Fasting and Warfarin

Document Type: Letter to the Editor

Authors

1 Department of Pharmacy, Singapore General Hospital, Singapore

2 Department of Haematology, Singapore General Hospital, Singapore

Abstract

Recently, we reported the findings of a study on the effects of Ramadan fasting on a group of 32 Muslim patients taking warfarin.13 Weekly INR (international normalized ratio) readings were taken from subjects with previously stable INRs over a three-month period spanning pre-Ramadan to post-Ramadan. We found a statistically significant increase in the mean INR by 0.23 (p=0.006) during Ramadan from the pre-Ramadan month and decreased by 0.28 (p<0.001) after Ramadan. There was no significant difference (p=1.000) in mean INR between the non-Ramadan months. Importantly, there was a decline in the time within therapeutic range (TTR) during Ramadan with a corresponding increase in TTR above the therapeutic target range. %TTR declined from 80.99% before Ramadan to 69.56% during Ramadan (p=0.453). The first out-of-range INR was seen around 12.1 days (95% CI 9.0-15.1) after the start of fasting and returned within range about 10.8 days (95% CI 7.9-13.7) after Ramadan. Time above range increased from 10.80% pre-Ramadan to 29.87% during Ramadan (p=0.027), while time below range increased from 0.57% during Ramadan to 15.49% post-Ramadan (p=0.006). This observation is directly attributable to the effects of fasting.

Keywords


  1. McArthur MC, Dzintars EK, Phillips RB, Bushardt RL. Oral anticoagulation: A review of the current and emerging therapies. JAAPA 2011; 24: 60-6.
  2. Hirsh J, Dalen J, Anderson DR, Poller L, Bussey H, Ansell J, Deykin D. Oral Anticoagulants: Mechanism of Action, Clinical Effectiveness, and Optimal Therapeutic Range. Chest 2001; 119: 8S-21S.
  3. Holmes MV, Hunt BJ, Shearer MJ. The role of dietary vitamin K in the management of oral vitamin K antagonists. Blood Rev 2012; 26: 1-14.
  4. Laliberté R, Chakrabarti S, Brodeur J. The influence of fasting and stress on the response of rats to warfarin. J Pharmacol Exp Ther 1976; 196: 194-203.
  5. Laliberte R, Chakrabarti S, Brodeur J. The influence of fasting on the disposition of warfarin in rats. J Pharmacol Exp Ther 1977; 200: 44-51.
  6. Charest-Boule L, Chakrabarati S, Brodeur J. Influence of Free Fatty Acid Anion on the Binding of Warfarin to Cytoplasmic Proteins from Rat Liver. Chem-Biol Interactions 1980; 29: 85-94.
  7. Harauchi T, Takano K, Matsuura M, Yoshizaki T. Liver and Plasma Levels of Descarboxyprothrombin (PVKA II) in Vitamin K Deficiency in Rats. Japan J Pharmacol 1986; 40: 491-499.
  8. Ramadan: health effects of fasting. Lancet 2009; 374: 588.
  9. Hawk TL, Havrda DE. Effect of stress on International Normalized Ratio during warfarin therapy. Ann Pharmacother 2002; 36: 617-20.
10. Ziaee V, Razaei M, Ahmadinejad Z, Shaikh H, Yousefi R, Yarmohammadi L, Bozorgi F, Behjati MJ. The changes of metabolic profile and weight during Ramadan fasting. Singapore Med J 2006; 47: 409-14.

11. Saour JN, Sieck J, Khan M, Mammo L. Does Ramadan fasting complicate anticoagulation therapy?. Ann Saudi Med 1989; 9:538–40.

12. Chamsi-Pasha H, Ahmed WH. The effect of fasting in Ramadan on patients with heart disease. Saudi Med J 2004; 25: 47–51.

13. Lai YF, Cheen MHH, Lim SH, Yeo FHI, Nah SC, Kong MC, Mya D, Lee LH, Ng HJ . The effects of fasting in Muslim patients taking warfarin. J Thromb Haemost 2014; 12: 349–54