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Genotype-guided warfarin dosing is safer than clinically guided dosing for patients undergoing elective hip or knee arthroplasty, according to a study published in JAMA.
Investigators found that genotype-guided dosing reduced a patient’s combined risk of experiencing major bleeding, having an international normalized ratio (INR) of 4 or greater, and developing venous thromboembolism (VTE).
Death was also included in this combined endpoint, but there were no deaths in either dosing group.
“Physicians have been prescribing warfarin since the Eisenhower administration,” said study author Brian F. Gage, MD, of Washington University School of Medicine in St. Louis.
“It’s a widely used anticoagulant, but it causes more major adverse events than any other oral drug. Thousands of patients end up in the emergency department or hospital because of warfarin-induced bleeding, but we continue to prescribe it because it is highly effective, reversible, and inexpensive. So our goal is to make warfarin safer.”
With this in mind, Dr Gage and his colleagues set out to determine if genotype-guided dosing would be safer for patients starting warfarin because of elective hip or knee replacement.
The investigators noted that earlier studies of genotype-guided warfarin dosing had produced conflicting results. However, these studies were smaller and included fewer genetic variants than the current trial, known as GIFT.
The GIFT study included 1650 patients, age 65 and older. They were genotyped for the following polymorphisms: VKORC1-1639G>A, CYP2C9*2, CYP2C9*3, and CYP4F2 V433M.
Then, patients were randomized to clinically guided (n=789) or genotype-guided warfarin dosing (n=808) on days 1 through 11 of therapy and to a target INR of either 1.8 or 2.5. (Clinically guided dosing was based on standard factors such as age, height, and weight, while genotype-guided dosing was influenced by clinical factors plus the aforementioned genetic variants.)
Results
The primary endpoint was a combination of major bleeding, INR of 4 or greater, VTE, and death.
This endpoint was met by 10.8% (n=87) of patients in the genotype-guided group and 14.7% (n=116) of patients in the clinically guided warfarin group. The relative rate (RR) was 0.73 (P=0.02).
The incidence of major bleeding on days 1 to 30 was 0.2% (n=2) in the genotype-guided group and 1.0% (n=8) in the clinically guided group. The RR was 0.24 (P=0.06).
The proportion of patients with an INR of 4 or greater on days 1 to 30 was 6.9% (n=56) in the genotype-guided group and 9.8% (n=77) in the clinically guided group. The RR was 2.8 (P=0.04).
The incidence of VTE on days 1 to 60 was similar—4.1% (n=33) in the genotype-guided group and 4.8% the clinically guided group. The RR was 0.85 (P=0.48).
There were no deaths in either group (on days 1 to 30).
The investigators noted that this study has limitations. In particular, the benefits of genotype-guided dosing may differ when applied to patients of other ages or to general clinical practice.
The team also said additional research is needed to determine the cost-effectiveness of personalized warfarin dosing.
“Although genetic testing is more expensive than clinical dosing, the cost is falling,” Dr Gage said. “In our study, we estimated that genetic testing costs less than $200 per person, which is less than 1 month of a newer anticoagulant.”
Finally, the investigators said future studies should assess the impact of additional genetic variants.
“There are additional genetic variants that may help to guide warfarin dosing, especially among patients with African ancestry,” Dr Gage said. “In the future, we hope to quantify how these variants affect warfarin.” 
Genotype-guided warfarin dosing is safer than clinically guided dosing for patients undergoing elective hip or knee arthroplasty, according to a study published in JAMA.
Investigators found that genotype-guided dosing reduced a patient’s combined risk of experiencing major bleeding, having an international normalized ratio (INR) of 4 or greater, and developing venous thromboembolism (VTE).
Death was also included in this combined endpoint, but there were no deaths in either dosing group.
“Physicians have been prescribing warfarin since the Eisenhower administration,” said study author Brian F. Gage, MD, of Washington University School of Medicine in St. Louis.
“It’s a widely used anticoagulant, but it causes more major adverse events than any other oral drug. Thousands of patients end up in the emergency department or hospital because of warfarin-induced bleeding, but we continue to prescribe it because it is highly effective, reversible, and inexpensive. So our goal is to make warfarin safer.”
With this in mind, Dr Gage and his colleagues set out to determine if genotype-guided dosing would be safer for patients starting warfarin because of elective hip or knee replacement.
The investigators noted that earlier studies of genotype-guided warfarin dosing had produced conflicting results. However, these studies were smaller and included fewer genetic variants than the current trial, known as GIFT.
The GIFT study included 1650 patients, age 65 and older. They were genotyped for the following polymorphisms: VKORC1-1639G>A, CYP2C9*2, CYP2C9*3, and CYP4F2 V433M.
Then, patients were randomized to clinically guided (n=789) or genotype-guided warfarin dosing (n=808) on days 1 through 11 of therapy and to a target INR of either 1.8 or 2.5. (Clinically guided dosing was based on standard factors such as age, height, and weight, while genotype-guided dosing was influenced by clinical factors plus the aforementioned genetic variants.)
Results
The primary endpoint was a combination of major bleeding, INR of 4 or greater, VTE, and death.
This endpoint was met by 10.8% (n=87) of patients in the genotype-guided group and 14.7% (n=116) of patients in the clinically guided warfarin group. The relative rate (RR) was 0.73 (P=0.02).
The incidence of major bleeding on days 1 to 30 was 0.2% (n=2) in the genotype-guided group and 1.0% (n=8) in the clinically guided group. The RR was 0.24 (P=0.06).
The proportion of patients with an INR of 4 or greater on days 1 to 30 was 6.9% (n=56) in the genotype-guided group and 9.8% (n=77) in the clinically guided group. The RR was 2.8 (P=0.04).
The incidence of VTE on days 1 to 60 was similar—4.1% (n=33) in the genotype-guided group and 4.8% the clinically guided group. The RR was 0.85 (P=0.48).
There were no deaths in either group (on days 1 to 30).
The investigators noted that this study has limitations. In particular, the benefits of genotype-guided dosing may differ when applied to patients of other ages or to general clinical practice.
The team also said additional research is needed to determine the cost-effectiveness of personalized warfarin dosing.
“Although genetic testing is more expensive than clinical dosing, the cost is falling,” Dr Gage said. “In our study, we estimated that genetic testing costs less than $200 per person, which is less than 1 month of a newer anticoagulant.”
Finally, the investigators said future studies should assess the impact of additional genetic variants.
“There are additional genetic variants that may help to guide warfarin dosing, especially among patients with African ancestry,” Dr Gage said. “In the future, we hope to quantify how these variants affect warfarin.”
Genotype-guided warfarin dosing is safer than clinically guided dosing for patients undergoing elective hip or knee arthroplasty, according to a study published in JAMA.
Investigators found that genotype-guided dosing reduced a patient’s combined risk of experiencing major bleeding, having an international normalized ratio (INR) of 4 or greater, and developing venous thromboembolism (VTE).
Death was also included in this combined endpoint, but there were no deaths in either dosing group.
“Physicians have been prescribing warfarin since the Eisenhower administration,” said study author Brian F. Gage, MD, of Washington University School of Medicine in St. Louis.
“It’s a widely used anticoagulant, but it causes more major adverse events than any other oral drug. Thousands of patients end up in the emergency department or hospital because of warfarin-induced bleeding, but we continue to prescribe it because it is highly effective, reversible, and inexpensive. So our goal is to make warfarin safer.”
With this in mind, Dr Gage and his colleagues set out to determine if genotype-guided dosing would be safer for patients starting warfarin because of elective hip or knee replacement.
The investigators noted that earlier studies of genotype-guided warfarin dosing had produced conflicting results. However, these studies were smaller and included fewer genetic variants than the current trial, known as GIFT.
The GIFT study included 1650 patients, age 65 and older. They were genotyped for the following polymorphisms: VKORC1-1639G>A, CYP2C9*2, CYP2C9*3, and CYP4F2 V433M.
Then, patients were randomized to clinically guided (n=789) or genotype-guided warfarin dosing (n=808) on days 1 through 11 of therapy and to a target INR of either 1.8 or 2.5. (Clinically guided dosing was based on standard factors such as age, height, and weight, while genotype-guided dosing was influenced by clinical factors plus the aforementioned genetic variants.)
Results
The primary endpoint was a combination of major bleeding, INR of 4 or greater, VTE, and death.
This endpoint was met by 10.8% (n=87) of patients in the genotype-guided group and 14.7% (n=116) of patients in the clinically guided warfarin group. The relative rate (RR) was 0.73 (P=0.02).
The incidence of major bleeding on days 1 to 30 was 0.2% (n=2) in the genotype-guided group and 1.0% (n=8) in the clinically guided group. The RR was 0.24 (P=0.06).
The proportion of patients with an INR of 4 or greater on days 1 to 30 was 6.9% (n=56) in the genotype-guided group and 9.8% (n=77) in the clinically guided group. The RR was 2.8 (P=0.04).
The incidence of VTE on days 1 to 60 was similar—4.1% (n=33) in the genotype-guided group and 4.8% the clinically guided group. The RR was 0.85 (P=0.48).
There were no deaths in either group (on days 1 to 30).
The investigators noted that this study has limitations. In particular, the benefits of genotype-guided dosing may differ when applied to patients of other ages or to general clinical practice.
The team also said additional research is needed to determine the cost-effectiveness of personalized warfarin dosing.
“Although genetic testing is more expensive than clinical dosing, the cost is falling,” Dr Gage said. “In our study, we estimated that genetic testing costs less than $200 per person, which is less than 1 month of a newer anticoagulant.”
Finally, the investigators said future studies should assess the impact of additional genetic variants.
“There are additional genetic variants that may help to guide warfarin dosing, especially among patients with African ancestry,” Dr Gage said. “In the future, we hope to quantify how these variants affect warfarin.”