Israel Medical Association Journal

Background: Oral anticoagulants (OAC) reduce the risk for stroke and death from all causes in patients with non-valvular atrial fibrillation (NVAF)

Objective: To explore adherence rates of OAC among patients with NVAF in long-term use in a real-world setting and to examine patient characteristics associated with good adherence.

Methods: We conducted a population-based cohort study with members of Clalit Health Services, Israel. All patients aged ≥ 30 years with a diagnosis of NVAF before 2016 who were treated with OAC were included. We included patients who filled at least one prescription per year in the three consecutive years 2016–2018. We analyzed all prescriptions that were filled for the medications from 1 January 2017 to 31 December 2017. We considered purchasing of at least nine monthly prescriptions during 2017 as good medication adherence.

Results: We identified 26,029 patients with NVAF who were treated with OAC; 10,284 (39.5%) were treated with apixaban, 6321 (24.3%) with warfarin, 6290 (24.1%) with rivaroxaban, and 3134 (12.0%) with dabigatran. Rates of good medication adherence were 88.9% for rivaroxaban, 84.9% for apixaban, 83.6% for dabigatran, and 55.8% for warfarin (P < 0.0001). Advanced age was associated with higher adherence rates (P < 0.001). Socioeconomic status was not associated with medication adherence. Good adherence with OAC was associated with lower low density lipoprotein (LDL) cholesterol and glucose levels.

Conclusions: Adherence rates to OAC in chronic use among patients with chronic NAVF are high. Investing in OAC adherence may have a wider health impact than expected.

Background: Real-world information regarding the use of direct oral anticoagulants therapy and the outcome in patients with renal dysfunction is limited.

Objectives: To evaluate the clinical characteristics and outcomes of patients with atrial fibrillation (AF) and severe renal dysfunction who are treated with apixaban.

Methods: A sub-analysis was conducted within a multicenter prospective cohort study. The study included consecutive eligible apixaban- or warfarin-treated patients with non-valvular AF and renal impairment (estimated glomerular filtration rate [eGFR] modification of diet in renal disease [MDRD] < 60 ml/min/BSA) were registered. All patients were prospectively followed for clinical events and over a mean period of 1 year. Our sub-analysis included the patients with 15 < eGFR MDRD < 30 ml/min/BSA. The primary outcomes at 1 year were recorded. They included mortality, stroke or systemic embolism, major bleeding, and myocardial infarction as well as their composite occurrence.

Results: The sub-analysis included 155 warfarin-treated patients and 97 apixaban-treated ones. All had 15 < eGFR MDRD < 30 ml/min/BSA. When comparing outcomes for propensity matched groups (n=76 per group) of patients treated by reduced dose apixaban or warfarin, the rates of the 1-year composite endpoint as well as mortality alone were higher among the warfarin group (30 [39.5%] vs. 14 [18.4%], P = 0.007 and 28 [36.8%] vs.12 [15.8%], P = 0.006), respectively. There was no significant difference in the rates of stroke, systemic embolism, or major bleeding.

Conclusions: Apixaban might be a reasonable alternative to warfarin in patients with severe renal impairment.

Objectives: To determine the effect of vitamin K on hip fracture patients treated with warfarin.

Methods: We retrospectively examined the management of 21 patients with hip fractures who were being treated with warfarin at the time of admission. Vitamin K was given to 11 of the 21 patients. A third group, which served as a control, consisting of 35 hip fracture patients who were not being treated with anticoagulants was also evaluated.

Results: Patients who received vitamin K took fewer days to reach target international normalized ratio (INR) (1.73 ± 0.90 vs. 4.30 ± 1.89, P < 0.001) and had less preoperative time (2.64 ± 1.12 vs. 5.10 ± 2.42 days, P < 0.008) when compared with patients who did not receive vitamin K. In addition, these patients had statistically significantly shorter hospitalization stays (9.4 ± 1.9 and 13.2 ± 4.9 days, one-sided P < 0.06). There was no difference in the amount of blood found in the wound drains (111.8 ± 68.5 vs. 103.0 ± 69.4 ml) or the number of blood units administered (1.45 ± 1.29 vs. 2.00 ± 2.75 units).

Conclusions: Treatment with vitamin K for hip fracture patients who receive warfarin shortens preoperative time, reduces the length of hospitalization and probably reduces morbidity and mortality.

Background: Ethnicity has been associated with variance in warfarin treatment regimens in various settings.

Objectives: To determine whether ethnicity is associated with variance in patient management in Israel.

Methods: Data were extracted from the electronic patient records of Clalit Health Services clinics in the Sharon Shomron region. The study group comprised all patients treated with warfarin who performed international normalized ratio tests for at least 6 months in 2003. The proportion of tests of each patient within the target range was calculated, as was the crude average rates and 95% confidence intervals for Jewish and Arab patients. The data were then stratified by patient's gender, specialty of attending physician, patient's age, and the country where the physician studied medicine.

Results: We identified 2749 Jews and 293 Arabs who met the inclusion criteria of the study. The crude average rate of patients’ INR[1] tests within the target range was 62.3% among Jews (95% CI[2] 61.5–63.1) and 52.7% (95% CI 49.9–55.5) among Arabs. When stratified by gender, age, and the treating physician's specialty and country of education, the stratum-specific rates among Jewish patients were consistently higher than among Arabs.

Conclusions: These results suggest that cultural differences regarding adherence to recommendations for drug therapy in addition to genetic factors may be associated with this variance.

Background: Oral anticoagulation with warfarin can lead to life-threatening events as a result of either over-anticoagulation or undertreatment. One of the main contributors to an undesirable warfarin effect is the need to adjust its daily dose for a specific patient. The dose is adjusted empirically based on the experience of the clinician, a method that is often imprecise. There is currently no other well-accepted method for predicting the maintenance dose of warfarin.

Objective: To describe the application of an artificial neural network to the problem of warfarin maintenance dose prediction.

Methods: We designed a neural network that predicts the maintenance dose of warfarin. Data on 148 patients attending a large anticoagulant clinic were collected by file review. Using correlational analysis of the patients' data we selected the best input variables. The network was trained by using the back-propagation algorithm on a subset of our data and the results were validated against the rest of the data. We used a multivariate linear regression to create a comparable model.

Results: The neural network generated reasonable predictions of the maintenance dose (r = 0.823). The results of the linear regression model were similar (r = 0.800).

Conclusion: Neural networks can be applied successfully for warfarin maintenance dose prediction. The results are promising, but further investigation is needed.