Investigators, Robert D McBane, Kimberly Metzger, Nancy Lexvold, Amy Streichert-Blair, Waldemar Wysokinski, Terri Ransone, Jill Randolph, John Black, Dennis O'Kane, Philip Christiansen, Sherif Z Abdel-Rahman, Carlos A Clark, Leah E Snow, Hans vonMarrensdorff, Karl E Anderson, Ilona Nekhayeva, Csilla Kormos Hallberg, Christal Garcia, Kathleen J Albright, Cindy Mitchell, Scott M Stevens, Scott C Woller, Chrissa P Peterson, Amy R Butler, John F Carlquist, Steven Yale, Diane Kohnhorst, Sandra K Strey, James K Burmester, John Schmelzer, Michael Caldwell, Joseph J Mazza, Satay Bhupathi, Julie A Johnson, Larry Lopez, Marc Zumberg, Taimour Langaee, Hazem Elewa, Mohamed Shahin, Mohamed Mohamed, Shirley Shin-Wen Chang, Emile R Mohler 3rd, Elizabeth Medenilla, Giovanni Rivera, Vivianna van Deerlin, Margaret C Fang, Yimdriuska Magan, Jaekyu Shin, Loren Yglecias, Alan Wu, Vinay Shah, Scott Kaatz, Stacy Ellsworth, Helen Gikas, Dhananjay Chitale, Richard B Horenstein, Richard Y Zhao, Alan R Shuldiner, Jennifer Marron, Oladapo Fred-Omojole, Katie Kiser, Deborah Sturpe, Myounhee Lee, Nita A Limdi, Todd M Brown, John Alexander, Ludwine M Messiaen, Roberta Hill, Allyson Dudley, James A S Muldowney 3rd, Tami Neal, Darla Freehardt, Cindy Vnencak-Jones, Jaspal Gujral, Gyanendra Sharma, Carol Smith, Peggy Best, Hazem Elewa, Christina E Deremer, Kimble J Keller, Siyang Liu, Cong-Yi Wang, Patrice Delafontaine, Anand Irimpen, Gholam Ali, Salman Arain, Lawrence O'Meallie, Sheryl B Martin-Schild, Roberta McDuffie, Shanker Japa, Nana O Asafu-Adjaye, Suzanne Bowers, Sandra Eloby-Childress, Edward Morrison, Robert J Desnick, Jonathan L Halperin, Sarina van der Zee, Elizabeth Rothlauf, Ivy Cohen, Dana O Doheny, Leah Blanchard, Stuart Scott, Thomas L Ortel, Mary Ann Gleim, Patricia A Sexton, Sharon Hall, Lynn Jordan, Henny H Billett, Rizwan C Naeem, Clarice Maala-Gentolia, Brian F Gage, Elizabeth Do, Brett Venker, Robert C Pendleton, Lynnae Napoli, Matthew Rondina, Gwen McMillin, Robert M Califf, Sherif Z Abdel-Rahman, Jeffrey L Anderson, Henny H Billett, Ebony Bookman, Michael D Caldwell, Patrice Delafontaine, Robert J Desnick, Charles S Eby, Jonas H Ellenberg, Margaret C Fang, Benjamin French, Brian F Gage, Nancy L Geller, Suzanne Goldberg, Samuel Z Goldhaber, Jaspal Gujral, Robert G Hart, Lucia A Hindorff, Richard B Horenstein, Julie A Johnson, Stephen E Kimmel, Nita A Limdi, Robert D McBane, Teri A Manolio, Emile R Mohler 3rd, James A S Muldowney 3rd, Thomas Ortel, Robert C Pendleton, Yves D Rosenberg, Vinay Shah, Scott M Stevens, Dihua Xu, Steven Yale, Robert M Califf, Jeffrey L Anderson, Brian F Gage, Julie A Johnson, Stephen E Kimmel, Yves D Rosenberg, D George Wyse, Jack Ansell, Mark Crowther, Patricia Deverka, DeJuran Richardson, Russell Tracy, Stephen E Kimmel, Jonas H Ellenberg, Benjamin French, Scott E Kasner, Don A Baldwin, Shawn Ballard, Colleen Brensinger, Denise Cifelli, Marie Durborow, Steve Durborow, Henry A Glick, Christopher Helker, Jane Jaskowiak, Rosemary A Madigan, Kenneth Rockwell Jr, Xingmei Wang, Yanli Wang, Yves D Rosenberg, Suzanne Goldberg, Nancy L Geller, Yolanda Bursie, Ahmed Hasan, Erin Iturriaga, Dihua Xu, Ebony Bookman, Lucia A Hindoff, Teri A Manolio, Charles S Eby, Rhonda Porche-Sorbet, Cristi King, Scott E Kasner, Steven Messé, Samuel Z Goldhaber, Jonathan L Halperin, Scott M Stevens
Abstract
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.).
Conflict of interest statement
No other potential conflict of interest relevant to this article was reported.
Figures
Figure 2. Range of INRs during the…
Figure 2. Range of INRs during the 4-Week Study
Shown are the INRs from the…
Source: PubMed