The objective of this paper is to systematically review the literature on drugdrug 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),

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.

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