Study On Anticoagulant Quality Of Patients With Non - Valvular Atrial Fibrillation

BackgroundAtrial fibrillation (Atrial fibrillation, AF) is one of the most common arrhythmia, affecting life quality of patients, with the most serious consequences of cerebrovascular events, disability and even death. The total prevalence of AF is 0.4-1.0% and the incidence is increasing with age. According to ATRIA research, there were 2.3 million AF patients in the United States in the year of 2000, and this number is expected to reach 5.6 million in 2050. In Europe,17.9 million adults over 55 years have AF in 2060. One epidemiological survey enrolled individuals of 30-85 years old in 14 provinces and municipalities in China in 2004, which pronounced that the prevalence of AF was 0.77%, and the adjusted prevalence was 0.61%, the prevalence is higher in men (0.9%) than in women (0.7%).Among all AF cases, non-valvular AF (NVAF) was 65.2%.In recent years, with the changes of incidence, comorbidities and treatment changes of AF, there is still no large scale research focus on AF. This study is a prospective, single center, registry about the characteristics, treatment and prognosis of AF in the real world.According to the Framingham study, stroke caused by NVAF accounted for 15% to 20% of all strokes, the relative risk of stroke in NVAF is 5.6 compared with person without AF and anti-thrombotic therapy is essential in the treatment of AF. Oral anticoagulation with warfarin is the most effective therapy for the prevention of stroke in AF. Clinical evidences had shown that the OAC therapy could reduce the risk of AF thromboembolism by 62.0%, while the risk of bleeding did not increase significantly. However, anticoagulation status in our country is not optimistic. Previous studies showed that anticoagulation percentage in China was only 2%. Recently, with the improvement of the guidelines and the degree of cognition, the percentage of anticoagulation therapy in AF is increasing, but there is still no large-scale epidemiological evidence to confirm it. A large number of studies have explored the possible reasons for the low utilization rate of warfarin, but the predictors of warfarin use need to be further discussed in China. In addition to improving the utilization of warfarin, the anticoagulation quality of warfarin is also an important factor which might affect the efficacy. TTR is one of anticoagulation quality evaluation indexes, previous studies found that TTR more than or equal to 65% indicated significant benefit in clinic. At present, there is quite a lack in relative research. A single center prospective registration study and long-term follow-up were conducted to explore the above three parts:1) to describe the demographic data, concomitant diseases, anticoagulant therapy and long-term prognosis of patients with NVAF; 2) to investigate the effecting factors in the use of warfarin; 3) to explore anticoagulation quality (TTR, time in therapy range) of warfarin in NVAF patients and possible influencing factors.Part I Anticoagulation treatment and prognosis of NVAF patients-A Single Center Registry AnalysisObjective:Through prospective single center registry study and long-term follow-up, to explore the anticoagulant therapy and long-term prognosis in patients with NVAF.Methods:NVAF patients from Aug,2011 to Dec,2015 were enrolled in Peking union medical college hospital. The demographic data, concomitant disease and cardiovascular risk factors and treatment of the patients were collected in the form of case registration form. All patients were followed up every 6 months, recording the related treatment and clinical events during the follow-up period.Results:Of the 911 registered patients,526 were male (57.7%), with the mean age of 66.3±11.3 years. The most common comorbidities or cardiovascular risk factors were hypertension (63.6%), diabetes mellitus (20.2%), coronary heart disease (15.3%), thromboembolism (12.3%), heart failure (7.8%), etc.280 patients (30.7%) were treated with AADs at baseline, and 558 patients (61.3%) were prescribed to control ventricular rates.227 patients (24.9%) chose radiofrequency ablation. Paroxysmal AF patients with the highest proportion (35.7%) underwent radiofrequency ablation. Anticoagulation therapies at baseline were prescribed in 414 cases (45.4%) with warfarin,427 cases (46.9%) with aspirin,37 cases (4.1%) with clopidogrel and 51 cases (5.6%) with NOACs. During patients receiving medical therapy without ablation, percentage of warfarin usage was 33.8%, while the percentage in aspirin was 56.4%, in clopidogrel was 4.8% and in NOACs was 1%.39.7% of NVAF patients with CHA2DS2-VASc≥2 had a warfarin prescription, while the percentage in aspirin was 55%, in clopidogrel was 5.7% and in NOACs was 1%.14.1% patients began anticoagulation therapy in the follow-up period, while 15.5% patients terminated their anticoagulation therapy during follow-up. The long-term anticoagulation ratio in AF patients without ablation therapy was 31.1% and 10.0% in patients who underwent ablation therapy. During the follow-up period, the annual incidence of all-cause mortality, cardiovascular death and MACE was 2.76%,1.48% and 5.2%, respectively. The advanced age (HR 1.064,95%CI 1.034-1.094, P=0.0001), heart failure (HR 2.094, 95%CI 1.15-3.812, P=0.016), dilated cardiomyopathy (HR 6.799,95%CI 2.38-19.42, P=0.0001),chronic pulmonary disease (HR 1.955,95%CI 1.10-3.474, P=0.022), anemia (HR 3.085,95%CI 1.707-5.574, P=0.0001) and DM (HR 1.727,95%CI 1.043-2.858, P=0.034) were associated with higher all-cause mortality of NVAF patients. On multivariate analysis of NVAF patients, independent predictors of cardiovascular death were advanced age (HR 1.06,95%CI 1.019-1.102, P=0.004), heart failure (HR 2.171,95%CI 1.273-6.217, P=0.011), DM (HR 2.018,95%CI 1.081-4.111, P=0.029),dilated cardiomyopathy (HR 5.142,95%CI 1.126-23.485, P=0.035), anemia (HR 4.434,95%CI 2.059-9.55, P=0.0001). Multivariable analysis showed that advanced age (HR 1.03,95%CI 1.01-1.049, P=0.003), heart failure (HR 2.171,95%CI 1.36-3.419 P=0.001), dilated cardiomyopathy (HR 3.382,95%CI 1.348-8.488, P=0.009), stroke/systemic embolism (HR 1.726,95%CI 1.142-2.609, P=0.01),anemia (HR 2.04,95%CI 1.236-3.367, P=0.005) and chronic pulmonary disease (HR 1.808,95%CI 1.146-2.85, P=0.011)were independently associated with MACE.Conclusions:1. Comorbidities or risk factors, such as hypertension, DM, CAD, heart failure were common in our registration study of NVAF patients.2. Rate control agents were used more frequently in NVAF patients than AADs; one third patients of paroxysmal AF chose radiofrequency ablation.3. In baseline, warfarin was used in 45.4% of NVAF patients and 33.8% of NVAF patients without radiofrequency ablation.39.7% of NVAF patients with CHA2DS2-VASc≥2 received warfarin in baseline.4.31.1% of NVAF patients without radiofrequency ablation and 10.3% of patients who underwent radiofrequency ablation were persistent on warfarin in long-term follow-up.5. The annual incidence of all-cause mortality, cardiovascular death and MACE of NVAF patients was 2.76%,1.48% and 5.2%, respectively. The advanced age, heart failure, anemia, chronic pulmonary diseases were associated with prognosis of NVAF patients.PART Ⅱ Predictors of warfarin persistence in non-valvular atrial fibrillation patients with high risk of strokeObjective:To identify predictors of prescription and persistence of warfarin in NVAF patients with high risk of stroke (CHA2DS2-VASc≥2).Methods:NVAF patients from Aug,2011 to Dec,2015 were enrolled in Peking union medical college hospital.. Patients who underwent radiofrequency catheter ablation were excluded. Patients were divided into two groups (warfarin and non-warfarin). Logistic regression was used to estimate the predictors of warfarin prescription. Kaplan-Meier survival and Cox proportional hazards model were performed to determine rate of persistence and factors associated with warfarin persistence.Results:A total of 611 NVAF patients were enrolled. And 481 patients with CHA2DS2-VASc≥2,481 patients were followed up with a mean follow-up period of 38.9±13.8months. Of which 252 NVAF patients (51%) had a warfarin prescription. Patients with ischemic stroke (HR 2.543,95%CI 1.525-4.241, P=0.0001), heart failure (HR 1.93,95%CI 1.064-3.051, P=0.030) and persistent AF (HR 2.208,95%CI 1.448-3.366, P=0.0001) had a higher likelihood of warfarin prescription. Traditional Chinese Medicine (TCM) (HR 0.628, 95%CI 0.413-0.954, P=0.029),CAD (HR 0.601,95%CI 0.37-0.974,P=0.039) and longer distance to hospital (HR 0.689,95%CI 0.584-0.897, P=0.003) decreased the likelihood of warfarin prescription. One hundred and sixty-seven (66.3%) warfarin users were persistent on therapy; the overall proportion of warfarin persistence was 81.3% for one year,67.0% for 3 years. Sixty-nine continuing warfarin users continued therapy (73%,69/94), ninety-six new users were persistent on therapy (62.0%, 96/158).Warfarin use before enrollment significantly increased warfarin persistence than new prescription (P=0.008).Variables clearly associated with higher discontinuation were new prescription (HR 1.786,95%CI 1.029-3.1, P=0.0039), TCM (HR 1.687,95%CI 1.201-2.37, P=0.003), longer distance to hospital (HR 1.446, 95%CI 1.121-1.865, P=0.005).Conclusions:1. The independent predictors of warfarin medication include heart failure, coronary heart disease, thrombosis, distance to hospital, etc. The longer distance to hospital decreased the likelihood of warfarin prescription and warfarin persistence.2. New warfarin users decreased the likelihood of warfarin persistence.3. Traditional Chinese medicine reduced the rate of use of warfarin, and was significantly associated with the withdrawal percentage of warfarin.PartⅢ The quality of long-term oral anticoagulation therapy in patients with non-valvular atrial fibrillation.Objective:TTR is a commonly used index to evaluate the quality of warfarin anticoagulation. This study was to investigate the TTR of NVAF patients and its predictors.Methods:NVAF patients who were persistent on warfarin from Aug,2011 to Dec, 2015 were enrolled in Peking union medical college hospital.The Rosendaal method was used to calculate TTR. Single factor and multiple regression analysis were applied for identify predictors of TTR.Results:A total of 118 patients met the inclusion criteria, including 62 male patients (52.5%). The average age was (70.3±8.7 years). During the follow-up period,2915 INR test results were recorded. The average number of INR monitoring was 24.7 ± 12.6 times, the average time interval was 45.7±15.3 days (range 13.8～84.5 days). The mean TTR was 55.5±19.3% (0%-99.0%). Below the TTR ratio (INR< 2) was 39.0±20.1% (0%～93.81%), higher than the TTR range (INR> 3) ratio was 4.69±8.60% (0%-60.52%). Multivariate analysis revealed that hypertension and HF were independent factors influencing the level of TTR (P< 0.05).Conclusions:The TTR in NVAF patients was 55.5±19.3%.Hypertension and HF were the independent factors of TTR.