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Influence of regular physical activity on warfarin dose and risk of hemorrhagic complications.

ABSTRACT: OBJECTIVE:To determine the influence of regular physical activity on stable warfarin dose and risk of major hemorrhage in patients on chronic anticoagulation therapy. DESIGN:Regular physical activity (maintained over > 80% of visits) was ascertained by self-report at initiation of warfarin therapy (target international normalized ratio [INR] = 2-3) in 1272 patients, with changes documented at monthly anticoagulation clinic visits in a population-based prospective cohort. Multi-variable linear regression and survival analysis, respectively, were used to assess influence on warfarin and risk of hemorrhage. SETTING:Outpatient anticoagulation clinic PARTICIPANTS:1272 anticoagulated patients MEASUREMENT AND MAIN RESULTS:There were 683 (53.7%) patients who were regularly physically active (? 30 min ? 3 times/week). Physically active patients required warfarin doses that were 6.9% higher (p=0.006) than in physically inactive patients after controlling for sociodemographic factors, vitamin K intake, clinical factors, and genetic variations.The overall incidence of major hemorrhagic events was 7.6/100 person-years (p-yrs, 95% confidence interval [CI] 6.4-8.9) in our population. The incidence was lower for physically active patients (5.6/100 p-yrs, 95% CI 4.2-7.2) than in inactive patients (10.3/100 p-yrs, 95% CI 8.2-12.9, p=0.0004). Active patients had a 38% lower risk of hemorrhage (hazard ratio 0.62, 95% CI 0.42-0.98, p=0.03) compared with inactive patients. CONCLUSIONS:Regular physical activity is associated with higher warfarin dose requirements and lower risk of hemorrhage. The influence of physical activity on drug response needs to be further explored, and the mechanisms through which it exerts these effects need to be elucidated

SUBMITTER: Shendre A

PROVIDER: S-EPMC4109410 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Influence of regular physical activity on warfarin dose and risk of hemorrhagic complications.

Shendre Aditi A Beasley Timothy Mark TM Brown Todd M TM Hill Charles E CE Arnett Donna K DK Limdi Nita A NA

Pharmacotherapy 20140601 6

<h4>Objective</h4>To determine the influence of regular physical activity on stable warfarin dose and risk of major hemorrhage in patients on chronic anticoagulation therapy.<h4>Design</h4>Regular physical activity (maintained over > 80% of visits) was ascertained by self-report at initiation of warfarin therapy (target international normalized ratio [INR] = 2-3) in 1272 patients, with changes documented at monthly anticoagulation clinic visits in a population-based prospective cohort. Multi-var ...[more]

PMID: 25032265

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Project description:ObjectiveThe p.V433M in cytochrome P450 4F2 (rs2108622, CYP4F2*3) is associated with a higher warfarin dose and lower risk of hemorrhage among European Americans. We evaluate the influence of CYP4F2*3 on warfarin dose, time to target international normalized ratio (INR), and stable dose, proportion of time spent in target range (PTTR), as well as the risk of overanticoagulation and hemorrhage among European and African Americans.DesignCYP4F2*3 was genotyped in 1238 patients initiated on warfarin in a prospective inception cohort. Multivariable linear regression was used to assess warfarin dose and PTTR; proportional hazards analysis was performed to evaluate time to target INR and stable dose, overanticoagulation, and hemorrhage.SettingTwo outpatient anticoagulation clinics.ParticipantsA total of 1238 anticoagulated patients.OutcomesWarfarin dose (mg/day), time to target INR and stable dose, PTTR, overanticoagulation (INR more than 4), and major hemorrhage.ResultsMinor allele frequency for the CYP4F2*3 variant was 30.3% among European Americans and 8.4% among African Americans. CYP4F2*3 was associated with higher dose among European Americans but not African Americans. Compared to CYP4F2*1/*1, *1/*3 was associated with a statistically nonsignificant increase in dose (4.5%, p=0.22) and *3/*3 was associated with a statistically significant increase in dose (13.2%, p=0.02). CYP4F2 genotype did not influence time to target INR, time to stable dose, or PTTR in either race group. CYP4F2*3/*3 was associated with a 31% lower risk of over anticoagulation (p=0.06). Incidence of hemorrhage was lower among participants with CYP4F2 *3/*3 compared with *1/*3 or *1/*1 (incidence rate ratio = 0.45, 95% confidence interval 0.14-1.11, p=0.09). After controlling for covariates, CYP4F2 *3/*3 was associated with a 52% lower risk of hemorrhage, although this was not statistically significant (p=0.24).ConclusionPossession of CYP4F2*3 variant influences warfarin dose among European Americans but not African Americans. The CYP4F2-dose, CYP4F2-overanticoagulation, and CYP4F2-hemorrhage association follows a recessive pattern with possession of CYP4F2*3/*3 genotype likely demonstrating a protective effect. These findings need further confirmation.

Dataset Information

Influence of regular physical activity on warfarin dose and risk of hemorrhagic complications.

Publications

Influence of regular physical activity on warfarin dose and risk of hemorrhagic complications.

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