In the APHRS survey most respondents

In the APHRS survey, most respondents (86%) answered that OACs were discontinued before endoscopy or surgery. With novel OACs, physicians will be able to discontinue anticoagulant therapy before the surgical procedure without concern for thrombotic complications. The APHRS survey did not investigate whether physicians performed periprocedural bridging therapy for their patients. The survey revealed that 56% of physicians in India continued OAC during procedures despite the risk of bleeding. If they continue OAC because of the fear of perioperative thrombotic complications, discontinuation may be encouraged on the basis of the report by Healey et al. [31], as mentioned above. Although the bleeding risk is low during tooth extraction even in patients continuing OAC, physicians in almost all countries, excluding Japan, answered that they discontinued OAC before tooth extraction. The survey revealed that 78% of the physicians in Japan continue anticoagulation therapy during tooth extraction but most in other countries stop the anticoagulation therapy before the tooth extraction procedure. The risk of embolism may increase during interruption of antithrombotic therapy, and this leads to concern that the patients could have a risk of embolism while the anticoagulation therapy is stopped. It has been reported that serious thromboembolism occurs in about 1% of patients with AF after discontinuation of warfarin [32,33]. Randomized controlled studies and observational studies have reported that tooth extraction can be safely performed on patients receiving antithrombotic drugs [34,35].
Racial/ethnic difference in anticoagulant effects Shen et al. [23] investigated a stroke-free cohort of 18,867 patients who were hospitalized for nonvalvular AF (78.5% white, 8% black, 9.5% Hispanic, and 3.9% Asian). During the follow-up aminopeptidase inhibitor of 3.3 years, 173 patients experienced ICH. Anticoagulation intensity (INR) was lower among blacks but not different between the other groups. Warfarin was associated with increased ICH risk in all races; however, the magnitude of risk was greater among nonwhites. There were no sex differences. The hazard ratio for ICH with whites as reference was 4.06 for Asians, 2.06 for Hispanics, and 2.04 for blacks. It has been reported that the dose of warfarin to achieve the same INR was the smallest in Asian patients and the highest in black patients, and Caucasian patients were between Asian and black patients [36,37]. It is also an important point to discuss whether all races need the same INR to ensure the prevention of thromboembolic events in patients with AF. You et al. [38] have reported that an INR of 1.8–2.4 appeared to be associated with the lowest incidence rate of major bleeding or thromboembolic events as compared with an INR of 2–3. In the APHRS survey, 58% of physicians answered that they set different INR ranges for different age groups (Fig. 6), although 29% of Australian physicians and only 10% of New Zealand physicians adjust INR depending on age. The threshold age was 74 years on average. As Fig. 7 shows, physicians in most countries, excluding India, target the INR value at 2–3 in younger patients, which is consistent with the guidelines, and at 1.6–2.6 in elderly patients. The JCS 2008 guidelines recommend that the target INR be 2–3 for patients <70 years of age and 1.6−2.6 for patients >70 years of age on the basis of the results of a prospective study of elderly patients (≥70 years) in Japan in whom low-dose warfarin therapy to target an INR of 1.6−2.6 was confirmed to be safe and effective [39]. The results of the APHRS survey indicated that all countries used similar criteria. It is desirable that the APHRS\'s statement should specify warfarin regimens for different age and racial/ethnic groups. A subanalysis of the RE-LY trial reported important data about the risk of bleeding in Asian patients [40]. In a comparison between Asian and non-Asian patients receiving warfarin, the risks of ischemic stroke and hemorrhagic stroke were twice higher in Asian than in non-Asian patients. It is possible that a racial or genetic factor is involved in energy flow difference, which has been pointed out for years, but we should also consider other factors because no such differences were observed in a comparison between Asian and non-Asian patients receiving dabigatran. The low average INR value and the low TTR in Asian patients may be the biggest reasons for the higher risks of ischemic stroke and hemorrhagic stroke. The subanalysis of the RE-LY trial [40] revealed that the percentage of patients with a mean INR of <2 was 19.8% among non-Asian patients and 35.4% in Asian patients, and the percentage of patients with a mean INR of 2–3 was 66.2% and 54.5% in non-Asian and Asian patients, respectively. These results suggest that Asian patients are not receiving sufficient warfarin therapy. Additionally, a comparison of the TTR among countries participating in the RE-LY trial [41] has indicated insufficient warfarin therapy in Asian countries. In fact, TTR exceeded 60% only in Australia (74%), Singapore (68%), and Hong Kong (64%), whereas TTR was lower in Japan (58%), Korea (55%), China (55%), India (49%), and Taiwan (44%) (no data were available in New Zealand). It is plausible that this may explain the high incidences of ischemic stroke and hemorrhagic stroke among Asian patients. Physicians in Asian countries should be encouraged to maintain TTR at an appropriate level (≥60%) when elderly patients receive warfarin therapy at a low target INR level as recommended in the JCS 2008 guidelines and this APHRS statement. Interestingly, the incidence of major gastrointestinal bleeding was much lesser in the Asian than in the non-Asian cohort in the RE-LY trial.