Effect of SAMe-TT2R2 score and genetic polymorphism on the quality of anticoagulation control in Qatari patients treated with warfarin

Abstract

There is no strong evidence on pharmacogenetics role on the quality of INR control after the initiation phase and on the maintenance of stable INR on the long term as measured by the time in therapeutic range (TTR). The benefit of a score such as SAMe-TT 2 R 2 is that it can preemptively guide clinicians on whether to start the patient on warfarin or direct oral anticoagulant. To determine the association between genetic variants in CYP2C9, VKORC1, and CYP4F2 and TTR. To validate SAMe-TT 2 R 2 score predictive ability on the quality of anticoagulation in Qatari patients. This is an observational nested case-control study that was conducted on a cohort of Qatari patients treated with warfarin with previously identified genotype for the CYP2C9, VKORC1, and CYP2F4. The sample size of this cohort was 148 patients. Mean TTR was 62.7 ± 21%. TTR was not significantly different among carriers of the CYP2C9*2 &*3, VKORC1(-1639G>A) or CYP4F2*3 compared to their non-carriers alleles. None of the factors in the SAMe-TT 2 R 2 score had a significant effect on the TTR except for the female gender where TTR was significantly lower in females (n = 89) compared to males (n = 59) (59.6 ± 21% vs. 67.2 ± 20%, p = 0.03). Furthermore, patients with SAMe-TT 2 R 2 score of zero had significantly better TTR compared to those with higher scores (76.5 ± 17% vs. 61.8 ± 21%, p = 0.04). Logistic regression analysis showed that high SAMe-TT 2 R 2 score was the only statistically significant predicting factor of poor INR control (odds ratio (OR) 5.7, 95% confidence interval (CI) 1.1-28.3, p = 0.034). Genetic variants have no contribution to the quality of INR control. SAMe-TT 2 R 2 score was predictive for the poor quality of anticoagulation in a cohort of Qatari patients. Keywords Same-TT 2 R 2 • Pharmacogenetics • Warfarin • Direct oral anticoagulants • Time in therapeutic range Highlights • SAMe-TT 2 R 2 is a tool that can preemptively guide clinicians on whether to start the patient on warfarin or direct oral anticoagulant. • There is no strong evidence on pharmacogenetics role on the quality of INR control and TTR after the initiation phase. • This research shows that genetic variants have no contribution to the quality of INR control. • Our results also indicate that SAMe-TT 2 R 2 score is predictive for the poor quality of anticoagulation in a cohort of Qatari patients.

Genetic Associations With Stable Warfarin Dose Requirements in Han Chinese Patients

“…3,9 In particular, genetic variations have been found to play a key role in influencing the maintenance dose of warfarin. 10,11 Recently, a randomized, prospective study has reported that warfarin loading dose guided by pharmacogenetics can improve the efficacy of warfarin initiation without increasing the risk of adverse events. 12 So there is pressing need to identify genetic factors which can significantly affect on warfarin therapy.…”