Optimal INR level in elderly and non-elderly patients with atrial fibrillation receiving warfarin: a report from the COOL-AF nationwide registry in Thailand

Background Asian population are at increased risk of bleeding during the warfarin treatment,so the recommended optimal international normalized ratio(INR)level may be lower in Asians than in Westerners.The aim of this prospective multicenter study was to determine the optimal INR level in Thai patients with non-valvular atrial fibrillation(NVAF).Methods Patients with NVAF who were on warfarin for stroke prevention were recruited from 27 hospitals in the nationwide COOL-AF registry in Thailand.We collected demographic data,medical history,risk factors for stroke and bleeding,concomitant disease,electrocardiogram and laboratory data including INR and antithrombotic medications.Outcome measurements included ischemic stroke/transient ischemic attack(TIA)and major bleeding.Optimal INR level was assessed by the calculation of incidence density for six INR ranges(<1.5,1.5–1.99,2–2.49,2.5–2.99,3–3.49,and≥3.5).Results A total of 2,232 patients were included.The mean age of patients was 68.5±10.6 years.The mean follow-up duration was 25.7±10.6 months.There were 63 ischemic stroke/TIA and 112 major bleeding events.The lowest prevalence of ischemic stroke/TIA and major bleeding events occurred within the INR range of 2.0–2.99 for patients<70 years and 1.5–2.99 for patients≥70 years.Conclusions The INR range associated with the lowest risk of ischemic stroke/TIA and bleeding in the Thai population was 2.0–2.99 for patients<70 years and 1.5–2.99 for patients≥70 years.The rates of major bleeding and ischemic stroke/TIA were both higher than the rates reported in Western population.

Frailty and Anticoagulant Therapy in Patients Aged 65 Years or Older with Atrial Fibrillation

Background:Elderly adults with atrial fi brillation(AF)are at increased risk of frailty and thromboembolic complications.However,studies on the prevalence of frailty in AF patients and data on the relationship between frailty and the use of anticoagulants are limited.Methods:We conducted a cross-sectional study involving 500 participants.Patients aged 65 years or older were consecutively selected from the Chinese Atrial Fibrillation Registry study.The patient’s frailty status was assessed with use of the Canadian Study of Health and Aging Clinical Frailty Scale.We assessed the prevalence of and factors associated with frailty,and how frailty affects anticoagulant therapy.Results:In 500 elderly adults with AF(age 75.2±6.7 years;51.6%female),201 patients(40.2%)were frail.The prevalence of frailty was higher in females(P=0.002)and increased with age and CHA 2 DS 2-VASc score(P for trend less than 0.001 for both).The factors associated with frailty were a history of heart failure(odds ratio[OR]2.40,95%confi dence interval[CI]1.39–4.14),female sex(OR 2.09,95%CI 1.27–3.43),and advanced age(OR 1.13,95%CI 1.09–1.17).Frail patients were signifi cantly less likely to have ever been prescribed anticoagulants compared with nonfrail patients(81.7 vs.54.9%,P<0.001).Conclusions:Frailty is prevalent in elderly adults with AF,especially in females,those of advanced age,and those with heart failure.Frailty status has a signifi cant impact on prescription of anticoagulants for high-risk AF patients.

Evaluation of Albuminated Curcumin as Soluble Drug Form to Control Growth of Cancer Cells <i>in Vitro</i>

Curcumin (Curc) is well known for its anticancer activity, but its poor solubility in aqueous medium is a major concern for little therapeutic outcome. Therefore, the effort to improve its bioavailability is a major research interest. The current study aimed at conjugation of Curc to serum albumin (Alb) to increase aqueous solubility of the former without affecting its drug action on cancer cell lines and primary cells in culture. Conditions for preparation of albumin-curcumin (Alb-Curc) conjugate were standardized to obtain pure and stable drug. The product was obtained in sufficient quantity to test its effect on cells in culture at different doses. Briefly, the conjugate was prepared by mixing Curc dissolved in DMSO with the Alb dissolved in phosphate buffered saline;conjugate was purified by gel filtration chromatography and was analyzed using UV-Vis spectroscopy for characteristic peaks of both molecules. The conjugate was added to culture medium to identify the effect of conjugate on cell cycling and apoptosis. Albuminated curcumin that showed 100-fold higher solubility than free Curc was stable and inhibitory to proliferation, induced cell cycle arrest and apoptosis. The conjugate showed apoptotic effects on endothelial cells indicating its anti angiogenic property. Primary fibroblast growth was also inhibited but at the higher dose. The in vitro results suggest that Alb-Curc which is free of insoluble native drug may find application in cancer therapy after appropriate in vivo evaluations.