Shifting from vitamin K antagonists to non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: predictors, patterns and temporal trends.

BACKGROUND: Non-Vitamin K antagonist oral anticoagulants (NOACs) emerged as an alternative with comparable or superior efficacy and safety to vitamin K antagonists (VKAs) for stroke prevention in patients with non-valvular atrial fibrillation (AF). OBJECTIVES: The aim of the current study was to investigate the patterns, predictors, timelines and temporal trends of shifting from VKAs to NOACs. METHODS: In this retrospective observational study, the computerized database of a large healthcare provider in Israel, Maccabi Healthcare Services, was searched to identify patients with AF for whom either a VKA or NOAC was prescribed between 2012 and 2015. Time from diagnosis to therapy initiation and to shifting between therapies was evaluated. RESULTS: Out of 6987 eligible AF incident patients, 2338 (33.4%) initiated treatment with a VKA and 2221 (31.7%) with a NOAC. In addition, 5259 prevalent patients were analyzed. During the study period, NOAC prescriptions proportion among the newly diagnosed cases increased from 32 to 68.4% (p for trend <  0.001). The median time from diagnosis to first dispensing was greater in NOAC than VKA and decreased among patients treated with NOAC during the study period (2012: 1.9 and 0.3 months, 2015: 0.7 and 0.2 months, respectively). During follow-up, 3737 (49%) patients (54.3% and 47.1% of the incident and prevalent cases, respectively), shifted from a VKA to a NOAC, after a median of 22 months and 39 months in the incident and prevalent cases, respectively, decreasing throughout the study period. Female gender, younger age, southern district, higher CHADS2 and CHA2DS2-VASC score, non-smoking, and treatment with antiplatelets were associated with a greater likelihood for therapy shift. Shifting from a NOAC to a VKA decreased over time from 8 to 4.5% in 2012 to 0.5% and 0.7% in 2015 in the incident and prevalent groups, p <  0.001 respectively. CONCLUSIONS: Shifting from VKA to NOAC occurred in 50% of the cases, more frequently among incident cases, and younger patients with greater stroke risk. Shifting from a NOAC to a VKA was much less frequent, yet it occurred more often in incident cases and decreased over time. A socially and economically sensitive program to optimize the initiation of OAC therapy upon diagnosis is warranted.

Drug interactions involving antiepileptic drugs: assessment of the consistency among three drug compendia and FDA-approved labels.

Interactions of antiepileptic drugs (AEDs) with other substances may lead to adverse effects and treatment failure. To avoid such interactions, clinicians often rely on drug interaction compendia. Our objective was to compare the concordance for twenty-two AEDs among three drug interaction compendia (Micromedex, Lexi-Interact, and Clinical Pharmacology) and the US Food and Drug Administration-approved product labels. For each AED, the overall concordance among data sources regarding existence of interactions and their classification was poor, with less than twenty percent of interactions listed in all four sources. Concordance among the three drug compendia decreased with the fraction of the drug excreted unchanged and was greater for established inducers of hepatic drug-metabolizing enzymes than for the drugs that are not inducers (R-square=0.83, P<0.01). For interactions classified as contraindications, major, and severe, concordance among the four data sources was, in most cases, less than 30%. Prescribers should be aware of the differences between drug interaction sources of information for both older AEDs and newer AEDs, in particular for those AEDs which are not involved in hepatic enzyme-mediated interactions.

Cancer-associated venous thromboembolism in Israel: Incidence, risk factors, treatment, and health care utilization in a population based cohort study.

Background: Recent international guidelines recommend thromboprophylaxis in patients with cancer at intermediate-high venous thromboembolism (VTE) risk. Objectives: We aimed to assess the current incidence, risk factors and management of cancer-associated VTE and associated health care resource utilization in a 2.5-million-member state-mandated health service in Israel. Methods: Patients aged ≥18 years with newly diagnosed cancer, initiating systemic anticancer treatment from 2010 through 2018 were identified from the Israel National Cancer Registry. The index date was fixed as the first day of systemic anticancer treatment. The cumulative VTE incidence from the first day of systemic anticancer treatment and the respective hazard ratios for VTE risk factors were calculated at 12 months of follow-up. Health care resource utilization (primary care physician, emergency room, and hospital visits) during the study period was compared between patients with and without VTE. Results: A total of 15 388 patients were included, and 338 had VTE with a 12-month cumulative incidence of 2.2% (95% confidence interval, 1.96%-2.43%). In a multivariable model, older age, higher comorbidity index, intermediate-high-risk Khorana score, certain malignancy types, and chemotherapy were significantly associated with an increased VTE risk in the year after initiating anticancer treatment. Compared with matched controls, the VTE subcohort were more likely to be hospitalized (81.4% vs 35.2%), have longer hospital stays (20.1 days vs 13.1 days), have an emergency room visit (41.5% vs 19.3%), and have a larger number of primary care physician visits (17.6 vs 12.5). Conclusion: Several risk factors, including the Khorana score, were associated with VTE incidence. VTE was associated with long-term use of anticoagulation. Health care utilization was higher in patients with VTE.

Pain Pharmacotherapy in a Large Cohort of Patients with Osteoarthritis: A Real-World Data Analysis.

INTRODUCTION: There is limited evidence on the consumption of analgesics in real-world large cohorts of patients with osteoarthritis (OA), especially in those with comorbidities. We aimed to characterize the use of pharmacological analgesic treatments, evaluate standardized comorbidity rates, and assess treatment trends. Our hypotheses were: (1) OA patients generally consume low and inconsistent pharmacological analgesic treatments; (2) analgesic treatment is often non-congruent with comorbidity-related safety concerns. METHODS: The study was carried out at the second largest health maintenance organization in Israel. Members aged 18 years or above who were diagnosed with OA before December 31, 2018, were included. Information was obtained from the members' electronic medical record (EMR) including data on dispensed prescriptions, which were used to estimate analgesic consumption. RESULTS: A total of 180,126 OA patients were included in our analyses; analgesics were dispensed to 64.2% of the patients, with oral NSAIDs and opioids dispensed to 34.1 and 22.9% of the OA population, respectively. Analgesic use increased with time lapsed from OA diagnosis (p < 0.001), up to a median of 59 days covered (IQR, 20-175) after 21 years. Rates of most comorbidities in the OA population were higher compared to the MHS general population. Patients with comorbidities used more NSAIDs and opioids compared to those without them. CONCLUSIONS: Most OA patients use analgesics, usually oral NSAIDs. Analgesic use remains relatively low throughout the years, indicating that many OA patients are not being treated pharmacologically for pain on a regular basis. Despite having higher rates of several comorbidities compared to MHS general population, many OA patients are still treated with analgesics that can be associated with a worsening in comorbidity.

Prevalence and Incidence of Osteoarthritis: A Population-Based Retrospective Cohort Study.

While trends data of osteoarthritis (OA) are accumulating, primarily from Western Europe and the US, a gap persists in the knowledge of OA epidemiology in Middle Eastern populations. This study aimed to explore the prevalence, incidence, correlations, and temporal trends of OA in Israel during 2013-2018, using a nationally representative primary care database. On 31 December 2018, a total of 180,126 OA patients were identified, representing a point prevalence of 115.3 per 1000 persons (95% CI, 114.8-115.8 per 1000 persons). Geographically, OA prevalence was not uniformly distributed, with the Southern and Northern peripheral districts having a higher prevalence than the rest of the Israeli regions. OA incidence increased over time from 7.36 per 1000 persons (95% CI 6.21-7.50 per 1000 persons) in 2013 to 8.23 per 1000 persons (95% CI 8.09-8.38 per 1000 persons) in 2017 (p-value for trend = 0.02). The incidence was lowest in patients under 60 years (in both sexes) and peaked at 60-70 years. In older ages, the incidence leveled off in men and declined in women. The growing risk of OA warrants a greater attention to timely preventive and therapeutic interventions. Further population-based studies in the Middle East are needed to identify modifiable risk factors for timely preventive and therapeutic interventions.

Sex-specific contemporary trends in incidence, prevalence and survival of patients with non-valvular atrial fibrillation: A long-term real-world data analysis.

INTRODUCTION: Atrial fibrillation (AF) is a major increasing public health problem worldwide, with clinical and epidemiological differences between men and women. However, contemporary population-level data on incidence and survival are scarce. AIM: To evaluate sex-specific contemporary trends in the incidence, prevalence, and long-term survival of non-valvular AF in a real-world setting. METHODS: AF patients diagnosed between 2007-2015, insured by a large, state-mandated health organization in Israel (Maccabi Healthcare Services) were included. AF was diagnosed based on registered diagnoses. Patients with valvular disease, active malignancy, cardiac surgery ≤ 6 months, or recent pregnancy, were excluded. Annual incidence rate, period prevalence, and 5-year survival for each calendar year during the study period, were calculated. RESULTS: A total of 15,409 eligible patients (8,288 males, 7,121 females) were identified. Males were more likely to be younger, have higher rates of underlying diseases (ischemic heart disease, heart failure, and chronic obstructive pulmonary disease), but with lower rates of hypertension and chronic kidney diseases as compared to female patients. During the study period, age-adjusted incidence decreased both in men: (-0.020/1,000-person year, p-for trend = 0.033) and, women (-0.025/1,000 person-year p = 0.009). The five-year survival rate was significantly higher among men vs. women (77.1% vs. 71.5%, respectively, p<0.001). Age-adjusted prevalence increased significantly among men (+0.102 per year, p-for trend<0.001) yet decreased among women (-0.082 per year, p-for trend = 0.005). A significant trend toward improved long-term survival was observed in women and not in men. CONCLUSIONS: The current study shows significant sex-related disparities in the incidence, prevalence, and survival of AF patients between 2007-2015; while the adjusted incidence of both has decreased over-time, prevalence and mortality decreased significantly only in women.