Advertisement

Improved Dosing of Vitamin-K Antagonists: Does Genotype Hold the Key?

Summary and Comment |
November 19, 2013

Improved Dosing of Vitamin-K Antagonists: Does Genotype Hold the Key?

  1. Joel M. Gore, MD

In two EU-PACT trials, the incremental value of including genotype information in initial dosing algorithms was modest at best.

  1. Joel M. Gore, MD

Findings from small studies have suggested that genotype-guided dosing algorithms can increase the effectiveness and safety of warfarin-type oral anticoagulants. Now, the European Pharmacogenetics of Anticoagulant Therapy (EU-PACT) group presents two analyses of data from three multicenter, randomized, controlled trials in patients with atrial fibrillation or venous thromboembolism. Investigators used point-of-care tests to genotype for CYP2CP*2, CYP2C9*3, and VKORC1. In the intervention groups, anticoagulant dosing for the first 5 to 7 days of treatment was based on an algorithm that included patient genotype information; in the control groups, the initial dosing algorithms did not include genotype.

In a warfarin trial involving 455 patients (61% men; 98.5% white), genotype-guided dosing was compared with a standard dosing regimen. At 12 weeks, the primary outcome — unadjusted time with an international normalized ratio (INR) of 2.0 to3.0 — was 67.4% in the genotype-guided group and 60.3% in the control group (P<0.001). The between-group differences in mean INR were greatest shortly after initiation of therapy and were nonsignificant after week 8. Compared with patients in the control group, those in the genotype-guided group were less likely to have an INR of 4.0 or higher and reached therapeutic INR more quickly (in 21 vs. 29 days).

In trials of acenocoumarol and phenprocoumon involving a total of 548 patients, genotype-guided dosing was compared with dosing based on an algorithm that included various clinical variables. The time in therapeutic INR range was 61.6% in the genotype-guided group and 60.2%in the control group (P=0.52). The percentages of patients in therapeutic INR range during the first 4 weeks of therapy were 52.8% and 47.5% in the genotype-guided and control groups, respectively. The incidence of bleeding or thromboembolic events did not differ significantly between the two groups.

Comment

These two studies produced divergent results. In the warfarin study, in which the control strategy was a fixed dosing schedule, pharmacogenetic-based dosing was associated with a higher percentage of time in therapeutic INR range. However, in the studies of acenocoumarol and phenprocoumon, in which the control strategy included clinical variables, genotyping did not improve the percentage of time in therapeutic INR, underscoring the importance of nongenetic factors in achieving a therapeutic INR. At the present time, these studies should not lead physicians to incorporate genotyping into their current practice.

  • Disclosures for Joel M. Gore, MD at time of publication Grant / research support NIH; NIH-NHLBI; NSF

Citation(s):

Your Comment

(will not be published)

Filtered HTML

  • Allowed HTML tags: <a> <em> <strong> <cite> <blockquote> <code> <ul> <ol> <li> <dl> <dt> <dd>
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Do you have any conflict of interest to disclose?
CAPTCHA
This question is for testing whether you are a human visitor and to prevent automated spam submissions.
Image CAPTCHA
Enter the characters shown in the image.

Vertical Tabs

* Required

Reader comments are intended to encourage lively discussion of clinical topics with your peers in the medical community. We ask that you keep your remarks to a reasonable length, and we reserve the right to withhold publication of remarks that do not meet this standard.

PRIVACY: We will not use your email address, submitted for a comment, for any other purpose nor sell, rent, or share your e-mail address with any third parties. Please see our Privacy Policy.

Advertisement
Advertisement
Advertisement