CLINICAL AND ECONOMIC IMPACT OF GENETIC AND NON-GENETIC FACTORS ON INR NORMALIZATION IN PRE-OPERATIVE MANAGEMENT OF WARFARIN PATIENTS

Abstract

The aim of this Ph.D. was to evaluate the periprocedural anticoagulation management of patients receiving warfarin in Qatar clinically and economically. In addition, exploring the clinical and economic impact of genetic and non-genetic factors on INR normalization in pre-operative management of warfarin patients in Arab population. our review concluded that the clinical decision regarding perioperative warfarin management is a complex aspect of care. Indeed, such an issue would ultimately lead to undesirable variation in care. This would be complicated by the lack of institutional standardized protocols and hence differences in practices, attitudes and periprocedural outcomes. A local cross-sectional survey on the periprocedural management of warfarin was developed for a better understanding of the current practice, the gap in knowledge and attitude among health care providers in Qatar. It has found that the awareness median (IQR) score was moderate [64.28% (21.43)]. The level of awareness was associated with the practitioner's specialty and degree of education (P= 0.009, 0.011 respectively). Practice leans to overestimate the need for warfarin discontinuation as well as the need for bridging. Participants expressed interest in using genetic tests to guide periprocedural warfarin management [median (IQR) score (out of 10) = 7 (5)]. The results of the mentioned survey were influencer to evaluate the real-world clinical practice of warfarin periprocedural management and investigate the clinical outcomes associated with warfarin bridging versus non-bridging. This prospective cohort study demonstrated that warfarin was interrupted in 90% of patients, out of them 82% received anticoagulant bridging medication. Minor or low-bleeding risk procedures represented 75% of the performed procedures. The median (IQR) of preoperative warfarin interruption days was 3 (2). No thromboembolic events were observed, while 39.1% of patients experienced bleeding events during the study period. The incidence of overall bleeding and major bleeding were numerically higher for bridging group compared to non-bridging but did not reach statistical significance [(30.6% Vs 22.2%, p= 0.478) and (12.9% Vs 5.6%, p=0.375), respectively]. The results of the above study showed significant limitations that undermine the benefit of bridging and showed that this benefit may not worth the monetary spending and may not achieve cost-effectiveness. To our knowledge, there are no evaluations of the economic value of bridging in the literature. Consequently, a study was conducted to assess the economic consequences of peri-procedural warfarin management of AF patients in Qatar. The economic evaluation of the above practice demonstrated that the mean overall cost of peri-procedural warfarin management per patient was USD 3,260 (QAR 11,900), associated with an overall success rate of 0.752. Based on the cost-effective analysis (CEA), predominant bridging was dominant (lower cost, higher effect) over the predominant non-bridging practice in 62.2% of simulated cases, with a cost-saving of up to USD 2,001 (QAR 7,303) at an average of USD 272 (QAR 993) and was cost-effective in 36.9% of cases. To optimize the period of preprocedural warfarin interruption to decrease the incidence of bleeding in case of bridging and the incidence of thromboembolism in case of non-bridging, a study was conducted to determine the influence of CYP2C9, VKORC1, CYP4F2, FII, and FVII genetic polymorphisms and non-genetic factors on INR decline in a cohort of Arabs undergoing a procedure that requires warfarin interruption and developing an algorithm to tailor the duration of warfarin interruption before the procedure. The study revealed that bridging, INR index and being Sudanese are significant predictors of INR normalization. Moreover, CYP2C9 and VKORC1 genetic polymorphisms are influencers to warfarin maintenance weekly dose but none of the genetic factors were associated with the INR decline rate. A more extensive study may be warranted to confirm such findings. Equally important, cost-effective analysis of implementing pharmacogenetics-based algorithm will guide decision-makers to which approach must be subsidized. To the best of our knowledge, no economic evaluation study investigated the use of pharmacogenetics information in pre-operative warfarin interruption to direct decision-makers. Therefore, a cost-benefit analysis was conducted to examine if the benefits of implementing a genetic-testing in periprocedural warfarin management outweigh the cost. The study showed that the average cost per patient was USD 573.72 (QAR 2,094.07) less with the genetic-guided approach of management compared to the standard of care. This led to an average benefit to cost ratio of 4; whereby, for each USD 1 spent on genetic testing, USD 4 is generated in benefit. This was maintained in 100% of simulated cases.