Drug-drug interactions with warfarin: A systematic review and meta-analysis.

AIMS: The objective of this paper is to systematically review the literature on drug-drug interactions with warfarin, with a focus on patient-important clinical outcomes. METHODS: MEDLINE, EMBASE and the International Pharmaceutical Abstract (IPA) databases were searched from January 2004 to August 2019. We included studies describing drug-drug interactions between warfarin and other drugs. Screening and data extraction were conducted independently and in duplicate. We synthesized pooled odds ratios (OR) with 95% confidence intervals (CIs), comparing warfarin plus another medication to warfarin alone. We assessed the risk of bias at the study level and evaluated the overall certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Of 42 013 citations identified, a total of 72 studies reporting on 3 735 775 patients were considered eligible, including 11 randomized clinical trials and 61 observational studies. Increased risk of clinically relevant bleeding when added to warfarin therapy was observed for antiplatelet (AP) regimens (OR = 1.74; 95% CI 1.56-1.94), many antimicrobials (OR = 1.63; 95% CI 1.45-1.83), NSAIDs including COX-2 NSAIDs (OR = 1.83; 95% CI 1.29-2.59), SSRIs (OR = 1.62; 95% CI 1.42-1.85), mirtazapine (OR = 1.75; 95% CI 1.30-2.36), loop diuretics (OR = 1.92; 95% CI 1.29-2.86) among others. We found a protective effect of proton pump inhibitors (PPIs) against warfarin-related gastrointestinal (GI) bleeding (OR = 0.69; 95% CI 0.64-0.73). No significant effect on thromboembolic events or mortality of any drug group used with warfarin was found, including single or dual AP regimens. CONCLUSIONS: This review found low to moderate certainty evidence supporting the interaction between warfarin and a small group of medications, which result in increased bleeding risk. PPIs are associated with reduced hospitalization for upper GI bleeding for patients taking warfarin. Further studies are required to better understand drug-drug interactions leading to thromboembolic outcomes or death.

Barriers and facilitators to optimal oral anticoagulant management: a scoping review.

Oral anticoagulants (OACs) are high alert medications and require high-quality management to optimize health outcomes. The objective of this scoping review was to identify barriers and facilitators (B&Fs) associated with the quality of OAC management. We searched MEDLINE, EMBASE, and CINAHL databases until July 12, 2018, and cross-referenced the bibliographies of the retrieved studies. We included quantitative and qualitative studies that assessed B&Fs to OAC management. The study selection and data extraction processes were performed in duplicate. Analyses included measuring the prevalence of reported B&Fs from studies reporting quantitative data, identifying B&Fs in narrative analyses, and identifying their impact on important outcomes of OAC management. B&Fs were coded and aggregated to higher-level themes using a consensus approach. Factors were described as "key" if they were statistically associated with important outcomes in a randomized trial or observational study. We included 62 studies-three randomized clinical trials (RCTs), 46 observational studies (cross-sectional studies, cohort studies, and case-control studies), 11 qualitative studies, and two mixed-methods studies. Factors identified could be grouped into four themes-therapy-related, patient-related, healthcare provider-related, and health system-related. Key barriers to optimal OAC management were mostly patient-related, whereas interventions focused on education or implementing protocols were shown through RCTs to be effective at improving knowledge scores of OAC patients. While multiple barriers and some facilitators were identified in this review, none was proven to be associated with clinical outcomes. With this in mind, individual physicians may wish to address the key barriers in their practice as a quality improvement initiative but system-wide or policy changes should await high-quality evidence. Future trials should address these factors.Systematic review registration: PROSPERO CRD42017069043.

Do telehealth interventions improve oral anticoagulation management? A systematic review and meta-analysis.

The benefits and harms of telehealth interventions compared to usual care for oral anticoagulation management are unclear. A systematic review and meta-analysis was conducted to assess their impact on clinically important outcomes. A search was conducted through MEDLINE, EMBASE and CENTRAL databases, and the retrieved citations were independently screened and extracted by two review authors. Cochrane Collaboration-recommended tools were used to assess for risk of bias. Co-primary outcomes were major bleeding and major thromboembolic events. Of 2145 retrieved citations, 7 were included for qualitative synthesis (1 randomized controlled trial, 1 prospective cohort and 5 retrospective cohorts). None addressed direct oral anticoagulants. Telehealth interventions were mainly consisted of telephone visits by clinicians, pharmacists and specialists. Meta-analysis of 3 studies (n = 6955) showed significant improvements in the telehealth group for major thromboembolic events (RR 0.43, 95% CI 0.25-0.74, p = 0.002), but no significant difference for major bleeding events (RR 0.83, 95% CI 0.52-1.33, p = 0.44). There was no significant difference in any of the secondary outcomes. The overall GRADE quality of evidence was rated very low due to high risk of bias and low precision. Based on very low quality evidence, telehealth interventions may lower the risk of major thromboembolic events, but not other clinically important outcomes. A high quality study is likely to strongly influence these results. High quality randomized trials are recommended to better assess the benefits and harms of telehealth interventions for anticoagulation management.

Comparability of Objective Structured Clinical Examinations (OSCEs) and Written Tests for Assessing Medical School Students' Competencies: A Scoping Review.

Objective Structured Clinical Examinations (OSCEs) and written tests are commonly used to assess health professional students, but it remains unclear whether the additional human resources and expenses required for OSCEs, both in-person and online, are worthwhile for assessing competencies. This scoping review summarized literature identified by searching MEDLINE and EMBASE comparing 1) OSCEs and written tests and 2) in-person and online OSCEs, for assessing health professional trainees' competencies. For Q1, 21 studies satisfied inclusion criteria. The most examined health profession was medical trainees (19, 90.5%), the comparison was most frequently OSCEs versus multiple-choice questions (MCQs) (18, 85.7%), and 18 (87.5%) examined the same competency domain. Most (77.5%) total score correlation coefficients between testing methods were weak (r < 0.40). For Q2, 13 articles were included. In-person and online OSCEs were most used for medical trainees (9, 69.2%), checklists were the most prevalent evaluation scheme (7, 63.6%), and 14/17 overall score comparisons were not statistically significantly different. Generally low correlations exist between MCQ and OSCE scores, providing insufficient evidence as to whether OSCEs provide sufficient value to be worth their additional cost. Online OSCEs may be a viable alternative to in-person OSCEs for certain competencies where technical challenges can be met.

Adverse event rates associated with oral anticoagulant treatment early versus later after hospital discharge in older adults: a retrospective population-based cohort study.

BACKGROUND: Oral anticoagulants are commonly used high-risk medications, but little is known about their safety in transition from hospital to home. Our objective was to measure the rates of hemorrhage and thromboembolic events among older adults receiving oral anticoagulant treatment early after hospital discharge compared to later. METHODS: We conducted a retrospective population-based cohort study among Ontario residents aged 66 years or more who started, continued or resumed oral anticoagulant therapy at hospital discharge between September 2010 and March 2015. We calculated the rates of hemorrhage and thromboembolic events requiring hospital admission or an emergency department visit over a 1-year follow-up period, stratified by the first 30 days after discharge and the remainder of the year. We used multivariable regression models, adjusting for covariates, to estimate the effect of sex, prevalent versus incident use, and switching anticoagulants on events. RESULTS: A total of 123 139 patients (68 408 women [55.6%]; mean age 78.2 yr) were included. About one-quarter (32 563 [26.4%]) had a Charlson Comorbidity Index score of 2 or higher. The rates of hemorrhage and thromboembolic events per 100 person-years were highest during the first 30 days after hospital discharge (25.8, 95% CI 24.8-26.8 and 19.3, 95% CI 18.4-20.2, respectively), falling to 15.7 (95% CI 15.3-16.1) and 6.9 (95% CI 6.6-7.1), respectively, during the subsequent 11 months. Multivariable analysis showed that patients whose anticoagulant was switched in hospital and men had more hemorrhages and thromboembolic events in follow-up. INTERPRETATION: The first few weeks following hospital discharge represent a very high-risk period for adverse events related to oral anticoagulant treatment among older adults. The results support an intervention trial addressing anticoagulation management in the early postdischarge period.

Cost-related medication nonadherence in Canada: a systematic review of prevalence, predictors, and clinical impact.

BACKGROUND: Cost-related nonadherence to medications (CRNA) is common in many countries and thought to be associated with adverse outcomes. The characteristics of CRNA in Canada, with its patchwork coverage of increasingly expensive medications, are unclear. OBJECTIVES: Our objective in this systematic review was to summarize the literature evaluating CRNA in Canada in three domains: prevalence, predictors, and effect on clinical outcomes. METHODS: We searched MEDLINE, Embase, Google Scholar, and the Cochrane Library from 1992 to December 2019 using search terms covering medication adherence, costs, and Canada. Eligible studies, without restriction on design, had to have original data on at least one of the three domains specifically for Canadian participants. Articles were identified and reviewed in duplicate. Risk of bias was assessed using design-specific tools. RESULTS: Twenty-six studies of varying quality (n = 483,065 Canadians) were eligible for inclusion. Sixteen studies reported on the overall prevalence of CRNA, with population-based estimates ranging from 5.1 to 10.2%. Factors predicting CRNA included high out-of-pocket spending, low income or financial flexibility, lack of drug insurance, younger age, and poorer health. A single randomized trial of free essential medications with free delivery in Ontario improved adherence but did not find any change in clinical outcomes at 1 year. CONCLUSION: CRNA affects many Canadians. The estimated percentage depends on the sampling frame, the main predictors tend to be financial, and its association with clinical outcomes in Canada remains unproven.